Sunday 19 June
09:00

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B01
09:00 - 10:40

ISRS EDUCATIONAL COURSE
Basic principles of brain radiosurgery and stereotactic body radiation therapy - General part

Moderators: Laura FARISELLI (director) (milan, Italy), Marc LEVIVIER (Chef de Service) (Lausanne, Switzerland), Ian PADDICK (Consultant Physicist) (London, United Kingdom)
09:00 - 09:25 Principles of radiosurgery. Douglas KONDZIOLKA (New York, USA)
09:25 - 09:50 Basic radiosurgery: radiobiology. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Lausanne, Switzerland)
09:50 - 10:15 Quality assurance in radiosurgery. Ian PADDICK (Consultant Physicist) (London, United Kingdom)
10:15 - 10:40 Radiosurgery for brain metastases. Alberto FRANZIN (Head) (Brescia, Italy), Silvia SCOCCIANTI (Chief) (Florence, Italy)
RED 2 ROOM
10:40

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B01.1
10:40 - 11:00

COFFEE BREAK

RED 2 ROOM
11:00

"Sunday 19 June"

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B02
11:00 - 13:00

ISRS EDUCATIONAL COURSE
Basic principles of brain radiosurgery and stereotactic body radiation therapy - Body part

Moderators: Nadia DI MUZIO (Director) (Milano, Italy), Niels HAASBEEK (Radiation Oncologist) (Amsterdam, The Netherlands), Barbara JERECZEK-FOSSA (Associate Professor - Head of Division) (MILAN, Italy), Maris MEZECKIS (radiation oncologist) (Sigulda, Latvia)
11:00 - 13:00 Indications to SBRT for central and peripheral primary lung cancer. Alessio BRUNI (MD) (Modena, Italy)
11:00 - 13:00 Patient’s positioning and motion-control for lung SBRT. Alessia SURGO (Acquaviva Delle Fonti, Italy)
11:00 - 13:00 Ablative SBRT: dose prescription and constraints for OARs. Davide FRANCESCHINI (Milan, Italy)
11:00 - 13:00 Indication to SBRT for prostate cancer (radical and post-operative setting). Stefano ARCANGELI (Milan, Italy)
11:00 - 13:00 Real-time tracking and adaptive treatments with different technologies (eg. Linac, Cyberknife, MRI-Linac). Rosario MAZZOLA (Verona, Italy)
11:00 - 13:00 Dose prescription and focal boost for prostate cancer. Giulia MARVASO (Milano, Italy)
RED 2 ROOM

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C01.2
11:00 - 13:00

ISRS EDUCATIONAL COURSE
Basic principles of brain radiosurgery and stereotactic body radiation therapy - Brain part

Moderators: Antonella DEL VECCHIO (Director) (Milan, Italy), Jean REGIS (PROFESSEUR) (MARSEILLE, France), Daniel ZWAHLEN (Winterthur, Switzerland)
11:00 - 13:00 From imaging to treatment - Radiosurgery for AVM. Alessandro LA CAMERA (Neurosurgeon) (MILAN, Italy), Edoardo BOCCARDI (milano, Italy), Zeno PERINI (Neurosurgeon) (Vicenza, Italy)
11:00 - 13:00 From imaging to treatment - Radiosurgery for Vestibular Schwannoma. Antonio NICOLATO (Neuroradiosurgeon) (Verona, Italy), Marcello MARCHETTI (physician) (Milano, Italy)
11:00 - 13:00 From imaging to treatment - Basic principles of radiosurgery in functional disease. Giorgio SPATOLA (Neurosurgeon) (Brescia, Italy), Piero PICOZZI (Consultant) (Milano, Italy)
BLUE 2 ROOM
13:00 LUNCH BREAK
14:00

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B03
14:00 - 17:00

ISRS EDUCATIONAL COURSE - HANDS-ON

14:00 - 17:00 Presentations & Hands-On with the participation of the leading SRS and SBRT companies.
ELEKTA - BRAINLAB - ACCURAY
RED 2 ROOM

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C03
14:00 - 17:00

ISRS EDUCATIONAL COURSE - HANDS-ON

14:00 - 17:00 Presentations & Hands-On with the participation of the leading SRS and SBRT companies.
ZAP SURGICAL - VIEWRAY - VARIAN
BLUE 2 ROOM
17:30

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A04
17:30 - 18:15

OPENING CEREMONY

17:30 - 18:15 Opening ceremony. Laura FARISELLI (director) (milan, Italy)
SILVER ROOM
18:15 OPENING OF EXHIBITION
Monday 20 June
08:00

"Monday 20 June"

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A10
08:00 - 09:00

BREAKFAST SEMINAR
Vestibular Schwannomas

Moderators: Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil), Alberto FRANZIN (Head) (Brescia, Italy)
Coordinator: Jean REGIS (MARSEILLE, France)
08:00 - 08:20 Point – Counter point : Early versus late radiosurgery for small vestibular schwannomas with good hearing. Douglas KONDZIOLKA (New York, USA)
for “early”
08:20 - 08:40 Point – Counter point : Early versus late radiosurgery for small vestibular schwannomas with good hearing. George BOVIS (Neurosurgeon) (Chicago, USA)
for “late”
08:40 - 09:00 Biological and radiological predictors of growth in vestibular schwannomas before and after SRS. Patrick LANGENHUIZEN (Researcher) (Tilburg, The Netherlands)
SILVER ROOM

"Monday 20 June"

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B10
08:00 - 09:00

BREAKFAST SEMINAR
Physics - New Technologies (FLASH, Lattice, Small Fields, ...)

Moderators: Antonella DEL VECCHIO (Director) (Milan, Italy), Thierry GEVAERT (Head of Medical physics) (Brussels, Belgium)
Coordinator: Ian PADDICK (London, United Kingdom)
08:00 - 09:00 Oxygen-guided radiotherapy (OGRT). Gianluca FERINI (Chief of Radiation Oncology Unit) (Viagrande, Italy)
08:00 - 09:00 FLASH and innovative / personalized fractionation schemes. Jean BOURHIS (Head of the Department of Radiation Oncology) (Lausanne, Switzerland)
08:00 - 09:00 Combined radiation / thermal dose models for hyperthermia + SRS. Iuliana TOMA-DASU (Head of Medical Radiation Physics Division) (Stockholm, Sweden)
RED 2 ROOM

"Monday 20 June"

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C10
08:00 - 09:00

BREAKFAST SEMINAR
SBRT for Genito-Urinary Tumors

Moderators: Nadia DI MUZIO (Director) (Milano, Italy), Barbara JERECZEK-FOSSA (Associate Professor - Head of Division) (MILAN, Italy)
Coordinator: Ciro FRANZESE (Milano, Italy)
08:00 - 09:00 SBRT for primary prostate cancer: the time is now. Barbara JERECZEK-FOSSA (Associate Professor - Head of Division) (MILAN, Italy)
08:00 - 09:00 Focal boost with stereotactic radiotherapy in prostate cancer. Linda KERKMEIJER (Radiation oncologist) (Nijmegen, The Netherlands)
08:00 - 09:00 SBRT for primary renal cell carcinoma: A novel tool in the toolbox. Alexander MUACEVIC (Director) (Munich, Germany)
BLUE 2 ROOM
09:15

"Monday 20 June"

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A11
09:15 - 10:15

PLENARY SESSION
Special Topics: ISRS Guidelines & ISRS Certification Programme

Moderators: Laura FARISELLI (director) (milan, Italy), Marc LEVIVIER (Chef de Service) (Lausanne, Switzerland), Arjun SAHGAL (Professor) (Toronto, Canada)
Coordinator: Arjun SAHGAL (Toronto, Canada)
09:15 - 10:15 Recurrent glioblastomas. Valentina PINZI (senior assistant) (Milan, Italy)
09:15 - 10:15 Vestibular Schwannomas – Koos I-II. Anne BALOSSIER (Dr) (Marseille, France)
09:15 - 10:15 Vestibular Schwannomas – Koos IV. Constantin TULEASCA (Staff neurosurgeon, senior lecturer) (Lausanne, Switzerland)
09:15 - 10:15 Pediatric SBRT. Erin MURPHY (Radiation Oncologoy) (Cleveland, USA)
09:15 - 10:15 ISRS Certification Programme. Ian PADDICK (Consultant Physicist) (London, United Kingdom)
SILVER ROOM
10:15 COFFEE BREAK AND EXHIBITION
10:45

"Monday 20 June"

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A13
10:45 - 12:00

PLENARY SESSION
Special Topic: Brain Metastases

Moderators: Francesco DI MECO (Head Department of Neurosurgery) (Milan, Italy), Lucia SCHWYZER (Senior Physician) (Aarau, Switzerland), Paul W. SPERDUTO (2HBK7YS$) (Durham, USA)
Coordinator: Paul W. SPERDUTO (Durham, USA)
10:50 - 11:07 Re-irradiation. Steve BRAUNSTEIN (Faculty) (San Francisco, USA)
11:07 - 11:24 Pre-irradiation before surgery. Stuart BURRI (Chairman) (Charlotte, USA)
11:24 - 11:41 Pros & Cons: Staged SRS versus fractionation in large brain metastases. Eduardo LOVO IGLESIAS (Brain and Spine Radiosurgery Program) (San Salvador, El Salvador)
for “staged”
11:41 - 12:00 Pros & Cons: Staged SRS versus fractionation in large brain metastases. Giuseppe MINNITI (Consultant) (roma, Italy)
for “fractionation”
SILVER ROOM
12:00

"Monday 20 June"

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A14
12:00 - 13:00

PARALLEL SESSION
Skull-base Societies Session: Combined Approaches in Skull-base Tumors

Moderators: Paolo CAPPABIANCA (Italy), Marc LEVIVIER (Chef de Service) (Lausanne, Switzerland), Davide LOCATELLI (Professor, Head neurosurgery dpt.) (Varese, Italy)
Coordinator: Giovanni DANESI (Bergamo, Italy)
12:00 - 13:00 Vestibular Schwannomas. Roy Thomas DANIEL (Médecin Chef, Associate Professor) (lausanne, Switzerland)
12:00 - 13:00 Pituitary tumors. Douglas KONDZIOLKA (New York, USA)
12:00 - 13:00 Paragangliomas. Giovanni DANESI (head of Dept.) (Bergamo, Italy)
SILVER ROOM

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B14
12:00 - 13:00

PARALLEL SESSION
SBRT for Pancreatic and Liver Tumors

Moderators: Nicolaus ANDRATSCHKE (Consoultant) (Zürich, Switzerland), Marta SCORSETTI (Director Department) (Rozzano-Milan, Italy)
Coordinator: Marta SCORSETTI (Rozzano-Milan, Italy)
12:00 - 13:00 The role of SBRT for hepatocellular carcinomas. Alejandra MENDEZ-ROMERO (Medical Staff) (Rotterdam, The Netherlands)
12:00 - 13:00 Liver metastases treated with SBRT: results and comparison with other local treatments. Tiziana COMITO (Rozzano, Italy)
12:00 - 13:00 SBRT for inoperable and borderline resectable pancreatic cancer. Anna BRUYNZEEL (Amsterdam, The Netherlands)
RED 2 ROOM
13:00

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A15b
13:00 - 14:00

SPONSORED LUNCH SYMPOSIUM

SILVER ROOM
LUNCH - EXHIBITION
14:00

"Monday 20 June"

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A16
14:00 - 15:00

ORAL PRESENTATIONS
Skull-base Societies Session: Vestibular Schwannomas

Moderators: Maurizio IACOANGELI (President) (Italy), Jeroen VERHEUL (neurosurgeon) (Tilburg, The Netherlands)
14:00 - 14:10 #29389 - OP01 Multisession compared to single-session radiosurgery to preserve the hearing in patients affected by sporadic vestibular schwannoma. The results from a prospective randomized clinical trial.
OP01 Multisession compared to single-session radiosurgery to preserve the hearing in patients affected by sporadic vestibular schwannoma. The results from a prospective randomized clinical trial.

Objective. Radiosurgery for acoustic schwannoma is continuously increasing.

The attention is actually focusing on the hearing function sparing.

The aim of the present study is to investigate about potential advantages of multisession radiosurgery(mRS) compared to single session radiosurgery(sRS) in terms of hearing preservation in patients with serviceable hearing.

Patients and methods. The primary end-point of this prospective, randomized clinical trial is the difference in term of hearing preservation between patients treated with mRS and sRS because of a sporadic acoustic neuroma.

The conditions for patient eligibility are:

-sporadic acoustic neuroma diagnosis.

-Age≥18 years old

-KPS≥70

-Serviceable hearing: class A/B (AAOHNS classification)

-Written consent

All the enrolled patients are clinically, radiologically and audiometrically evaluated.

The volumetric analysis of the tumor is always performed.

Results. One-hundred-eight patients were enrolled and treated according to the study protocol.

Three patients refused the treatment after the randomization process and in 4 cases the eligibility criteria were not satisfied, 101 patient were therefore evaluated.

Forty-seven patients had a 12Gy sRS on a mean volume of 1.9cc; 54 patients had a mRS (18Gy/3 fractions) on mean volume of 1.7cc.

After a mean follow-up period of 34 months (range 4-97 months) 59 patients (58%) maintained a serviceable hearing. No significant differences were observed between sRS and mRS in term of hearing preservation. Particularly, forty-two patients (42%) experienced a hearing deterioration (class C and D); with 21 patients undergoing sRS and 21 mRS. The most important predictor factor was the pre-treatment haring status. The treatment related toxicity was always mild. The most common side effect was a transient balance impairment.

Along all the observation period three patients required surgery because of tumor progression. One patient had an excellent surgical outcome (HB1); one had an intermedium outcome (HB2-3),while the third developed a complete facial palsy (HB4). In all these cases, the histology confirmed the radiological diagnosis of schwannoma.

Conclusions. At our knowledge, the present clinical trial is the first one comparing two different radiosurgical regimens in terms of hearing sparing.

While we are waiting for a longer follow-up period, the preliminary results from this study suggest that mRS has no advantages compared to sRS in terms of hearing preservation.

Our preliminary results suggest that the better is the auditory function at the moment of the treatment, the more probable is the hearing preservation.

The volumetric analysis confirms the very good post radiosurgery tumor control rate.


Marcello MARCHETTI (Milano, Italy), Valeria CUCCARINI, Irene TRAMACERE, Irene CANE, Francesco GHIELMETTI, Sara MORLINO, Valentina PINZI, Cecilia IEZZONI, Laura FARISELLI
14:10 - 14:20 #29314 - OP02 - WITHDRAWN - TUMOR CONTROL AND HEARING PRESERVATION AFTER GAMMA KNIFE RADIOSURGERY FOR VESTIBULAR SCHWANNOMAS IN NEUROFIBROMATOSIS TYPE 2.
OP02 - WITHDRAWN - TUMOR CONTROL AND HEARING PRESERVATION AFTER GAMMA KNIFE RADIOSURGERY FOR VESTIBULAR SCHWANNOMAS IN NEUROFIBROMATOSIS TYPE 2.

OBJECTIVE : One of the first-line treatment options for small to medium-large VSs is radiosurgery. Although radiosurgery shows excellent results in sporadic VS, its use in NF2- related VS is still a topic of debate. The aim of this study was to evaluate long-term tumor control, hearing preservation rates, and assess factors which could predict these outcomes. Also tumors which underwent retreatment following GKRS was evaluated.

METHODS : This was a Single institute retrospective analysis of all cases of NF2 associated VS fulfilling Manchester criteria who underwent GKRS between 2009 and 2019.The median marginal dose was 12 Gy. Patients’ case records,radiology and audiometric charts were analysed. Patients with follow up of less than one year were excluded. Loss of tumor control was defined as greater than 10% increase in volume in more than one follow up imaging or the need for retreatment in the form of repeat GKRS or surgery.Actuarial tumor control rates were estimated using the Kaplan-Meier curves. Trigeminal and facial nerve function were assessed before and after treatment.Hearing preservation rates waere assessed at last follow up.

RESULTS: A total of 85 patients with 133 VSs were included in the study. The mean age was 29.8 years(12-65 years).The tumor was more common in males with M: F ratio of 11:6. 71 patients had a median follow up duration of 34.1 months(14- 111 months).57 tumors(49.6%) showed tumor regression, 35 tumors(30.4%) showed stable disease and 23 tumors progressed in size(15%) at last follow up.Actuarial tumor control rates in NF2 patients after 1, 3, 5 and 9 years were 95%, 79%, 75%, and 55% respectively with overall tumor control rate being 85%.Serviceable hearing preservation rate at last follow up was 61.7% with total hearing preservation rate of 66.9%.There was no treatment related mortality.One patient developed transient trigeminal neuralgia.Facial nerve function worsened in 4 patients(3.3%) two of whom received secondary GKRS.4 patients(5 tumors) underwent retreatment with GKRS at a median duration of 27.6 months(19-36 months) following first GKRS.All tumors had regressed in the follow up with one case of worsening of hearing grade and new onset facial palsy.2 patients required surgery following GKRS.

CONCLUSIONS :This is the largest radiosurgical series of NF2 associated VS reported till date.GKRS provides a high rate of long-term local tumor control with a low risk of neurological injury for patients with these tumors.The need for retreatment with GKRS although low,is associated with good tumor control and lesser complications.


Bhavya PAHWA (New Delhi, India), Gour Surya SRI KRISHNA, Deepak AGRAWAL
14:20 - 14:30 #30185 - OP03 An update on the influence of the pretreatment growth rate on the efficacy of gamma knife radiosurgery for vestibular schwannomas.
OP03 An update on the influence of the pretreatment growth rate on the efficacy of gamma knife radiosurgery for vestibular schwannomas.

Introduction

Prognostic factors of tumor control after Gamma Knife radiosurgery (GKRS) for vestibular schwannomas (VS) remain largely unknown. Four years ago, we reported that the growth rate of VS before GKRS is indicative of the probability that radiosurgery achieves tumor control. These findings may have important implications for treatment strategies and may lead to advise for either microsurgery or higher marginal doses for fast-growing tumors. The objective of this study is to validate the previously obtained results in the correlation between the pretreatment growth rate and tumor control after GKRS, using an updated and significantly larger dataset.

 

Methods

Patients treated between 2002 and 2015 were identified, who had a pretreatment scan available of at least 6 months prior to treatment and had at least 2 years of follow-up after GKRS. Tumor volumes before, at, and after treatment were assessed. GKRS was performed in a uniform way with a marginal dose between 11 and 13 Gy. Treatment failure was defined as radiological progression beyond 2 years after GKRS. Volume doubling times (VDTs) before treatment were correlated with the observed tumor control rates and volumetric responses after treatment. Kaplan-Meier and Cox regression analyses were employed to investigate the effect of the VDT on the treatment response.

 

Results

A total of 402 patients met the inclusion criteria. The median follow-up time is 85 months. In this cohort, 50 patients showed a radiological failure. The resulting 5- and 10-year tumor control rates are 92.7% and 83.2%, respectively. The calculated VDTs vary between 3 and 344 months, with a median VDT of 15 months. Splitting the cohort into two sub-cohorts using the median VDT, results in 5- and 10-year control rates of 87.1% and 74.3% for the faster growing tumors, and 97.8% and 91.8% for the slower growing tumors, respectively (log-rank, p<0.001) (Figure 1). The Cox regression analyses demonstrate a statistically significant effect (p=0.009) of the pretreatment growth rate on tumor control, thereby enabling the probability calculation of obtaining tumor control after GKRS.

 

Conclusion

This updated and more extensive study clearly verifies our earlier findings: the pretreatment growth rate correlates with the observed tumor control after GKRS. More specifically, it denotes that fast-growing tumors are less likely to obtain tumor control. Our Cox regression model enables the calculation of the risk at treatment failure on an individual basis. Furthermore, these results might justify alterations in the management of VS.


Patrick LANGENHUIZEN, Patrick LANGENHUIZEN (Tilburg, The Netherlands), Stefan CORNELISSEN, Sammy SCHOUTEN, Henricus KUNST, Peter DE WITH, Jeroen VERHEUL
14:30 - 14:40 #29961 - OP04 Combined approaches for large vestibular schwannomas in a series of 50 consecutive cases.
OP04 Combined approaches for large vestibular schwannomas in a series of 50 consecutive cases.

Background: The microsurgical management of large vestibular schwannomas (VS) yields a high risk for the facial and cochlear nerve functions. Gamma Knife radiosurgery (GKRS) allows optimal functional results in small- and medium-size VS, but cannot be used upfront in large VS because of the high rate of volume-related side effects. 

Methods: In this context,we developed of a new treatment paradigm of combined approach with microsurgery and GKRS,
aiming at optimal functional outcome for the facial and cochlear nerves in patients with large VS (i.e. Koos grade IV).
 Data pertaining to patient characteristics, surgical and dosimetric features and outcome were collected prospectively at time of treatment and during the follow-up course. We report our long-term follow-up using this approach on 50 consecutive patients.  

Results: The mean presurgical tumor volume was 11.25 cm3 (1.47-34.9) and mean follow-up after surgery was 39.4 months (range 6-102).All cases had normal facial nerve function (HB I) before surgery, except for one who was in HB IV, and one in HB III. Postoperative status showed normal facial nerve function (House-Brackmann grade I) in all patients, with the exception of the one who was in HB III preoperatively and which remained in HB III after surgery. In a subgroup of 29 patients in which cochlear nerve preservation was attempted at surgery (patients with residual hearing before surgery), 27 of them (93.1%) retained residual hearing. 19 patients had normal hearing (Gardner-Robertson class 1) before surgery, and 16 (84.2%) retained normal hearing after surgery. The mean duration between surgery and GKRS was 6.2 months (4-13.9, median 6 months). The mean tumor volume at the time of GKRS was 3.3 cm3 (0.5-9.9), which corresponds to a mean residual volume of 31.7% (range 3.6-50.2) of the pre-operative volume. There was a tendency towards larger postoperative residual volume in patients with attempt to cochlear nerve preservation. The mean marginal prescription dose for GKS was 11.9 Gy (range 11-12, median 12 Gy). Four patients were considered a failure and benefitted from a second combined approach in 3 cases and only GKRS, in one case. Three patient benefitted from a VP shunt.  

Conclusion: Our data suggest that the combined management of large VS with planned subtotal resection followed by GKRS may yield an excellent clinical outcome with respect to retaining facial and cochlear nerve functions. Our results with this approach are comparable to those obtained with GKRS alone in small- and medium-size VS. 


Marc LEVIVIER (Lausanne, Switzerland), Constantin TULEASCA, Mercy GEORGE, Raphael MAIRE, Luis SCHIAPPACASSE, Roy Thomas DANIEL
14:40 - 14:50 #29399 - OP05 Hypofractionated Stereotactic Radiosurgery for Koos Grade IV Vestibular Schwannomas.
OP05 Hypofractionated Stereotactic Radiosurgery for Koos Grade IV Vestibular Schwannomas.

Objectives: The Koos classification is frequently used for vestibular schwannomas (VS), and Koos grade IV VS are large tumors with brainstem and cranial nerve displacement. These giant tumors adversely affect patients, and the goal of treatment is to achieve oncological control against a good postoperative functional outcome in facial or cochlear nerves. Although microsurgical resection is suggested as the treatment of choice, a tendency towards hypervascularity and adhesion to neurological structures should be kept in mind. Hypofractionated Gamma Knife radiosurgery (hf-GKRS) has been suggested as an alternative for VS. This retrospective, single-center study evaluated patient outcomes of upfront hf-GKRS for Koos grade IV VS.

Methods: Twenty-two patients (12 males and 10 females) were treated with upfront hf-GKRS. The median age of the patients was 48 years (range, 27-74 years). The most common indication for hf-GKRS was patient preference (22.7%). Prior to hf-GKRS, 11 patients (50%) had hearing loss (defined as Gardner-Robertson Grade III and IV), one patient (4.6%) had House-Brackmann Grade II facial palsy, and four patients (18.2%) had trigeminal nerve dysfunction. The median time from diagnosis to hf-GKRS was 3 months (range, 0-48 months). The median tumor volume was 10.55 cm3 (range, 6.2-18.6 cm3). The most commonly used fractionation scheme was 3x6 Gy (81.8%).

Results: The median follow-up was 23 months (range, 17-38 months), and tumor control was achieved in all patients, with regression in 11 patients (50%). A serviceable hearing was retained in all 11 patients at the last follow-up. Adverse radiation effects were observed in three patients (13.6%), with one patient having brainstem edema and two patients having trigeminal neuralgia. All patients were managed with medical treatments. One patient (4.6%) had new-onset hydrocephalus and underwent ventriculoperitoneal shunting.

Conclusions: We have demonstrated that hf-GKRS can be an effective and safe alternative to surgery in select patients with Koos IV VS. Further, well-designed studies are required to establish the long-term efficiency of hf-GKRS in the management of Koos IV VS. 


Yavuz SAMANCI (Istanbul, Turkey), Mustafa BUDAK, Fatih KARAKÖSE, Selçuk PEKER
14:50 - 15:00 #30085 - OP06 20-year follow up of neuromas and meningiomas after linac-based srs.
OP06 20-year follow up of neuromas and meningiomas after linac-based srs.

   Intracranial tumors have been traditionally treated with surgery. Novel RT techniques, such as stereotactic radiosurgery (SRS), have expanded therapeutic options in this field. As the literature reports high control rates and limited toxicity after stereotactic radiosurgery for intracranial neuromas and meningiomas SRS has been established as an appealing option for both clinicians and patients. Although radiosurgery has been traditionally performed as Gamma Knife or Cyberknife surgery nowadays widely available linac-based approaches have gained popularity.

   In this single institution study, we present the results of linac-based stereotactic radiosurgery after a long follow up of patients treated for benign intracranial neuromas and meningiomas focusing on local control and toxicity. Thirty-four consecutive patients were treated during 2000-2004 with primary or postoperative SRS for tumors less than 3.5 cm in maximum diameter.

   Stereotactic radiosurgery was performed using the 6 MV beam of a non-dedicated Elekta SL-18 linear accelerator converted for radiosurgery with the attachment of an isocentric subsystem (Phillips SRS200XK). Non-coplanar arc irradiation was delivered with circular collimators ranging in diameter from 10-30 mm. A stereotactic headring fixation was used. A treatment plan was achieved using 1-8 isocenters. Neuroma patients were treated with 11-12 Gy, while larger doses of 12-15.5 Gy were given to meningioma patients. Combining a different number, span and weight of noncoplanar arcs, as well as weight and collimator size of each isocenter used, high conformality of the treatment dose to the borders of the tumor was established.    Since nervous tissue is a late responding tissue, a long follow up is required after radiosurgery for benign intracranial tumors to assess not only tumor control but also RT-related toxicity. SRS patients were followed up twice yearly for the first year and annually thereafter. Imaging studies as well as cranial nerve assessment were mandatory. Clinical follow up was obtained from the patients or their referral doctors.

   After twenty years 26 patients are still in follow up and high rates of local control are documented with no cases of treatment failure Tumor shrinkage was observed in 61,5% and 58%  of neuroma and meningioma patients, respectively. Toxicity was minimum with no patient developing new permanent facial or trigeminal neuropathy.

   Overall, our study confirms the efficacy and safety of linac-based stereotactic radiosurgery after extended follow up for neuroma and meningioma patients.


George PISSAKAS (Athens, Greece), Paraskevi GEORGOLOPOULOU, Maria Angeliki KALOGERIDI, Kleanthi DOUKAKI, Efthimios ANDRIOTIS, George ARCHONTAKIS, Nikolaos KORDIOLIS
SILVER ROOM

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B16
14:00 - 15:00

ORAL PRESENTATIONS
Physics (1)

Moderators: Georgios KRITSELIS (ATHENS, Greece), Giacomo REGGIORI (Medical Physicist) (Milan, Italy)
14:00 - 14:10 #30153 - OP07 Benchmarking Tests of Contemporary SRS Platforms: Have Technological Developments Resulted in Improved Treatment Plan Quality?
OP07 Benchmarking Tests of Contemporary SRS Platforms: Have Technological Developments Resulted in Improved Treatment Plan Quality?

Introduction

The technological evolution of SRS equipment, where the demands of conformity, gradient and accuracy are at its highest, is significant. Six years on from the 2016 UK benchmarking study [Eaton et al], new technology poses the question “have technological improvements led to a corresponding improvement in treatment plans?”. This benchmarking study assesses the capabilities of the following platforms which were selected as ‘state of the art’ in 2022: Gamma Knife Icon with Lightning inverse planning (GK), Cyberknife S7 with M6 MLC, BrainLab Elements (Elekta VersaHD and Varian TrueBeam), Varian Edge with HyperArc (both 6X-FFF and 10X-FFF), Zap-X.

Methods and Materials

Six cases (two multiple metastasis cases, four benign targets) were used from the previous study. In order to reflect the evolution of the increased number of metastases treated per patient, a case with 14 targets was added. 28 targets amongst the seven patients ranged from 0.02cc to 7.2cc in volume.

Participating centres were sent DICOMRT files containing images, target contours and potential OARs for each treatment plan. They were asked to plan each treatment to the best of their ability using experienced staff (defined as at least two years’ experience with the relevant platform). 

While some variation in local practice was allowed (eg. the use of margins), groups were asked to prescribe a specified dose to each target and tolerance doses to organs at risk were agreed in advance.

Parameters used for comparison between the plans, included coverage, selectivity, Paddick Conformity Index (PCI), Gradient Index (GI), R50%, Efficiency Index, doses to OARs, estimated planning and estimated treatment time.

Results

Mean coverage for all targets ranged from 98.2% (Brainlab/Elekta) to 99.7% (Hyperarc 6X). PCI values ranged from 0.722 (Zap-X) to 0.900 (CyberKnife). GI ranged from a mean of 3.15 (Zap-X), representing the steepest dose gradient to 5.08 (HyperArc 10X). The GI appeared to follow a trend with beam energy, with the lowest values from the lower energy platforms (Zap-X; 3MV, GK; 1.25MeV) and the highest value from the highest energy (HyperArc 10X).

R50% values (excluding case 7), which are combination of conformity and gradient indices, had a minimum mean value of 3.65 (GK) and a maximum mean value of 4.76 (Hyperarc 10X). Treatment times were lowest with modified linacs.

Conclusion

Compared with earlier studies, newer equipment appears to deliver higher quality treatments. CyberKnife and Linac platforms appear to give better conformity while lower energy platforms give better dose gradient.


Ian PADDICK (London, United Kingdom), James BEDFORD, Peter FILATOV, Judith MOTT, Gavin ORCHIN, Diana GRISHCHUK, David EATON
14:10 - 14:20 #29586 - OP08 Evaluation of a novel dose optimization software Leksell Gamma Knife Lightning – comparison of treatment plans for 40 challenging clinical cases.
OP08 Evaluation of a novel dose optimization software Leksell Gamma Knife Lightning – comparison of treatment plans for 40 challenging clinical cases.

Purpose: There are three approaches in treatment planning for Leksell Gamma Knife Icon: 1) manual, 2) inverse planner for Icon and 3) Lightning dose optimization. In the first two methods a reasonable number of isocenters are being placed inside the target volume with relatively small overlap. Various weighting factors and hybrid isocenters (mixture of 4, 8, 16 mm collimators together with blocks) can be used. In opposite the Lightning is using a very large number of isocenters with a very large overlap. It can be described as a “painting” of dose distribution due to very small position change in individual isocenters.

Materials and Method: Fourty patients (10 meningiomas, 10 acoustic schwannomas, 10 pituitary adenomas, 10 metastases) were selected for comparison. Patients with larger treatment volumes (1.8 – 23.0 cm3, median 7.6 cm3) and challenging cases were selected. Following parameters were used to assess benefits in new treatment planning approach: target mean dose, target coverage, selectivity, gradient index, Shaw conformity index, volume of 12 Gy, volume of 80% and 90% isodose, maximal dose to optic nerve, brainstem and cochlea, mean dose to cochlea and pituitary, beam-on time and number of isocenters used. Time for Lightning to calculate the treatment plan was also measured.        

Results: Extremely short time (14 – 108 s, median 35 s) was observed for calculation of all cases when using Lightning. With the same target volume coverage (median 0.99), Lightning used always more (16 - 86, median 41) isocenters to achieve the goal. Following percentages are given for medians to compare Lightning with former methods. Target mean dose was reduced by 5.7%, selectivity improved by 8.9%, gradient index improved by 0.2 %, Shaw conformity index improved by 8.7%, volume of 12 Gy was reduced by 5.2%, volume of 80% and 90% isodose increased by 9.1% and 5.0%, respectively. Doses to critical structures improved by 12.3% (optic), 8.9% (cochlea), 5.0% (pituitary). Beam-on time was reduced in the case of Lightning by 14.4%.   

Conclusions: Practically in all studied parameters Lightning dose optimization software was superior to former methods. It is capable to generate not even better plans in terms of dosimetry characteristics, lower doses to critical structures but also plans with shorter beam-on time.   

Keywords: Leksell Gamma Knife, inverse planning, dose optimization, Lightning

This study was supported by the Ministry of Health, Czech Republic - conceptual development of research organization (Na Homolce Hospital - NNH, project No. IG174701).


Josef NOVOTNY (Prague, Czech Republic), Lucie HAMACKOVA, Marketa FARNIKOVA, Roman LISCAK, Dusan URGOSIK
14:20 - 14:30 #29647 - OP09 Implementation of IAEA TRS 483 in small field dosimetry of Leksell Gamma Knife Icon – transition from IAEA TRS 398 to IAEA TRS 483.
OP09 Implementation of IAEA TRS 483 in small field dosimetry of Leksell Gamma Knife Icon – transition from IAEA TRS 398 to IAEA TRS 483.

Purpose: Traditional dosimetry calibration of small Leksell Gamma Knife (LGK) beams was based on IAEA TRS 398 protocol. New IAEA TRS 483 protocol is available since 2017. Contrary to TRS 398, new small field TRS 483 protocol takes into account non-standard conditions e.g. very small field size, specific geometry, phantom used for measurement and etc. The purpose of this study was to perform transition from TRS 398 to TRS 483.

Materials and Method: Two Elekta plastic spherical phantoms were used: 1) acrylonitrile butadiene styrene (ABS) and 2) Solid Water (SW). Special inserts were made in each phantom to accommodate PTW 31010 Semiflex ion chamber with sensitive volume 0.125 cm3 (used for absolute dose calibration) and PTW 60019 microDiamond detector with sensitive volume 0.004 mm3 (used for output factors (OF) measurement). PTW Unidos electrometer was used for both absolute and relative dosimetry. Both TRS 398 and TRS 483 protocols and both ABS and SW phantoms were used for absolute and relative dosimetry.

Results: The optimal conditions for dose rate measurement are in SW phantom and following TRS 483 protocol. SW phantom is almost water equivalent (and thus very small corrections need to be applied), better mimics real clinical situation (patient fixation in treatment position) and due to longitudinal ion chamber orientation minimizing stem effect. Other results showed following deviations compare to SW and TRS 483: -1.97%, -0.55% and -0.37% for ABS phantom and TRS 398, for ABS phantom and TRS 483 and for SW phantom and TRS 398, respectively. OF measurements with microDiamond in ABS phantom for 8 mm collimator showed -0.1% and 0.6% deviation to Monte-Carlo calculated vendor default values when using TRS 398 and TRS 483, respectively, for 4 mm 2.1% and 1.4% deviation for TRS 398 and TRS 483, respectively. OF measurements with microDiamond in SW phantom for 8 mm collimator showed -1.5% and -1.0% deviation when using TRS 398 and TRS 483, respectively, for 4 mm 2.1% and 1.4% deviation for TRS 398 and TRS 483, respectively.    

Conclusions: Re-calibration of LGK Icon was made based on TRS 483 protocol which better reflects small field dosimetry conditions. Relatively small (within 2%) deviations to existing calibration and default OF values were observed.

 

Keywords: small field dosimetry, IAEA TRS 483, Leksell gamma knife Icon

 

This study was supported by the Ministry of Health, Czech Republic - conceptual development of research organization (Na Homolce Hospital - NNH, project No. IG 141202).


Josef NOVOTNY (Prague, Czech Republic)
14:30 - 14:40 #29701 - OP10 Gantry triggered x-ray verification of patient positioning during single-isocenter stereotactic radiosurgery using ExacTrac Dynamic: increasing certainty of lesion localization.
OP10 Gantry triggered x-ray verification of patient positioning during single-isocenter stereotactic radiosurgery using ExacTrac Dynamic: increasing certainty of lesion localization.

1.       Introduction and purpose

 

Single-isocenter linac-based stereotactic radiosurgery (SRS) has emerged as a dedicated treatment option for multiple brain metastases. To do so, image-guidance for patient positioning and motion management is becoming very important. The purpose of this study was to analyze the translational and rotational intra-fraction errors during SRS, by applying surface-guidance coupled with gantry triggered stereoscopic x-ray verifications during the arc delivery. The benefits of such a positioning system were also assessed.



2.                  Materials and methods

 

Treatments were planned with non- coplanar dynamic conformal arcs for 24 patients corresponding to 93 brain lesions. Intra-arc positioning errors were measured using stereoscopic x-rays (ExacTrac Dynamic, BrainLAB, Munchen, Germany), triggered in the middle of every treatment arc (234 arcs in total). Couch corrections above 0. mm and 0.5° are always applied. Intra-arc positioning data was analyzed and compared to those of a previous study in our department, where intra-fraction stereoscopic x-rays were only taken after each couch rotation.



3.                  Results and discussion

 

Intra-arc errors ranged between 0 mm and 1.64mm for translations and 0° and 0.88° for rotations (Figure 1). Total 3D displacement ranged between 0.03 mm and 1.64mm. 95th percentiles of errors across all arcs delivered were 0.58mm, 0.47mm and 0.32mm for longitudinal, lateral and vertical displacements, and 0.46°, 0.27° and 0.43° for roll, pitch and yaw rotations respectively. Mean errors across all patients were 0.18mm, 0.07mm and 0.16mm for longitudinal, lateral and vertical displacements, and 0.13°, 0.12° and 0.11° for roll, pitch and yaw rotations (Table 1). 6 out of 24 patients showed at least one arc above the correction thresholds (0.7mm for translations, 0.5° for rotations), corresponding to 17 treatment arcs (7% of delivered beams). When compared to inter-beam errors measured after table rotation, the mean errors measured were considerably smaller (Figure 2), ranging from 38.2% (lateral) to 80% (longitudinal) reduction. 

 

 

4.                  Conclusions

 

Gantry triggered x-ray verification provides information of the real position of the patient during irradiation and allows verification of the couch corrections performed before every arc. When comparing inter-arc and intra-arc positioning errors, we could identify table rotation as an important source of patient motion. A beam-off strategy is to be considered when measured intra-arc errors are out of tolerance, as the frequency of corrections would not increase treatment times considerably. Intra-arc monitoring and correction with stereoscopic x-rays increases the certainty of lesion localization, making a 0 mm margin strategy possible.


Adrián GUTIÉRREZ (Brussels, Belgium), Thierry GEVAERT, Jelle SMEULDERS, Boussaer MARLIES, Tim EVERAERT, Anne-Sophie BOM, Cristina FERRO TEIXEIRA, Mark DE RIDDER
14:40 - 14:50 #30148 - OP11 Evaluation of the timing and quality of a reference beam model-based “short” commissioning.
OP11 Evaluation of the timing and quality of a reference beam model-based “short” commissioning.

Purpose and objective

Commissioning measurements are time-consuming and require high precision in execution. Reference Beam Models (RBM) consist of predefined Pencil Beam and Monte Carlo dose profiles that may dramatically reduce the number of measurements necessary to commission a beam. The purpose of this work was to evaluate the accuracy and robustness of using  the RBMs offered by BrainLab®(Munich, Germany) with the treatment planning system (TPS) Elements® for multiple brain metastases.

Materials and method

The 6MV and 10MVFFF beams of a TrueBeamSTX Linac were considered. The Linac was equipped with a HD120 MultiLeafCollimator (MLC) whose central leaves have a width of 2.5mm at isocenter.

A Beamscan water tank (PTW, Freiburg, Germany) was used with a SSD=900. Absolute dose was measured at isocenter with a Farmer-type calibrated ion chamber for a 10x10cm2 field. Profiles and PDDs were measured for 4 different MLC-defined square fields ranging from 5x5 to 220x220mm2. Output Factors were measured for the same fields and in the same set-up. A PTW MicroDiamond detector and a 0.125cc PTW Semiflex 3D ion chamber were used for all measurements. A comparison between these measurements and calculations performed in a virtual water phantom with MC-Elements and Acuros algorithms were performed.

Once the TPS was configured, some “simple” plans (i.e. without MLC) and 5 patients were planned with the Multiple Brain Metastases module and delivered. The dose distribution was verified with three different methods. The 2D fluence distribution was evaluated with Portal Dosimetry. The log-file reconstructed 3D dose distribution was evaluated with an indipendent algorithm (M3D, Mobius). The measured 3D dose distribution was evaluated with the octavius detector.

Results     

The total time required for the commissioning measurements was less than 6 hours. The best agreement between measured and modeled values both for OFs and profiles was obtained selecting a spot size of 0.4mm and 0.Xmm for 6MV and 10MVFFF beams respectively (figure 1). Calculated OFs were within 1.6% for all field sizes except for the 5x5mm were it was 4.8% (figure 2). The 3%-3mm 3DGamma >96.3% (96.3%-99.8%) for the “simple” plans. Gamma values for the 5 clinical plans were 99.5%-100% for Portal Dosimetry, 99.8%-100% for the M3D calculation and 97.3%-99.1% for the Octavius4D measurements.    

Conclusion

Machine commissioning times are dramatically reduced and compatible with clinical practice. The configuration and selection of the RBM is simple and intuitive. Good agreement between measured and calculated dose distributions was observed down to very small field sizes.


Giacomo REGGIORI (Milan, Italy), Francesco LA FAUCI, Pasqualina GALLO, Lucia PAGANINI, Francesca LOBEFALO, Andrea BRESOLIN, Pietro MANCOSU, Pierina NAVARRIA, Elena CLERICI, Luisa BELLU, Marta SCORSETTI, Stefano TOMATIS
14:50 - 15:00 #29992 - OP12 A comparative dosimetric study of Pencil Beam, Acuros XB, and Monte Carlo algorithms for stereotactic body radiosurgery of lung lesions.
OP12 A comparative dosimetric study of Pencil Beam, Acuros XB, and Monte Carlo algorithms for stereotactic body radiosurgery of lung lesions.

Introduction: The IGRT VMAT dose delivery allows more precise dose deposition and superior local control. The quality of these techniques can be enhanced by more accurate dose calculation such as Monte Carlo Algorithm (MC). The purpose of this study is to compare three commercially available dosimetric algorithms in 5 patients with Non Small Cell Carcinoma (NSCCA) and validate and compare with an in-house heterogeneous phantom mimicking the lung tumors.

Materials and methods: The GTVs and PTVs  (5mm margin) were generated for 5 anonymized patients with NSCCA. Treatment plans with 3 co-planar VMAT arcs were made to deliver 50Gy in 5 fractions to PTVs using MC and PB. The plans then exported to Eclipse planning system (EPS) and dose were recalculated using the Acuros XB (AXB) algorithm using the same leaf sequences and MUs for each VMAT beam and compared to the MC and PB results. Furthermore, an in-house heterogeneous phantom was created consisted of a Sun Nuclear diode phantom placed symmetrically between 7cm Styrofoam (HU, -800) and 3 cm solid water, on top and bottom simulating a lung cancer treatment. 3 VMAT arcs were used to deliver 16Gy to three PTVs contoured on the phantom with volumes of 4, 2, and 0.4ml using both the MC and PB dosimetric algorithms. The plans exported to EPS and the dose was recalculated using the AXB algorithm. The mean dose to the PTVs was compared with the measured dose in the phantom for each dosimetry algorithm. 

 

Results: The patients’ dose was significantly overestimated by PB when compared with MC. There is a statistically significant difference between the mean, maximum PTV dose, the conformity index, and total MUs between the PB and MC, (p-Values 0.008, 0.007, 0.03, 0.02, respectively). The mean measured and calculated dose in the phantom with MC for the 3 PTVs was within 1.1% (0.18Gy, p-Value 0.77). In comparison, the PB resulted in a statistically significant dose difference from the in-phantom measured dose (10.44%, 1.78Gy, p-Value 0.002). The mean absolute dose difference between MC and AXB was also statistically significant (4.9%, p-Value 0.01).

 

Conclusions: When compared to MC, the PB and AXB overestimated the lung tumor dose by 10.44% and 4.9%, respectively. We found the in-house phantom to be useful for this study. In the absence of MC algorithm, the limitations of the PB and AXB for lung cancer treatments should be kept in mind. Further study is warranted.

 


Javad RAHIMIAN (Los Angeles, USA), Juying ZHANG, Justin P. VINCI, Michael COHEN
RED 2 ROOM

"Monday 20 June"

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C16
14:00 - 15:00

3D Skull-base Anatomy for Safe Radiosurgery (1)

Coordinator: Siviero AGAZZI (Tampa Florida, USA)
Keynote Speaker: Siviero AGAZZI (Tampa Florida, USA)
BLUE 2 ROOM
15:00

"Monday 20 June"

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A17
15:00 - 16:00

ORAL PRESENTATIONS
Skull-base Societies Session: Meningiomas

Moderators: Lina Raffaella BARZAGHI (Consultant) (MILAN, Italy), Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)
15:00 - 15:10 #30208 - OP13 Radiosurgery for skull base meningiomas: outcomes from over 3500 cases – update a comparative analysis with anatomical nuances.
OP13 Radiosurgery for skull base meningiomas: outcomes from over 3500 cases – update a comparative analysis with anatomical nuances.

Objective: Skull base Meningiomas are the most frequent benign tumours treated with Gamma Knife Radiosurgery . However, the assessment of its efficacy and safety in slow growing tumours is an ongoing process, requiring analysis of long-term results. This study involves the experience of several European Gamma Knife Centres. We report on the efficacy of radiosurgery for the treatment of skull base Meningiomas, clinical and radiological control and side effects

Methods: From 15 participating centers, we performed a retrospective observational analysis of a cohort of 3752 benign meningiomas treated with GKRS. All were treated with Gamma Knife radiosurgery at least 5 years before assessment for this study. Clinical and imaging data were retrieved from each center and uniformly entered into a database by 1 author. A statistical analysis is presented.

Results: 3451 patients harbouring 3752 meningiomas treated in fifteen institutions recruited were evaluated. The median age was 56 years (range 6 - 89 years). The median tumour volume was 5.20 ccm (range
0.5 - 85 ccm) and tumour margin dose to the 50 % isodose line 13.5 Gy (range 3 - 45 Gy). The median radiological follow-up was 61 months, but detailed results were only available for 3259 meningiomas (86.8 %). The volume of treated tumours decreased in 1753 lesions (54 %) did not change in 1305 lesions (40 %) and increased in 200 lesions (6 %). The temporary morbidity rate after GKRS was 5.3 % and the permanent morbidity rate was 5.6 %. The actuarial control rate was 97.9 % at 5 years post Radiosurgery.

Conclusions: Radiosurgery is a safe and not invasive method of treatment of skull base meningiomas and the large number analysed confirms a high tumour control and low morbidity rate even after a long-term follow-up period.


Santacroce ANTONIO (Munich, Germany)
15:10 - 15:20 #29321 - OP14 PERIOPTIC MENINGIOMAS TREATED WITH CYBERKNIFE RADIOSURGERY (1 - 5 SESSIONS): CLINICAL RESULTS.
OP14 PERIOPTIC MENINGIOMAS TREATED WITH CYBERKNIFE RADIOSURGERY (1 - 5 SESSIONS): CLINICAL RESULTS.

Single session radiosurgery has established itself as an effective therapeutic modality in the primary or postoperative treatment of intracranial meningiomas. However, the treatment of lesions located less than 3 mm from the anterior optic pathway, represents a radiosurgical challenge due to the poor tolerance of these structures to high doses of radiation. In our study 42 patients with perioptic meningiomas were retrospectively treated with radiosurgery using Cyberknife in 1, 3 and 5 sessions, between April 2011 and April 2019. 3 patients (7%) had received previous radiotherapy and 25 patients (60%) had undergone surgery. In 62% of the cases, the lesions surrounded the anterior optic pathway, with no separation distance. 27 patients (64%) had visual impairment prior to treatment and 11 patients (26%) had involvement of other cranial nerves. 37 patients (88%) were treated in 5 sessions with a median tumor volume of 11.5 cc (0.14-37 cc). 34 of these patients received 25 Gy (5x5Gy) and one patient diagnosed with grade II meningioma received 30 Gy (5x6Gy). The other two patients, previously radiated, received 23Gy (5x4.6 Gy) and 20 Gy (5x4 Gy), respectively. 3 patients (7%) were treated in 3 sessions of 7 Gy (21 Gy) and 2 patients (5%) in a single session of 14 Gy with a median tumor volume of 6.2 cc (0.8-7.6 cc). The median tumor coverage with the prescription isodose was 98% and the median homogeneity and conformity index was 1.2 in both cases. The maximum dose in the optic pathway did not exceed 25 Gy in 5 sessions, 13 Gy in 3 sessions, and 7.7 Gy in a single session. The median clinical follow-up after treatment was 35 months (6-84 months) with MRI and campimetry. 18 patients (43%) experienced tumoral reduction and 23 patients (55%) presented stability. Only one patient had marginal progression and was surgically rescued. 19 patients (45%) had visual improvement after treatment, 21 patients (50%) remained clinically stable and two patients experienced worsening, one of them in the context of progression and the other already had previous symptoms and a bulky lesion compressing the optic pathway. Conclusions: This study shows that hypofractionated radiosurgery is a safe alternative, with excellent local control results and very low toxicity in the treatment of meningiomas whose proximity to the anterior optic pathway prevents single-dose treatments. However, a longer follow-up is necessary to fully validate these results.


Morena SALLABANDA (Madrid, Spain), Kita SALLABANDA
15:20 - 15:30 #29895 - OP15 Single-session stereotactic radiosurgery for large parasellar meningiomas.
OP15 Single-session stereotactic radiosurgery for large parasellar meningiomas.

Background

Meningiomas in close proximity to the optic pathway are commonly candidates for microsurgical decompression. More so large perioptic meningiomas. However, microsurgery itself imposes risk to vision and the larger the tumor the more the risk and lesser possibility of postoperative visual recovery. Fractionated radiotherapy is usually reserved for such cases.

 

Objective

The purpose of this study is to assess the long-term efficacy and safety of single-session stereotactic radiosurgery for large (10 cc or more) perioptic intracranial benign meningiomas.

 

Patients and methods

In this retrospective study we included 175 patients with large perioptic benign meningiomas (³ 10 cc) who were treated by single-session SRS. Perioptic meningiomas were defined as meningiomas touching, compressing or within 3 mm of the optic pathway. The median tumor volume was 15 (10-57.3 cc (IQR 8.4 cc)). The median prescription dose was 12 Gy (9-14 Gy (IQR 1 Gy)).

 

Results

The median follow up period was 72 months (13-217 months (IQR 65 months)). The tumor control rate was 92%. The PFS at 5- and 10- years was 97% and 80%. Favorable (better/stable) visual outcome was reported in 169 patients (97%) and unfavorable (worse) outcome in 6 patients (3%). Temporary adverse radiation effects were observed in 21 patients (12%) but only 7 (4%) were symptomatic. Sixty-three patients had a blind/non-useful eye according the pre-treatment visual field examination. Visual improvement was observed in blind/non-useful eye in 17 patients (27%) while vision remained unchanged in 46 patients (73%). Ocular nerve palsy improved in 36 patients (61%). Tumor shrinkage was not a prerequisite for cranial nerve improvement.

 

Conclusion

Stereotactic radiosurgery provides an effective and safe treatment option for large perioptic meningiomas.


Amr ELSHEHABY (CAIRO, Egypt), Wael A REDA, Khaled ABDEL KARIM, Reem EMAD ELDIN, Ahmed NABEEL, Sameh ROSHDY
15:30 - 15:40 #30024 - OP16 Postoperative radiosurgery in patients with meningiomas: improved planning using 68Ga-DOTATATE PET.
OP16 Postoperative radiosurgery in patients with meningiomas: improved planning using 68Ga-DOTATATE PET.

 

ABSTRACT

Background: Patients with meningiomas are typically treated with maximal safe surgical resection. After subtotal resection or at the time of tumor recurrence, stereotactic radiosurgery (SRS) is often used as the treatment of choice. While contrast-enhanced magnetic resonance imaging (MRI) is typically used for SRS target delineation, differentiating tumor growth from postoperative change can be challenging. 68Ga-DOTATATE, a positron emission tomography (PET) radiotracer targeting the somatostatin receptor type 2 (SSTR2), has been shown to be a reliable biomarker of meningiomas.

Objective: The aim of this study was to evaluate the impact of 68Ga-DOTATATE on treatment planning in patients who had previously undergone meningioma resection.

Methods: We present a consecutive case series of 13 patients with histologically-proven meningioma who received a 68Ga-DOTATATE PET between April 2019 and April 2021. Treatment planning was done at first using MRI only. The DOTATATE-PET images were then used to assess the accurate identification of tumor.

Results: Ten of the patients had WHO grade 2 meningioma and three patients had grade 1 tumor. Nine patients had recurrent meningiomas and four patients had newly diagnosed disease. Overall, the 68Ga-DOTATATE PET scan led to a change in the previously formulated treatment plans in 6 of 13 patients. Additionally, 8 of the 13 patients had foci of disease not appreciated on post-contrast MRI.

Conclusion: In this series, incorporation of 68Ga-DOTATATE PET imaging had clinical utility for most patients in whom it was used. It proved particularly useful in demonstrating intraosseous meningiomas, differentiating between recurrence and post-operative changes, and identifying sub-centimeter foci of disease. We recommend incorporating this imaging method as part of postoperative SRS for patients with meningiomas.


Michael SCHULDER (Lake Success, NY, USA)
15:40 - 15:50 #29904 - OP17 Growth dynamics of incidental meningiomas - A prospective long-term follow-up study.
OP17 Growth dynamics of incidental meningiomas - A prospective long-term follow-up study.

Background: There is no consensus for the management of incidental meningiomas. The literature on long-term growth dynamics is sparse and the natural history of these tumors

remains to be illuminated.

Methods: We prospectively assessed long-term tumor growth dynamics and survival rates during active monitoring of 62 patients (45 female, mean age 63.9) harbouring 68 tumors.

Clinical and radiological data was obtained every 6 months for two years, then annually.

Results: The natural history of incidental meningiomas during 12 years of monitoring was growth (p < 0.001). However, mean growth decelerated and became insignificant at 1.5 years.

Self-limiting growth patterns were seen in 43 (63.2 %) tumors, non-self-limiting in 20 (29.4%) and 5 (7.4 %) were indecisive due to ≤ 2 measurements. Decelerating growth persisted

once established. During follow-up, 38 (97.4 %) of 39 tumor treatments were initiated within 5 years. None developed symptoms prior to intervention. Tumor volume (p < 0.001) and relation to

venous sinuses (p = 0.039) correlated with more aggressive growth. Since inclusion 16 (25 %) patients died of unrelated causes and 2 (3 %) from atypical tumors.

Conclusion: Active monitoring seems an optimal first line management for incidental meningiomas. Intervention was avoided in > 40 % with indolent tumors. Nearly all treatments

were initiated within five years and were not compromised by tumor growth. Clinical follow-up seems sufficient beyond five years if self-limiting growth is established. Tumors with

steady or accelerating growth warrant monitoring until they reach a stable state or treatment is mandatory.


Torbjørn Austveg STRØMSNES (Bergen, Norway), Morten LUND-JOHANSEN, Geir Olve SKEIE, Geir Egil EIDE, Bente Sandvei SKEIE
15:50 - 16:00 #30046 - OP18 Assessment of post-radiosurgery response for intracranial meningiomas: is volumetric analysis the proper outlook?
OP18 Assessment of post-radiosurgery response for intracranial meningiomas: is volumetric analysis the proper outlook?

Defining both a threshold of progression and the optimal endpoint for clinical trials on radiation therapy for benign meningiomas is difficult. In fact, the growth rates of meningiomas are variable, overall survival (OS) is often very long, and progression-free survival (PFS) requires long-term follow-up. To assess radiation response various strategies have been evaluated. Although most of the published studies describe the criteria for control assessment, there is no uniform definition. Volumetric analysis of magnetic resonance imaging (MRI) imaging has been proposed as the most appropriate method for detecting change in slowly evolving brain tumors. In this scenario, we analyzed this method in post-radiosurgical intracranial meningiomas as part of a prospective clinical trial.

The primary aim of the present study was to validate a volumetric assessment method after fractionated radiosurgery or fractionated stereotactic radiotherapy (fSRS) for benign intracranial meningiomas. Secondary aims were evaluation of a cut-off to define progression, stable or partial response and volumetric response after fSRS treatment. To validate the volumetric assessment, we appraised delta values (ΔV) of volume variations. To evaluate tumor response, a volumetric analysis has been performed by means of co-registration of each follow-up MRI on baseline MRI and contouring of the lesion on each post-treatment exam.

Overall, 150 patients were considered eligible for the purpose of the volumetric analysis. After a mean follow-up of 60.5 months (SD 17.45, median 59, range 14–101 months) the median reduction in tumor volume was -21.26%, (range -82.26% to 91.36%) to reach a median final tumor of 8.65 cm3 (range 0.38 - 56.28 cm3) that differed significantly from baseline (p < 0.001). Among 150 irradiated meningiomas, 75 (50%) ultimately regressed, 67 (45%) remained stable, and 8 (5%) progressed. Baseline volumes were similar in each group (p = 0.092), and final volumes were significantly larger in tumors that progressed (p < 0.001) supporting the use of a ΔV of 20% as a cutoff for progression. The mean %ΔV became significantly different by 10 months, with continued diversion up to 36 months.

Our results suggest quantitative volumetric assessment of tumor response to fSRS may help clinicians to better understand early response profiles and provide a valuable tool for patient management following fSRS for meningiomas.


Valentina PINZI (Milan, Italy), Anna VIOLA, Irene TRAMACERE, Sara MORLINO, Elena DE MARTIN, Marcello MARCHETTI, Laura FARISELLI
SILVER ROOM

"Monday 20 June"

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B17
15:00 - 16:00

ORAL PRESENTATIONS
Physics (2)

Moderators: Alexandru DASU (Chief Medical Phyicist) (Uppsala, Sweden), Elena DE PONTI (Director) (Monza, Italy)
15:00 - 15:10 #30138 - OP19 - WITHDRAWN - Image-guided margin assessment to LINAC-based radiosurgery for single and multiple brain metastases based on post-treatment CBCT shifts.
OP19 - WITHDRAWN - Image-guided margin assessment to LINAC-based radiosurgery for single and multiple brain metastases based on post-treatment CBCT shifts.

Purpose/Objective(s): The goal of single isocenter LINAC-based stereotactic radiosurgery (SRS) using non-coplanar HyperArc™ (Varian) technique is high-precision treatment delivery for patients with brain metastases (BM) while sparing normal brain tissue to avoid complications such as radionecrosis.  LINAC-based SRS is desirable due to patient comfort and short treatment times. Planning target volume (PTV) margin is critical for targeting the gross tumor volume (GTV) and while avoiding geometric miss.  The caveat to adding PTV margin is potentially increasing the risk of radiation necrosis. Therefore, setting a proper PTV margin is crucial for SRS. The purpose of our study is to provide image-guided margin assessment based on post-treatment cone beam CT (CBCT) shifts and its dosimetric impact to target coverage for single and multiple BM patients.

Materials/Methods: 55 BM patients with total of 117 brain lesions, receiving SRS treatments were retrospectively evaluated. All patients were immobilized with the Encompass support device (Qfix) and planned with HyperArc technique. The plans consisted of 52 single, and 17 multiple BM (number of lesions ranging from 2 to 7) plans. All multiple BM targets were within 6 cm of the planning isocenter. In total, 120 single and 72 multiple BM fractions were evaluated based on post-treatment CBCTs. To evaluate target coverage loss due to intrafraction motion, MIM software was used. Shifts from post-treatment CBCTs were applied to the planning CT, and PTV/GTV dosimetric coverage was evaluated.

Results:  To evaluate target coverage loss due to intrafraction motion, 117 single BM were considered.  Of those, 25 (21%) patients had 0-1 mm margin and 92 (79%) patients had 2 mm PTV margin. The significant loss of the target coverage was observed in PTVs and GTVs in patients with 0-1 mm margin. The maximum target coverage losses were as high as 40% for PTV, and 28% for GTV with the mean target loss of 10.57±8.80% for PTVs, 6.51±8.16% for GTV. In comparison, plans with 2-mm margin showed maximum PTV target coverage loss of 16%, and mean of 4.14±3.34%. GTV losses in this group was maximum of 1% with mean value of 0.04±0.11%. For all multiple metastases BM patients, a 2-mm margin was used and no significant GTV coverage loss was noted.

Conclusions: This study demonstrates that a 2-mm margin is adequate for treating single isocenter single and multiple BM patients using LINAC-based radiosurgery based on post-treatment CBCT shifts analysis of the target coverage loss due to intrafraction motion


Tatsiana REYNOLDS (St Paul, USA), Mustafa OZER
15:10 - 15:20 #29791 - OP20 Dosimetric impact of setup errors in single-isocenter VMAT radiosurgery for multiple brain metastases.
OP20 Dosimetric impact of setup errors in single-isocenter VMAT radiosurgery for multiple brain metastases.

Purpose

In stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) of multiple brain metastases (BM) using single-isocenter volumetric arc therapy (VMAT), intra-fraction positioning errors may affect target coverage. This study aims to investigate geometric and dosimetric accuracy in such applications.

 

Material and Methods

Twenty-eight patients (79 BM) treated with single-isocenter coplanar FFF-VMAT technique were analyzed. PTV was defined by a 2 mm isotropic GTV expansion. Pre-treatment setup errors were evaluated with cone-beam CT (CBCT) and corrected with a robotic six degrees-of-freedom couch. Intra-fractional errors for each fraction were measured by post-treatment CBCT and applied to the planning CT. Plans involving translations and rotations (Fx-plan) were re-calculated with Monaco Monte Carlo TPS. Original and Fx-plans were compared in terms of dosimetric parameters, performing the Wilcoxon-Mann-Whitney test (alpha=0.05). The relationships of the BM volume, maximum dimension, distance-to-isocenter, and barycentre shift with the difference in target coverage between the two plans were investigated.

 

Results

The median post-treatment 3D error was 0.4 mm (0.1–1.5) and the median maximum rotational error was 0.3° (0.1–1.2). Consequently, the median BM barycentre shift between original and Fx-plans was 0.5 mm (0.1–2.7). The median GTV volume was 0.16 cc (0.01–3.91), while the PTV had a median volume of 0.72 cc (0.12–7.46). Median values of BM maximum dimension and distance-to-isocenter were 9.4 mm (2.9–24.0) and 5.11 cm (0.89–7.52), respectively. The GTV D95% was reduced by >4% in only 2 BM (1 patient), while in 61 lesions (17 patients) a loss of coverage below 1% in the Fx-plan was observed. The PTV D95% decreased by 1.4% on average, and a dose reduction >1% occurred in 31 PTVs (16 patients). The mean increase of brain V12Gy (SRS) and V20Gy (fSRS) observed in Fx-plans was 0.4% (-0.6–3.6). The dosimetric comparison did not result statistically significant (p>0.05). The difference in target coverage did not show a good correlation with BM volume, maximum dimension, and distance-to-isocenter, but an acceptable linear regression was found with the BM barycentre shift: R2=0.45 and R2=0.50 for GTV and PTV D95% variations, respectively.

 

Conclusion

Due to the optimal patient setup, as well as the full six degrees-of-freedom corrections, the safety PTV margin, and the fast beam delivery, the dosimetric effects of residual setup and patient motion errors for multiple metastases cases are negligible. These findings warrant a potential reduction in the PTV margin with this treatment technique.


Valeria FACCENDA, Valeria FACCENDA (Monza, Italy), Denis PANIZZA, Denis PANIZZA, Sara TRIVELLATO, Valerio PISONI, Paolo CARICATO, Paolo CARICATO, Raffaella LUCCHINI, Raffaella LUCCHINI, Stefano ARCANGELI, Stefano ARCANGELI, Elena DE PONTI, Elena DE PONTI
15:20 - 15:30 #29870 - OP21 Improved Small Field Dosimetry for Radiosurgery Planning through Optimized MLC Modeling.
OP21 Improved Small Field Dosimetry for Radiosurgery Planning through Optimized MLC Modeling.

Purpose: Optimized multi-leaf collimator (MLC) parameters are essential for accurate beam modeling in radiosurgery planning, particularly in plans that involve very small fields, fields with high modulation and/or heterogenous medium. In collaboration with Brainlab (Munich, Germany), we demonstrate how improved MLC modeling yields greater consistency between measured and calculated dose for the Pencil Beam (PB) and Monte Carlo (MC) models used in Elements (Brainlab, Germany).

Methods: MLC parameters that define the tongue and groove (TnG) effect and transmission through rounded leaf tips were determined from 32 asynchronous sweeping gap fields, comprised of 8 TnG ratios for four different leaf gaps (Hernandez, 2017). Measurements were performed with 6FFF on a HDMLC Truebeam (Varian, USA). Dose was measured in water using an Exradin A12 (Standard Imaging, USA) positioned at isocenter at a depth of 10 cm and an SSD of 90 cm. Brainlab’s analysis of our measured data yielded updated MLC parameters for both PB (Dynamic Leaf Shift (DLS) and TnG) and MC (Radiological Leaf Shift (RLS) and TnG) models. Validation of these models were performed using multiple plans, with differing complexities, optimized and calculated in each planning Element – Multiple Metastases, Cranial SRS and Spine SRS.  29 PB and MC plans were calculated using a 1 mm dose grid and 1% uncertainty (MC). Validations were performed with Gafchromic XD film (Ashland, USA) in multiple heterogeneous and homogenous phantoms, using ExacTrac (Brainlab, Germany) for positioning. FilmQAPro (Ashland, USA) was used to compare calculated and measured dose.

Results: For PB, DLS and TnG were changed from 0.12 mm and 0.49 mm to 0.18 mm and 0.32 mm, respectively. Based on our measurements, Brainlab modified their MC model (version 3.0) to allow adjustment of RLS and TnG, which was not configurable in earlier versions (2.5 or earlier). RLS and TnG were determined to be 0.25 mm and 0.7 mm, respectively. Excellent agreement between calculated and measured dose was observed for all plans. Average gamma score of >98% + 2% for PB and >98% + 1.8% for MC using 2%/1mm criteria. Plans calculated with MC 2.5 showed marked improvement in gamma scores when recalculated with MC 3.0, with up to a 68% higher gamma score (3%/1mm) for a highly complex plan.

Conclusion: Accurate modeling of MLC can be achieved using asynchronous sweeping gap measurements. Improved Elements' beam models are critical to achieving excellent agreement between measurement and calculation, even for very complex and/or small fields.


Lauren WEINSTEIN (South San Francisco, USA), Matthew SKINNER, Thorsten BSCHORR, Wolfgang ULLRICH
15:30 - 15:40 #29373 - OP22 Appliance of CBCT of Leksell Gamma Knife Icon for improving accuracy of stereotactic radiosurgery.
OP22 Appliance of CBCT of Leksell Gamma Knife Icon for improving accuracy of stereotactic radiosurgery.

The Leksell frame G is well-known fixation device for stereotactic radiosurgery. There is an opinion that accuracy of fiducial-based CT registration is better in comparison to MRI. Some centers use only MRI scans for stereotactic radiosurgery without any clinical issues. However, different models of MRI scanners and protocols have different level of geometrical distortion, so the accuracy of 1 mm is a worldwide acceptance. The novel model of gamma knife Icon has received a build-in cone-beam CT module with quality assurance tools. Gentle calibration of CBCT results in greater level of expected accuracy (less than 0.1 mm). The distortion of MRI can therefore be defined for each patient before the start of the treatment. The partial displacement of the frame and in opposite frame deformation due to overtightening the fixation screws in addition to imaging error, can lead to lost of accuracy during treatment. 

The purpose of the research is to assess geometrical deviation of the stereotactic space defined by MRI fiducials with the help of integrated CBCT module.

We have analyzed 3-Tesla MRI and CBCT mean and axis-depended differences obtained from 110 patients. Median X, Y and Z linear shift was 0.05 mm, -0.05 mm and 0,6 mm respectively. Median X, Y and Z axial shift was 0.72º, 0.01º and -0,11º respectively. Median maximal shift displacement was 1,09 mm. CBCT-based definition was needed in 80.9% cases. Acceptable shift was found in 19,1% cases. The reasons for a decision were loss of coverage (below 95%), excess of tolerated dose to critical structures or shift more than 0.5 mm for functional radiosurgery. In one case, there was a shift of posterior screw with maximal shot displacement of 4.54 mm.

Correlation analysis showed positive correlation between length of anterior post and X-shift (p=0.02), X-rotation (p=0.003), Y-rotation (p=0.001). Strong negative correlation was shown between Z-coordinate of posterior commissure and maximal shot shift (p=0.000006). We have found also positive correlations between mean MRI fiducial error and X-shift (p=0.04), maximal MRI fiducial error and Y-shift (p=0,04). The calculated shift did not significantly differ between groups with short (29%) or long (71%) posts of the frame.

As conclusion, the calculated deviation of stereotactic space can depend on a number of factors like configuration of frame and Z-coordinate of target. Appliance of CBCT can prevent partial displacement of the stereotactic frame, reduce the impact of MRI distortion and frame deformation on accuracy of treatment.


Viacheslav RAK, Greg KOYNASH (Moscow, Russia), Olga EVDOKIMOVA
15:40 - 15:50 #30095 - OP23 A novel methodology for dosimetry audits focused on intracranial stereotactic radiosurgery applications.
OP23 A novel methodology for dosimetry audits focused on intracranial stereotactic radiosurgery applications.

With contemporary SRS, the interlinked dosimetry- and geometry-related treatment parameters, require a high-degree of accuracy and precision. This translates into the need for reduced uncertainties at each step of this complex procedure. This work presents an innovative phantom-based audit methodology that, combining results from different dosimetry methods, evaluates all stages of the radiotherapy chain, serving as an ideal tool to promote best practice and assure high-quality treatments. 

The phantom used was a 3D-printed head phantom, accommodating inserts for film, OSL, and gel dosimeters, calibrated at an SSDL. The user received an explicit, for the practice to be audited, RTstructure set, and was challenged to achieve a specific level of accuracy. Following the patient SRS treatment local protocol, the phantom treatment was simulated, planned, and exported to the delivery platform by the staff members who are normally involved at each step of the treatment chain. To assess whether QA results met the pre-defined standards, the latest recommendations of AAPM-RSS Medical Physics Practice Guideline 9.a. for SRS-SBRT were adopted for film dosimetry. A linac-based single-isocenter multi-focal SRS treatment was evaluated. 3 similar VMAT plans were generated, one for each detector type, taking into account the calibration dose range of each detector. Localization was performed with a kV CBCT. 6D corrections were applied prior to delivery. The OSL and film dosimeters were unloaded for analysis, and the phantom incorporating the irradiated gel-filled cylinder was MR scanned for the dose read-out 24 hours post-irradiation at a fully characterized MR scanner.

Results from one selected center audited has not indicated any concerns regarding the local practices for the specific aspects of dosimetry for intracranial SRS. Measured and calculated dose distributions were spatially co-registered and compared. Calculations were experimentally validated within uncertainties. The maximum deviation between measurements and TPS calculations for OSL dosimetry was 4.08%. The 3D GI of the film plane was 99.17% and the total spatial offsets of the planned and the corresponding gel-measured distributions for the targets involved were 0.77mm, 0.45mm and 0.81mm, respectively. Further work is required for the full characterization of OSLDs response to reduce the experimental uncertainties.

Novel dosimetry audit techniques allow the multi-step evaluation of the radiotherapy treatment chain. To keep up with the clinical need and novel equipment future developments will be focused on aspects such as treatment planning based on MR images and online intrafraction replanning strategies, as these are being increasingly applied into routine clinical services.


Kyveli ZOURARI, Emmanouil ZOROS, Georgios KALAITZAKIS, Themistoklis BOURSIANIS, Thomas MARIS, Evangelos PAPPAS (ATHENS, Greece)
15:50 - 16:00 #29878 - OP24 Iba myqa srs detector for cyberknife radiosurgery quality assurance.
OP24 Iba myqa srs detector for cyberknife radiosurgery quality assurance.

Background and Aims

Dose administration accuracy in radiosurgery (RS) treatments is of paramount importance to guarantee both the clinical outcome and the absence of severe toxicities. A comprehensive delivery quality assurance (DQA) program is therefore mandatory. In this study we evaluated the IBA myQA SRS® (IBA Dosimetry, Germany) high-resolution solid-state detector in a new context of RS delivered using CyberKnife® (Accuray, US) 6 MV robotic linac. The detector’s performance was investigated in periodic machine DQA and patient-specific treatments verification.

 

Methods

MyQA SRS [Figure 1] is composed of a 140×120 mm CMOS matrix with 400 um resolution, allocated in a cylindrical ABS phantom topped by a hemispheric cap. Dose calibration was ensured delivering 500 cGy to the matrix central area by an ad-hoc optimized plan.

System performance evaluation included: periodic dosimetry tests (dose linearity and reproducibility, output factors, off-axis-ratios) [Figure 2], detector angular response and dose rate dependence (in the clinically useful source-to-surface range between 650 mm and 1200 mm), and variable aperture IRIS® collimator field size measurement.

For patient-specific DQA, the system performance was studied for various RS intracranial targets considering complete optimized plans and plans corrected taking into account the device angular response (delivered after removal of beams above a threshold angle selected according to the angular dependence analysis). An evaluation by 3% 1 mm Gamma Index was performed [Figure 3].

 

Results

Detector response for periodic DQA tests was always found to be in accordance with the authors center’s   commissioning data. Dependence from dose rate was confirmed, corroborating the manufacturer requirement of a dose calibration specific for each dose rate of interest. Field dimensions for the IRIS collimator were consistent with commissioning values, with an accordance within 0.4 mm. Finally, angular dependence tests resulted in a signal decay greater than 5% when beams outside a ±50° amplitude cone with respect to the patient’s anterior-posterior direction were delivered.

Concerning patient-specific QA, >50° angled beams elimination from treatment delivery led to an improvement in Gamma Index passing rates ranging between +3% and +115%, depending on target and plan characteristics. 

               

Conclusions

IBA myQA SRS proved to be a suitable device for constancy and daily DQA, providing high-resolution real-time results and showing a potential for replacing radiochromic films in many dosimetric analyses. Preliminary patient-specific QA Gamma tests showed high passing rates once angular dependence corrections were performed, even when high complexity treatments, such as the trigeminal neuralgia case, were considered.


Francesco PADELLI (Milano, Italy), Domenico AQUINO, Laura FARISELLI, Elena DE MARTIN
RED 2 ROOM

"Monday 20 June"

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C17
15:00 - 16:00

3D Skull-base Anatomy for Safe Radiosurgery (2)

Coordinator: Siviero AGAZZI (Tampa Florida, USA)
Keynote Speaker: Siviero AGAZZI (Tampa Florida, USA)
BLUE 2 ROOM
16:00 COFFEE BREAK AND EXHIBITION
16:30

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A19
16:30 - 17:30

ORAL PRESENTATION
Other Benign Brain Tumors, Pediatric SRS, Ocular Disorders

Moderators: Isa BOSSI ZANETTI (Radiation Oncologist) (Milano, Italy), Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil)
16:30 - 16:40 #29449 - OP25 Stereotactic Radiosurgery for Rathke’s Cleft Cysts: An International Multicenter Study.
OP25 Stereotactic Radiosurgery for Rathke’s Cleft Cysts: An International Multicenter Study.

Objective: Rathke’s cleft cysts (RCC) are sellar collections from an incompletely regressed Rathke’s pouch. Common symptoms can include headaches, visual loss, and endocrinopathy. In some cases of symptomatic or growing RCC, surgery is required. Recurrence after surgery is common (10-40%). Stereotactic radiosurgery (SRS) has been used in an attempt to control growth and symptoms, but outcomes are not well known. We sought to study the outcomes of Rathke’s cleft cysts following Gamma Knife radiosurgery for both salvage and initial treatment.

Methods: We reviewed the outcomes of 25 Rathke’s cleft cyst patients that had stereotactic radiosurgery between 2001 and 2020. Four patients received upfront SRS, and 21 were treated with salvage SRS. Diagnosis was based on imaging or histopathology. Cyst control was defined as stability or regression of the cyst. Kaplan-Meier analysis was used to determine time-to-recurrence and determine potential factors for recurrence.

Results: The respective median clinical follow-up and margin dose were 6.5 years and 12 Gy. Overall control was achieved in 19/25 (76%) patients, and four recurrences required further intervention. For those that recurred, the average time to recurrence was 35.6 months. Visual recovery occurred in 14/15 (93.3%) patients, and no new post-radiosurgery visual deficits occurred. The presence of pre-treatment visual deficit was often an indicator of regrowth. 3 of 3 patients with hyperprolactinemia resolved after SRS. New endocrinopathy related to radiosurgery was noted in 5/25 (20%) patients, all of which were thyroid and/or cortisol axis related. Upfront SRS was used in four patients. No new endocrinopathies or visual deficits developed after upfront SRS, and the single patient with a pretreatment visual deficit recovered. One of the four upfront SRS patients recurred, after 7.5 years.

Conclusion: Stereotactic radiosurgery produced effective recovery of visual deficits, and carries a low risk for new visual deficits. Cyst control was achieved in about three quarters of the patients. Following radiosurgery, patients without pre-treatment visual deficits are less likely to regrow. Endocrinopathy can occur after radiosurgery, similar to other sellar mass lesions. Initial radiosurgery shows the potential for long-term cyst control, with improvement of symptoms and low risk for complications.


Douglas KONDZIOLKA (New York, USA), Roberto MARTINEZ-ALVAREZ, N MARTINEZ-MORENO, Joshua SILVERMAN, Kenneth BERNSTEIN, Jason SHEEHAN, Roman LISCAK, Jaromir HANUSKA, Huai-Che YANG, Cheng-Chia LEE
16:40 - 16:50 #30239 - OP26 Clinical analysis of gamma knife radiosurgery in the treatment of trigeminal schwannomas: 26-years’ experience of a single institution.
OP26 Clinical analysis of gamma knife radiosurgery in the treatment of trigeminal schwannomas: 26-years’ experience of a single institution.

We aimed to evaluate the radiographic and clinical outcomes after gamma knife radiosurgery (GKRS) for trigeminal schwannomas (TSs). A total of 87 patients who underwent GKRS for TSs between 1991 and 2020 were enrolled. The mean tumor volume was 4.3 cm3. The median prescribed dose for the margins of the tumor was 13 Gy. The median follow-up duration was 284.6 months (range 12.0–311.5 months). The overall local tumor control rate was 90%, and the symptom response rate was 93%. The response rate for each symptom was 88% for facial pain, 97% for facial sensory change, and 86% for cranial nerve deficits. Fifteen (21%) patients showed transient swelling, which had regressed at the time of the last follow-up. Cystic tumors were associated with transient swelling (p = 0.04). A tumor volume of < 2.7 cm3 was associated with local tumor control in univariable analysis. Transient swelling was associated with symptom control failure in both univariable and multivariable analyses (p = 0.04, odds ratio 14.538). GKRS is an effective treatment for TSs, both for local control and symptom control. Transient swelling and tumor progression were associated with symptom control failure. Tumor volume < 2.7 cm3 was associated with local control.


Dong-Won SHIN, Young-Hoon KIM (Seoul, Korea), Sang Woo SONG, Young Hyun CHO, Chang-Ki HONG, Jeong Hoon KIM
16:50 - 17:00 #29908 - OP27 Long term Outcomes after Gamma Knife Stereotactic Radiosurgery for Glomus Jugulare tumors. Analysis of 47 patients.
OP27 Long term Outcomes after Gamma Knife Stereotactic Radiosurgery for Glomus Jugulare tumors. Analysis of 47 patients.

Introduction

Glomus jugulare tumors are benign but locally destructive lesions located in one of the most poorly accessible regions of skull base. Excision is potentially curable but is fraught with risk of injury to the surrounding neurovascular structures. Even with preoperative embolisation bleeding during operative removal may be excessive.

The aim of the present study was to ascertain the long term safety and efficacy of Gamma Knife Radiosurgery as primary or adjunctive form of therapy.

Methods

From May 2008 till December 2020, 3525 patients underwent radiosurgery with Leksell Gamma Knife unit (Model C) and ICON at Pakistan Gamma Knife Center. Forty seven patients had glomus jugulare tumor. A retrospective analysis of treatment results was performed. There were 26 female and 21 male patients. The age of the patients ranged from 20 to 70 yrs.(Mean 42.8 yrs.). Two pts. had undergone microsurgery with incomplete resection. None of the patient had previous radiotherapy or undergone embolisation.

A median tumor volume 13.49 cm3 ,(range 466.7mm3 to 27.5cm3) was covered by median isodose volumes of 45%(range 43-50%). A median isodose of 14 Gy (range 12 to 16 Gy) was applied to the tumor margin. The median no. of isocenters was 18 (range 2-28).Treatment planning was conducted using MR imaging along with CT scanning in all cases. The mean coverage of the tumor with the prescribed minimal radiation dose was 95.2% (range 82 to 99%).

Results

Thirty two patients had a follow up of at least six months with a median interval of 60 months following GKS (range 6-144 months). Neurological follow up examinations revealed improved clinical condition in 24 patients (75%),a stable neurological status in 6 patients (19%), and progression in symptoms in two patient(6%). Follow up MR imaging was conducted in 24 patients. Tumor size has decreased in 15 patients (66%) and the volume remained unchanged in the seven (28%). Two of the tumors showed volumetric increase during the observation period for which repeat gamma knife radiosurgery was done.

Conclusions

Our long term results show that gamma knife radiosurgery is a safe and efficacious treatment option for primary or residual glomus jugulare tumors with no significant morbidity.

Gamma knife radiosurgery can be used as an upfront treatment of glomus jugulare tumors.

 

 

Correspondence:

Dr M Abid Saleem

 Consultant Neurosurgeon,Gamma Knife Radiosurgery Center. Dow University of Health Sciences.Ojha campus.Karachi

Email.abid.saleem@duhs.edu.pk

Cell:00923323414304.


M Abid SALEEM (Karachi, Pakistan), Atif MANSHA, Amjad SHAHANI, Sohail HUSSAIN
17:00 - 17:10 #29420 - OP28 Hypofractionated Stereotactic Radiosurgery for Craniopharyngioma.
OP28 Hypofractionated Stereotactic Radiosurgery for Craniopharyngioma.

Objectives: Craniopharyngiomas are benign tumors arising from embryonic remnants of the Rathke’s pouch and often present with visual impairment and hypopituitarism. Although surgery with gross total resection is considered the treatment of choice, it is mostly not feasible due to proximity to critical structures such as the optic nerve and hypothalamic-pituitary axis. Gamma Knife radiosurgery (GKRS) has been reported as a reasonably safe and effective management option in selected craniopharyngioma patients; however, there is no data regarding hypofractionated GKRS (hf-GKRS) in these patient group. This retrospective, single-center study evaluated patient outcomes of hf-GKRS for craniopharyngioma.

Methods: Twenty-two patients with histologically verified craniopharyngiomas were treated with hf-GKRS. The mean age of the patients was 36 years (range, 3-66 years). Prior to hf-GKRS, the vast majority (82%) of patients presented with visual deficits and panhypopituitarism was detected in 6 patients (27.3%). Cystic morphology was observed in 12 lesions (54.5%). Fifteen patients (71%) received single surgical resection and 6 patients (29%) underwent multiple surgeries. One patient was diagnosed with biopsy. The mean tumor volume was 2.3 cm3, ranging between 0.2-7.8 cm3The most commonly used fractionation scheme was 5x4 Gy (82%).

Results: The mean follow-up was 21.7 months (range, 14-35 months). Local tumor control was achieved in 17 patients (77.3%), with 10 tumors (22.7%) decreased in size and 7 (31.8%) remained stable. Local tumor control rates showed a wide variety among lesions of different morphologies; 100% in solid lesions, 91.7% in cystic, and 33.3%in mixed lesions (p<0.05). Visual, endocrinological, and clinical status were stable in 18 (81.8%) and worsened in four (18.2%) patients. No adverse radiation effects were observed. Only 13.5% of patients underwent additional treatments, represented by additional surgical resection in two patients (9.1%) and repeat hf-GKRS in one patient (4.6%).

Conclusions: To the best of our knowledge, this is the largest single-center study that addressed the outcomes of hf-GKRS utilized in the management of post-operative craniopharyngiomas. A high tumor control rate was achieved over sufficient follow-up, which demonstrates the efficacy and safety of hypofractionation in both prevention of tumor growth and additional risks of alternative treatments. Further, well-designed studies are required to establish the long-term efficiency of hf-GKRS in the management of craniopharyngiomas. 


Yavuz SAMANCI (Istanbul, Turkey), Muhammed Amir ESSIBAYI, Mustafa BUDAK, Fatih KARAKÖSE, Selçuk PEKER
17:10 - 17:20 #29408 - OP29 Demographic of Gamma Knife Radiosurgery in pediatric patients.
OP29 Demographic of Gamma Knife Radiosurgery in pediatric patients.

Objective

 

Although radiation modalities are common among pediatric patients, GKRS is a rare modality. The objective is to show the patient demographic in a reference GKRS service over 20 years and different applicability.

 

Method:

 

Retrospective review of patients under 18 years treated with GKRS from 1999 to 2020. It was considered the primary pathology, age, dose, lesion volume, use of frame versus mask, single session versus hypofractionation. Gamma Knife Model C, Perfection and Icon were used.

 

Results

 

Fifty-five patients were submitted to 80 treatments, age varied from 3 to 18, being the majority between 15 and 18 yo. Tumors represented 55% and AVMs 45%. Seventy-three procedures used Leksell frame and 7 used thermoplastic mask, being 6 for single session and 1 for 5-session hypofractionation for chiasm protection. Median dose was 20Gy (8-28) and lesion volume was 1.066cc (0.081-34.791). Eloquent area and brain stem lesions were safely treated with good response

 

Conclusion

GKRS is a visible modality for radiation treatment for pediatric patients allowing several techniques for a great variety of pathologies. For younger patients, sedation is needed for tolerance and safety. GKRS is an applicable treatment modality for pediatric patients and individual considerations with a multi-disciplinary team should be made.


Victor GOULENKO, Dheerendra PRASAD (Buffalo, NY, USA)
17:20 - 17:30 #30026 - OP30 Single fraction radiosurgery as an eye salvage treatment of children with resistant or recurrent intraocular retinoblastoma.
OP30 Single fraction radiosurgery as an eye salvage treatment of children with resistant or recurrent intraocular retinoblastoma.

Background: Conventional external beam radiotherapy is currently in use only as a second-line (salvage) therapy of intraocular retinoblastoma (Rb) because of serious complications including secondary malignant tumours in the field of irradiation. There is no data of using stereotactic radiosurgery (SRS) in Rb treatment.

The aim of the study is to present 6-year experience of using SRS in children with intraocular Rb.

Materials and methods: Nineteen children (20 eyes) were treated using SRS in the period from 2015 to 2021. Seventeen eyes were treated with GammaKnife SRS, 3 with Cyber-knife SRS. Mean patient age was 34.4 months (range, 12-114 months). The eyes were classified as group B (n=4), C (n=1), D (n=14), E (n=1). Four children had the only eye. All patients were pretreated with systemic and local chemotherapy and all types of focal treatment before using SRS. Recurrent and resistant Rb with parent’s refusal to remove the eye was the indication for SRS. There was mean dose 21.8 Gу (range, 20-24) with marginal 50% isodose for GammaKnife SRS and mean dose 31.5 Gу (range, 27.5-35) with prescribed dose 26.8 Gy (range, 24-28.5) and mean 75% Isodose for Cyber-knife treatment, depending on tumour type and location. Radiation doses were evaluated accounting critical eye structures and the orbit bones. Three types of target planning were evaluated according to Rb location and extension.

Results: Complete tumour regression was achieved in 15 patients, partial in 3. Fifteen eyes (75%) were salvaged. Two eyes were enucleated because of tumour growth, 3 eyes because of severe complications - vitreous hemorrhage with total retinal detachment. Hemorrhagic complications of different severity occurred in 50% of patients within the period from 1.5 to 58 months (mean, 8.6) as a late sign of vascular radiation damage. It was treated using both intraocular surgery or medication. Cataract occurred in 3 patients and was removed successfully. There were no acute complications, no cases of keratopathy or damage of orbital tissues. Mean follow-up 39.4 months (range, 3-74 months).

Conclusion: SRS as an alternative to enucleation in patients with Rb was proved to be a reasonable option to save the eye despite the high amount of vascular complications. Differences between GammaKnife and Cyber-knife SRS should be analyzed. Outcomes within the longer follow up is essential.

Andrey YAROVOY (Moscow, Russia), Andrey GOLANOV, Vera YAROVAYA, Valery KOSTJUCHENKO, Natalya ANTIPINA, Arina LESTROVAYA
SILVER ROOM

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B19
16:30 - 17:30

ORAL PRESENTATION
Brain Metastases (1)

Moderators: Hyun-Tai CHUNG (Professor) (Seoul, Korea), Antonio SANTACROCE (neurosurgeon radiation oncologist) (Munich, Germany)
16:30 - 16:40 #29809 - OP37 Significant Survival Improvements for Patients with Melanoma Brain Metastases: Can We Reach Cure in the Current Era?
OP37 Significant Survival Improvements for Patients with Melanoma Brain Metastases: Can We Reach Cure in the Current Era?

Objective

New therapeutic options for both brain metastases (BM) and extracranial melanoma care have been associated with increasing survival expectations. Ten years ago, median survivals after the diagnosis of a melanoma brain metastasis were in the range of 5 to 7 months. Using a prospective registry, our aim was to define current survival goals for melanoma patients with brain metastases, based on state-of-the-art multimodality care.

Methods

We reviewed 171 consecutive melanoma patients with brain metastases receiving stereotactic radiosurgery (SRS) who were followed with point-of-care data collection between 2012-2020. Demographic, clinical, histological and imaging data were collected, including systemic treatment, radiosurgical parameters and outcomes.  We evaluated factors predicting survival and tumor control, including survival without any need for systemic or local therapy.   

Results

The mean patient age was 65 years (20-91), 39% were female and 29% had BRAF-mutated tumors. The median overall survival after radiosurgery was 15.7 months (95% Confidence Interval [CI]: 11.4-27.7 months). We identified 32 patients who had survival of at least 5 years from an initial brain tumor radiosurgery.

Patients on immunotherapy had a significantly longer survival in comparison to the rest of the population (p=0.012). BRAF mutations did not show a significant influence on survival in comparison to the wild type (p=0.2) and use of targeted therapies showed survival advantage in comparison to chemotherapy (p=0.009), but not to immunotherapy (p=0.09).  In a multivariate analysis, both immunotherapy and the number of metastases treated at the first SRS were significant predictors of long-term survival of over 5 years from initial SRS (p=0.023 and p=0.018, respectively). Five patients (16%) of the long-term survivors’ cohort required no active treatment for more than 5 years.

 

Conclusions

Long-term survival in patients with melanoma brain metastases is achievable in the current era of stereotactic radiosurgery combined with systemic immunotherapies. For those patients alive more than 5 years after first SRS for brain metastases, 16% had been also off systemic or local brain therapy for over 5 years. Given late recurrences of melanoma, caution is warranted, however prolonged survival off active treatment in a small subset of our patients raises the potential for cure.


Assaf BERGER (New York, USA), Kenneth BERNSTEIN, Juan Diego ALZATE, Reed MULLEN, Joshua.s SILVERMAN, Erik SULMAN, Bernadine R. DONAHUE, Anna C. PAVLICK, Jason GUREWITZ, Monica MUREB, Janice MEHNERT, Kathleen MADDEN, Amy PALERMO, Jeffrey S. WEBER, John G. GOLFINOS, Douglas KONDZIOLKA
16:40 - 16:50 #30082 - OP38 Risk of symptomatic intracranial hemorrhage exceeds the risk of radiation necrosis in patients with melanoma brain metastases following definitive SRS treatment.
OP38 Risk of symptomatic intracranial hemorrhage exceeds the risk of radiation necrosis in patients with melanoma brain metastases following definitive SRS treatment.

Background: Melanoma brain metastases (MBM) are prone to hemorrhage. It is unclear how that risk of bleeding is influenced by treatment with SRS with or without concurrent immunotherapy (IO) compared to the risk of radiation necrosis (RN).

 

Methods: We performed a retrospective study of 182 melanoma patients treated at a single institution with at least one course of SRS. We captured several covariates including the type and timing of brain radiotherapy and concurrent systemic treatment (BRAF-targeted therapy, IO, chemotherapy, or none). Toxicity was graded using the Common Terminology Criteria for Adverse Events v5.0 criteria. Cumulative incidence (CI) of post-SRS hemorrhage and RN were estimated using models with death and WBRT as competing risks. Secondary endpoints included: local failure (LF), distant brain failure (DBF), time to post-SRS brain surgery, and overall survival (OS).

 

Results: A total of 595 MBM were treated with definitive SRS. CI of grade 2+ post-SRS hemorrhage at 12 months was 24%, in the absence of any systemic treatment, 13% in patients who received BRAF-targeted therapy (HR 0.49 [0.13-1.78], p=0.28), and 7% in patients who received IO (HR 0.27 [0.13-0.71], p=0.0071). CI of grade 2+ RN 12 months after SRS was 4%, 5%, and 3% with dual agent IO, single agent IO, and no IO, respectively (NS). Lesion size correlated to the risk of symptomatic RN (HR 1.1, p<0.001) but not post-SRS hemorrhage. Similarly, prescription dose correlated to the risk of grade 2+ RN (HR 37.84, p<0.001) but not hemorrhage. CI of LF at 24 months was 5% with no IO, 3% with dual agent, 2% with Ipilimumab (HR 0.71, p=0.67), 11% with Pembrolizumab (HR 4.3, p=0.031) and 18% with Nivolumab (HR 4.27, p=0.052). CI of DBF was similar in patients who did or did not receive IO (~70%).

 

Conclusions: Following SRS for MBM, the risk of symptomatic RN with or without IO was low, whereas the risk of hemorrhage was considerable, but significantly decreased with concurrent IO administration. We hypothesize that intracranial bleeding is the predominant risk in MBM patients following SRS and is reduced by concurrent administration of IO. Future efforts will include studying the risk of bleeding with IO alone as well as the mechanisms by which IO might decrease the risk of intracranial hemorrhage.


Paola Anna JABLONSKA (Toronto, Canada), Jessica WEISS, Amy Liu ZHIHUI, Paul KONGKHAM, Marcus BUTLER, David B. SHULTZ
16:50 - 17:00 #30142 - OP39 Low-dose radiosurgery for brain metastases: can acceptable local control be achieved?
OP39 Low-dose radiosurgery for brain metastases: can acceptable local control be achieved?

 

 

Objectives:

Dose selection for SRS classically has been based on tumor diameter with reduction of dose in the settings of prior brain irradiation, larger volumes, eloquent location, and larger number of metastases. RTOG recommended a dose of 15 Gy for lesions >3 cm in diameter, however, retrospective series have shown local control rates to be potentially as low as 50% for larger lesions. However, the literature has not been consistent when exploring low-dose response. The aim of this study is to report the local control (LC) and toxicity when low-dose SRS is used to treat BM and to explore for predictors of these outcomes.

 

Methods:

A single institution, IRB-approved retrospective analysis was conducted of our prospective Gamma Knife (GK) SRS registry to identify patients with BM treated with low-dose, defined as margin dose ≤ 14Gy, from 2014 to 2020. Of the 107 patients with BM treated during this time, we identified 65 patients with 350 BM. Patient, tumor, and treatment characteristics were identified, and LC and toxicity was correlated to demographic, clinical, and dosimetric data.

 

Results:

Mean patient age was 58.3ys (21-82); histology of the primary was lung in 31, breast in 19, melanoma in 5, gastrointestinal in 4, renal cell carcinoma in 3, prostate in 2, ovary in 1 patient.  Median tumor volume was 0.93cc IQR (0.21-0.59), and mean margin dose was 13.1Gy (8-14). At a mean follow-up of 11.6 months (6-58), local failure (LF) was detected in 41/350 (11%). Actuarial LC at 1 year and at 18 months were 91.2% and 83% respectively. On univariate analysis, maximum dose ≤ 18.5Gy and mean dose ≤ 17Gy were significant predictors for LF (p=.024, p=.029). On multivariate analysis mean dose, volume and previous SRS was significant. Adverse radiation effects (AREs) were diagnosed in 4 (1.1%) patients, all of whom had received prior WBRT (p=0.005).

 

Conclusions:

It is feasible to achieve acceptable local control in BMs with low-dose SRS. Mean dose, maxim dose, and volume appear to be predictors for LF, and AREs are associated with previous WBRT. The value of low dose radiosurgery may be in the palliative management of patients with higher numbers of small tumors with the aim of brain tumor control and preservation of neurological function for as long as possible.

 

 


Juan Diego ALZATE (New York, USA), Assaf BERGER, Kenneth BERNSTEIN, Joshua SILVERMAN, Tanxia QU, Bernadine DONAHUE, Douglas KONDZIOLKA
17:00 - 17:10 #29867 - OP40 Gamma knife radiosurgery for cystic brain metastases: Institutional experience.
OP40 Gamma knife radiosurgery for cystic brain metastases: Institutional experience.

Introduction:

Gamma-Knife radiosurgery (GKRS) is a well-established treatment for brain metastases (BM). The imaging features of BM can variably have either homogeneous and heterogenous enhancement, or cystic-like appearances. These features can represent different biological behaviors concerning the treatment of these lesions. Cystic BM (cBM) are perceived to be more resistant to treatment than solid BM (sBM). In this study, we sought to compare the response rates and overall survival of patients with cBM relative to sBM after GKRS.

Method:

Patients treated for BM with GKRS over a 2-year interval (2016-2017) were evaluated. GKRS dosing was delivered per RTOG 90-05 according to our standard protocol. Patients were divided in 3 groups: those with cBM only, sBM only, and both cystic and solid BM (csBM). Kaplan-Meier analysis with the log-rank test was used to calculate and compare overall survival (OS) between groups. Local control was analyzed utilizing RECIST criteria at 3, 6, and 12 months. Chi-square analysis compared the response rate for cBM and sBM.

Result:

73 patients (59% female) with a mean age 67 years (range: 43-91) were analyzed. The most frequent pathologies were lung (54%) and breast (18%). KPS was ≥70 in 66 patients (90%). Prior to GKRS treatment, 22% of patients received WBRT, 71% chemotherapy, 22% had prior surgery, and 16% received immunotherapy. No significant differences were found in the clinical characteristics between patient groups. Mean OS was 20 months (2-38, 95% CI) for the cBM patient group, 17 months (12-22, 95% CI) for sBM patient group and 13 months (7-19, 95% CI) for csBM patient group (p = .967). Of the 416 lesions evaluated, 15% (n=62) were cBM and 85% (n=354) were sBM.cBM were significantly larger than sBM (p < 0.0001) and therefore cBM received significantly lower doses of radiation (p 0.001). No other significant differences were found between cBM and sBM. Local control at 6 months was 92% for cBM and 89% for sBMs (p =.49).

Conclusion:

Despite a perceived worse prognosis, our results suggest that patients harboring cBM treated with GKRS achieve similar oncologic outcomes when compared with patients with sBM. cBM are usually larger than sBM and therefore these lesions may be treated with less radiation dose than their solid counterparts. Regardless, cBM and sBM are suitable stereotactic radiosurgery targets with comparable local control rates.


Lilyana ANGELOV (Cleveland, USA), Josue AVECILLAS CHASIN, Auston WEI WEI, Yusuke HORI, Sam CHAO, Alireza MOHAMMADI, Glen STEVENS, John SUH, Gene BARNETT
17:10 - 17:20 #29985 - OP41 Stereotactic radiosurgery for bladder cancer brain metastases: International Radiosurgery Research Foundation (IRRF) multicenter study.
OP41 Stereotactic radiosurgery for bladder cancer brain metastases: International Radiosurgery Research Foundation (IRRF) multicenter study.

Introduction. Bladder cancer only rarely metastasizes to the brain. As such, the optimal management strategy is not well defined. This study was performed to evaluate the results of SRS as part of the management of bladder cancer brain metastases.

Methods. Centers participating in the IRRF were asked to review their database to identify bladder cancer patients who had SRS for related brain metastases and at least one clinical or imaging follow-up. Outcomes included post-SRS overall survival, local and distant control and clinical evolution.

Results. 103 patients from 10 institutions met inclusion criteria and received SRS for a total of 301 brain metastases. Median age at SRS was 68 (range, 31-84) and 73.8% of patients were male. Median KPS was 80% (range, 50-100%). Median time from primary to brain metastases diagnosis was 18 months. At the time of SRS, 50% of patients had active non-CNS disease. Prior management of brain disease included surgical resection in 28.4% and WBRT in 4.9% of patients. At SRS, the median number of metastases treated per patient was 1 (range, 1-22), and median cumulative SRS volume was 1.16 cc (range, 0.01-44 cc). Most patients had single fraction SRS using a median margin dose of 18 Gy (range, 12-33 Gy). At the time of analysis, 9.7% of patients were still alive. The median overall survival after SRS was 7 months. Actuarial survival was 58.8%, 36.9% and 17.0% at 6, 12 and 24 months, respectively. Local control as defined by RANO criteria was achieved in 89.3% of metastases. Actuarial local control of treated metastases was 88.3% at 12 months and 74.2% at 24 months. During follow-up, 42% of patients developed new remote brain metastases and 4.9% had leptomeningeal dissemination. Subsequent management of uncontrolled brain metastases included repeat SRS in 21.7%, surgical resection in 8.8% and WBRT in 7.6% of patients. At last follow-up, 32.1% of patients had improvement of their neurological condition, whereas 38.5% remained stable. Steroids were discontinued in 50.9% of patients. Radiation necrosis was seen in 4.3% of treated metastases. On multivariate Cox regression analyses, female sex and better KPS were predictors of improved survival. For local control, lower SRS volume, absence of corticosteroid intake and adjuvant chemotherapy were predictors of better tumor control.

Conclusion. SRS is a safe and effective management option for the management of brain metastases in bladder cancer patients.


Rémi PERRON, Christian IORIO-MORIN, Tomas CHYTKA, Gabriela SIMONOVA, Veronica CHIANG, Charu SINGH, Ajay NIRANJAN, Zishuo WEI, L.dade LUNSFORD, Selcuk PEKER, Yavuz SAMANCI, Jennifer PETERSON, Richard ROSS, Chad RUSTHOVEN, Cheng-Chia LEE, Huai-Che YANG, Ulas YENER, Jason SHEEHAN, Douglas KONDZIOLKA, David MATHIEU (Sherbrooke, Canada)
17:20 - 17:30 #29907 - OP42 Treatment of multiple metastases and high volume disease with stereotactic radiosurgery: a single centre experience.
OP42 Treatment of multiple metastases and high volume disease with stereotactic radiosurgery: a single centre experience.

Background:

Stereotactic radiotherapy for patients with 10 or more brain metastases is controversial. Difficulties with planning, treatment times and concerns about survival lead to whole-brain radiotherapy for many. High-volume intracranial disease (≥10cc) has also been shown to correlate with poor survival. However, prospective, randomised data is lacking.

 

Methods:

A radiosurgical-board approved, retrospective cohort study was performed. 353 patients treated for metastatic brain disease at a single Gamma Knife centre from Jan-2010 to Aug-2021 were analysed. Data was censored from January 2022. A Kaplan-Meier analysis was performed to determine survival post-stereotactic radiosurgery of patients with 10 or more metastases against a matched group of 5-9 metastases and 1-4 metastases. A further Kaplan-Meier analysis was performed of patients with 10cc or more intracranial metastatic disease treated against a matched group of less than 10cc. A logrank test assessed for statistical differences in survival. A multivariate Cox regression was performed to assess the relationship between overall survival and: number of metastases; total volume; primary malignancy; the use of systemic anti-cancer therapies with intracranial penetrance; and whether there was controlled extracranial disease. Data was checked for multicollinearity with the Belsley-Kuh-Welsch technique and for proportional hazards according to Schoenfeld residuals. Results with p-values <0.05 were considered significant.

 

Results:

Survival data was available for all 353 patients, and for 85-100% of patients for factors analysed in multivariate analysis. The minimum follow-up period was 5 months. 63 patients with ≥10 metastases (median 19 metastases) were identified. Median survival measured 13.3 months, compared with 15.1 months for the 5-9 metastasis group and 19.0 months for the 1-4 metastases group. Differences in survival did not reach statistical significance (p-value 0.14). 85 patients with ≥10cc total intracranial disease (median 14.85cc) were identified. Median survival for the ≥10cc group measured 17 months compared with 18.5 months in the <10cc group. Differences in survival reached statistical significance (p-value <0.01). Increasing total volume of disease (HR 1.05 [1.01-1.09], p-value: 0.01), non-small cell lung cancer primaries (HR 3.5 [1.35-9.09] p-value: 0.01) and the use of systemic anti-cancer therapy with intracranial penetrance (HR 0.239 [0.105-0.547] p-value: <0.01) had a statistically significant effect on survival on multivariate analysis.

 

Conclusions:

Carefully selected patients with multiple metastases or high volume intracranial metastatic disease have acceptable survival outcomes following stereotactic radiosurgery. Increasing volume of disease and non-small cell lung cancer primaries negatively affects survival, while the use of intracranially active systemic therapy is associated with improved survival.


Hamoun ROZATI (London, United Kingdom), Ian PADDICK, Ian SABIN
RED 2 ROOM

"Monday 20 June"

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16:30 - 17:30

ORAL PRESENTATION
Body SRS/SBRT (1)

Moderators: Laura LOZZA (Responsible Breast Tumor Radiotherapy) (Milano, Italy), Alexander MUACEVIC (Director) (Munich, Germany)
16:30 - 16:40 #30108 - OP31 Stereotactic Body Radiation Therapy (SBRT) for lung metastasis from Soft Tissue Sarcoma (STS): results of a phase 2 clinical study.
OP31 Stereotactic Body Radiation Therapy (SBRT) for lung metastasis from Soft Tissue Sarcoma (STS): results of a phase 2 clinical study.

Background: Soft-tissue sarcomas (STS) are a rare group of malignancies, accounting about 1% of all cancers in adults. Many patients with STS develop metastatic disease, and lung is the most frequent site of distant spread of disease (18-35%). Although surgery is the main modality used, more recently Stereotactic Body Radio Therapy (SBRT) is emerging as an effective alternative  with comparable results in term of local control,  but to date no consolidate data exist regarding the effective role of SBRT. Based on this background we designed a prospective phase 2 study aiming to evaluate the efficacy of SBRT for lung metastases from STS.

Materials and Methods: Patients aging 18-85 years, good PS, confirmated STS diagnosis, up to 4 metastatic lung lesion with maximum tumor diameter ≤5cm, were enrolled. Total doses prescribed were 30 Gy/1 fr for peripheral lesions ≤10 mm, 60 Gy/3 fr for peripheral lesions between 10-20 mm, 48 Gy/4 frs for peripheral lesions 20-50 mm, and 60 Gy/8 fr for central lesions. Clinical outcome was evaluated by thoracic and abdominal CT scan 2 months after SBRT and every 3 months thereafter. Tumor response was defined using European Organization for Research and Treatment of Cancer Response Evaluation Criteria in Solid Tumors (EORTC-RECIST1.1). Toxicity was recorded using Common Terminology Criteria for Adverse Events version 4.2.

Results: Between January 2015 and December 2020, 44  patients for 71 lung lesion treated were evaluated. The majority had leiomyosarcoma histology (13), grade 3 (28) sarcoma, and limbs location (18). Pulmonary metastases were present at diagnosis in 6 patients, while others developed lung lesion at a median time of 24 months (range 4-282 months). The median follow-up time  from SBRT was 48 months (12–154  months). No severe toxicity (grades III–IV) was recorded, and no patients required hospitalisation. The 5-years local control rate (from SBRT treatment) was 93%. Overall survival at 2 and 5 years was 66.2% and 48%, respectively.  On univariate and multivariate analysi factors conditioning OS were grade (p=0.0175), interval time from diagnosis to pulmonary lesions occurence (p=0.0416), and the number of metastatic lung lesions (=0.0076). At last observation time  26 patients (59%) were alive. All other died because of distant progression.

Conclusions: SBRT provides excellent local control of pulmonary metastasis from soft tissue sarcoma (STS) and may improve survival in selected patients. SBRT should be considered for all patients with pulmonary metastasis (PM) and evaluated in a multidisciplinary team.


Beatrice MARINI (Milano, Italy), Pierina NAVARRIA, Elena CLERICI, Davide BALDACCINI, Marco BADALAMENTI, Ciro FRANZESE, Davide FRANCESCHINI, Luisa BELLU, Giuseppe Roberto D'AGOSTINO, Marta SCORSETTI
16:40 - 16:50 #30105 - OP32 Could Stereotactic Body RadioTherapy be a valid option in metastatic lung cancer with oligoprogressive disease?
OP32 Could Stereotactic Body RadioTherapy be a valid option in metastatic lung cancer with oligoprogressive disease?

Purpose or Objective

Oligoprogression (OPD) is defined as a condition where limited progression (1-3 metastases) is observed in patients undergoing systemic cancer treatment. Local treatment of OPD might delay systemic therapy line switch, which could be beneficial in patients experiencing prolonged global disease control with novel targeted or immune therapies. In this study we investigated the impact on outcome of stereotactic body radiotherapy (SBRT) in patients with OPD from metastatic lung cancer.  

Materials and Methods

Data from a cohort of consecutive patients treated with Cyberknife and Linac-based SBRT between June 2015 and August 2021 were collected.  All extracranial metastatic sites of OPD from lung cancer were included. Dose regimens consisted of 24 in 2 fractions, 30-51 Gy in 3 fractions, 30-55 Gy in 5 fractions, 52.5 Gy in 7 fractions and 44-56 Gy in 8 fractions. Dose was expressed as Biological Effective Dose for α/β=10 (BED10). Kaplan-Meyer method was used to calculate Overall Survival (OS), Local Control (LC) and Disease Progression-free Survival (DPFS) from the start date of SBRT to event.

Results

Sixty-three patients, 34 female and 29 male were included. Median age was 75 years (range 25–83). All patients received concurrent systemic treatment before the start of the SBRT: 19 chemotherapy (CT) alone (30%), 26 CT plus immunotherapy (IT) or plus Tyrosin kinase inhibitors (TKI) (41%) and 18 IT/TKI alone (29%).  SBRT was delivered to lung (n=29), mediastinal node (n=9), bone (n=7), adrenal gland (n=19), other visceral metastases (1) and other node metastases (n=4). A median BED10 of 104 (range 39-151) Gy10 was delivered.  After a median follow up of 20 months (range 1-48), median overall survival  was median OS was 23 months (figure 1). LC was 93% at 1 year and 87% at 2 years. DPFS was 7 months. At univariate analysis, age, type of systemic treatment, metastatic site receiving SBRT and BED were not significant prognostic factors for overall survival. 

Conclusion

SBRT in lung cancer patients for oligoprogression resulted in a long median OS of 23 months. One-year LC was 93%. Median DPFS was 7 months, translating into continuation of effective systemic treatment as other metastases grow slowly. SBRT could be useful to postpone the change of chemotherapy and/or immunotherapy. More research is needed to select OPD patients eligible for SBRT.

 


Michele AQUILANO (Firenze, Italy), Mauro LOI, Lorenzo LIVI, Joost NUYTTENS
16:50 - 17:00 #30211 - OP33 Single fraction SABR for lung oligometastases guided by artificial intelligence real time tumor tracking on helical Radixact.
OP33 Single fraction SABR for lung oligometastases guided by artificial intelligence real time tumor tracking on helical Radixact.

Aims: Herein we report preliminary results of a pilot study of single fraction SABR in elderly and multiple lung oligometastatic patients. This study investigates the feasibility and the compliance to lung radiosurgery. 

Materials: Lung tumor tracking allows to reduce the healthy tissue irradiation and is theoretically faster than the gating technique. Single fraction SABR in lung nod- ules is established as an appropriate treatment in oligometastatic patients. However, the risk of target missing in single fraction is higher than in fractionated SABR. Recently and only present in few centers worldwide, Accuray Int, developed a free breathing real time tumor tracking based on artificial intelligence for helical IMRT delivery (Synchrony on Radixact system). 28 Gy single fraction SABR was planned in 10 patients in both peripheric and central lesions. In room time, nodule volumes, local response, real time tracking verification have been assessed for all the patients involved. 

Results: Mean patients age was 79 years old (75-84) and 7 ones were men and the remaining 3 were women; in all cases their PS was 0. All patients had oligometastatic disease: primary melanoma (5), primary NSCLC (2) and CRC (1), HCC (1) and sarcoma (1). Concurrent immunotherapy (respectively Pembrolizumab, Nivolumab and Ipilimumab) was delivered in 6 patients. Lesions were both central (5/10) that peripheral (5/10). Mean GTV volume was 8,50 cc (from 1,9 cc up to 18,2 cc), minimum diameter of lesions was 129 mm to 312 mm. Median beam on time was 17,6 min (910 sec – 1255 sec). The analysis of the cumulative vector of nodules movement, measured a median excursion of 7 mm with a median respiratory cycle time of 4 seconds. No lesions progressed, due to the short follow up, the shrinkage time-volume plot is currently under evaluation. Median follow-up was 8 months, during which we observed no clinical acute toxicity, four patients showed a radiological pattern of diffuse consolidation. All the lesions reduced their volume from 40% up to 90%. For those patients with a follow-up longer than 1 year, no relevant toxicity was radiologically reported.

Conclusions: The preliminary results of our pilot study, showed that lung SABR executed throughout Synchrony on Radixact system is a high compliance treatment in elderly oligometastatic patients. This advanced technique needs a high expertise of all the per- sonnel but is very promising in specific cohort of patients.


Stefano VAGGE (Genova, Italy), Marco GUSINU, Zefiro DANIELE, Genova CARLO, Spagnolo FRANCESCO
17:00 - 17:10 #29467 - OP34 Preoperative robotic stereotactic radiotherapy in early breast cancer: phase II ROCK trial (NCT03520894).
OP34 Preoperative robotic stereotactic radiotherapy in early breast cancer: phase II ROCK trial (NCT03520894).

Background

Breast-conserving surgery (BCS) followed by postoperative radiation therapy (RT) to the residual breast represents the current standard of care for most women affected by early breast cancer. However, standard postoperative regimens are characterized by postsurgical waiting time and potential acute and late locoregional adverse events. Several studies suggested that breast cancer cells can be more sensitive to high doses administered in short intervals. Preoperative robotic stereotactic radiotherapy (SBRT) followed by BCS may yield potential advantages in selected patients. An exploratory phase II study (ROCK trial – NCT03520894) was conducted in our institution.

Materials

Women with histologically proven unifocal invasive hormonal receptors positive, HER2 negative breast cancer, sized less than 25 mm, with negative clinical nodal status, aged 50+ and eligible for BCS were enrolled. Fiducial markers were introduced in peri/intralesional position. Magnetic resonance imaging (MRI) was used in addition to standard CT-based planning. Patients received 21 Gy in single fraction with CyberKnife® followed by BCS two weeks after preoperative SBRT. The primary endpoint was the acute skin toxic effect rate. Secondary objectives were the pathological response rate and the late adverse events rate. Echocardiography and spirometry were performed before preoperative SBRT and yearly thereafter. Translational research was conducted to identify correlations between radiogenomic, immunological and biochemical biomarkers with treatment-related response and toxicity.

Results

From August 2018 to September 2021, a total of 70 patients were screened on mammography; 29 of them were eligible following inclusion criteria. Seven were excluded due to multiple foci disease at basal MRI, and 22 patients were successfully treated. All required dosimetric parameters and normal tissue constraints were met in all cases. Median age at diagnosis was 68 years (range 50-86) and median tumor size was 13 mm (range 7.5-25). All treated patients received surgery within 14 days from preoperative SBRT without any delay or complication. No patients experienced acute skin toxicity of grade (G) 2 or higher; only one patient had a G1 erythema one month after BCS. Two patients reported a pathological complete response, according to Chevallier’s classification. At a median follow up of 18 months, no patients experienced locoregional recurrence or distant metastases. No clinically meaningful changes were observed regarding left-ventricular ejection fraction and spirometric parameters.

Conclusion

Results from the ROCK trial showed that single fraction preoperative robotic SBRT is a feasible technique in selected breast cancer patients with a good safety profile and encouraging activity. This new approach warrants further investigations.


Luca VISANI, Viola SALVESTRINI (Florence, Italy), Icro MEATTINI, Carlotta BECHERINI, Isacco DESIDERI, Erika SCOCCIMARRO, Vanessa DI CATALDO, Monica MANGONI, Chiara BELLINI, Jacopo NORI, Marco BERNINI, Lorenzo ORZALESI, Luis SANCHEZ, Simonetta BIANCHI, Raffaella DORO, Laura MASI, Lorenzo LIVI
17:10 - 17:20 #29915 - OP35 Stereotactic body radiotherapy (SBRT) and concomitant systemic therapy in oligoprogressive breast cancer patients.
OP35 Stereotactic body radiotherapy (SBRT) and concomitant systemic therapy in oligoprogressive breast cancer patients.

Purpose: breast cancer is a heterogenous disease with a deep tailoring level. Evidence is accumulating on the role of stereotactic body radiotherapy (SBRT) in the management of oligometastatic disease, however this is limited in breast cancer. The aim of the present study is to show the effectiveness of SBRT in delaying the switch to a subsequent systemic treatment in oligoprogressive breast cancer patients.

Methods and materials: retrospective analysis from two Institutions. Primary endpoint: time to next systemic treatment (NEST). Secondary endpoints: freedom from local progression (FLP), time to the polymetastatic conversion (tPMC) and overall survival (OS).

Results: One-hundred fifty-three (153) metastases in 79 oligoprogressive breast cancer patients were treated with SBRT. Median follow-up 24 months. Median NEST 8 months. Predictive factor of NEST at the multivariate analysis (MVA) was the number of treated oligometastases (HR 1.765, 95%CI 1.322-2.355; p=0.00). Systemic treatment after SBRT was changed in 29 patients for polymetastatic progression and in 10 patients for oligometastatic progression 70Gy10 was associated with improved FLP (90% versus 74.2%). The median tPMC was 10 months. At the MVA the only factors significantly associated with tPMC were the number of oligometastases (HR 1.172, 95%CI 1.000-1.368; p=0.03), and the local control of the treated metastases (HR 2.726, CI95% 1.108-6.706; p=0.02).

Conclusions: SBRT can delay the switch to a subsequent systemic treatment, however patient selection is necessary. Several predictive factors for treatment tailoring have been identified.


Luca NICOSIA (ITALY, Italy), Vanessa FIGLIA, Nicola RICOTTONE, Francesco CUCCIA, Rosario MAZZOLA, Niccolò GIAJ-LEVRA, Francesco RICCHETTI, Michele RIGO, Fatemeh JAFARI, Stefano Maria MAGRINI, Andrea GIRLANDO, Filippo ALONGI
17:20 - 17:30 #29441 - OP36 Five fractions schedule radiotherapy for early breast cancer with simultaneous intergraded boost. Our early single-institution experience.
OP36 Five fractions schedule radiotherapy for early breast cancer with simultaneous intergraded boost. Our early single-institution experience.

Background: Adjuvant breast radiotherapy practice standard is 40 Gray in 15 fractions. 10 patients with early breast cancer were treated after primary surgery, with ultra-hypofractionated 5 fractions in one week schedule WBI regimen of 26 Gray (Gy), based on the FAST FORWARD trial results, and 0,6Gy/fraction of simultaneous integrated boost (SIB) for a total dose of 29Gy/5,8Gy delivered in 5 fractions. This study attempts to identify the safety, low toxicity profile and patient convenience compared to other hypofractionated schemes.

Methods: In the present study, 10 cases of patients, aged 40-70 with invasive carcinoma of the breast T1–2, pN0, M0 who underwent radiotherapy after breast conservation surgery are presented. Concurrent trastuzumab and/or endocrine therapies were allowed. For patient participation, all the inclusion criteria of the FAST FORWARD trial were met. 26 Gy in five fractions to the whole breast, with SIB of 29Gy to the tumor bed over one week, was delivered. At the breast conservation surgery, two pairs of titanium clips were implanted into the walls of the tumour excision cavity (tumor bed) to assist target delineation. Planning Target Volumes PTVwb and PTVTB were created by adding a 3d uniform expansion of 10mm to the CTVwb and 5mm to the CTVboost containing the tumour bed (clips), respectively. For dose-volume histogram assessment, lungs, heart, contralateral breast, and ipsilateral ribs were contoured. VMAT treatment plans using 6MV beams were used for the patient treatment. Daily pretreatment imaging verification was performed (CBCT), and all corrections were applied (6dCouch). Ultrasound examination and photographs were taken as baseline before the treatment. Follow-up assessment performed in week 1, week 4 and then every 3 months.

Results: All patients completed the 5 fractions schedule. The titanium clips proved to be necessary for the accuracy of the tumor bed delineation. The prescription dose was uniformly delivered to the whole breast and the tumor bed (V95%(PD)>95%). All dose constraints for OARs described by Fast-Forward trial were met. During the first year follow up, no changes in breast appearance or shape were observed, while the skin reaction was grade 2 or less.

Conclusions: WBI regimen of 26 Gy in 5fx with SIB is a well-tolerated and safe hypofractionated radiotherapy scheme. It is also time efficient as it reduces the overall treatment time of EBRT to 1 week, with no differences in normal tissue toxicity or changes in breast appearance versus other radiotherapy schemes. 


Georgios KRITSELIS (ATHENS, Greece), Fiorita POULAKAKI, Ioannis FLOROS, Chrysoula STEFANIDOU, Katerina SILIVRIDOU
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EPOSTERS1
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01. Eposters - Brain - Malignant

00:00 - 00:00 #28839 - P001 Importance of interval between MRI and frameless Gamma Knife SRS for brain metastases with peritumoral edema under steroid treatment.
P001 Importance of interval between MRI and frameless Gamma Knife SRS for brain metastases with peritumoral edema under steroid treatment.

Purpose: For brain metastases (BM) with peritumoral edema, the tumor volume and location may change quickly. Steroid is used to reduce the edema extent, but may cause tumor shift. This study aims to evaluate the impact of time interval between planning MRI and frameless Gamma Knife (GK) stereotactic radiosurgery (SRS) on tumor size, location and isodose coverage for BM.

 

Materials and methods: Five patients who underwent frameless GK SRS for BM with peritumoral edema were reviewed retrospectively. All patients were receiving steroid during SRS. Every patient had one diagnostic MRI (median 22 days before SRS), and one planning MRI (median 7 days before SRS). There were a total of 18 lesions in this study. We contoured tumors on the contrast enhanced T1 weighted images of both diagnostic MRI and planning MRI, and assigned them as diagnostic GTV and planning GTV, respectively. Research SRS plans were generated based on diagnostic MRI, with 100% prescribed dose (PD) covering GTV, and 100% PD covering at least 95% PTV (1 mm GTV expansion), which is the same as the clinical plans. The changes in tumor volumes, centroid locations, and isodose distribution were evaluated.   

 

Results: The median of tumor volume difference was 30.8% (maximum 400%). The median of tumor shift was 0.1 mm (maximum 2.7 mm) in X-axis, 0.5 mm (maximum 2.2 mm) in Y-axis, and 0.2 mm (maximum 0.4 mm) in Z-axis. The shifting distance was 0.62 mm (maximum 3.57 mm). The variation of dose-volume histogram and Paddick conformity index (PCI) were also noted. The volumes covered by 100% PD (VPD) of planning GTVs dropped to 93.11% from 100%. The VPD of planning PTVs dropped to 79.82% from 98.31%. PCI decreased from 0.8 to 0.61, which is farther away from the ideal value. If the diagnostic MRI were used in SRS planning, instead of the planning MRI, a detrimental consequence of missing 6.89% of GTV and 18.81% of PTV would occur, and the isodose conformity would also be worse.

 

Conclusion: BM with peritumoral edema in this patient group changes rapidly despite the use of steroid. To assure the target accuracy, a short interval between MRI and SRS delivery is ideal. An alternative way is to deliver framed SRS in such cases, because it guarantees the shortest interval. In frameless GK SRS, the interval between planning MRI and SRS should be kept as short as possible to avoid marginal miss.


Kuanyin HSIAO, Huichuan WANG (Houston, USA), Ramiro PINO, E. Brian BUTLER, Bin S TEH
00:00 - 00:00 #29312 - P002 Our Experience in the Treatment of Glioblastoma with Radiosurgery, Multicentric Study, Long Term Follow-Up.
P002 Our Experience in the Treatment of Glioblastoma with Radiosurgery, Multicentric Study, Long Term Follow-Up.

The treatment of glioblastoma multiforme is a challenge for the neurosurgeons and radiation oncologohist . The current treatment include surgery, radotheraphy , imunologic treatment, virus tretment and etc. Radisorugery has been introduce in the last ten years and the recently results did not change the philosophy of treatment.  Only one prospective randomized trial has been published investigating the effect of SRS added to conventional external beam radiation therapy (EBRT) on the survival of patients with newly diagnosed GBM and found no benefit in patient outcome giving SRS as boost before standard radiotherapy and carmustine ]. Evidence regarding SRS in tumor recurrence is unconclusive for establishing SRS as standard practice 

We present a retrospective multicentric study , three  different radiosurgery centers of patients with GBM ,who were treated at tumor recurrence with SRS aiming to evaluate the efficacy of SRS as treatment modality considering treatment outcome and overall survival.

 

Materials and Methods

We retrospectively reviewed patients who received SRS for recurrent glioblastoma  between January 1992 and February  2021, a total of 48 patients were included in this study.  One center used the frame based rigid fixation stereotactic radiosurgery system 200 (SRS 200) developed by the Gainesville University of  Florida in a Precise LINAC (Linear Accelerator) developed by Elekta (Stockholm, Sweden) the second center used Cyberknife (Accuray, Sunnyvale, California, USA) and the third center in used Infini gamma ray (GR), rotating, intracranial, stereotactic radiosurgery system (Masep Medical Company, Shenzhen, China).

Patients received SRS at a median time of 10 months (1-94) after initial diagnosis. Single lesions were documented and treated in 38 (81%) patients and 11 (22.9%) patients had multiple lesions treated at the time of SRS. A group of five (10.9%) patients received a second SRS treatment session due to tumor recurrence

Median survival after SRS was compared between both time frames 1992-2011 and 2012-2020. Median OS was nine months and 20 months since diagnosis for patients treated during second time span (2012-2020). A two-month difference of median survival after SRS was found between time frames (p=0.008, X2=7.008). Median overall survival since time of diagnosis did not achieve statistical significance (25.7 versus 20 months) (p=0.947, X2=0.004) between both periods 

Based on the results presented herein, GBM patients following a STUPP regimen plus SRS at time of recurrence along with concomitant immuno-chemotherapy can anticipate a superior survival rate as opposed to what has been reported with single therapeutic modalities.


Kita SALLABANDA DAIZ, Eduardo LOVO IGLESIAS, Maria Loreto YAÑEZ SEPULVEDA, Morena SALLABANDA HAJRO, Kita SALLABANDA DAIZ (Madrid, Spain)
00:00 - 00:00 #29313 - P003 Adaptive (two session) radiosurgery for large brain tumors with high alfa/beta.
P003 Adaptive (two session) radiosurgery for large brain tumors with high alfa/beta.

Introduction

Adaptive radiosurgery implies two and sometimes three sessions of radiosurgery for large brain tumors with time spans from 30 to 15 days apart in between them. The main objectives are a safe dose scaling allowed by tumor shrinkage and thus a new adaptation of a plan to the new target volume. Originally two-session radiosurgery was described and has been mainly used for metastatic tumors afflicting the brain, nevertheless there are also primary brain tumors with suspected high alfa/beta that can benefit from this radiosurgical technique.

Method

We reviewed our case series of patients that have been treated with adaptive radiosurgery in our centers in primary and secondary brain tumors. Dosimetry comparative studies regarding healthy tissue V12, V18, and V20 comparing adaptive radiosurgery versus fractionated three consecutive session radiosurgery were done using Time Dose Fraction (TDF)

Results

33 Patients with a total of 60 tumors (46 secondary and 14 primary) were identified. Mean tumor volume for primary tumors were 15 cc, the mean prescription dose was 13 Gy, during the second session, tumor volume was reduced to 73.6% of the original dimension, mean tumor volume was 5cc, mean prescription dose for the second session was also 13 Gy, 8 tumors were in the pineal region, 4 in the hypothalamic region and 2 else were. For secondary tumors mean tumor volume was 11.7cc mean prescription dose during the first session was 12 Gy, for the second session mean tumor volume was 5.5cc with a 66.6% reduction and the prescription dose was 15 Gy. Tumor response, tumor reduction between sessions was documented in 55 tumors (92%) local control at one year for the whole series was 92%, 4 patients with metastatic tumors required surgery, 1 patient with a primary tumor passed away from tumor progression. Potential healthy tissue sparing favored adaptive radiosurgery V12 versus fractionated radiosurgery V18 and V20 427% and 338% respectively

Conclusions

Adaptive radiosurgery is an effective technique in large tumors or those located in critical areas expected to have a high alfa/beta. It achieves rapid symptom alleviation and thus reducing the need for surgery. The potential of healthy tissue sparing due to tumor volume shrinkage and replanning is substantially higher than a traditional fractionated radiosurgery approach.


Eduardo LOVO (San Salvador, El Salvador), Kaory BARAHONA, Victor CACEROS, Fidel CAMPOS, Alejandro BLANCO, Julio ARGUELLO
00:00 - 00:00 #29327 - P005 CyberKnife for recurrent malignant gliomas: a systematic review and meta-analysis.
P005 CyberKnife for recurrent malignant gliomas: a systematic review and meta-analysis.

 

Background and Objective: Possible treatment strategies for recurrent malignant gliomas include surgery, chemotherapy, radiotherapy, and combined treatments.  Among different reirradiation modalities, the CyberKnife System has shown promising results.  We conducted a systematic review of the literature and a meta-analysis to establish the efficacy and safety of CyberKnife treatment for recurrent malignant gliomas. 

Methods: We searched PubMed, MEDLINE, and EMBASE from 2000 to 2021 for studies evaluating the safety and efficacy of CyberKnife treatment for recurrent WHO grade III and grade IV gliomas of the brain.  Two independent reviewers selected studies and abstracted data.  Missing information was requested from the authors via email correspondence.  The primary outcomes were median Overall Survival, median Time To Progression, and median Progression-Free Survival.  We performed subgroup analyses regarding WHO grade and chemotherapy.  Besides, we analyzed the relationship between median Time To Recurrence and median Overall Survival from CyberKnife treatment.  The secondary outcomes were complications, local response, and recurrence.  Data were analyzed using random-effects meta-analysis. 

Results: Thirteen studies reporting on 398 patients were included.  Median Overall Survival from initial diagnosis and CyberKnife treatment was 22.6 months and 8.6 months.  Median Time To Progression and median Progression-Free Survival from CyberKnife treatment were 6.7 months and 7.1 months.  Median Overall Survival from CyberKnife treatment was 8.4 months for WHO grade IV gliomas, compared to 11 months for WHO grade III gliomas.  Median Overall Survival from CyberKnife treatment was 4.4 months for patients who underwent CyberKnife treatment alone, compared to 9.5 months for patients who underwent CyberKnife treatment plus chemotherapy.  We did not observe a correlation between median Time To Recurrence and median Overall Survival from CyberKnife.  Rates of acute neurological and acute non-neurological side effects were 3.6% and 13%.  Rates of corticosteroid dependency and radiation necrosis were 18.8% and 4.3%. 

Conclusions: Reirradiation of recurrent malignant gliomas with the CyberKnife System provides encouraging survival rates.  There is a better survival trend for WHO grade III gliomas and for patients who undergo combined treatment with CyberKnife plus chemotherapy.  Rates of complications are low.  Larger prospective studies are warranted to provide more accurate results. 


Lucio DE MARIA (Brescia, Italy), Lodovico TERZI DI BERGAMO, Alfredo CONTI, Kazuhiko HAYASHI, Valentina PINZI, Taro MURAI, Rachelle LANCIANO, Sigita BURNEIKIENE, Michela BUGLIONE DI MONALE, Stefano Maria MAGRINI, Marco Maria FONTANELLA
00:00 - 00:00 #29351 - P006 Evaluation of biological effective dose for Gamma Knife staged stereotactic radiosurgery for large brain metastases.
P006 Evaluation of biological effective dose for Gamma Knife staged stereotactic radiosurgery for large brain metastases.

Objective: Gammaknife (GK) staged stereotactic radiosurgery (Staged-SRS) has emerged as an effective treatment option for large brain metastases (BMs) (> 2cm in diameter or > 4 cc in volume) with encouraging clinical results. However, because of the tumor shrinkage observed between two sessions of Staged-SRS, it has been challenging to evaluate the overall total composite treatment dose. This study aims to develop a novel workflow to evaluate the total biological effective dose (BED) delivered to both the tumor and normal brain tissue in Staged-SRS and to compare those in single fraction SRS (SF-SRS) and hypo-fractionated SRS (HF-SRS) treatment.

Methods: Patients treated with GK Staged-SRS at a single institution were retrospectively included. Deformable image registration was performed for MRI images acquired at each session using commercial software to account for tumor shrinkage. The dose delivered in two staged sessions was then summed based on the registration and the total BEDs to tumor/normal brain tissue of Staged-SRS were computed using the linear-quadratic model with and without considering cell repopulation during session interval. Each patient was also replanned for SF-SRS and HF-SRS where the BEDs were computed using the same formalism. Tumor BED98% ­and brain V84Gy2, which was equivalent to V12Gy commonly assessed in SF-SRS, were compared between SF-SRS, HF-SRS, and Staged-SRS plans with the Wilcoxon Rank Sum test.

Results: Twelve patients with a total of 24 BMs treated with GK Staged-SRS were retrospectively identified. We observed significant differences (p<0.05) in tumor BE­D98% but comparable brain V84Gy2 (p=0.677) between the Staged-SRS and SF-SRS plans. No dosimetric advantages of Staged-SRS over HF-SRS were observed. Tumor BED98% in the HF-SRS plans were significantly higher than those in the Staged-SRS plans (p<0.05). Despite the additional 1-mm setup margin added to the tumor with resultant larger PTV, brain V84Gy2 in the HF-SRS plans remained lower (p< 0.05).

Conclusion: We presented a novel approach to calculate the composite BEDs delivered to both tumor and normal brain tissue for Staged-SRS. Compared to SF-SRS, Staged-SRS delivers a higher dose to tumor but comparable dose to normal brain tissue. In addition, our results didn’t show any dosimetric advantages of Staged-SRS over HF-SRS.


Taoran CUI (New Brunswick, USA), Joseph WEINER, Shabbar DANISH, Anupama CHUNDURY, Nisha OHRI, Ning YUE, Xiao WANG, Ke NIE
00:00 - 00:00 #29385 - P007 Adaptive staged-dose Gamma Knife Radiosurgery for the treatment of large brain metastases. Report of 40 consecutive cases and review of literature.
P007 Adaptive staged-dose Gamma Knife Radiosurgery for the treatment of large brain metastases. Report of 40 consecutive cases and review of literature.

BACKGROUND: Brain metastases are the most common brain tumors, being one of the most frequent neurological complications of systemic cancer and an important cause of morbidity and mortality. Stereotactic Radiosurgery is efficacious and safe in treatment of brain metastases, with good local control rates and low adverse effects rate. Large brain metastases present some issues in balancing local control and treatment-related toxicity. Adaptive staged-dose GammaKnife Radiosurgery (ASD-GKRS) has shown to be a safe and effective treatment for large brain metastases.

METHODS: We retrospectively analyzed  and compared with data from  review of literature our series of patients treated with Adaptive staged-dose GammaKnife Radiosurgery for large brain metastases in ASST Grande Ospedale Metropolitano Niguarda, Milan - Italy, between February 2018 and May 2020.

RESULTS: Forty patients with  large brain metastases underwent Adaptive staged-dose GammaKnife Radiosurgery, with median prescription dose of 12Gy and a median interval between stages of 30 days. At 3-months follow-up the survival rate was 75,0% with a local control rate of 100%. At 6-months follow-up the survival rate was 75,0% with a local control rate of 96.7%. The mean volume reduction was 21.81 cm3 ( 16.76 - 26.86; IC95%). The difference between baseline volume and 6-months follow-up volume was statistically significant.

CONCLUSIONS: Adaptive staged-dose GammaKnife Radiosurgery is a safe, non invasive and effective treatment for brain metastases, with a low rate of side effects. Large prospective trials are needed to strengthen data obtained about the effectiveness and safety of this technique in managing large brain metastases.


Crisà FRANCESCO MARIA, Leocata FILIPPO, Arienti VIRGINIA MARIA, Picano MARCO, Berta LUCA, Brambilla MARIA GRAZIA, Mainardi HAE SONG, Monti ANGELO FILIPPO, Cenzato MARCO, Palazzi MAURO, La Camera ALESSANDRO (Milan, Italy)
00:00 - 00:00 #29397 - P008 Genetic algorithm and neural networks in radiosurgery for multiple metastases.
P008 Genetic algorithm and neural networks in radiosurgery for multiple metastases.

Purpose: To evaluate the optimization of PTV margins in multiple metastases radiosurgery (SRS) with single isocenter technique by the use of bio-inspired algorithms and neural networks.

Method: 10 plans were created and optimized with Elements Multiple Mets SRS v2.0 (Brainlab AG, Munchen, Germany). The mean number of metastases per plan was 5 ± 2 [3,9] and the mean volume of GTV was 1.1 ± 1.3 cc [0.02, 5.1]. The total number of metastases was 55. Considering all possible combinations of rotational and translational movements (6!x26=46080), the maximum displacement (roll, pitch, yaw, x, y, z) was optimized by a genetic algorithm (GA). By the use of a multilayer perceptron, the PTV margin (2 mm, 1 mm or 0.5 mm) was determined considering the target distance to isocenter and the volume of the lesion. The original plans were re-calculated using the PTV optimized margin and new dosimetric variations were obtained. The Paddick conformity index (PCI) and gradient index (GI) were analyzed.

Results: The GA parameters such as number of parents, cross-over point and mutation rate were optimized to reduce the computation time and to obtain global optimization points. Considering the maximum effective displacements due to rotations and translations, it is necessary to define larger and optimized PTV margins to reduce dosimetric variations on PCI and GI. The multilayer perceptron neural networks hyperparameters (learning rate, activation function, inner layers, number of neurons) were optimized for reducing the computation time and to obtain better loss functions.

Conclusion: The GA and neural networks are tools to facilitate the PTV margin decision on SRS for multiple metastases with single isocenter. These computational tools based on artificial intelligence consider a complete dosimetrical and geometrical study of the mechanical uncertainties due to rotations and translations in these treatments.


José Alejandro ROJAS-LÓPEZ (Argentina, Argentina), Daniel VENENCIA, Miguel Ángel CHESTA, Francisco TAMARIT
00:00 - 00:00 #29404 - P009 Contrast clearance analysis has direct impact on the survival of patients with brain metastasis treated with Gamma Knife.
P009 Contrast clearance analysis has direct impact on the survival of patients with brain metastasis treated with Gamma Knife.

Purpose

Pseudoprogression is a well-characterized toxicity associated with radiation for intracranial lesions which can be difficult to differentiate from tumor progression on follow-up MRI, making treatment decisions challenging. Serial MRIs can lead to delay of the treatment and allows tumor growth. This study shows that the clinical application of the contrast clearance for early differentiation has a direct impact on patient’s survival.

Methods

Fifty-seven consecutive patients diagnosed with brain metastasis and treated with Gamma Knife Radiosurgery (GKRS) who had presented suspicious lesion growth on their follow-up were submitted to contrast clearance analysis to distinguish between treatment effect from tumor progression. Lesions considered to have recurrence were retreated with GKRS. Kaplan-Meir Survival Analyses was used at the end of the follow-up period.

Results

The most common primary disease was non-small cell lung cancer (40%), followed by breast (12%) and melanoma (11%). The use of contrast clear analysis suggested 24 lesions to be tumor recurrence and 35 to be pseudoprogressions. Total follow-up period was of 72 months. Kaplan-Meir Survival Analyses showed that retreated patients had greater survival with p< .05 according to Wilcoxon test.

Conclusion

The use of contrast clearance imaging is a promising tool to distinguish tumor progression from radiation necrosis in the setting of radiosurgical treatment. Early differentiation allows early retreatment and improvement of the patient survival. Further studies are needed to clearly show its sensitivity and positive predictive value in metastatic disease.


Victor GOULENKO, Matthew RECKER, Dheerendra PRASAD (Buffalo, NY, USA), Robert PLUNKETT
00:00 - 00:00 #29418 - P010 Single isocenter radiosurgical treatments for multiple brain metastases.
P010 Single isocenter radiosurgical treatments for multiple brain metastases.

Purpose/Objective(s):

To communicate our institutional experience with single isocenter radiosurgery treatments for multiple brain metastases, including challenges with determining planning target volume (PTV) margins and resulting consequences, image-guidance translational and rotational tolerances, intra-fraction patient motion, and prescription considerations with larger PTV margins. 

Materials/Methods:

Eight patient treatments with 51 targets were planned with various margins using Elements Multiple Brain Mets SRS treatment planning software (Brainlab, Munich, Germany). Forty-eight plans with 0mm, 1mm and 2mm margins were created, including plans with variable margins, where targets more than 6cm away from the isocenter were planned with larger margins. The dosimetric impact of the margins were analyzed with V5Gy, V8Gy, V10Gy, V12Gy values. Additionally, 12 patient motion data were analyzed to determine both the impact of the repositioning threshold and the distributions of the patient translational and rotational movements. 

Results:

The V5Gy, V8Gy, V10Gy, V12Gy volumes approximately doubled when margins change from  0mm to 1mm and tripled when change from 0mm to 2mm. With variable margins, the aggregated results are similar to results from plans using the lower of two margins, since only 12.2% of the targets were more than 6cm away from the isocenter.

With 0.5mm re-positioning threshold, 57.4% of the time the patients are repositioned.  Reducing the threshold to 0.25mm results in 91.7% repositioning rate, due to limitations of the fusion algorithm and actual patient motion. 

The 90th percentile of translational movements in all directions is 0.7mm, while the 90th percentile of rotational movements in all directions is 0.6 degrees. Median translations and rotations are 0.2mm and 0.2 degrees, respectively.

Conclusions:

Based on the data presented, we have switched our modus operandi from 2mm to 1mm PTV margins, with an eventual goal of using 0.5 and 1.0mm variable margins when an automated margin assignment method becomes available. The 0.5mm and 0.5 degrees repositioning thresholds are clinically appropriate with small residual patient movements.


Nzhde AGAZARYAN (Los Angeles, USA), Steve TENN, Tania KAPREALIAN
00:00 - 00:00 #29425 - P011 Efficacy of a biweekly 3-Stage stereotactic radiosurgery for large brain metastases: The effect of EGFR tyrosine-kinase inhibitor on tumor response and clinical outcomes.
P011 Efficacy of a biweekly 3-Stage stereotactic radiosurgery for large brain metastases: The effect of EGFR tyrosine-kinase inhibitor on tumor response and clinical outcomes.

Stereotactic radiosurgery(SRS) is one of the primary treatment modalities for brain metastases. However, radiosurgical control of large brain metastases(LBM) remains challenging and shows suboptimal local control rates and an increased risk of radiation injury. To overcome these limitations, fractionated or staged SRS has been used. This study was performed to evaluate the clinical outcomes of a biweekly 3-stage SRS for LBM.

A total of 53 patients were treated with a biweekly 3-stage SRS for 62 LBM. Female was 27, and the mean age was 63.7years. The mean Karnofsky Performance Score(KPS) was 79.2. Non-small cell lung cancer(NSCLC) was the most common primary cancer in 31 patients, the others include 6 patients of small cell lung cancer(SCLC), 9 patients of gastro-intestinal tract cancer, 5 gynecological cancer patients, and so on. Epidermal growth factor receptor(EGFR) mutation was identified in 13 patients, and EGFR tyrosine-kinase inhibitor(TKI) was used in 10 patients during and/or after the staged SRS. The mean tumor volume was 19.1cm3. The mean marginal dose of 11.7Gy was delivered to the 50% isodose line based on a new treatment planning every two weeks. 

Among 53 patients, 6 patients were dropped from the treatment. The tumor volume gradually decreased with each treatment stage. The mean tumor volume at the second and third stage was 14.8cm3 and 11.0cm3, respectively. The lesions from squamous cell of NSCLC decreased most rapidly, and followed by gynecological cancer, SCLC and adenocarcinoma of NSCLC (the volume ratio at the third stage was 0.39, 0.53, 0.56, and 0.64, respectively). However, the lesions from gastro-intestinal tract cancer were slow to respond, and only reduced to 83.2% of the initial volume at the 3rd stage. The most significant factor related with tumor volume reduction by the 3rd stage was usage of EGFR-TKI(p=0.016). The mean overall survival was 15.3 months, and the estimated overall survival rates were 62% and 46% at 6 and 12 months, respectively. In the multivariate analysis, KPS(p=0.002) and usage of EGFR-TKI(p=0.021) were significantly associated with overall survival. The mean overall survival of the group of usage of EGFR-TKI was significantly longer than that of the others(20.7 and 13.1months, respectively).

The biweekly 3-stage SRS seems to be effective treatment for patients with LBM, especially in patients who were treated with EGFR-TKI during and/or after SRS. However, patients were selected cautiously considering the primary tumor site and possible treatment options for their systemic tumor control.


Ji-Eyon KWON (Seoul, Korea), So Young JI, Jung Ho HAN
00:00 - 00:00 #29426 - P012 Analysis of the metastases brain tumor to predict the overall survival within three-months for non-small cell lung cancer using machine learning algorithms.
P012 Analysis of the metastases brain tumor to predict the overall survival within three-months for non-small cell lung cancer using machine learning algorithms.

Purpose: Gamma knife radiosurgery (GKRS) is commonly employed in patients with brain metastases, but the predictions of overall survival within 3 months after GKRS are inaccurate. ­All patients with brain metastases do not share the same prognosis and should not receive the same treatment. Especially, non-small cell lung cancer (NSCLC) patients revealed more than 10% of the treated patients died within 8 weeks [1]. The early death could denote overtreatment and questionable to treat. The purpose of this study was to predict the overall survival with machine learning algorithms including decision-tree and random forest modeling in NSCLC patients. And we also investigated the important features for overall survival. 

Methods: We randomly selected 120 NSCLC patients treated the GKRS at Chungbuk National University Hospital. The patients were randomly divided into 80 training groups and 40 testing groups with 14 features. The categorical variable was executed to preprocessing using one-hot encoding methods. Root mean squared logarithmic error is used to find out differences between prediction and actual values. And all data was verified by the three neurosurgeons and two medical physicists. To predict overall survival, we used to machine learning algorithms and extracted important features. 

Results: Accuracy of algorithms to predict overall survival was 77.5%, 72.5%, and 73.68 %, decision-tree, random forest, and boosted tree classifier. The important features commonly showed age, chemotherapy, and pre-operation each algorithm. And permutation features commonly showed the age, which is important variable for predicting overall survival in NSCLC patients. 

Conclusions: These results suggest that machine learning algorithms are a useful tool for predicting the overall survival and finding important variables in NSCLC patients. Among of algorithms, decision-tree showed high accuracy, and considering to age, volume size, and number of lesions in sequence when make a treatment planning in patients with NSCLC. 


Hyeong Cheol MOON, Dong Suk JANG, Young Seok PARK (Cheongju, Korea)
00:00 - 00:00 #29465 - P014 Viable tumor recurrence is a major cause of local failure after bevacizumab therapy for radiation necrosis in brain metastases treated with stereotactic radiosurgery.
P014 Viable tumor recurrence is a major cause of local failure after bevacizumab therapy for radiation necrosis in brain metastases treated with stereotactic radiosurgery.

Background

Bevacizumab (BVZ) is known to be effective to control radiation necrosis (RN) following stereotactic radiosurgery (SRS) for brain metastases (BMs), although treatment failure may occur. Here, we investigated the incidence and pattern of local failure after BVZ therapy for RN and its underlying biological mechanism.

 

Methods

We conducted a retrospective analysis on 17 patients who had been treated with BVZ for RN following SRS for BMs between 2016 and 2021. In each patient, the diagnosis of RN was made based on the conventional and advanced MR with or without positron emission tomography. Median 5 cycles (range, 2-10 cycles) of BVZ (5 mg/kg) were administered at 2-week intervals. Treatment response was assessed by volumetric changes of the lesions on MR and patients’ neurological status.

 

Results

Treatment response was typically brisk and substantial. Best MR response was seen at median 13 weeks (range, 3-56 weeks) after the start of BVZ with a median volume decrease of 84.5% (range, 38.7-100%) of perilesional brain edema on T2WI and of 54% (range, 2.9-100%) of contrast enhancing lesions on T1WI. Patients’ neurological status improved in 16 patients (94.1%) and was stationary in 1 (5.9%). During the median follow-up of 12 months (range, 2-60 months), delayed local failure was observed in 6 patients (35.3%) at median 10 months (range, 6-14 months) after starting BVZ treatment, where viable tumor recurrence was demonstrated in all of them. No reconstitution of RN without viable tumor was observed during the follow-up.

 

Conclusions

Although BVZ was highly effective to control RN following SRS for BMs, delayed local failure frequently occurs owing to viable tumor recurrence. This may imply that much predominant vascular stabilizing effect of BVZ over anti-tumor effect transiently obscures the presence of potential viable tumor cells but does not prevent them from eventual recurrence.


Young Hyun CHO, Kyoungjun YOON, Do Hee LEE, Young-Hoon KIM (Seoul, Korea), Sang Woo SONG
00:00 - 00:00 #29466 - P015 Validation of lexicographic optimisation-based planning for brain metastasis radiosurgery with coplanar arcs.
P015 Validation of lexicographic optimisation-based planning for brain metastasis radiosurgery with coplanar arcs.

Purpose: Recent advances in automated treatment planning demonstrated improved plan quality and best practice reducing routine planning workload. In this study, a not yet commercially available fully-automated lexicographic optimisation planning, called mCycle (Elekta AB, Stockholm), was validated for intracranial stereotactic radiosurgery (SRS).

Material and Methods: Twenty-one single-lesion SRS treatment plans (21 Gy/1 fx) delivered between November 2019 and December 2021 were retrospectively selected and re-planned by mCycle (Monaco 5.59.13). Constraints and objectives were sequentially optimized by multi-criterial optimization (MCO) according to an a-priori assigned priority list, a so-called Wish List (WL). Four patient sets were used to achieve a robust WL. All plans were optimized with 2 coplanar 140°-arcs and calculated with the Monte Carlo algorithm (1 mm-dose grid, 0.5%-statistical uncertainty). The main criteria for planning approval was a brain volume receiving more than 12 Gy less than 10 cm3 (V12Gy < 10 cm3). A target coverage as high as possible was requested, with at least the 80% of the prescription dose covering the 99% of the PTV. Manual plans (MP) and mCycle plans (mCP) were compared in terms of dose-volume constraints and monitor units (MUs). Statistical significance was assessed performing the Wilcoxon Mann Whitney test with Bonferroni correction for multiple tests (alpha=0.05). Plan deliverability was verified by pre-treatment QA.

Results: The 21 mCP re-planning took only 5 working days. Dose statistic comparison is reported in Table 1. Plan comparison showed a statistically significant increase in target dose coverage, both for CTVs and PTVs, without significantly increasing the near-maximum doses. The PTV Paddick’s conformity index (CI) was equally improved and the brain V12Gy in mCP was comparable to the one in MP. Other organs at risk (OARs) were never significantly interested by clinically relevant doses. These results were obtained with a lower median number of MU (-11.6%) even if this difference was not statistically significant and plans registered a comparable gamma analysis (local 2%/2mm).

Conclusions: The novel mCycle autoplanning produced high-quality clinically acceptable radiosurgery plans with coplanar arcs significantly reducing the overall planning time: the planning of one MP and one mCP took about 1 working day and 2 hours, respectively. While the OAR sparing was comparable between MP and mCP, the target coverage was significantly increased, reducing the MU number and preserving the plan deliverability. The validation showed the mCycle capability to generate high-quality deliverable plans according to institutional-specific planning protocols.


Sara TRIVELLATO (Monza, Italy), Paolo CARICATO, Paolo CARICATO, Roberto PELLEGRINI, Gianluca MONTANARI, Denis PANIZZA, Denis PANIZZA, Valeria FACCENDA, Valeria FACCENDA, Stefano ARCANGELI, Stefano ARCANGELI, Elena DE PONTI, Elena DE PONTI
00:00 - 00:00 #29555 - P016 Radiosurgery for recurrent glioblastoma.
P016 Radiosurgery for recurrent glioblastoma.

Abstract Background. Despite the combined treatment in accordance with modern standards, recurrent glioblastoma usually occurs with in several months after resection and causes low relapse-free and overall survival. One of the most effective methods for malignant glioma progression is repeated radiotherapy. Indications for this approach have expanded after introduction of stereotactic irradiation into routine clinical practice.

Objective. To evaluate the results of radiosurgery in patients with recurrent glioblastoma and to identify the factors determining its effectiveness. Material and methods. Radiosurgery has been carried out in 168 patients with relapses of glioblastoma between 2005 and 2021. This study enrolled 88 patients with 180 foci of local and distant progression. Mean age of patients was 42.8±2.1 years (range 4—73). Mean period between diagnosis and repeated irradiation was 12.7 months. Mean volume of focus was 2.4 cm3, mean dose — 20 Gy. Median follow-up period after radiosurgery was 11.2 months.

Results. Repeated irradiation with correction of systemic therapy improved progression-free survival and overall survival with significant radiation-induced toxicity (CTCAEv4.0, Grade 3 - 8.4%). Annual overall survival was 62.2%, median of overall survival after radiosurgery — 15.1 months. Significant factors of local control were marginal dose of at least 18 Gy and distant relapse. Median of progression-free survival in the group of distant progression of glioblastoma was only 3.6 months vs. 9.1 months in patients with local recurrence.

Conclusion. Repeated irradiation in radiosurgery mode with a dose of 18 Gy and higher is an effective option for local treatment increasing progression-free and overall survival in patients with progression of glioblastoma.


Ivan OSINOV, Andrey GOLANOV (Moscow, Russia), Valery KOSTYUCHENKO, Sergey BANOV, Anjelika ARTEMENKOVA
00:00 - 00:00 #29556 - P017 Dose-staged radiosurgery in the treatment of patients with large (>4cc) brain metastasis.
P017 Dose-staged radiosurgery in the treatment of patients with large (>4cc) brain metastasis.

Background: Stereotactic radiosurgery (SRS) is the primary modality for treating brain metastases. However, effective radiosurgical control of brain metastases ≥ 2,5 cm in maximum diameter remains challenging. The SRS possibilities in the treatment of such patients are limited by the high risks of developing post-radiation complications. The use of dose-staged SRS (DSSRS) allows delivering of high dose to the lesions in several treatment sessions with minimize radiation exposure to normal brain tissues.

Objective: The article presents the results of dose-stage radiosurgery using Leksell Gamma Knife to patients with metastatic brain lesions >4,0 cc.

Methods: Volumetric measurements were performed at the moment of first and second stages of treatment and on follow-up. Outcome was evaluated using methods for binary data, PFS and OS - using conventional time-to-event methods.

Results: Data from 42 patients (pts) with 203 lesions were analyzed. The median age was 56.6 years (24-77). 42 lesions >4,0 cc, were treated in 2 stages DSSRS, other 161 lesions treated in one fraction. Median tumor volume at first stage was 11,4 cc (4,5–22,5 cc) and at second stage - 8,0 cc (1,7–20,8 cc). The median prescription dose at first and second stages were 12,0 Gy (10–15 Gy) and 15,0 Gy (10–18 Gy) respectively. The median duration between stages was 23 days. Three month follow-up imaging results were available for 42 lesions: the median volume was 1.3 cc (0,01-26,0 cc), local control (LC) at 3, 6, 12 month was 96,9%, 93,3%, 78,6% respectively. Median PFS was 8,7 month, 17 pts (40,4%) had new metastasis at 12 month after DSSRS. PFS at 6 and 12 month was 71,0±8,8%, and – 36,7±10,5% respectively. In univariate analyzes pts receiving systemic drugs therapy after DSSRS had significantly better PFS rate (p=0,03). Estimated OS rates at 6 and 12 months were 58,3±8,1% and 42,6±8,4% respectively. In multivariate analyze KPS>80 and systemic drugs therapy had significant impact to OS (p=0,01). Grade 2-3 adverse radiation effects (ARE) appeared at 16.6% with median 4,0 month (1,5-12,0).

Conclusion: DSSRS is an effective treatment modality that resulted in significant reduction of brain metastases >4,0 cc, with excellent 6-month (93,3%) and 12-month (78,6%) LC rates and an overall grade 2-3 ARE rate of 16,6%. Prospective studies with larger cohorts and longer follow-up are necessary to assess long-range durability and toxicities of DSSRS.


Ivan OSINOV, Andrey GOLANOV (Moscow, Russia), Sergey BANOV, Aleksandr SAVATEEV, Valery KOSTYUCHENKO
00:00 - 00:00 #29807 - P018 Distinguishing tumor progression from adverse radiation effects after brain metastasis radiosurgery: the longitudinal GRASP imaging experience.
P018 Distinguishing tumor progression from adverse radiation effects after brain metastasis radiosurgery: the longitudinal GRASP imaging experience.

Abstract

We investigated the utility of a novel imaging technique, golden-angle radial sparse parallel (GRASP) dynamic contrast-enhanced permeability MRI, in distinguishing brain metastasis progression and treatment-induced adverse radiation effects (ARE) following stereotactic radiosurgery (SRS).

 

Methods:

We retrospectively analyzed patients with brain metastases treated with gamma-knife SRS at our institution from 2013-2020 who had GRASP MRI before and at least once after SRS. The contrast-enhanced GRASP sequence, a single acquisition of about 6 minutes, is obtained in routine MRI. For each scan, three non-overlapping regions of interest (ROIs) in the maximally enhancing tumoral components and a control ROI in the superior sagittal sinus (SSS) were drawn. Analysis was limited to the first 100 seconds of acquisition. Slopes of the ROIs’ signal intensity-time curves during wash-in (period of maximally increasing SSS signal intensity) and wash-out (period of monotonically decreasing signal intensity after peak SSS enhancement). Tumor ROIs’ wash-in slope (nWin) and wash-out slope (nWout) normalized to the SSS were compared between tumor progression and ARE groups. Tumor progression was pathologically confirmed from post-GK surgically resected lesions. ARE was diagnosed on either surgically resected tissue with no signs of tumor or on lesion resolution on imaging follow-up. Two-sample t-tests with significance level p<0.05 and receiver-operating characteristic (ROC) analysis with optimal threshold identification by Youden’s index were performed.

 

Results:

32 patients comprised this study population: 16 had tumor progression and 16 had ARE. Seventeen patients underwent surgical resection of their lesion, with 16 (94%) showing pathology-confirmed recurrences and 1 (6%) showing ARE. Fifteen patients were followed closely and their imaging and clinical outcomes were consistent with ARE. Primary cancer types included lung (31%), melanoma (31%) and breast (19%).

Post-SRS, ARE had significantly lower nWin than tumor progression on all three follow-up scans (scan 1: 0.17±0.08 vs. 0.26±0.14, p=.03; scan 2:  0.18±0.09 vs. 0.34±0.15, p=.001; scan 3: 0.17±0.07 vs. 0.32±0.11, p<.001). No significant differences were found in pre-SRS nWin or pre- or post-SRS nWout (p>.05). Post-SRS nWin differentiated ARE and tumor progression with area under the ROC curve of 0.82 on scan 1, 0.86 on scan 2, and 0.88 on scan 3. Optimal threshold 0.18 yielded sensitivity of 75% and specificity of 69% on scan 1 and sensitivity of 92% and specificity of 69% on scan 2. Threshold 0.28 on scan 3 yielded sensitivity of 67% and specificity of 100%.

 

Conclusions:

Longitudinal GRASP MRI may help differentiate brain metastasis progression from adverse radiation effects.


Assaf BERGER (New York, USA), Matthew LEE, Eyal LOTAN, Girish FATTERPEKAR, Douglas KONDZIOLKA
00:00 - 00:00 #29810 - P019 Can lung cancer with brain metastases be cured in the current era?
P019 Can lung cancer with brain metastases be cured in the current era?

Background

Metastatic brain cancer has been considered a terminal condition with the goal of long term palliation but little hope for cure. Use of brain radiosurgery and/or resection, in addition to advanced systemic immunological and targeted therapies have enabled improvements in overall and progression free survival, often after systemic therapy is stopped. This study aimed to explore the possibility of curing patients with non-small cell lung cancer (NSCLC) brain metastases in the current era. 

 

Methods

During the years 2008-2016, 236 NSCLC patients underwent their first gamma knife radiosurgery (GKS) for brain metastases at our institution. Of these, using a prospective registry, we found 22 (9%) lung cancer patients that had an overall survival of at least 5 years from the initial GKS.  Demographic, clinical and histological data were collected, including GKS parameters, systemic treatments and survival analysis.

 

Results

In the lung cancer population, all patients (aged 58±9, 73% female) had non-small cell lung cancer, of which 9% and 27% were EGFR and ALK mutation positive, respectively. Overall survival from the first GKS was 113 months (95% CI, 101-125) and 43% (95% CI, 9-76) had at least 10 years survival. Five patients (23%) required no active treatment by the end of their follow-up for a period of 29 months, 7-118. Brain metastases locations included lobar hemispheres (100%), cerebellum (59%) and brainstem (18%) with the median largest treated tumor measuring 1.05 (0.14-17.81).

The median total number of treated metastases was 10 (range 1-29) and the median number of procedures was 4 (1-13). Spread to sites other than CNS was evident in 36%, and therapeutic regimens included immunotherapy, biological targeted therapy and chemotherapy in 18%, 55% and 55% of patients respectively.

 

Conclusions

Long-term survival in patients with NSCLC and brain metastases is feasible in the current era of radiosurgery combined with targeted systemic therapeutics. Of those living more than 5 years, the chance for living with stable disease and no need for active treatment for at least 2 years was 18%.  With modern multimodality therapy, perhaps there is now potential for eventual cure.


Assaf BERGER (New York, USA), Reed MULLEN, Kenneth BERNSTEIN, Joshua.s SILVERMAN, Erik SULMAN, Bernadine R. DONAHUE, Elaine SHUM, Joshua SABARI, Abraham CHACHOUA, John G. GOLFINOS, Douglas KONDZIOLKA
00:00 - 00:00 #29910 - P020 Re-irradiation of recurrent anaplastic ependymoma using radiosurgery.
P020 Re-irradiation of recurrent anaplastic ependymoma using radiosurgery.

Introduction:  anaplastic ependymomas are quite rare tumors that often relapse after preliminary removal with subsequent conventional radiation therapy, while often the optimal tactics for treating relapses has not been precisely determined

OBJECT: To evaluate the role stereotactic radiosurgery with GammaKnife (GKRS) in patients with recurrent or residual intracranial anaplastic ependymomas after resection and fractionated radiation therapy (RT).

METHODS: From April 2005 till January 2022 at “Moscow GammaKnife Center”, which affiliated with Burdenko Neurosurgical Institute (National scientific research Center of neurosurgery named after N.N. Burdenko) 114 patients (65 males and 49 female) with anaplastic ependymoma was treated at 214 procedures (13 – hypofractionated with LGK Icon, other – radiosurgicaly (2005-2011 – LGK C, 2011-2018 – PFX; 2018-2022 – Icon). Most patients were younger than 19 years – 96 vs 18 pts. Median age at first GK procedure was 9 years (from 2 to 59). 44 patients had 2 and more GK treatment (up to 10) (additionally to surgeries and RT with other units). All patients underwent resection of an ependymoma followed by cranial or neuraxis (if spinal metastases were confirmed) RT and adjuvant chemotherapy. The median time from initial treatment to GKRS was 17.5 months.

RESULTS: The median radiosurgical target volume was 1.2 (from 0.002 to 33 cc) and the median dose to the tumor margin was 18 Gy (range 15-24 Gy). Total number of irradiated targets is 712 (72% supratentorial, 28% – subtentorial). Median number of tumors treated in one session was 2 (from 1 to 23). 43 tumors (6%) treated with GK more than once (up to 4 times). Average 83 patients followed at least 1 year (max 15 years). Progression-free survival after the initial GKRS was 68.4%, at 1 year. The distant tumor relapse rate despite RT and GKRS was 20.6% at 6 months and 45.0% at 12 months, respectively. Overall survival (OS) after GKRS was 89.5% at 1 year, and 5-year OS reaches 69.0%, respectively. Adverse radiation effects developed in 10 patients (8.7%).

CONCLUSIONS: Stereotactic radiosurgery in different modes is the treatment of choice, along with reoperation, in patients with residual or recurrent ependymomas after initial combine  treatment.


Ivan OSINOV, Valery KOSTYUCHENKO, Aleksandr SAVATEEV, Andrey GOLANOV (Moscow, Russia)
00:00 - 00:00 #29913 - P021 Experience of preoperative Gamma Knife radiosurgery for recurrent brain metastases.
P021 Experience of preoperative Gamma Knife radiosurgery for recurrent brain metastases.

Introduction Resection of brain metastases (BM) without additional radiation therapy yields a high local failure rate. Drawbacks of postoperative stereotactic radiosurgery (SRS) include uncertainty in target delineation, potential delay in the administration of SRS and intraoperative risk of tumor spillage. Preoperative SRS might address these potential drawbacks. We present our experience with preoperative Gamma Knife radiosurgery (GKRS) for recurrent BM.

 

Methods Data of patients with recurrent BM treated with GKRS followed by surgical resection between June 2019 and June 2021 at the Elisabeth-TweeSteden Hospital Tilburg were retrospectively collected. Surgery was performed because of mass effect, a symptomatic lesion or a large tumor volume not eligible for salvage stereotactic radiosurgery. Pre-operative SRS was performed with GKRS followed by surgery within 24 hours. All patients had follow-up appointments with MRI scan as long as clinical meaningful. In case of new intracranial disease new treatment was offered if appropriate. Descriptive analyses were used to give an overview of the patient characteristics. Kaplan-Meier curves were used to analyze overall survival.

 

Results 25 patients (male 8, female 17; median age 64 years (range 20-79 years)) underwent preoperative GKRS for recurrent brain metastases. Most patients were previously treated with GKRS (68%). Most patients had non-small cell lung cancer (44%), followed by breast (12%), small cell lung cancer (12%) and melanoma (12%). The median total tumor volume of the index lesion was 22.2cc (range 6.4cc - 73.6cc). A dose of 18-22 Gy, was prescribed to the isodoseline (mean 45%; range 40-53%) covering 99-100% of the target. The median overall survival was 18.5 months (95% CI, 4.9 to 32.1 months). Eight patients (32%) had (multiple) surgical complications, three of these patients died due to these complications. Twelve patients (48%) developed a local recurrence. The median time to local recurrence was 6.9 months (95% CI, 4.7 to 9.1 months). Of the 16 patients with a subtotal resection, 10 patients developed a local recurrence, with 6 recurrences at the place of the macroscopic residual tumor. Two patients (8%) developed leptomeningeal disease at 2.8 months and 3.9 months and two patients (8%) developed new brain metastases (distant failure) at 5.4 months and 23.8 months, respectively.

 

Discussion Pre-operative radiosurgery was well tolerated in a group of patients with recurrent BM who were eligible for surgery. Larger series are needed to perform multivariate analyses on predictors of local recurrence in order to evaluate for which patients this treatment option is best suited.


Eline VERHAAK, Tom VAN SEETERS, Hilko ARDON, Liselotte LAMERS, Suan Te LIE, Hazem AL-KHAWAJA, Jeroen VERHEUL, Wouter VERFAILLIE, Bart BROUWERS, Bart DE BOER, Bram VAN DER POL, Wim DE JONG, Jannie SCHASFOORT - VAN DEN TILLAART, Diana GROOTENBOERS, Patrick HANSSENS (Tilburg, The Netherlands)
00:00 - 00:00 #29925 - P022 Stereotactic radiosurgery of local recurrences of brain metastases.
P022 Stereotactic radiosurgery of local recurrences of brain metastases.

Brain metastases (BM) are the most frequent tumors of the central nervous system. Nowadays stereotactic radiosurgery (SRS) is treatment of choice  for BM in many situations.  Local recurrences after radiosurgery seriously complicate the course of cancer diseases and worse the prognosis of life duration, neurological status and quality of life in patients with BM. Currently, there are no standards of treatment for recurrent BM.

The purpose of the study to evaluate the efficacy and safety of repeated radiosurgical (rRS) procedures for local relapses (LR)  in patients with brain metastases after prior stereotaxic surgery.

Materials and methods.

An analysis of the re-irradiation local treatment of 59 patients were carried out. There were 110 lesions of LR detected after the previously performed SRS with Gamma Knife (GK). Primary cancer was: non-small cell lung cancer in 10 (17%), breast cancer in 29 (49%), melanoma in 13 (22%), renal cell carcinoma in 5 (8.5%) and colorectal cancer in 2 (3.5%) patients. All patients underwent repeated radiosurgery with median marginal dose 22 Gy (15 to 24 Gy).

Results.

The local control of repeated irradiated BM for the 6- and 12-month periods was 95.5% and 83.9%, respectively. Statistically significant prediction factors for lower risk of LR after rRS were: the volume of the lesion  ≤1 cc (p=0.0241) and dose >20Gy/D99% (p=0,031), according to multifactorial analysis. The frequency of local radionecrosis after repeated radiosurgery was higher than after first SRS: 28.2% vs. 13.3%. The volume of LR ≤1 cc was a significant predictor of lower risk of post-radiation edema (p=0.01) and radio necrosis (p=0.0224) according to multifactorial analysis.

Conclusions:

The SRS of LR is an effective treatment for controlling tumor growth of repeated irradiated BM with acceptable post-radiation toxicity. Repeated stereotactic radiosurgery (SRS) of local recurrences (LR) of GM is designed to improve treatment outcomes, maintain quality of life and prolong it in patients with brain metastases who relapse after prior radiosurgery. The volume of the LR focus can change the treatment tactics: it is possible that with a metastasis recurrence size of more than 1 cm3, it is preferable to use surgical treatment or stereotactic radiation in the hypofractionation mode, which needs to be confirmed in further studies.


Amayak DURGARYAN, Andrey GOLANOV (Moscow, Russia), Sergey BANOV, Elena VETLOVA, Valeriy KOSTYUCHENKO, Ivan OSINOV, Elena IGOSHINA
00:00 - 00:00 #29927 - P023 Re-irradiation of relapsed intracranic lesions with stereotactic radiotherapy: a monoinstitutional experience.
P023 Re-irradiation of relapsed intracranic lesions with stereotactic radiotherapy: a monoinstitutional experience.

Purpose: The treatment of relapses of already irradiated primary brain tumors and metastases is difficult, given the limited effectiveness of systemic therapy and the risks of surgery or re-irradiation. Here we present the results of salvage Stereotactic Radiotherapy (SRT) for the treatment of recurrent primary brain tumors and metastases (mts) after previous radiotherapy (RT).

Material/Methods: From January 2018 to October 2021, 137 intracranial lesions (33 patients) were re-irradiated with robotic SRT. Primary histology was: NSCLC (n=10), breast cancer (n=9), glioblastoma (n=4), meningioma (n=2), oligodendroglioma (n=2), hemangiopericytoma (n=2), pituitary adenoma (n=2), prostate cancer (n=1), and melanoma (1). Previous RT on the same volume were performed with: GammaKnife (n=11), CyberKnife (n=8), Whole-Brain RT (n=8), post-operative IMRT/Helical IMRT (n=8), VMAT-SRT (n=5), post-operative 3D-CRT (n=3). Eight patients had multiple previous treatments. Median time from the previous radiotherapy was 13 (3-377) months. Gross Tumor Volume (GTV) was delineated on computed tomography and contrast-enhanced T1 magnetic resonance. Median GTV was 5.24 (0.22-78.32) cc. Planning Target Volume (PTV) was obtained adding an expansion to GTV of 1 mm (for brain metastases), or 3 mm (for glioblastoma). Median PTV was 10.19 (0.43-136.9) cc. Median prescribed dose was 30 (24-37.5) Gy in 1-5 fractions (median number of fractions was 5), at a median isodose of 76% (67-80%).The patients were followed up with contrast-enhanced MRI performed every three months.

Results: SRT was delivered on a median number of 2 (1-24) lesions; 7 patients were treated on 5 lesions simultaneously (from 5 to 24 lesions). Acute toxicity was G2 headache in three patients (GTV>1cc or >3 lesions), controlled by increasing the dose of steroids.

Median follow-up after re-irradiation in 20 evaluable patients was 9 (1-37) months. Radionecrosis occurred in only one patient (GTV>1cc). He underwent two previous VMAT SRT (prescribed dose 30 Gy in 5 fractions and 21 Gy in 3 fractions) and presented seizures. He was treated with steroids and levetiracetam. Six-, 12-, 18-month overall survival (OS) was 79.2%, 51.7%, 37.7% respectively. Six-, 12-, 18-month local relapse free survival was 70.7%, 64.8%, 48.6% respectively (see Figure 1).

Conclusions: SRT for re-irradiation is feasible, with only one case of radionecrosis registered. The treatment is effective with 12-month local control registered in 65% of pts. An accurate patient selection is warranted in order to avoid toxicity and a longer follow-up is needed to confirm the low radionecrosis rate.


Stefano Lorenzo VILLA (Milan, Italy), Chiara Lucrezia DEANTONI, Andrei FODOR, Roberta TUMMINERI, Flavia ZERBETTO, Sara BROGGI, Jessica SADDI, Barbara LONGOBARDI, Antonella DEL VECCHIO, Italo DELL'OCA, Nadia Gisella DI MUZIO
00:00 - 00:00 #29932 - P024 Pre-operative Stereotactic Radiosurgery Followed by Surgical Resection of Local Recurrence Brain Metastasis.
P024 Pre-operative Stereotactic Radiosurgery Followed by Surgical Resection of Local Recurrence Brain Metastasis.

Salvage-therapy of local recurrence brain metastasis (LRBMs) after previous treatment (surgical or stereotactic radiotherapy) is a seriously problem due to combination of local re-growth of a metastatic tumor and radiation necrosis. Re-irradiation deteriorates the radiation necrosis. Surgical resection is often the only reasonable solution. However, according to the multivariate analysis of Cagney DN at al. 2019, surgical resection followed by stereotactic radiation of previously irradiated LRBMs was complicated by leptomeningeal disease (LMD) in 32.7% (HR, 2.39; 95% CI, 1.25-4.57; P = .008). It is necessary to search for new modalities for the treatment of LRBMs.

Objectives:   The goal of this study is to analyze the effectiveness of pre-operative stereotactic radiosurgery (PreSRS) followed by surgical resection (SR) of LRBMs.

Methods: Between December 2015 and June 2021, 25 patients of 26 LRBMs (Me=10.1 ccm (range 2.9-59) in volume) after previous treatment (SR n=5 or stereotactic radiotherapy n=20) were undergone PreSRS followed by SR. Radiation dose the median (Me) = 19.35 Gy (range 17.3-24), and was determined by tolerance of intact brain tissues. SR was performed on the same day after PreSRS in 5 cases, on the next day - 10, on the second day - 8, 3-5 day - in 2 cases.

Results: 25 patients (Me=57 years (range 30-71 )) were observed with Me = 11.5 months. Primary tumor site was the breast in 10 cases, lung in 5, melanoma in 5, kidney in 3, and other in 3. LRBMs occurred after 14 months - Me(range 4-62 ) after the first line of therapy.

12-months OS was 52% after PreSRS followed by SR of LRBMs. New metastases were observed in 48 % (n=12), Me = 9 months (range 2-35).  Local re-recurrence was in 4 cases (15%), at 5/6/10/17 months respectively and was independent of the primary tumor. 4 patients (15%) had symptomatic radiation necrosis.  One year LMD was observed in 4 cases (16%).

Conclusion: PreSRS  followed by SR for LRBMs reduces the rates of  re-recurrences brain metastasis and  LMD compared with the  surgery followed by stereotactic radiotherapy. PreSRS followed by SR of LRBMs could be reasonable decision that is necessary to confirm during further studies.


Elena VETLOVA, Andrey GOLANOV (Moscow, Russia), Natalia ANTIPINA, Elena IGOSHINA, Valeriy KOSTJUCHENKO, Ivan OSINOV, Vasiliy LUKSHIN, Dmitriy USACHEV
00:00 - 00:00 #29938 - P025 Intra-fraction error analysis of homemade mouth-bite masks in linac-based SRS for brain metastases.
P025 Intra-fraction error analysis of homemade mouth-bite masks in linac-based SRS for brain metastases.

Purpose

This study aims to evaluate the intra-fraction accuracy of stereotactic linac-based radiosurgery (SRS) for brain metastases (BM) using a frameless homemade mouth-bite thermoplastic mask in combination with cone-beam computed tomography (CBCT) and six-degrees of freedom (6-DOF) couchtop.

 

Methods 

A frameless approach using a homemade mouth-bite thermoplastic mask (figure 1) was implemented during Covid-19 pandemic emergency period to offer BM SRS under conditions of limited mobility. All patients were treated at a single institution with single-isocenter coplanar 6 MV flattening filter free (FFF) volumetric modulated arc therapy (VMAT) radiosurgery, with a 2 mm isotropic expansion from the gross tumor volume (GTV) to the planning target volume (PTV). Before treatment delivery, patients underwent a low-dose CBCT to check position accuracy. Through image co-registration, translational (x, y, z) and rotational errors (pitch, roll, and yaw) were determined and validated by experienced radiation oncologists. The 6-DOF couchtop was used to automatically relocate the patient with sub-millimetric precision. Immediately after irradiation, patients underwent a second CBCT to evaluate the intra-fraction motion, and data were collected and analyzed.

 

Results 

From February 2020 to November 2021, 40 patients (74 lesions) received BM SRS (14-21 Gy). The whole procedure, from the pre-treatment CBCT scan to the end of irradiation and subsequent CBCT, required a median time of 11 minutes [8-19]. Mean translational error was 0.1 mm ± 0.4 mm [-0.7; 1.4] in lateral direction, and 0.0 mm ± 0.4 mm [-1.4; 1.0] in longitudinal direction. A 2.2 mm maximum shift was recorded on the vertical axis, although the mean translation error was 0.1 mm ± 0.4 mm. Pitch, roll and yaw registered a mean value of 0.0° ± 0.3° [-0.8°; 0.7°], 0.0° ± 0.2° [-0.8°; 0.6°], and 0.0° ± 0.3° [-0.9°; 0.9°], respectively. The results are summarized in figure 2.

 

Conclusion 

This study demonstrates that homemade mouth-bite thermoplastic masks provide a steady patient fixation and, combined with CBCT, 6-DOF couchtop, and fast FFF coplanar treatment delivery allow minimal intra-fraction uncertainties in BM SRS. These results, coupled with the study of the dosimetric impact of residual rotational and translational errors, might lead to a reduction of the PTV margin in this setting.


Valerio PISONI (Monza, Italy), Valerio PISONI, Sara TRIVELLATO, Valeria FACCENDA, Valeria FACCENDA, Paolo CARICATO, Paolo CARICATO, Raffaella LUCCHINI, Raffaella LUCCHINI, Denis PANIZZA, Denis PANIZZA, Stefano ARCANGELI, Stefano ARCANGELI
00:00 - 00:00 #29939 - P026 Fractionated Stereotactic Radiosurgery (fSRS) for patients with recurrent high grade gliomas. A retrospective study of Hellenic Neuro-Oncology Society (HeNOS) investigating independent prognostic factors prolonging overall survival.
P026 Fractionated Stereotactic Radiosurgery (fSRS) for patients with recurrent high grade gliomas. A retrospective study of Hellenic Neuro-Oncology Society (HeNOS) investigating independent prognostic factors prolonging overall survival.

Fractionated Stereotactic Radiosurgery (fSRS) for patients with recurrent high grade gliomas.

A retrospective study of Hellenic Neuro-Oncology Society (HeNOS) investigating independent prognostic factors

prolonging overall survival

Boskos Christos, MD, PhD, Tsioukis Vasileios, MD, Korovila Alexandra, MD, Baziotis Ioannis, MD, Kapsalis Panagiotis, MD, Paschalis Theodoros, PhD, Katsaros Vasileios, MD, PhD, Liouta Evangelia, PhD, Koutsarnakis Christos, MD, PhD, Stranjalis George, MD, PhD, (Hellenic NeuroOncology Society- HeNOS)

PURPOSE: To evaluate the efficacy of fractionated Stereotactic Radiosurgery (fSRS) as reirradiation, combined with surgery and systemic therapy for patients with recurrent high grade gliomas.

METHODS AND MATERIALS: Between April 2015 and November 2021, 48 patients with recurrent malignant glioma received fractionated Stereotactic Radiosurgery (fSRS), 30 Gy in 6-Gy/5 fractions) plus systemic therapy with rechallenge Temozolomide or lomustine/bevacizumab. For fSRS we used a Linac and a Robotic Radiosurgery system. Re-operation was opted before fSRS for 11 patients with locally recurrent or progressive malignant glioma. All patients had a Karnofsky performance score (KPS) ≥ 60 and were previously treated with standard chemoradiotherapy (Temozolomide). Thirty-three patients had a GBM, 10 had an anaplastic astrocytoma (AA) and 5 an anaplastic oligodendroglioma (AO), according to WHO 2016 classification. No grade III+ side effects were observed.

RESULTS: Median overall survival (OS) and median Progression Free Survival (PFS) was 9,43 months and 7,83 months respectively. 6- and 12-month OS rates after fSRS was 71% and 37% respectively, while 6- and 12-months PFS rates were 58% and 24% respectively. Surgical resection (p = 0.013). higher KPS (p = 0.001) and AO histology proven with 1p19q co-deletion (p=0.028) were independent favοrable prognostic factors for OS after multivariate analyses.

CONCLUSION: In general, fSRS treatment may be a safe and effective option for patients with recurrent malignant gliomas in combination with/without surgical resection and systemic therapy. Re-operation, high KPS and AO histology (1p19q co-deletion) positively affected the results of fSRS treatment.


Christos BOSKOS (ATHENS, Greece), Vasileios TSIOUKIS, Alexandra KOROVILA, Ioannis BAZIOTIS, Panagiotis KAPSALIS, Theodoros PASCHALIS, Vasileios KATSAROS, Evangelia LIOUTA, Christos KOUTSARNAKIS, George STRANJALIS
00:00 - 00:00 #29948 - P027 Re-irradiation with SRS on recurrent high grade astrocytoma.
P027 Re-irradiation with SRS on recurrent high grade astrocytoma.

Introduction:

High-grade gliomas account for about half of all brain tumors in adults. Re-irradiation in combination with systemic bevacizumab therapy has been shown to be a meaningful option for patients with recurrent high-grade glioma.
The aim of this report was to present a case of irradiation and re-irradiation of astrocytoma with SRS, with excellent tolerance and response to treatment.

Case:

56-year-old patient. In October 2017 the woman began with headache and dysarthria.
CNS MRI: 26x17mm lesion in the left cerebral hemisphere, with post-contrast enhancement.
In December 2017, surgery was performed, anatomical pathology: Astrocytoma WHO Grade IV.  

June/2018 she presents dyslalia, photophobia, headache, abulia, amnesia.
CNS MRI: in surgical bed, polylobulated image with 52x41mm post-contrast enhancement, recurrence of previous lesion. Biopsy: WHO Grade IV Pleomorphic Astrocytoma

October/2018 SRS is performed in 5 fractions. She was prescribed  temozolamide.
(a/b: 6)
GTV:                       DT:36Gy DD:7Gy EQD2:59.4Gy
CTV: Edema            DT:25Gy DD:5Gy EQD2:34.37Gy

February/2019 presents expressive aphasia, photophobia, altered right eye campimetry, headache, mild ataxia and decreased visual acuity.
CNS MRI with high resolution treatment response assessment maps post contrast injection (TRAMS) reports persistence of a known lesion with an inflammatory component, radionecrosis, and disease progression.

May/2019 re-irradiation and bevacizumab treatment were decided. 

May/2019 SRS 5 fractions.
GTV  (tumor volume delimited by TRAMS)      DT:36Gy DD:7Gy EQD2:59.4Gy
CTV: 5mm expansion of tumor volume           DT:25Gy DD:5Gy EQD2:34.37Gy

August/2019 TRAMS shows a notable decrease in tumor volume. Improvement of previous symptoms.
July/2020 MRI CNS: no regrowth or signs of radionecrosis are observed.
February/2022 the patient is in good general condition, presents mild expressive aphasia, dyslexia and ataxia. She continues in systemic treatment.

Discussion and conclusion:

The patient presented good tolerance to both SRS. Control with TRAMS  was decisive in defining the volume to be treated, since it allowed radionecrosis to be differentiated from disease progression.
With a follow-up of 4 years after the initial diagnosis and after 2 years and 9 months after re-irradiation, the patient continues to have an excellent quality of life.
SRS seams to be a safe and effective treatment option for re-irradiation in recurrent high-grade glioma.


Maria Milla GALETTO (Cordoba, Argentina), Daniela Mariel ANGEL SCHUTTE, Oscar Ariel MURIANO, Veronica VERA, Agustin GIRAUDO, Valentina GREGORAT, Agostina VILLEGAS, Mercedes CHIBAN, Silvia ZUNINO
00:00 - 00:00 #29973 - P028 Radiosurgery and Stereotactic brain Radiotherapy with systemic therapy in recurrent high grade gliomas: is it feasible?
P028 Radiosurgery and Stereotactic brain Radiotherapy with systemic therapy in recurrent high grade gliomas: is it feasible?

Purpose. For recurrent high-grade gliomas (HGG) no standard therapeutic approach has been reported thus surgery, chemotherapy and reirradiation (re-RT) may all be proposed. The aim of the present study was to evaluate safety and efficacy of re-RT by radiosurgery or fractionated stereotactic radiotherapy (SRS/FSRT) in association to chemotherapy in patients with recurrent HGG.

Material/Methods. We included retrospectively all patients with histological diagnosis of HGG that, in the study period, suffered by recurrent disease diagnosed by magnetic resonance imaging (MRI), according to Response Assessment in Neuro-Oncology (RANO) criteria after primary/adjuvant chemo-radiotherapy treatment and underwent to re-RT by SRS/FSRT. Median dose was 24 Gy (range 18-36 Gy) and median number of fractions was 5 (range 1-6). Outcome was evaluated by clinical neurological examination and brain MRI performed 1 month after re-RT and then every 2-3 months.

Results. From November 2019 to September 2021, 30 patients presenting recurrent HGG underwent re-RT. Median time between primary/adjuvant RT and disease recurrence was 8 months (range 2-27). In 6 cases (20%) reoperation was performed and, in most cases, (84%), a second line of systemic therapy was administrated. Median OS after recurrence was 12.1 months (95%CI 7.1-23.5). Six-month and 1-year OS were, respectively, 81% (95%CI 57-93%) and 51% (95%CI 26-72%). Median PFS after recurrence was 11.2 months (95%CI 6.2-23.1). Six-month and 1-year PFS were, respectively, 70% (95%CI 48-84%) and 32% (95%CI 13.12-52.8%). Regarding SRS/FSRT, no acute or late neurological side effects grade ≥ 2 were reported. No case of radio-necrosis was detected.

Conclusion. Re-RT with SRT/FSRT in association with second line systemic therapy is a safe and feasible treatment for patients with HGG recurrence. However, validation of these results by prospective studies is needed.


Alessia SURGO (Acquaviva Delle Fonti, Italy), Fabiana GREGUCCI, Roberta CARBONARA, Letizia LAERA, Maria Paola CILIBERTI, Morena CALIANDRO, Ilaria BONAPARTE, Alba FIORENTINO
00:00 - 00:00 #29993 - P029 TTF-1 and napsin A predict local failure and survival after Gamma-knife radiosurgery in patients with brain metastases from lung adenocarcinoma.
P029 TTF-1 and napsin A predict local failure and survival after Gamma-knife radiosurgery in patients with brain metastases from lung adenocarcinoma.

Objectives

 

Gamma-knife radiosurgery (GKRS), combined with contemporary targeted therapies and immunotherapies, has improved the overall survival of patients with lung adenocarcinoma (ADC). Given that histological subtypes reflect prognosis in primary ADC, it is important to integrate pathological biomarkers to predict clinical outcomes after GKRS in patients with brain metastases from lung ADC. Therefore, we investigated the prognostic relevance of various biomarkers of primary lung ADC for clinical outcomes after GKRS.

 

Materials and Methods

 

A total of 95 patients with 136 brain metastases (1–4 oligometastases) treated with GKRS between January 2017 and December 2020 were enrolled. The Kaplan–Meier method and univariate and multivariate analyses using Cox proportional hazard regression models were used to identify prognostic factors for local control, survival, and distant brain control.

 

Results

 

Multivariate analysis revealed thyroid transcription factor-1 as an independent prognostic factor for local control (hazard ratio [HR] = 0.098, confidence interval [CI] = 0.014–0.698, P = 0.0203) and napsin A as a significant predictor of overall survival after GKRS (HR = 0080, CI = 0.017–0.386, P < 0.01). In EGFR mutation subset analysis, patients with EGFR exon 19 mutations showed better distant brain control than those with EGFR exon 21 mutations (P < 0.01).

 

Conclusion

 

Pathological biomarkers of primary cancer should be considered to predict clinical outcomes after GKRS in patients with lung ADC. Using such biomarkers can also help provide personalized treatment to each patient, improving clinical outcomes after stereotactic radiosurgery.


Roh HAEWON, Jong Hyun KIM (Seoul, Korea), Lee SUNG YOUNG
00:00 - 00:00 #29999 - P030 Number fractionated radiosurgery for numerous small brain metastases.
P030 Number fractionated radiosurgery for numerous small brain metastases.

Background:

Treatment of multiple brain metastases more than 10 is challenging and has been controversial. Whole brain radiotherapy (WBRT) is generally believed to be the first treatment choice. However, this is not always adequate because of the inconsistent effects and combined adverse effects such as dementia which may be resulted afterward. In order to escape from mental deterioration, WBRT has to be replaced by the other treatment methods like radiosurgery. We have performed such a treatment for numerous small brain metastases by Gamma Knife stereotactic radiosurgery (GKS).

Methods:

Twelve cases of numerous (more than 30) brain metastases were treated by GKS retrospectively during a period from July, 2016 to June, 2021. They were seven males and five females with the mean age of 63.4 years. All of them were with lung cancers. Mean total session number was 5.42 times, ranging 2 to 17. Each tumor was treated with the margin dose between 14 to 20 Gy. The tumor number treated in whole sessions was ranged from 31 to 144 (mean, 70.8).

Results:

Almost all the irradiated tumors either disappeared or shrank at the patient’s death or at the last follow-up, though new metastatic tumors were subsequently developed in some cases which required an additional treatment with GKS. At the last follow-up (3 to 51 months after GKS), nine cases were alive and well and three were dead. As adverse effects, two cases demonstrated seizures by radiation brain injury and another showed a gait disturvance. No apparent mental deterioration was observed during follow-up.

Conclusions:

Local tumor control without any severe side effects including mental deterioration was achieved, which seemed to be consistent with radiosurgery in cases with 10 or less brain metastases. Radiosurgery for numerous small brain metastases may be preferable rather than whole brain irradiation.


Yoshimasa MORI (Kawasaki, Japan), Yasuhiro MATSUSHITA, Yoshihisa KIDA
00:00 - 00:00 #30002 - P031 Upfront GKS in combination with high-dose MTX and Rituximab for primary CNS lymphoma in elderly patients: A single-center pilot study.
P031 Upfront GKS in combination with high-dose MTX and Rituximab for primary CNS lymphoma in elderly patients: A single-center pilot study.

OBJECTIVES 

Primary central nerve system lymphoma (PCNSL) is rare aggressive non-Hodgkin lymphoma. Current standard of care for PCNSL typically includes high-dose methotrexate (MTX), rituximab, radiotherapy, and chemotherapy with autologous stem cell rescue. These treatment strategies have improved the prognosis but still eluded half of the patients, that is, immunocompetent elderly patients. Given the risk of neurologic and hematologic toxicity, these patients may be poor candidates for whole-brain radiotherapy or myeloablative chemotherapy. We offered stereotactic radiosurgery (SRS) for upfront regimen followed by high-dose MTX and rituximab in elderly patients of newly diagnosed PCNSL.

 

MATERIAL AND METHODS 
The author conducted the retrospective review of 13 immunocompetent patients >60 years with PCNSL who underwent gamma knife radiosurgery (GKS) as first-line therapy in combination with the standard chemotherapy based on high-dose MTX and rituximab. Local recurrence (LR) was defined as tumor progression expanding more than 20% in the prescribed isodose line. The progression-free survival (PFS) was measured starting from first-line treatment completion. Overall survival (OS) was calculated from the date of the histologic diagnosis of PCNSL to the date of death or last follow-up.

 

RESULTS

Overall, 13 patients received GKS for 14 lesions with a median volume of 8.59cm3 (range 2.95-120.89cm3). The median age at GKS was 71 (range 60-86) and the median KPS was 80. GKS was given via single fraction to the median dose of 17 Gy (range 12-22Gy) in 10 patients and 3 or 4 fractionations with a cumulative dose of 24 Gy at 50% isodose line in 3 patients. During the follow-up period (median 16.3 months; range 5.3-31.3 months), 2 patients had LR and 3 patients developed distant recurrence with a median 9.1 months of the time to progression. 2 patients were expired due to hematologic complications after chemotherapy. In terms of GKS, no major complication or radiation necrosis was observed. 6-month and 12-month PFS were 83.1% and 60.6%, respectively, and OS were 92.3% and 82.1%, respectively. The median values of both PFS and OS were not reached.

 

CONCLUSION

With favorable local control, SRS may have a role as the first-line treatment of elderly patients in newly diagnosed PCNSL. The comparative efficacy of such an approach should be examined in prospective trials.


Jeong-Hwa KIM (Seoul, Korea), Jung-Won CHOI, Doo-Sik KONG, Ho Jun SEOL, Do-Hyun NAM, Jung-Il LEE
00:00 - 00:00 #30033 - P032 Radiosurgery for brain metastases from breast cancer.
P032 Radiosurgery for brain metastases from breast cancer.

Background: Brain metastasis (BM) occur in approximately 15% of patients affected by advanced breast cancer (BC). In the last two decades, overall prognosis of metastatic BC patients has improved with the introduction of new target therapies. Integration of systemic therapy of local ablative therapy may represent an effective, non-invasive approach to control intracranial metastasis, in particular in oligometastatic patients. This report analyzes clinical outcome of BM from BC treated with GammaKnifeRadiosurgery (GKRS).

Materials and Methods: Data of 58 consecutive BC patientstreated with GKRS from November 2012 to August 2020, accounting for 149 metastases, were retrospectively examined. We assessed the correlation between clinical-pathological factors and outcome. Overall survival (OS), local control (LC) and distant brain control (DBC) were calculated from the date of GKRS using the Kaplan-Meier method.

Results: Medianage was 56 years (range: 31-80). RPA class was 1 in 28 out of 57 patients. Estrogen receptor positive, HER-2 positive and triple negative BC was found in 42%, 44% and 16% of   patients.  In 19 (34%) patients the brain was the only metastatic site. At the time of GKRS all patients had controlled extracranial disease. Ten patients (17%) had an history of surgical BM excission and 5 (9%) patients had a prior WBRT.  Mean number of brain metastasis treated with GKRS was 2 (range:1-11). Mean prescription dose was 21 Gy (15-24): 9 patients underwent a second radiosurgery course. At the time of BM diagnosis 41 (72%) patients received GKRS and continuation of the same chemotherapy schedule. Fifteen radiological radio necrosis were reported: however, 3 patients had symptomatic radionecrosis, two treated with steroids and one with surgery. Local control was 95%, 92% and 86% at 6, 12 and 24 months, respectively. Median distant brain control after GKRS was 47months (95%CI:20-60 months), DBC was 85%, 72% and 63% at 6, 12 and 24months, respectively. Median overall survival was 24months (95% CI:15-45 months). Overall survival was 85% at 6months, 68% and 48% at 1 and 2 years. Patients with RPA class I had improved survival (median 45 versus 18 months, p=0.036,  HR 2 C95% 1.1-3.9).

Conclusions: Our study showed that GKRS is associated with high local control rates and rare severe side effects. Use of GKRS for progressive BMs allowed for continuation of the same chemotherapy line in the majority of patients. This may be of particular in RPA I patients that show longer survival and may draw the higher benefit from GKRS.

 


Daniela GRETO, Manuele ROGHI, Chiara BELLINI, Isacco DESIDERI, Mauro LOI, Emanuela OLMETTO, Icro MEATTINI, Luca VISANI, Viola SALVESTRINI (Florence, Italy)
00:00 - 00:00 #30037 - P033 Single versus multiples shorts dose planning for Gamma Knife Radiosurgery of brain metastases.
P033 Single versus multiples shorts dose planning for Gamma Knife Radiosurgery of brain metastases.

Aims. Brain metastases (BMs) represent a significant medical concern in cancer patients. A valuable treatment option in selected patients with BMs is radiosurgery (RS), in particular using dedicated platforms such as the GammaKnife (GK). However, the impact on treatment response of different technical solutions, in particular use of multiple or single isocenters (shots), has not been established. The aim of our study is to evaluate differences in dosimetric parameters and clinical outcome among patients receiving multiple or single shot GammaKnife radiosurgery (GKRS)  for BMs measuring less than 1 cm .

Methods: Demographic, disease- and treatment-related features of 86 consecutive patients treated with the Leksell Gamma Knife® Perfexion™ for a total of 282 BMs were retrospectively collected. Each lesion was irradiated using one or two shots with a diameter of 4 and/or 8 mm. Selectivity Coverage and Gradient Index (GI) were examined for each lesion. Radiological response to RS treatment was observed according to RANO (Response Assessment in Neuro Oncology) criteria with MRI at 1, 3, 6 and 9 months.

Results:  Mean volume of metastases was 103.1 mm3 (2.4-721 mm3). Among treated BMs, 210 (74%) and 72 (25%) BMs were treated with one or two shots, respectively.  Mean coverage of the plans executed with one shot was 99.9% (range: 92-100%) while it was 99.7% (range: 95-100%) using two shots. Mean selectivity and mean gradient were respectively 0,25 (range: 0.001-0.63) and  3.2 (range: 0.85-8.10)  in single shot plans,  and 0.35 (range: 0.07-0.78) and  3.2 (range: 2.11-9.8) in two shots plans. A statistically significant improvement in coverage was found in one shot plans (0.9995 vs 0.9968, p=0.0001), while selectivity was significantly better using two shots (0.2494 vs 0.3546, p=0.0001).

Considering patient and disease-related characteristics, breast histology correlated with a poorer local control (p=0.0001) at 3 and 6months MRI, while a GPA (Graded Prognostic Assessment) < 3 was predictive of local failure (p=0.018) at 9months MRI. Concerning local control, overall local control rate at 1 month was 96%: patients treated with one shot had an improved local control at 1 (1.0% vs 11.6% p=0.0001) and 6months (5.9% vs 20.7%, p=0.026) as to two shots.

 Conclusion: Our study suggested that, in BMs with a diameter inferior to 1 cm receiving GKRS, the use of a single shot resulted in a better coverage and a better local control at one and three months. However, GPA score and histology affect clinical outcome of patients with BMs. 


Daniela GRETO, Manuele ROGHI, Maria Grazia CARNEVALE, Isacco DESIDERI, Giulio FROSINI, Barbara GUERRIERI, Viola SALVESTRINI (Florence, Italy)
00:00 - 00:00 #30051 - P034 Stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) as adjuvant treatment for resected brain metastases (BMs): a single-center series.
P034 Stereotactic radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) as adjuvant treatment for resected brain metastases (BMs): a single-center series.

Post-operative SRS and fSRS are effective and safe approaches commonly used to treat BMs. In our series, 71 patients (pts) who underwent partial or total resection for BM and adjuvant SRS or fSRS with Cyberknife (CK) were retrospectively analyzed. Pts with prior whole brain irradiation (WBRT) or leptomeningeal disease (LMD) were excluded. The main represented histologies were breast and non-small cell lung cancers. Almost all pts had no ongoing systemic therapies at the moment of CK. Twenty-nine pts underwent SRS (14-20 Gy in single fraction), 42 fSRS (21-24 Gy in 3 fractions). They all had a Karnofsky performance status ≥ 70. The cumulative 1-year local control (LC) rate and progression free survival (PFS) were 78.5% and 87%, respectively. The cavity recurrence rate was 38% versus (vs) 17% for SRS and fSRS group, respectively (p=0.15), with a median time to progression of 17 months vs 12. Only 4 events of late brain radiation necrosis (RN) were registered, all G2 graded according to CTCAE v.5. No other G2 toxicities were reported. The median overall survival (OS) was 47 months, with a 12-months OS rate of 83%. A 20% rate of LMD was reported; the type of surgical resection of the BM (piecemeal vs en-bloc), and the inclusion or exclusion of the surgical corridor leading to the cavity in PTV volume did not show a statistically significant correlation with the onset of LMD. A better trend for PFS emerged for pts with a waiting time from surgery to treatment ≤ 45 days vs > 45 days (p=0.07). PTV volume, dose prescription, fractionation and histology seemed not to affect LC, nor OS. A DS-GPA score ≥ 3 vs < 3, an extracranic (EXC) disease absent or oligometastatic vs present not oligometastatic, and an EXC disease at last follow-up stable vs in progression were found to be significantly correlated with a better OS (p=0.0000, p=0.02, p=0.0009, respectively). We can confirm that both SRS and fSRS are effective and safe approaches in the adjuvant setting of resected BMs; dose prescription and fractionation must be selected according to PTV volume. With regards to OS, they are a valid alternative to WBRT. Further data are needed to better assess the role of target delineation, waiting time from surgery to irradiation, and systemic therapies to improve pts outcomes.


Valentina PINZI (Milan, Italy), Anna ROMEO, Marcello MARCHETTI, Sara MORLINO, Irene TRAMACERE, Laura FARISELLI
00:00 - 00:00 #30081 - P035 The ghost lesion: delayed post GK brain metastasis recurrent enhancement between 8 and 36 months as a manifestation of benign radiation change mimicking recurrent malignancy.
P035 The ghost lesion: delayed post GK brain metastasis recurrent enhancement between 8 and 36 months as a manifestation of benign radiation change mimicking recurrent malignancy.

Successful Gamma Knife brain metastasis treatement, with complete lesion resolution, can be followed by delayed post SRS recurrent MRI enhancement at the treatment site, up to 36+ months after treatement, but as a manifestation of benign post treatment delayed radiation change and not recurrent malignancy. This enhancment can then be persistent for many months and even enlarge subsequently, and also with elevated choline using Magnetic Resonance Spectroscopy. These are usually reported as recurrent malignancy by the radiologist but needs to be correlated with the pre Gamma Knige SRS plan and then observed rather than re-treated by radiation or chemotherapy. I have many of these "Ghost Lesions" which have been confirmed as delayed radiation change to validate this important concept.


Stephen HOLMES (honolulu, USA)
00:00 - 00:00 #30084 - P036 The interval between surgery and stereotactic radiosurgery is critical for local control of resected brain metastases.
P036 The interval between surgery and stereotactic radiosurgery is critical for local control of resected brain metastases.

Purpose: Stereotactic radiosurgery (SRS) is commonly employed for resected brain metastases. Because of uncertainty about the optimal timing of SRS delivery after surgery, we retrospectively evaluated local control (LC) at the site of postoperative SRS to study this question.

Materials & Methods: We identified a consecutive series of 133 patients with surgically managed BM who received SRS or fractionated SRS at our institution from 2012 to 2018. We assessed the interval between surgery and SRS with LC, local recurrence-free survival, distant recurrence, distant recurrence-free survival, and overall survival.

Results: The median age of our cohort was 64.5 years. 72 patients (54.1%) had a single BM, and the median BM diameter was 2.9 cm. Postoperative MRI showed a gross total resection was achieved in 111 patients (83.5%). 123 patients (92.5%) received fractionated SRS. The median time from resection to SRS was 37.0 days, and the overall LC rate was 83.6%. The interval between surgery and SRS was predictive of LC. For patients with LC at the surgical site, the median time from surgery to SRS was 34.0 days. For patients without LC, the median time from surgery to SRS was 61.0 days (p<0.01). The LC rate was 97.7% when SRS was administered ≤4 weeks postoperatively, compared with 76.4% if SRS was administered after an interval >4 weeks (p<0.01). Local recurrence-free survival was improved for patients who underwent SRS at ≤4 weeks (P = .02). Delayed SRS was also predictive of distant recurrence (p=0.02) but not overall survival.

Conclusions: In this retrospective study, LC after postoperative SRS for BM was most strongly predicted by time to SRS, and a cutoff of 4 weeks was a reliable predictor of recurrence. These findings merit investigation in a prospective, randomized trial.


Diana ROTH O'BRIEN, Sydney M. KAYE, Philip POPPAS, Sean E. MAHASE, Anjile AN, Paul J. CHRISTOS, Benjamin L. LIECHTY, David J. PISAPIA, Rohan RAMAKRISHNA, A. Gabriella WERNICKE, Susan C. PANNULLO, Jonathan KNISELY (New York, USA), Theodore E. SCHWARTZ
00:00 - 00:00 #30087 - P037 A Simple Temporal Empirical Model Application for Fractionated SRS Boost Post Whole Brain Irradiation.
P037 A Simple Temporal Empirical Model Application for Fractionated SRS Boost Post Whole Brain Irradiation.

Introduction: The dose prescription for radiotherapy is based on the phenomenon linear-quadratic model which was originally developed for the experimental result in cellular scale. And a biologically effective dose (BED) concept was defined. This empirical model was applied to clinical practice by adjusting the time and amplitude of fractionated dose. Another empirical model was through direct collecting of clinical outcomes or tolerance in actual patients with exponential power index fitting, and a nominal standard dose (NSD) concept was defined.  In this study, the combination of both analytical empirical models was applied to estimate the approximate dose level in fractionated SRS post whole brain irradiation situation, and the practical goal is to develop accurate dose prescriptions for SRS retreat patients.

Methods and Materials: A patient was under the treatment of whole brain with prescription at 30Gy in 10 fractions and the procedure elapsed in 13 days.  This whole brain treatment covered the whole brain volume at 1483.01cc and equivalent spherical diameter at 14.1cm.  The coverage the brain is 97.4% with conformity index at 1.30.  After 222 days, the follow-up imaging showed that more lesions were shown up, so a 5 factions SBRT treatment with 6Gyx5 was delivered with elapsing in 10 days. One of the lesions was 17.66cc in 3.5cm diameter. A two single ARC method was employed to deliver the prescription dose to the target and reached the coverage at 98.8% with conformity index at 1.12. Two methods were employed to compute the dose in NSD, and BED.  First is a direct computation, the second is considering the residual dose due to temporal effect.  Finally, the two results were compared to those of a single fraction SRS volume-based prescription. 

Results:  Given the alpha beta ratio at 10, the total NSD and BED were 39.5Gy and 59.3Gy when both temporal effect and 5 fraction SRS being considered. Without considering the temporal effect, the total NSD and BED for 5 fraction SRS post whole brain irradiation were 60Gy and 87.0Gy; And for the single fraction volume-based SRS situation, the total NSD and BED were 48Gy and 89.4Gy. 

Conclusion and discussion: Temporal empirical model could be used for high precise dose estimation for post whole brain irradiation with SRS and SBRT. And the temporal effect could generate significant variation in dose prescription. Moreover, the efficacy in multiple lesion SRS prescription could be further analysis and dose energy delivery pattern effect could be explored.


Kaile LI (Martinsburg WV, USA), Cengiz AYGUN
00:00 - 00:00 #30088 - P038 Stereotactic radiosurgery for treatment of lung cancer patients with brain metastasis before and after the era of targeted therapy.
P038 Stereotactic radiosurgery for treatment of lung cancer patients with brain metastasis before and after the era of targeted therapy.

Introduction: Radiosurgery has been an important part of treating lung cancer patients who develop brain metastasis. The timing and utilization of radiosurgery is not as clear in more recent years with the availability of targeted agents and discovery of druggable mutations for treatment of these patients. We examine our experience with these patients over a period of time before and after the routine of testing for known lung cancer mutations and use of agents that target these mutations. 

 

Methods: We retrospectively reviewed the charts of 267 (133 female, average age 64, range 34-86) patients with brain metastases from lung cancer patient treated with stereotactic radiosurgery over a 20-year period of time. We report a median follow up of 25 months after first radiosurgery for patients with non-small cell carcinoma (182 adenocarcinoma, 32 squamous, 6 large cell, and 19 unknown subtype) as well as, 28 small cell carcinomas that failed initial whole brain radiotherapy. We examine the number and timing of radiosurgical treatments, outcomes of the treated lesions including suspected treatment related imaging changes, and the use and type of targeted therapy for these patients. 

 

Results: Of the 265 patients examined, 80 patients were never smokers, 76 had brain surgery sometime during their course of which 45 patients had radiosurgery performed to a postop resection cavity. We treated an average number of 2 lesions with a range 1-12. 191 patients required only one SRS treatment while 77 had two radiosurgery sessions, 22 with three sessions, 7 with four sessions, and 2 with 5 sessions. We found 34 (13%) cases of confirmed radiation necrosis within this group. PD-1 mutation data was available on 151 patients with 30 (20%) with PD-1 expression greater than 10% and 43 (28%) greater than 1%. We are currently exploring ALK and EGFr mutational status in a similar manner The majority (87%) of our patients, including those with unknown mutational status were treated with some form of targeted therapy. The average number of targeted agents were 2 with a range of 1-6. The effect on overall survival and local control is also under examination for factors to predict these patient outcomes. 

 

Conclusion: The treatment algorithms for lung cancer patients with brain metastasis is evolving, the results of our study can help guide future best practices for management of these patients. 


Randy L. JENSEN (Salt Lake City, USA), Lindsay BURT, Don CANNON, Dennis C. SHRIEVE
00:00 - 00:00 #30091 - P039 Bio-inspired algorithms on multiple metastases single isocenter radiosurgery for PTV margin optimization.
P039 Bio-inspired algorithms on multiple metastases single isocenter radiosurgery for PTV margin optimization.

Purpose: To compare the genetic operators (mutation, crossover and number of individuals in the population) between genetic algorithm (GA) and differential evolution (DE) to determine the optimization-efficiency for the maximum displacement produced by the combined effect of rotations and translations in single isocenter multiple metastases radiosurgery (SIMM-SRS).

Method: The order and direction of rotational/translational displacements for 144 targets (21 SIMM-SRS plans) was studied for the 0.5º/0.5 mm case using GA and DE. To determine the maximum displacement produced, in-house software was performed. It allowed the handling of the DICOM files of the plans. The relationship between genetic operators such as mutation rate (m), crossover point (p) and population size (n) with respect to the search for maximum global displacements was studied.

Results: The GA showed better benefits with respect to DE. By the selection of a low mutation rate, crossover point equals to 6 and medium population size, the GA reached global maxima displacements in low computation time without the problem of fall into local maxima. The mean maximum displacement produced by the combination of rotations and translations is 2.2 ± 0.6 mm with a mean distance to isocenter of 53 ± 11 mm.

Conclusion: The implementation of GA is feasible in SIMM-SRS for the determination of the maximum displacements produced by rotations and translations.


José Alejandro ROJAS-LÓPEZ (Argentina, Argentina), Daniel VENENCIA, Miguel Ángel CHESTA, Francisco TAMARIT
00:00 - 00:00 #30116 - P040 Large brain metastasis treated with adaptive staged-dose Gamma Knife radiosurgery: preliminary results of a single centre retrospective analysis of 76 patients.
P040 Large brain metastasis treated with adaptive staged-dose Gamma Knife radiosurgery: preliminary results of a single centre retrospective analysis of 76 patients.

Purpose: to retrospectively analyse plans of patients with large brain metastasis (BM) treated with adaptive staged-dose gamma knife radiosurgery in two stages.

Material and Methods: since 2018, 76 patients with large BM  (>10 cm3) has been treated with a two-stages radiosurgery protocol using a dose prescription of 12 Gy at 50% of maximum of the dose distribution and planned time interval of 1 months between the two stages. The plans were elaborated with Gammaplan v.11.1.1 treatment planning system and delivered on a Gamma knife Perfexion unit. MR T1 weighted images, dose distribution and structures were exported to MIM software v. 7.1.4 for subsequent analysis. A rigid deformation between MR images of the two stages was calculated and the two dose distributions of the two plans were linearly summed up on the MR image of the second sessions. The initial tumour volume, its change after the time interval Δt between the two stages  (ΔVol%), and the volume of surrounding healthy tissues receiving 12Gy in the summed dose distribution (V12GyHTacc) were calculated.  The volume of treated BM and the presence of side effects will be considered and analysed as follow-up parameters at 3, 6, and 12 months after the second stage.

Results: Two distinct BM were treated simultaneously in 5 patients using the same prescription of 12 Gy in both stages. For 33 patients one or more smaller BM with higher dose prescription were treated during one of the two stages. The tumour volume at the first stage was (24.±15.4)cm3 and the shrinkage ΔVol% resulted in (-32±29)% after a Δt of (31.3±5.5) days. In only 9 patients out of 76 (11.8%) the tumour increased volume during the time interval between the two stages and in one of these cases (1.3%) ΔVol% was greater than 30%. The dose accumulated to the healthy tissues surrounding tumours resulted in V12HTGyacc of (48.7±31.5)cm3. No acute treatment-related toxicity was recorded between the two fractions. We reported the preliminary data about the volume of treated BM and the presence of side effects, collected and analysed as follow-up parameters at 3, 6, and 12 months after the second stage.

Conclusions: adaptive staged-dose gamma knife radiosurgery in two session for brain metastases is highly effective on local control with a low rate of complications due to low dose irradiation to surrounding brain tissue. Further information will come from the analysis of follow-up data taking accumulated dose distribution into account.


Luca BERTA, Hae Song MAINARDI, Maria Grazia BRAMBILLA, Angelo Filippo MONTI, Paola Enrica COLOMBO, Alberto TORRESIN, Filippo LEOCATA, Marco PICANO, Alessandro POZZA, Virginia Maria ARIENTI, Mauro PALAZZI, Alessandro LA CAMERA (MILAN, Italy)
00:00 - 00:00 #30127 - P041 A prospective single arm phase II study to evaluate safety and efficacy of silibinin in patients with brain metastases treated with stereotactic radiotherapy: preliminary results from SUSTAIN TRIAL.
P041 A prospective single arm phase II study to evaluate safety and efficacy of silibinin in patients with brain metastases treated with stereotactic radiotherapy: preliminary results from SUSTAIN TRIAL.

Purpose

Brain metastases (BMs) accounts for more than one-half of all intracranial tumors. Survival of patients (pts) with BMs has increased in recent years with the entry of stereotactic radiosurgery (SRS), providing excellent rates of local disease control. Silibinin or silybin, a natural polyphenolic flavonoid isolated from milk thistle seed extracts, showed promising antitumor activity in preclinical studies. Furthermore, the use of a silibinin-based nutraceutical has resulted in significant clinical and radiological improvement of BMs in pts with progressive non-small cell lung cancer (NSCLC) after whole brain radiotherapy and chemotherapy. The aim of our exploratory study is to evaluate whether the use of a silibinin-based nutraceutical significantly reduces distant-brain failure (DBF) at 6 months in pts with first-diagnosed BMs treated with SRS with or without surgery. Here a preliminary analysis on the first 18 pts enrolled is reported. 

 

Methods

SUSTAIN is a prospective, single arm, phase II study. A total of 80 pts with newly diagnosed BMs treated in our center and complying with the entry criteria are planned to be enrolled. Pts receive 2 capsules (cps) of SILLBRAIN® per day for the first month after SRS and 1 cp per day thereafter. The 6-month DBF rate is assessed according to RANO criteria for brain metastases (RANO-BM). Contrast-enhanced magnetic resonance (MRI) of the brain is performed at baseline and every 12 weeks after SRS. Validated health-related quality of life questionnaires (EORTC QLQ-C30 and BN20) are administered at baseline and every 12 weeks after SRS.

 

Results

Eighteen pts had been enrolled at the time of this primary analysis. NSCLC and breast cancer were the prevalent histologies, with 9 and 4 cases respectively. Ten pts had metachronous BMs onset, and 8 pts synchronous. Nine pts received at least 1 line of systemic therapy and 17 pts reported a controlled extracranial disease at BMs diagnosis. The overall number of BMs was 55. All BMs were treated with SRS, with a median prescription dose and median prescription isodose of 24Gy and 80%, respectively. According to RANO-BM criteria, 2 pts reported distant intracranial failure with 3 and 19 months of DBF. One pts discontinued SILLBRAIN® assumption due to grade 1 nausea (CTCAE v5.0). No other adverse events were reported.

 

Conclusion

The use of silibinin-based nutraceuticals after SRS might prolong distant brain failure-free survival in BMs pts, with a favorable safety profile. Final results from SUSTAIN trial are awaited to confirm these encouraging findings.


Isacco DESIDERI, Maria Grazia CARNEVALE (Florence, Italy), Luca VISANI, Viola SALVESTRINI, Ilaria BONAPARTE, Ludovica ZISCA, Lorenzo LIVI
00:00 - 00:00 #30129 - P042 Stereotactic radiotherapy using a mask system of Leksell Gamma Knife Icon for patients with metastatic brain tumors.
P042 Stereotactic radiotherapy using a mask system of Leksell Gamma Knife Icon for patients with metastatic brain tumors.

[Objectives] Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment.

[Methods] We retrospectively analyzed 1125 patients (a total of 1572 treatments) with brain metastases who underwent Gamma Knife Icon using mask fixation for the first four years at Rakusai Shimizu Hospital. Patients with small, few, newly diagnosed, and non-eloquent area tumors were treated in a single session. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule. If the tumor number was large, we selected a multisession schedule. The most common origin was lung (734 patients), followed by breast (135), gastro-intestinal tracts (124), kidney (43), and others (88). Median tumor number was three and median cumulative tumor volume was 2.7 ml.

[Results] 433 cases were treated in a single session, 733 with fractionation, and 366 with multiple sessions. For large tumors, we selected fractionated schedules as follows; 7.0 Gy x 5Fr (5-10 ml), 4.2Gy x 10Fr (10-20ml), 3.7Gy x 10Fr (20-30ml), 3.2Gy x 10Fr (30ml-). Median survival times after Icon treatment was 20.3 months, with only 2/3/5% of neurological deaths at 6/12/24 months after treatment. Poor local control rates were 9/18/27% at 6/12/24 months post-treatment. Preservation of neurological function rates were 95/92/89% at 6/12/24 months post-treatment. Serious complications occurred in only 1/1/2% of patients at 6/12/24 months post-treatment.

[Conclusions] Although these results are limited to short periods, survival rates, local control rates and qualitative survival rated in patients unsuitable for stereotactic radiosurgery, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges.


Takuya KAWABE (Kyoto, Japan), Manabu SATO
00:00 - 00:00 #30143 - P043 Neoadjuvant stereotactic radiosurgery vs. postoperative radiosurgery for brain metastases: A Dosimetric study.
P043 Neoadjuvant stereotactic radiosurgery vs. postoperative radiosurgery for brain metastases: A Dosimetric study.

Objectives:

To investigate the potential of neoadjuvant SRS (stereotaxic radiosurgery)  versus surgical bed SRS by providing a detailed dosimetric comparison. To this end, we determined the difference of V12 Gy (Volume of the healthy brain receiving 12Gy) in neoadjuvant SRS versus posoperative SRS to the surgical bed in brain metastases.

 

Background:

Neoadjuvant SRS for brain metastases is an alternative approach that could help improve uncertainties regarding margins, targeting, and reduction of healthy irradiated brain tissue. Comparative clinical data are scarce, which is why we carried out this simulation study at the National Institute of Neurology and Neurosurgery in Mexico City.

 

Methods:

We reviewed the database of patients who underwent surgical resection of brain metastases who received SRS in the postoperative period between October 2017 and July 2020. The delimitation of the objective and the treatment planning were based on an MRI (resonance image magnetic) and computed tomography (CT). Two hypothetical treatment scenarios for the neoadjuvant tratments were created (preoperative and postoperative) and later the PTV (planning target volume) and V12 Gy were compared in the different scenarios.

 

Results: 

Fifteen patients were included, out of which the most common histologies were of pulmonary and renal origin (66.6%). The V12 Gy was larger in the postoperative setting and lower in the preoperative setting. These results had a significant difference (18.599 vs 8.013, p <0.0001).

 

Conclusion:

In our analysis, from a dosimetric point of view, the findings obtained favor the preoperative treatment and suggest that preoperative SRS may help reduce the risk of radiation necrosis due to the fact that there is better delineation of the PTV and less uncertainty regarding the delineation of the objective and therefore less exposure of healthy tissue to radiation.


Rocio MAMANI (Lima, Peru), Javier JACOBO, Jose ARROYO, Alfredo HERRERA, Carlos BARRIOS, Laura HERNANDEZ, Axayacatl GUTIERREZ, Sergio MORENO
00:00 - 00:00 #30151 - P044 Initial experience using IDENTIFY for motion monitoring during frameless VMAT radiosurgery.
P044 Initial experience using IDENTIFY for motion monitoring during frameless VMAT radiosurgery.

Purpose: We report our initial clinical experience using IDENTIFY, an optical surface guidance system, for monitoring intra-fraction motion during stereotactic radiosurgery with HyperArcTM.

Methods: The IDENTIFY system consists of three ceiling mounted camera pods. For each treatment fraction, a reference surface was captured after radiographic image guidance prior to the first beam on. Surface guidance and linear accelerator trajectory logs were used to evaluate the reported offsets relative to the reference surface. Offsets were obtained at the start of treatment (after radiographic image alignment), end of treatment, and during treatment at 4 gantry angles: 140 and 220 degrees, when all three camera pods had a clear view, and 50 and 310 degrees, when the view of one of the camera pods was obstructed.

Results: 733 fractions of 295 treatment plans were evaluated. The average treatment time was 3.35 min (range 1.87 to 7.45 min). The mean (x,y,z) translation offset at the end of treatment was (0.00, -0.01, -0.07) mm, with median magnitude 0.27 mm and 95% of magnitudes were less than 0.97 mm. The mean reported offset during treatment was (-0.40, 0.23, -0.08), (-0.25, 0.02, -0.16), and (-0.16, 0.21, -0.05) mm at table angles 45, 90, and 315 degrees, respectively. The mean change in translation when a camera pod was blocked by the gantry was (0.01, 0.14, 0.02), (0.10, 0.23, 0.07), and (-0.02, 0.15, -0.00) mm at table angles 45, 90, and 315 degrees, respectively. The fraction of offsets exceeding 1 mm was 4.4%, 6.9%, and 2.5% when all three cameras had an unobstructed view, and was 13.4%, 1.9%, and 10.6% when a camera pod was blocked at table angles 45, 90, and 315 degrees, respectively.

Conclusion: The IDENTIFY system can be used to monitor for intra-fraction motion with submillimeter accuracy; however, the accuracy is reduced when a camera is obstructed by the gantry and/or the couch is rotated. Action levels should be established accordingly to account for this behavior.


Richard A. POPPLE (Birmingham, USA), Elizabeth L. COVINGTON, Dennis N. STANLEY, John B. FIVEASH
00:00 - 00:00 #30166 - P045 Sarcopenia analysis as a tool for outcome prediction in patients with brain metastases treated with gamma knife radiosurgery.
P045 Sarcopenia analysis as a tool for outcome prediction in patients with brain metastases treated with gamma knife radiosurgery.

Introduction: 

Sarcopenia is defined as reduced muscle mass and is characterized by a significant increase in health risk and mortality. Although sarcopenia has been associated with worse outcomes in the surgical and oncological literature, its association with outcome in patients with brain metastases treated with Gamma Knife Radiosurgery (GKRS) has never been formally examined. We performed a retrospective study to determine the association of sarcopenia with survival in patients with brain metastases treated with GKRS. 

Methodology:

A single-centre cohort of 344 consecutive patients with brain metastases treated with GKRS at from 2017 to 2021 was studied retrospectively. Computed tomography images of the abdomen were acquired prior to each patient’s initial GKRS treatment, and axial sections at the third lumbar (L3) level were captured for quantification of muscle and adipose tissue using Slice-O-Matic Software® (Tomovision). Skeletal muscle index was calculated and sarcopenia was determined based on previously established literature thresholds. Chart reviews were performed to obtain patient information including age, sex, primary malignancy, quantity and total volume of brain metastases at time of treatment, and margin dose delivered. The primary outcome of interest is survival after GKRS, categorized in a binary fashion.

Results:

Metastatic tumors represented in the cohort were lung (47.1%), breast (19.5%), melanoma (10.5%) and renal (9.6%), with the remaining 13.5% being of miscellaneous primary origin. The median number of brain metastases was 2 with median tumor volume 4.7 cm3. Proportion of patients alive at 6- months and 1- year time point post-GKRS treament was 70.6% and 47.4% respectively. A preliminary Kaplan-Meier survival analysis suggests that severe muscle-depletion in male patients is associated with decreased survival after GKRS treatment. 

Conclusions:

Preliminary data suggest an association between pre-treatment muscle depletion and survival after GKRS for a subset of patients with brain metastases. Future work will need to address the value of sarcopenia analysis in patient selection for GKRS and prognostication in the setting of brain metastases.


Ryan CHRENEK (Edmonton, Canada), Vickie BARACOS, Rachel KHADAROO, Samir PATEL, Tejas SANKAR, Greg BOWDEN
00:00 - 00:00 #30168 - P046 LINAC-based stereotactic radiosurgery with co-planar beams in the treatment of brain metastases.
P046 LINAC-based stereotactic radiosurgery with co-planar beams in the treatment of brain metastases.

Aim Single-fraction radiosurgery (SRS) and fractionated stereotactic radiosurgery (fSRS) are established treatment options in the management of brain metastases (BM). Limited data are available using a LINAC-based approach with co-planar arcs. This study analyzed a mono-institutional series of patients treated with this technique. 

Methods From October 2019 to December 2021, 54 patients (102 BM) with different primary solid tumors were treated with SRS or fSRS delivered with single-isocenter coplanar FFF-VMAT on a Linac platform. Patients’ characteristics are summarized in Table 1. Post-treatment MRI scans were used to assess local control (LC) and disease progression (PD) according to the Response Evaluation Criteria in Solid Tumors (RECIST) scale. Survival curves were calculated from the date of treatment by using the Kaplan-Meier (KM) method. 

Results Median age at diagnosis of BM was 67 years (34-85). Median follow up was 5.0 months (0.3-22.9). At the time of treatment, the median Graded Prognostic Assessment (GPA) score was 2.0 (0.5-3.5). The majority of patients (45 [83.3%]) had extracranial metastases, of whom 28 (51.9%) had visceral metastases. 83.9% and 16.1% of lesions received SRS (18-21 Gy in 1 fraction) and fSRS (27 Gy in 3 fractions), respectively. The mean GTV was 0.85 (0.08-4.97) cm3 and the mean PTV was 2.58 (0.67-11.96) cm3. Dosimetry statistics are reported in Table 1. LC and PD were observed in 19 (33.9%) and 21 (37.5%) treatments, respectively. The pattern of PD was extra-field in 12 patients (57%), in-field in 5 patients (24%) and both in- and extra-field in 4 patients (19.0%). Seven patients and 4 patients with extra-field PD were treated with whole brain radiotherapy (WBRT) or additional SRS, respectively. At the last follow-up 22 patients died and 6 patients were lost. Median OS and PFS were 7.6 months and 3.1 months, respectively. 

Conclusions Our findings show that Linac-based SRS and fSRS with co-planar beams and a single isocenter is an effective treatment modality in the management of single or multiple BM. The analysis of a larger sample size and a longer clinical follow-up are needed to confirm these preliminary results.


Sofia Paola BIANCHI, Miriam TORRISI (Milano, Italy), Sara TRIVELLATO, Raffaella LUCCHINI, Giorgio PURRELLO, Paolo CARICATO, Valeria FACCENDA, Martina Camilla DANIOTTI, Denis PANIZZA, Stefano ARCANGELI
00:00 - 00:00 #30174 - P047 Small brain metastases treated with single isocenter SRS.
P047 Small brain metastases treated with single isocenter SRS.

Purpose:

A safety and efficacy of single-isocenter SRS (SI-MM-SRS) for small brain metastases is not well defined. Our study aim was to determine response to treatment of metastatic lesions after single isocenter SRS, especially lesions with PTV volume below 0.5 cm3.

 

Materials and methods:

The analysis included a group of 36 patients treated at Department of Neurooncology and Radiosurgery at Franciszek Lukaszczyk Oncology Center beetween 02.08.2018 r. and 15.09.2020 r. due to multiple brain metastases with a follow-up MRI 6 months after treatmentA total of 195 metastatic lesions were treated, including 71 lesions with PTV volume bellow 0.5 cm3All patients were treated with the BrainLab Elements MultiMets software using single isocenter Dynamic Conformal Arcs. The ExacTrac system was used to monitor the position during SRS. MRI was analyzed in all patients 6 months after treatment.

 

Results:

The patients' median survival was 14.63 months and the median follow-up was 23.45 months. Local control was found in 93% of all metastatic lesions; in lesions below 0.5 cm3 it was 96%. Tumors with a volume below 0.5 cm3 did not have a worse response rate (p = 0.626) and there was no increased risk of radiation necrosis (p = 0.541). Symptomatic radiation necrosis was diagnosed in 1 patient (3%) after 6 months. Twelve lesions (6%) with radiation necrosis were asymptomatic. A statistical relationship was found between survival and the sum of PTV volumes of metastatic lesions (p = 0.0182; HR = 1.06 (95% 1.01; 1.10)). There was no correlation between survival and the number of tumors (p = 0.337).

 

Conclusions: 

Multiple brain metastases irradiated with a single isocenter technique show a high response rate. Tumors below 0.5 cm3 have a high response rate with low risk of radiation necrosis.


Maciej BLOK (Bydgoszcz, Poland), Tomasz WISNIEWSKI, Magdalena ADAMCZAK-SOBCZAK, Izabela ZAREBSKA, Maciej HARAT
00:00 - 00:00 #30175 - P048 Long-term results of Linac-based Single-Isocenter Multiple-Metastases Stereotactic Radiosurgery.
P048 Long-term results of Linac-based Single-Isocenter Multiple-Metastases Stereotactic Radiosurgery.

Purpose: Linac-based SRS is an optional treatment of multiple brain metastases. Our study aim was to assess the safety and efficacy of a linac-based single-isocenter SRS (SI-MM-SRS) for multiple brain metastases in relation to various clinical factors.

 

Materials and methods: The analysis included a group of 123 patients treated at the Department of Neurooncology and Radiosurgery at Franciszek Lukaszczyk Oncology Center  between 02.08.2018 r. and 15.09.2020 r. due to multiple brain metastases.  The minimum follow-up was 12 months and the median follow-up was 23 months. The median number of lesions was 4 and median sum of PTV volume was 9.95 cm3. All patients were treated with the BrainLab Elements MultiMets software using single isocenter Dynamic Conformal Arcs. The ExacTrac system was used to monitor the position during SRS.

 

Results: Sixteen percent of patients was still alive in time of analysis. The 6- and 12-months rate was 60% and 33%. In the multivariate analysis the sum of PTV volumes (p=0.0007) but not a number of lesions was related to survival. Every increase by 1 cm3 of total brain metastatic volume increased the risk of death by 2%. A diagnosis of squamous cell carcinoma of the lung was related to worst outcomes. Out of 123 patients, 95 patients presented for the first follow-up visit (median 35 days after SRS). The reported neurological symptoms were stabilized or improved in 79% of patients. There was no relationship between the neurological deterioration and the parameter V12 for whole brain (p = 0.319).

 

Conclusions:  The survival results of patients with multiple metastases are encouraging but depends on histopathology and total PTV volume. V12 parameter was not related to onset of symptoms early after SRS.


Maciej BLOK (Bydgoszcz, Poland), Tomasz WISNIEWSKI, Magdalena ADAMCZAK-SOBCZAK, Izabela ZAREBSKA, Maciej HARAT
00:00 - 00:00 #30177 - P049 Radiosurgery to 53 brain metastases with complete response.
P049 Radiosurgery to 53 brain metastases with complete response.

Radiosurgery (SRS) is a stereotactic radiotherapy technique in a few fractions (1-5) in the central nervous system. Is a non-invasive, high-precision technique that enables the administration of a high dose of irradiation per fraction to one or multiple targets, with an ablative effect and low doses in healthy organs

The aim of this case report is to share the experience of a clinical case of a patient with brain metastases who received SRS twice. First SRS was in 2019 in 13 metastases and a second SRS 13 months later in 53 new metastases with excellent tolerance and complete response.

43-year-old woman with a history of breast cancer in 2014, underwent neoadjuvant chemotherapy, mastectomy and axillary dissection

2017 Local recurrence, performed surgery + radiotherapy

2018 Liver metastases, underwent chemotherapy

August/2019 MRI of the brain shows 13 metastases

        SRS in 1 fraction of 21 Gy in 13 brain metastases

Thirteen months free of symptoms with normal work activity

September/2020 MRI shows 53 new brain metastases

          SRS in 1 fraction of 21 Gy in each of the metastases

Continues in controls with MRI every 3 months

July/2021 MRI of the brain shows all the treated lesions, in both SRS, controlled, 4 new millimetric lesions appear that it is decided to control

September/2021 Clinical control patient in good general condition, performs normal work activities, no headache or cognitive impairment

Metastatic spread in the CNS is frequent in patients with primary breast, lung, kidney cancer or melanoma, with a 10-30% risk of developing brain metastases

Historically, these patients have been treated with whole brain radiotherapy (WBRT), with cognitive deficit as a chronic consequence

However, a select group of patients with brain metastases can now achieve longer survival with the maintenance of good neurological function if their brain metastases are controlled.

Radiosurgery with dedicated linear accelerator and mask (Frameless) is a safe and non-invasive technique capable of controlling brain metastatic disease

SRS in patients with good performance status and controlled systemic disease is an effective therapeutic approach with less toxicity than total brain irradiation

Low doses to the healthy irradiated brain, allows normal cognitive activity and better quality of life

 


Agostina VILLEGAS FRUGONI (Cordoba, Argentina, Argentina), Oscar Ariel MURIANO, Maria Milla GALETTO, Daniela Mariel ANGEL SCHUTTE, Veronica VERA, Agustin GIRAUDO, Valentina GREGORAT, Mercedes CHIBAN
00:00 - 00:00 #30178 - P050 Is still a challenge the treatment of large brain metastases as well as the treatment of metastases closed to critical areas? Our experience with Gamma Knife Icon and review of the literature.
P050 Is still a challenge the treatment of large brain metastases as well as the treatment of metastases closed to critical areas? Our experience with Gamma Knife Icon and review of the literature.

This study reports the experience of a single institute concerning the treatment of brain metastases in fractional mode (frame modality and frameless) with a review of the literature. We preferred fractionation for metastases close to critical structures or with a large volume.

We used two modalities of fractionation: hypofractionated stereotactic radiosurgery (HSRS), which consists of three or five consecutive days of treatment and staged stereotactic radiosurgery (SSRS), which consists of two fractions delivered with an interval of about four / five weeks.  All procedures were performed with  Gamma Knife Icon.

Seven patients were treated with HSRS and five patients with SSRS. In the HSRS group two patients have metastases close to critical organs; median volume was 6,441 cm3(range 0,815 – 17,357 cm3) and median total marginal dose was 25 Gy at 50% (range 21 – 32,5 Gy) in three or five days. For the SSRS group median volume at the first treatment was 11,214 cm3 (range 8,1 – 26,777 cm3) and 7,627 cm3 (range 3,757 – 18,46 cm3) at the second treatment; the median total marginal dose was 12 Gy for both first and second fraction. Follow up (FU): At 12 months 7 patients were alive and 4 deceased (extracranial disease progression), one patient was lost to FU. At 18 months 3 patients were alive and 7 deceased (in one case for cerebral progression, the other cases extracranial disease progression) while 2 patients were lost to FU. Complications: we observed one case of radionecrosis in a patient previously radiotherapy and one case of seizure. From the literature review it emerged that positive predictive factors are: controlled extracranial tumor, prolonged fractionation days in HSRS and decrease of the tumor volume between fractions in SSRS. Our experience partly reflects these results: the patients undergoing surgery post Gamma Knife surgery had not experienced a reduction in volume between the first and second fractions, while the patients with less favorable clinical course up to death presented extracranial metastates and poor control of the disease. We didn’t observe significant difference in survival in patients undergoing treatments lasting 3 days compared to 5 days.

Fractionated radiosurgery with Gamma Knife offers a slightly or non-invasive therapeutic alternative for treating more fragile patients and without long-term healing chances with large brain metastases or metastases closed to critical organs.


Alberto FRANZIN (Brescia, Italy), Lodoviga GIUDICE, Karol MIGLIORATI, Giorgio SPATOLA, Cesare GIORGI, Chiara BASSETTI, Corrado D'ARRIGO, Oscar VIVALDI, Mario BIGNARDI
00:00 - 00:00 #30179 - P051 Impact of molecular biomarkers in non-small cell lung cancer on local control of brain metastases treated with radiosurgery.
P051 Impact of molecular biomarkers in non-small cell lung cancer on local control of brain metastases treated with radiosurgery.

As the oncology treatment paradigm shifted from a palliative one-for-all treatment towards individually tailored patient-adapted therapy, stereotactic radiosurgery (SRS) is a gold standard in treatment of brain metastases (BM). Lung and bronchus cancer is the third most common cancer diagnosis in the world. At the time of diagnosis, approximately 10% of patients with advanced non-small cell lung cancer (NSCLC) already have BM. Using targeted therapy and immunotherapy increases the number of patients with BM eligible for SRS. 

We present a retrospective analysis of local control after SRS of BM depending on histology and molecular subtype of primary lung cancer.

Methods:

We analyzed patients with BM from NSCLC treated with SRS in our institution from 2017 till 2021. A total of 68 patients are reported, median age 66 (35-80) years. All patients had known status of molecular biomarkers EGFR, ALK, ROS1 and PD-L1. At least one positive biomarker was found in 45% of patients. A total of 186 targets were treated (173 BM and 13 resection cavities). Most of the patients (93%) were diagnosed with adenocarcinoma and 7% with squamous cell carcinoma.   For a final evaluation, there were 49 (72%) patients eligible. The patients were treated by the Varian Edge radiosurgery system. The planning and follow-up imaging was done on a Siemens Skyra 3T MRI system, the image data was analyzed using Syngo.via software suite. The pretreatment and posttreatment images were compared using RANO-BM criteria for target and non-target lesions. 

Results:

Stable disease had 67% of patients, 29% of patients had partial response and 4% had disease progression by RANO-BM.  There were no patients with a complete response, although some of the lesions were undetectable in follow-up images. A total of 7 patients were treated by whole brain radiotherapy prior to SRS, five of them showed stable disease and the rest fitted the criteria for partial response.The response pattern mostly consisted of lesions shrinking in volume with central necrosis and/or central hemosiderin deposits, indicating hemorrhage within the lesion. One of the lesions showed severe intralesional hemorrhage which caused enlargement of the lesion. The perilesional vasogenic edema was reduced in most of the patients. No irradiation necrosis of the surrounding normal brain tissue was observed.

Conclusion:

SRS is a valuable tool in treating BM of lung cancer, providing  therapy with favorable results visible in a relatively short time. No significant difference in response was observed in patients with positive biomarkers. 


Ana MISIR KRPAN (Zagreb, Croatia), Hrvoje VAVRO, Josip PALADINO, Matea LEKIC, Hrvoje KAUCIC, Hrvoje SOBAT, Asmir AVDICEVIC, Domagoj KOSMINA, Vanda LEIPOLD, Adlan CEHOBASIC, Ivo PEDISIC, Dragan SCHWARZ
00:00 - 00:00 #30182 - P052 THE IMPACT OF NEUTROPHILS TO LYMPHOCYTES RATIO ON SURVIVAL IN PATIENTS AFFECTED BY BRAIN METASTASES AND TREATED WITH GAMMA-KNIFE RADIOSURGERY.
P052 THE IMPACT OF NEUTROPHILS TO LYMPHOCYTES RATIO ON SURVIVAL IN PATIENTS AFFECTED BY BRAIN METASTASES AND TREATED WITH GAMMA-KNIFE RADIOSURGERY.

Purpose: Several studies investigated the correlation between neutrophil-to-lymphocyte ratio (NLR) in peripheral blood and the prognosis in different diseases including various cancers.However, little is known about the impact of NLR on the prognosis of patients with brain metastases. We aim to evaluate the predictive value of NLR in patients with brain metastasis from non-small lung cancer (NSCLC) and melanoma candidates to gamma knife (GK) radiosurgery. 

Methods: We retrospectively examined 111 consecutive patients with brain metastases (BMs) from NSCLC and melanoma treated with GK radiosurgery. NLR was calculated using N/L, where N and L, respectively, refer to peripheral blood neutrophils (N) and lymphocyte (L) counts. Kaplan-Meier curves depicted the time to survival according to NLR. Univariable and multivariable Cox regression analyses were used to confirm the impact of NLR on overall survival. 

Results: 

Median (IQR) age at diagnosis of brain metastases was 64 yrs. (55;70). Median (IQR) NLR was 7.25 (4.18;12.4). Median (IQR) overall survival was 5.0 months (2.0;11.5). 

At univariable Cox-regression analyses, NLR was associated with improved overall survival (HR: 1.05; p=0.004). On the other hand, total number of lymphocytes, neutrophils and monocytes were not associated with improved overall survival (all p>0.1). At multivariable Cox regression analyses, after adjusting for patient age, sex and the use of DEX therapy, NLR represented an independent predictor of overall survival (HR: 1.06; p=0.003).

Conclusion: NLR represents an independent prognostic factor in patients affected by brain metastases  from NSCLC and melanoma. Inflammation and immunity may play a critical role in these patients. Further analysis examining more specific neutrophils or lympocytes subsets may increase our understanding of cancer etiology and progression.


Filippo GAGLIARDI, Silvia SNIDER, Francesca RONCELLI (Milan, Italy), Edoardo POMPEO, Lina Raffaella BARZAGHI, Alessandra BULOTTA, Chiara LAZZARI, Antonella DEL VECCHIO, Pietro MORTINI
00:00 - 00:00 #30194 - P053 Impact of the neuro-radiologist and neuro-surgeon in contouring with the neuro-oncologist on local relapse rates for brain metastases treated with stereotactic radiosurgery.
P053 Impact of the neuro-radiologist and neuro-surgeon in contouring with the neuro-oncologist on local relapse rates for brain metastases treated with stereotactic radiosurgery.

Background:  The audit evaluates the value of MDT, including neuro-radiologist and neuro-surgeon, review of contouring carried out by a clinical oncologist in stereotactic radiosurgery (SRS).

Methods: A sequential audit was conducted of all patients receiving intracranial SRS at our local institution for the first 22 months of a new SRS service. Lesions were contoured first by clinical oncologist then reviewed/edited by MDT. The initial contour was compared with final using Jaccard conformity and geographical miss indices. The dosimetric impact of a contouring change was assessed using plan metrics to both original and final contour. The impact of the contouring review on local relapse, overall survival and radio necrosis rate was evaluated with at least 24 months follow up (24-46 months).

Results: 113 patients and 142 lesions treated over 22 months were identified. Mean JCI was 0.92 (0.32-1.00) and 38% needed significant editing (JCI<0.95). Mean GMI was 0.03 (0.0-0.65) and 17% showed significant miss (GMI>0.05). Resection cavities showed more changes, with lower JCI and higher GMI (p<0.05). There was no significant improvement on JCI or GMI shown over time. Dosimetric analysis indicated a strong association of conformity metrics with PTV dose metrics; a 0.1 change in GTV conformity metric association with 6-17% change in dose to 95% of resulting PTV. Greater association was seen in resection cavity suggesting the geographical nature of a typical contouring error gives rise to greater potential change in dose. Clinical outcomes compared well with published series. Median survival was 20 months and local relapse free rate in the treated areas of 0.89 (0.8-0.94) at 40 months, and 0.9 (0.83-0.95) radio-necrosis free rate at 40 months with a median 17 months to developing radionecrosis for those that did.

Conclusions: This work highlights that a MDT contour review adds significant value to SRS and the approach translates into reduced local recurrence rates at our local institution compared with previously published data. No improvement in clinical oncologist contouring over time was shown indicating a collaborative approach is needed regardless of experience of clinical oncologist. MDT input is recommended in particular in contouring of resection cavities.


K SAYAL, M ROBINSON, C TUNSTALL, S PADMANABAN, R WATSON, P PRETORIUS, R JOSEPH, S JEYARETNA (Oxford, United Kingdom), C HOBBS
00:00 - 00:00 #30198 - P054 Immediate response to Boswellia serrata extract of steroid-refractory, symptomatic edema after radiosurgery to 31 brain metastases.
P054 Immediate response to Boswellia serrata extract of steroid-refractory, symptomatic edema after radiosurgery to 31 brain metastases.

INTRODUCTION:

Both immediate and delayed peri-lesional post-treatment vasogenic edema is a commonly encountered phenomenon after intracranial metastases are treated with stereotactic radiosurgery. When the effect is symptomatic, steroids are usually employed as first-line management. In some cases, however, patient symptoms are refractory to steroids, even at escalated doses. Indian frankincense is an herbal extract from the sap of the Boswellia serrata tree which has been touted in Ayurvedic medicine for many years as a means of managing various inflammatory conditions. It was successfully tested in a small, pilot randomized clinical trial for cerebral edema associated with large volume of irradiated brain


Evan THOMAS (Columbus, OH, USA), Josh PALMER
00:00 - 00:00 #30199 - P055 Cranial Outcomes from Postoperative and Preoperative Stereotactic Radiosurgery in Large Brain Metastases: A meta-analysis.
P055 Cranial Outcomes from Postoperative and Preoperative Stereotactic Radiosurgery in Large Brain Metastases: A meta-analysis.

Purpose: Postoperative stereotactic radiosurgery (SRS) is currently the standard of care for adjuvant radiation treatment after surgical resection of a brain metastasis. Preoperative SRS might represent a more beneficial therapeutic option by decreasing leptomeningeal recurrence and radionecrosis (RN) risk without compromising local control (LC) rates or introducing delays in systemic therapy after craniotomy; however, results of phase 3 randomized control trials comparing both approaches are still underway. We analyzed the current level of evidence regarding intracranial outcomes in each setting for patients with large metastases.

 

Methods and Materials: A systematic search was conducted on PubMed, Cochrane and Embase from inception to April 2020 (update to be performed prior to meeting to maximize timeliness). PRISMA guidelines were used to select articles where patients with “large” brain metastases (>4 cm3 or >2 cm in diameter) received postoperative or preoperative SRS as treatment. Random effects meta-analyses using timing of SRS relative to surgery as covariates were conducted.

 

Results: Through search methods 1,235 studies were identified. After assessment for eligibility we included a total of 14 studies, 7 studies evaluating multi fraction postoperative SRS, 4 studies on single fraction postoperative SRS, and 3 studies on single fraction preoperative SRS. In the postoperative SRS group 608 patients were included, and 148 in the preoperative SRS group. The total number of metastatic lesions was 819; 660 in the postoperative SRS group and 159 in the preoperative SRS group. Median age for all patients was 58 years, with a median follow-up of 13.1 months [5.2-24 months] for postoperative SRS and 10.5 months [6.3-13 months] for preoperative SRS group. Median total radiation dose in the postoperative SRS group was 23 Gy [12-39 Gy], and 16 Gy [15-18 Gy] in the preoperative SRS group. Median overall survival was 13.1 months [5.5-28.1 months] for postoperative SRS and 15.1 months [13-17.2 months] for preoperative SRS groups. The 1-year local control (LC) random effects estimate was 79.0% (95% CI: 56-95.0%) for preoperative SRS and 78.8% (95% CI: 67.1-88.5%) for postoperative SRS (p=0.98). Radiation necrosis (RN) random effects estimate was 4.5% (95% CI: 0.4-12.5%) and 7.0% (95% CI: 1.9-15.0%) for preoperative and postoperative SRS respectively (p=0.63