Sunday 19 June
09:00

Sunday 19 June

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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 (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

Sunday 19 June

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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

Sunday 19 June

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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 (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

Sunday 19 June

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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

Sunday 19 June

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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

Sunday 19 June

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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 (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

Monday 20 June

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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

Monday 20 June

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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

Monday 20 June

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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 (Hamm, 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

Monday 20 June

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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

Monday 20 June

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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) (Hamm, 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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C19
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
BLUE 2 ROOM
17:30

Monday 20 June

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B15
17:30 - 18:30

SPONSORED SYMPOSIUM

RED 2 ROOM

Monday 20 June

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C15
17:30 - 18:30

SPONSORED SYMPOSIUM

BLUE 2 ROOM
Tuesday 21 June
08:00

Tuesday 21 June

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A20
08:00 - 09:00

BREAKFAST SEMINAR
Physics - Accuracy

Moderators: Elena DE MARTIN (Medical physicist) (Milan, Italy), Ian PADDICK (Consultant Physicist) (London, United Kingdom)
Coordinator: Ian PADDICK (London, United Kingdom)
08:00 - 08:20 Margins in the radiosurgery era: dosimetric, biological, physical limits. Tim SOLBERG (Senior Advisor for Emerging Technology) (Sonoma Valley, USA)
08:20 - 08:40 State of the art in motion management for SBRT treatments. Carlo CAVEDON (Verona, Italy)
08:00 - 09:00 Understanding « Robust » treatment planning in RT/SRS. Thierry GEVAERT (Head of Medical physics) (Brussels, Belgium)
SILVER ROOM

Tuesday 21 June

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B20
08:00 - 09:00

BREAKFAST SEMINAR
Re-irradiation for Body Tumors

Moderators: Alba FIORENTINO (BARI, Italy), Ciro FRANZESE (MD) (Milano, Italy)
Coordinator: Alba FIORENTINO (BARI, Italy)
08:00 - 08:20 Reirradiation for recurrent prostate cancer: state of art and future direction. Berardino DE BARI (Switzerland)
08:20 - 08:40 Dose constraints and tumor dose in the reirradiation setting. Nicolaus ANDRATSCHKE (Consoultant) (Zürich, Switzerland)
08:40 - 09:00 Reirradiation in head and neck tumors. Pierluigi BONOMO (Florence, Italy)
RED 2 ROOM

Tuesday 21 June

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C20
08:00 - 09:00

BREAKFAST SEMINAR
NF2 and Rare Brain Tumors

Moderators: Fabio BARONE (Consultant Neurosurgeon) (Catania, Italy), Bente Sandvei SKEIE (MD, PhD) (Bergen, Norway)
Coordinator: Alfredo CONTI (Bologna, Italy)
08:00 - 08:20 Vestibular schwannomas in NF2: which approach? Michele LONGHI (Neurosurgeon) (Verona, Italy)
08:20 - 08:40 Pilocytic astrocytomas. Andrey GOLANOV (Chief of the Department) (Moscow, Russia)
08:40 - 09:00 Brainstem tumors. Zeno PERINI (Neurosurgeon) (Vicenza, Italy)
BLUE 2 ROOM
09:15

Tuesday 21 June

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A21
09:15 - 10:15

PLENARY SESSION
Special Topics: SRS, HIFU, LITT, RF ablation : alternatives or complementary tools? / Integration of immunotherapy and interventional oncology

Moderators: Francesco DI MECO (Head Department of Neurosurgery) (Milan, Italy), Dheerendra PRASAD (Professor and Medical Director) (Buffalo, NY, USA), David SCHLESINGER (Medical Physics) (Charlottesville, VA, USA, USA)
Coordinator: Jason SHEEHAN (Charlottesville, USA)
09:15 - 09:30 Focused ultrasound for brain diseases. Francesco PRADA (Milan, Italy)
09:30 - 09:45 SRS versus HIFU for tremor. Jean REGIS (PROFESSEUR) (MARSEILLE, France)
for “SRS”
09:45 - 10:00 SRS versus HIFU for tremor. Andres LOZANO (Tasker Chair in Functional Neurosurgery, University of Toronto) (Toronto, Canada)
for “HIFU”
10:00 - 10:15 Integration of immunotherapy and interventional oncology. Gianpaolo CARRAFIELLO (Italy)
SILVER ROOM
10:15 COFFEE BREAK AND EXHIBITION
10:45

Tuesday 21 June

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A23
10:45 - 11:30

PLENARY SESSION
Special Topic: The Combination of Immunotherapy with SRS/SBRT

Moderators: Filippo DE BRAUD (CHEF OF DEPARTMENT) (MILANO, Italy), Paul W. SPERDUTO (2HBK7YS$) (Durham, USA)
Coordinator: Paul W. SPERDUTO (Durham, USA)
10:45 - 11:00 Introduction. Paul W. SPERDUTO (2HBK7YS$) (Durham, USA)
11:00 - 11:30 The philosophy of immunotherapy. Filippo DE BRAUD (CHEF OF DEPARTMENT) (MILANO, Italy)
SILVER ROOM
11:30

Tuesday 21 June

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A23.1
11:30 - 12:00

PLENARY SESSION
The Lars Leksell Lecture

ISRS President: Laura FARISELLI (director) (milan, Italy)
ISRS Past President: Ian PADDICK (Consultant Physicist) (London, United Kingdom)
ISRS Vice President: Marc LEVIVIER (Chef de Service) (Lausanne, Switzerland)
11:30 - 12:00 The Lars Leksell Lecture. Dade LUNSFORD (Pittsburgh, USA)
SILVER ROOM
12:00

Tuesday 21 June

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A24
12:00 - 13:00

PARALLEL SESSION
Advanced Integrated Imaging (e.g. MR-Linac)

Moderators: Filippo ALONGI (Verona, Italy), Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA), Robert SMEE (Senior Staff Specialist) (Randwick, Australia)
Coordinator: Caroline CHUNG (Houston, USA)
12:00 - 13:00 Pelvic lymph node metastases with MR-Linac. Petra KROON (Medical Physicist) (Utrecht, The Netherlands)
12:00 - 13:00 MRI-guided RT for heart sarcoma. Luca BOLDRINI (Medical doctor) (Rome, Italy)
12:00 - 13:00 PET-based SRS planning and response assessment in neuro-oncology. Jonathan KNISELY (Faculty) (New York, USA)
SILVER ROOM

Tuesday 21 June

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B25
12:00 - 13:00

PARALLEL SESSION
Functional SRS

Moderators: Alessandra GORGULHO (Director) (SÃO PAULO, Brazil), Jean REGIS (PROFESSEUR) (MARSEILLE, France), Giorgio SPATOLA (Neurosurgeon) (Brescia, Italy)
Coordinator: Jean REGIS (MARSEILLE, France)
12:00 - 13:00 Network mapping in SRS for psychiatric disorders. Sameer SHETH (Associate Professor of Neurosurgery) (Houston, USA)
12:00 - 13:00 Role of SRS in anorexia nervosa. Roberto MARTINEZ-ALVAREZ (Neurosurgeon) (Madrid, Spain)
12:00 - 13:00 Role of BED in Functional SRS. Constantin TULEASCA (Lausanne, Switzerland)
RED 2 ROOM
13:00 SPONSORED LUNCH SYMPOSIUM

Tuesday 21 June

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A25b
13:00 - 14:00

SPONSORED LUNCH SYMPOSIUM

BLUE 2 ROOM
14:00

Tuesday 21 June

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A26.1
14:00 - 18:30

VISIT OF POSTERS AND EXHIBITION

SILVER ROOM

Tuesday 21 June

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B26
14:00 - 18:30

Meeting of the Leksell Gamma Knife Society

Kindly note that this is a dedicated LGK Society meeting for LGK practitioners and LGKS members participating in the 15th Congress of the International Stereotactic Radiosurgery Society (ISRS).

> Please fill in the registration form here (use right clic for opening)
RED 2 ROOM

Tuesday 21 June

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C26
14:00 - 18:30

Affiliated Societies & Patients Associations

BLUE 2 ROOM
Wednesday 22 June
08:00

Wednesday 22 June

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A30
08:00 - 09:00

BREAKFAST SEMINAR
Clinical Trials in Brain Metastases (overview)

Moderators: Bodo LIPPITZ (Co-Director) (Hamburg, Germany), Silvia SCOCCIANTI (Chief) (Florence, Italy)
Coordinator: Paul W. SPERDUTO (Durham, USA)
08:00 - 09:00 Clinical trials on brain metastases (overview). Paul W. SPERDUTO (2HBK7YS$) (Durham, USA), Jonathan KNISELY (Faculty) (New York, USA), Arjun SAHGAL (Professor) (Toronto, Canada)
SILVER ROOM

Wednesday 22 June

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B30
08:00 - 09:00

BREAKFAST SEMINAR
Radiosurgery in the Pediatric Population

Moderators: Laura FARISELLI (director) (milan, Italy), Glen STEVENS (Neuro-oncology) (Cleveland, USA)
Coordinator: John SUH (Cleveland, USA)
08:00 - 08:20 SRS for recurrent pediatric brain tumors. Steve BRAUNSTEIN (Faculty) (San Francisco, USA)
08:20 - 08:40 SRS for pediatric brain AVMs. Iris GIBBS (Professor) (Stanford, USA)
08:40 - 09:00 Pediatric craniopharyngiomas. Erin MURPHY (Radiation Oncologoy) (Cleveland, USA)
RED 2 ROOM

Wednesday 22 June

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C30
08:00 - 09:00

BREAKFAST SEMINAR
Update on Emerging Body SBRT Indications

Moderators: Francesca CAPARROTTI (radiation oncologist, MD) (Geneva, Switzerland), Nadia DI MUZIO (Director) (Milano, Italy)
Coordinator: Ciro FRANZESE (Milano, Italy)
08:00 - 08:20 Cardiac ablation. Joost VERHOEFF (associate professor) (Utrecht, The Netherlands)
08:20 - 08:40 Pre-operative SBRT for breast cancer. Viola SALVESTRINI (Florence, Italy)
08:40 - 09:00 Post-operative SBRT for prostate cancer. Thomas ZILLI (Genève, Switzerland)
BLUE 2 ROOM
09:15

Wednesday 22 June

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A31
09:15 - 10:15

PLENARY SESSION
Special Topic: Spine Radiosurgery

Moderators: Francesco COSTA (Milano, Italy), Arjun SAHGAL (Professor) (Toronto, Canada), Dennis SHRIEVE (Professor and Chair) (Salt Lake City, USA)
Coordinator: Arjun SAHGAL (Toronto, Canada)
09:15 - 10:15 Surgical approaches to metastatic spine incorporating spine SBRT. Stefano BORIANI (MILANO, Italy)
09:15 - 10:15 Late complications of spine SBRT and strategies to mitigate the risk. Peter GERSZTEN (Professor) (PITTSBURGH, USA)
09:15 - 10:15 Current state of the evidence for spine SBRT. Emma Maria DUNNE (Radiation Oncologist) (Vancouver, Canada)
SILVER ROOM
10:15 COFFEE BREAK AND EXHIBITION
10:45

Wednesday 22 June

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A33
10:45 - 12:00

PLENARY SESSION
Special Topics: Radiobiology and OAR tolerance / Radiomics

Moderators: Luca BOLDRINI (Medical doctor) (Rome, Italy), Scott FLOYD (Durham, USA), Alessandra GORGULHO (Director) (SÃO PAULO, Brazil)
Coordinator: Constantin TULEASCA (Lausanne, Switzerland)
10:45 - 12:00 Radiobiology for dummies. Ian PADDICK (Consultant Physicist) (London, United Kingdom)
10:45 - 12:00 Radiobiological models and innovative dose-fractionation schedules (PULSAR). Robert TIMMERMANN (Interim Chair) (Dallas, USA)
10:45 - 12:00 Translation of Radiobiology in Clinical Practice. Constantin TULEASCA (Lausanne, Switzerland)
10:45 - 12:00 The promise of Radiomics and AI for treatment personalization of SRS/SBRT. Claudio FIORINO (Milano, Italy)
SILVER ROOM
12:00

Wednesday 22 June

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A34
12:00 - 13:00

PARALLEL SESSION
ESTRO session: SBRT for Oligo-Metastases

Moderators: Umberto RICARDI (Full Professor Radiation Oncology) (Turin, Italy), Ben SLOTMAN (Professor and Chairman) (AMSTERDAM, The Netherlands), Arjun SAHGAL (Professor) (Toronto, Canada)
Coordinator: Umberto RICARDI (Turin, Italy)
12:00 - 13:00 SBRT in oligo-recurrent nodal disease. Ciro FRANZESE (MD) (Milano, Italy)
12:00 - 13:00 SBRT in OMD prostatic cancer. Maris MEZECKIS (radiation oncologist) (Sigulda, Latvia)
12:00 - 13:00 OligoCare. Matthias GUCKENBERGER (Chairman) (Zurich, Switzerland)
12:00 - 13:00 De novo oligo-metastatic NSCLC. Fiona MC DONALD (United Kingdom)
SILVER ROOM

Wednesday 22 June

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B34
12:00 - 13:00

PARALLEL SESSION
SRS for Vascular Lesions

Moderators: Joao Gabriel GOMES (Neurosurgeon) (Recife, Brazil), Alessandro LA CAMERA (MILAN, Italy), Yigal SHOSHAN (Head of department) (Jerusalem, Israel)
Coordinator: Constantin TULEASCA (Lausanne, Switzerland)
12:00 - 13:00 What consensus about non-hemorrhagic arteriovenous malformations since ARUBA? Nicolas REYNS (Professor of Neurosurgery) (LILLE, France)
12:00 - 13:00 Radiosurgery for arteriovenous malformations using high-definition angiographic imaging. Aditya GUPTA (Head, Neurosurgery and CNS Radiosurgery) (Gurgaon, India)
12:00 - 13:00 Stereotactic radiosurgery with versus without embolization for brain arteriovenous malformations. Antonio DE SALLES (Professor - Chief) (SÃO PAULO, Brazil)
12:00 - 13:00 BED in predicting obliteration of arteriovenous malformations after SRS. Constantin TULEASCA (Lausanne, Switzerland)
RED 2 ROOM
13:00

Wednesday 22 June

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A35b
13:00 - 14:00

SPONSORED LUNCH SYMPOSIUM

SILVER ROOM

Wednesday 22 June

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B35b
13:00 - 14:00

SPONSORED LUNCH SYMPOSIUM

RED 2 ROOM

Wednesday 22 June

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C35b
13:00 - 14:00

SPONSORED LUNCH SYMPOSIUM

BLUE 2 ROOM
14:00

Wednesday 22 June

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A36
14:00 - 15:00

ORAL PRESENTATION
Prostate SBRT

Moderators: Andrei FODOR (Senior Radiation Oncologist) (Milano, Italy), Maris MEZECKIS (radiation oncologist) (Sigulda, Latvia)
14:00 - 14:10 #29706 - OP43 Preliminary report of toxicity and quality of life of the first 100 patients treated with 1.5T MR-guided stereotactic body radiotherapy for prostate cancer.
OP43 Preliminary report of toxicity and quality of life of the first 100 patients treated with 1.5T MR-guided stereotactic body radiotherapy for prostate cancer.

Purpose: In the present series we report preliminary acute and late toxicity of the first 100 patients who received 1.5T MR-guided daily-adaptive stereotactic body radiotherapy for prostate cancer. 

Methods: We report the outcomes of the first 100 patients treated from October 2019 to December 2020. All the patients were enrolled in a prospective study (MR Linac n°XXXX). Before the treatment, the insertion of the rectal spacer was proposed as optional and applied in 37 patients. Hormone therapy was prescribed according to international guidelines in 32 patients. Toxicity was prospectively collected and assessed using Common Terminology Criteria for Adverse Events (CTCAE v5.0). Quality of life was assessed using IPSS, ICIQ-SF, IIEF-5, EORTC QLQ-C30, QLQ-PR25 and EPIC-26 questionnaires.

Results:  100 patients were treated: 34 were low risk, 29 were favorable intermediate-risk, 31 were unfavorable intermediate-risk, 2 high risk, 4 were low-volume M1 patients. The median age was 71 years (range, 52-84 years), median IPSS was 3 (range, 0-7); SBRT was delivered using 1.5T MR-guided daily adaptive radiotherapy in 5 sessions for a median total dose of 35 Gy (35-36.25 Gy) on consecutive (n=75) or alternate days (n=25). The adapt-to-shape workflow was mainly adopted (480/500 sessions). The median treatment time was 40 minutes (range, 33-83 minutes). The median PTV volume was 105.8 cc (range, 13.98-196.4cc). Acute toxicity rates were as follows: 5 acute G2 genitourinary tract pain events, and two cases of urethral stenosis requiring catheterization fully resolved within the first follow-up. For gastrointestinal toxicity, only 4 cases of G2 events (rectal tenesmus or proctitis) were observed. All the G≥2 events occurred after an average time of 30 days from the end of RT. With a median follow-up of 12 months (range, 3-20 months), for late events, we have recorded 3 late G2 GU events (urinary tract pain) and one G3 GU event for a patient who received a TURP 8 months after radiotherapy. For late GI events, we have recorded 3 G≥2 GI proctitis, including one patient treated with argon laser for radiation-induced proctitis. All patients are alive and in disease control except for one M1-low volume patient who developed distant progression two months after RT. Preliminary QoL assessment revealed a transient decline in fatigue, fully recovered after first follow-up.

Conclusions: Our preliminary report on the first 100 patients who received 1.5T MR-guided daily-adaptive SBRT for prostate cancer reports excellent results in terms of acute toxicity, and minimal impact on QoL. 

 


Francesco CUCCIA, Rosario MAZZOLA (Verona, Italy), Vanessa FIGLIA, Niccolò GIAJ-LEVRA, Luca NICOSIA, Francesco RICCHETTI, Michele RIGO, Edoardo PASTORELLO, Giorgio ATTINÀ, Claudio VITALE, Ruggero RUGGIERI, Filippo ALONGI
14:10 - 14:20 #29707 - OP44 1.5T MR-guided daily-adapted stereotactic body radiotherapy for prostate re-irradiation: a preliminary report of toxicity and clinical outcomes.
OP44 1.5T MR-guided daily-adapted stereotactic body radiotherapy for prostate re-irradiation: a preliminary report of toxicity and clinical outcomes.

Background

Prostate re-irradiation is an attractive treatment option in the case of local relapse after previous radiotherapy, either in the definitive or in the post-operative setting. In this scenario, the introduction of MR-linacs may represent a helpful tool to improve the accuracy and precision of the treatment.

Methods

This study reports the preliminary data of a cohort of 22 patients treated with 1.5T MR-Linacs for prostate or prostate bed re-irradiation. Toxicity was prospectively assessed and collected according to CTCAE v5.0. Survival endpoints were measured using Kaplan-Meier method.
Results

From October 2019 to October 2021, 22 patients received 1.5T MR-guided stereotactic body radiotherapy for prostate or prostate-bed re-irradiation. In 12 cases SBRT was delivered to the prostate, in 10 to the prostate bed. The median time to re-RT was 72 months (range, 12-1460). SBRT was delivered concurrently with ADT in 4 cases. Acute toxicity was: for GU G1 in 11/22 and G2 in 4/22; for GI G1 in 7/22, G2 in 4/22. With a median follow-up of 8 months (3-21), late G1 and G2 GU events were respectively 11/22 and 4/22. Regarding GI toxicity, G1 were 6/22, while G2 3/22. No acute/late G≥3 GI/GU events occurred. All patients are alive. The median PSA-nadir was 0.49 ng/ml (0.08-5.26 ng/ml), for 1-year BRFS and DPFS rates of 85.9%. Twenty patients remained free from ADT with 1-year ADT-free survival rates of 91.3%.

Conclusions

Our experience supports the use of MR-linacs for prostate or prostate bed re-irradiation as a feasible and safe treatment option with minimal toxicity and encouraging results in terms of clinical outcomes.

 


Francesco CUCCIA, Michele RIGO, Rosario MAZZOLA (Verona, Italy), Vanessa FIGLIA, Niccolò GIAJ-LEVRA, Luca NICOSIA, Francesco RICCHETTI, Giorgio ATTINÀ, Edoardo PASTORELLO, Claudio VITALE, Ruggero RUGGIERI, Filippo ALONGI
14:20 - 14:30 #29792 - OP45 Intrafraction prostate motion management in dose-escalated linac-based SBRT.
OP45 Intrafraction prostate motion management in dose-escalated linac-based SBRT.

Purpose/Objective

This study reports the pioneering clinical experience using an electromagnetic (EM) tracking device for intrafraction prostate motion management during dose-escalated linac-based SBRT.

 

Material/Methods

Thirteen patients with organ-confined prostate cancer underwent dose-escalated SBRT using FFF–VMAT technique. A Foley catheter with a transmitter in a dedicated lumen was used for intrafractional tracking. Setup accuracy was achieved by CBCT matching. Treatment was interrupted when the signals exceeded a 2 mm threshold in any of the three spatial directions and, unless the offset was transient, target position was re-defined by repeating CBCT. Moreover, adjusting setup and delivery duration, the displacements that would have occurred without any organ motion management were simulated.

Results

Intrafractional tracking was successfully carried out in all the treatment sessions. In 31 out of 56 monitored fractions (55%), no intervention was required to correct the target position as a result of an excessive displacement. In 25 (45%) a correction was mandated, but only in 10 (18%) the beam delivery was interrupted. Overall mean treatment time was 10.2 minutes [5.5–22.7] with on average 3.5 minutes [2.5–7.3] for the gated beam delivery. The mean value of the target average deviation during the whole session was -0.18 mm, -0.01 mm, and -0.26 mm in lateral, longitudinal, and vertical direction, respectively. The prostate was found inside the 2 mm threshold in 96% of the treatment time, in 94% of the time during the setup, and in 98% during the delivery (beam on + interruptions). Without any intrafraction motion management, the overall mean treatment time and the mean delivery time would be 6.7 minutes [7.7–6.6] and 3.2 minutes [2.5–4.2], respectively. The prostate would have been found outside the tolerance in 9% of the session total time, in 4% of the time during the setup, and in 16% during the beam-on phase. The differences in the percentage of time spent by the prostate outside the threshold in the three spatial directions between the analysis without and with the organ motion management are shown in Figure 1.

 

Conclusion

Our findings show that EM tracking is a reliable technique for real-time non-ionizing prostate monitoring during dose-escalated SBRT by interrupting the beam delivery when the prostate was in an unsafe position. Without any intrafraction motion management, both the setup and the delivery would have been shorter, but significant displacements would have occurred leading to potential target missing and overdose to organs at risk.


Denis PANIZZA (Monza, Italy), Raffaella LUCCHINI, Valeria FACCENDA, Martina Camilla DANIOTTI, Paolo CARICATO, Valerio PISONI, Sara TRIVELLATO, Stefano ARCANGELI, Elena DE PONTI
14:30 - 14:40 #29879 - OP46 Extreme Stereotactic body Radiotherapy for primary prostate cancer : long term outcomes.
OP46 Extreme Stereotactic body Radiotherapy for primary prostate cancer : long term outcomes.

Objectives: The Effectiveness of extreme hypofractionated stereotactic radiotherapy (SBRT) for localized prostate cancer is tested.

Methods and Materials: between July 2007 and June 2016 221 consecutive patients (pts) with a mean age of 74 years (range 52 – 86), mean prostate volume of 51.58 cm^3 (range 27.03 -131.18) and clinically localized prostate cancer were treated with extreme stereotactic body radiotherapy . Pre-treatment PSAs ranged from 2.39 to 51.3 ng/ml (mean 8.53 ng/ml). Total does of 3800 cGy in four fraction of 950 cGy were administered using Cyberknife SBRT. According to D'amico risk classification, the majority of patients 116 (53%) were low risk , 71 pts (32%) were intermediate risk and 34 pts (15%) were high risk. Following the new grading System and the terminology "Grade Groups 1-5" patients were classified: Group 1 (GS 3+3) 116 pts (53%) , Group 2 (GS 3+4) 41 pts (18%), Group 3 (GS 4+3) 30 pts (13%), Group 4 (GS 4+4) 28 pts (12%) and Group 5 (GS 9-10) 6 pts (3%). Real-time intrafractional motion tracking was used. 42% of patients had moderate to severe lower urinary tract symptoms prior to treatment (baseline AUA > 8). Genitourinary (GU) and gastrointestinal (GI) toxicity grades were assigned according to RTOG scale.

Results: Acute urinary symptoms (frequency, dysuria, urgency, hesitancy and nocturia) were common with 47 % of patients experiencing grade I-II RTOG acute urinary toxicity. No patient experienced RTOG grade III acute urinary toxicity while 9 patients (4%) experienced RTOG grade II late urinary toxicity. No RTOG grade III acute and late rectal toxicities were observed.

With a mean follow up of 87 months (range 12 – 174 months) the seven years actuarial PSA relapse free survival rate is 89.1% (CI: 86.8% - 91.4%) with 91.8% for low risk, 89.5% for intermediate risk and 76.8% for high risk respectively according to D'Amico risk classification . The Kaplan-Meyer seven years actuarial PSA relapse free survival rates according to the new " Grade Group System” observed are: 91.8% for Group 1, 90.1% for Group 2, 88.6% for Group 3, 80.3% for Group 4 and 53.3% for Group 5 respectively.

Conclusions: Cyberknife SBRT produces excellent biochemical control rates with mild toxicity and minimal impact on quality of life. Mean PSA levels compare favourably with other radiation modalities and strongly suggest durability of our results.


Giancarlo BELTRAMO (Milan, Italy), Isa BOSSI ZANETTI, Cristina LOCATELLI, Giovanni LONGO, Achille BERGANTIN, Francesco MORETTI, Sergio PAPA, Laura FARISELLI
14:40 - 14:50 #29964 - OP47 Comparison of two protocols of robotic stereotactic body radiotherapy used in prostate cancer patients in a mono-institutional experience.
OP47 Comparison of two protocols of robotic stereotactic body radiotherapy used in prostate cancer patients in a mono-institutional experience.

Objective: We analyzed initial outcomes and toxicities of the 2 schedules of stereotactic body radiotherapy (SBRT) in use in our department for prostate cancer (PCa) patients. 

Materials and methods: Between 10/2017-05/2021, 102 PCa patients were treated using robotic SBRT with two different schedules. Group I included 73 patients treated at 36.25 Gy/ 5 fractions at the 79% median isodose, group II 29 patients treated at 38 Gy/ 4 fractions at the 63% median isodose (urethral sparing HDR-like technique). Median age was 74.5 vs 75.8 years, median initial PSA 7.20 vs 7.65 ng/ml. Gleason score was 3+3 in 11% vs 17.2%, 3+4 in 58.9% vs 51.7%, 4+3 in 17.8% vs 20.7% and not accorded (due to previous androgen deprivation) in 1.4% vs 3.5% of patients. Androgen deprivation therapy (ADT) was prescribed in 45% vs 31% of patients, with a median duration of 7 vs 6 months. Fiducial markers were implanted into the prostate in all patients. In 52% of patients steroid therapy and/or alpha-lytics were prescribed to prevent side effects. Toxicity was scored in accordance with CTCAE v 5.0. Biochemical failure was assessed using the nadir + 2 definition. 

Results: Median follow-up was 23.4 (0-47.2) months in group I vs 12 (2.78-36.07) months in group II. For acute and late toxicities see Table 1. No acute grade(G) 3 toxicities were registered. One (1.4%) late G3 genito-urinary toxicity (transurethral incision) occurred in a patient treated with 36.25 Gy. Median post-SBRT PSA level was 0.342 (0.001-231.00) ng/ml in group I and 0.603 (0.05-10.210) ng/ml in group II. At the last follow up 3 pts had died due to a non-cancer related cause, 4 pts had a biochemical failure with PSMA/Choline-PET positive progression: 3 treated at 36.25 Gy and 1 treated at 38 Gy. Two-year biochemical relapse-free survival(bRFS) was 94.8% for the patients of group I and 88.9% for the patients of group II, respectively (p= 0.6). Overall survival (OS) was 85.7%vs 98.4% at 2 years(p=0.35). Disease-free survival(DFS) was 94.8% and 88.9%, respectively (p=0.6). No correlation was found between target volume and toxicity. 

Conclusion: The urethral sparing technique allowed dose escalation (from 2 Gy equivalent dose-EQD2-91 Gy to EQD2 ≥ 120 Gy with α/β 1.5) without increasing G3 toxicity and with non-inferior bRFS despite less ADT prescription. Longer follow-up is needed to confirm these results.


Nadia DI MUZIO (Milano, Italy), Chiara BROMBIN, Chiara DEANTONI, Sara BROGGI, Cesare COZZARINI, Italo DELL'OCA, Lucia PERNA, Roberta TUMMINERI, Flavia ZERBETTO, Stefano VILLA, Paola MANGILI, Najla SLIM, Claudio FIORINO, Antonella DEL VECCHIO, Andrei FODOR
14:50 - 15:00 #29608 - OP48 Robotic SBRT in treatment of intermediate unfavorable to very high-risk prostate cancer: a single centre experience.
OP48 Robotic SBRT in treatment of intermediate unfavorable to very high-risk prostate cancer: a single centre experience.

Introduction. SBRT has been well accepted in  the treatment of low-risk and intermediate favorable risk prostate cancer(PC) while for intermediate-unfavorable, high- and very high-risk prostate cancer prophylactic pelvic lymph node irradiation with a boost to prostate and seminal vesicles is often used. The aim of the report is to evaluate the utility of robotic SBRT in the treatment of intermediate unfavorable (IUF), high (HR) and very high-risk (VHR) prostate cancer.

Materials and methods. From June 2016 to December 2020 62 patients from reviewed risk groups were treated: 43 patients with IUF PC, 10 with HR PC and 9 patients with VHR PC. Pretreatment PSA ranged from 2.03 ng/ml to 60 ng/ml (median 9.27 ng/ml). Follow-up ranged from 6 to 61 months (median 28). One patient was lost from follow-up. 15 patients (25%) received androgen deprivation therapy in combination with SBRT with length ranging from 3 to 60 months (median 24). 12 patients (19%) underwent PSMA PET-CT for exclusion of regional and distant metastasis and precise identification of dominant lesions within CTV. The target volume was prostate with 1-2cm proximal seminal vesicles according to MRI topometry with an expansion of 4-5mm in all directions except 2-3mm posteriorly. 35-36.25Gy was prescribed to target volume. Additionally, GTV was delineated according to multiparametric MRI (mpMRI) or PSMA PET-CT if available, to cover lesions and suspicious areas with a dose ≥40Gy. 39 (63%) patients received treatment in five consecutive days remaining 23 (27%) received treatment in 6-12 days.

Results. 5 relapses were observed during follow-up: three in the IUF group, one in the HR group and one in the VHR group. 3 of 5 relapses were investigated with PSMA PET-CT/MRI revealing all three relapses in regional lymph nodes. No local relapse was observed during follow-up. Kaplan-Meier analysis was performed to evaluate biochemical free survival. All five biochemical relapses were observed in 2-3 years during follow-up, accordingly 3 and 5-year biochemical control was 88.9% for all cohort, 89.6% for IUF subgroup, 87.5% for HR and VHR subgroups, respectively.

Conclusion. Initial data of this cohort shows acceptable biochemical control rates non-inferior to previously published data and non-inferior to conventional radiotherapy where prophylactic lymph node irradiation is usually applied in reviewed patient groups. However, a small number of patients, particularly in HR and VHR groups, raise statistical bias. Further follow-up and multi-institutional cohorts are needed for more precise data evaluation.


Maris MEZECKIS (Sigulda, Latvia), Vladislav BURYK, Sandra LEDINA, Egils VJATERS, Liva Marta SPIGULE
SILVER ROOM

Wednesday 22 June

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B36
14:00 - 15:00

ORAL PRESENTATION
Gliomas & Other Malignant Brain Tumors

Moderators: Paola ANSELMO (MD) (TERNI, Italy), Selcuk PEKER (Neurosurgeon) (Istanbul, Turkey), Antonio SILVANI (Chief Unit of Neuro-oncology) (Milano, Italy)
14:00 - 14:10 #29972 - OP55 Gamma knife stereotactic radiosurgery for intracranial ependymomas. The Sheffield experience.
OP55 Gamma knife stereotactic radiosurgery for intracranial ependymomas. The Sheffield experience.

Background. 

The standard treatment for primary intracranial ependymomas is maximal safe resection followed by fractionated radiation therapy. The extent of the resection has been shown to influence survival and tumour control. Stereotactic Radiosurgery by definition is a highly conformal, high dose radiation to the target with a rapid decline of the dose peripherally and is used to treat recurrent, residual or initially unresectable ependymomas.

Methods.

A retrospective review of 94 tumours in 51 consecutive patients with ependymoma and treated with Gamma Knife Stereotactic Radiosurgery (GKSRS) at the National Centre for Stereotactic Radiosurgery in Sheffield from 1993 to 2021, was undertaken. GKSRS planning and delivery was performed using Leksell Gamma Knife Models S, C, 4C and Perfexion. The diagnosis and grading of ependymomas were carried out according to the WHO criteria and a multidisciplinary team validated the indication for GKSRS treatment. The number of surgeries, location, time between surgery and GKSRS, prescribed dose, target volume, tumour control rate, overall (OS) and progression free survival were recorded.

Results.

Of the 51 patients treated, 38 patients underwent GKSRS for a single lesion, 7 patients had single session GKSRS for multiple lesions and 6 patients had multiple sessions for recurrent lesions. All patients received 12 - 25Gy (mean 18.23Gy) for tumour volumes between 0.053 - 48.30cm(mean 1.872cm3). In addition to the 88 cases of WHO grade II and III ependymomas, 6 subependymomas (WHO I) were also included in the analysis. OS in WHO grade III tumours (14 patients) was 71.42%, at 1 year (range 181–5750, mean 988.79 days). WHO grade II tumours (25 patients) fared better with verified survivorship and tumour control of 96% at 1 year (range 85-10408, mean 3953.38 days). WHO grade I tumours OS at 1 year was 100% (range 1969–6918, mean 3774 days). Post treatment adverse events were reported in 5 patients (9.8%). 80% of these were post radiation effects which occurred at 6 months post GKSRS and resolved with a short course of steroids.

 Conclusions.

 GKSRS is an excellent primary and adjuvant treatment for ependymomas including recurrent tumours with a good rate of local control. Patients with WHO grade I and II ependymomas have better local and regional control of the disease compared to WHO grade III tumours. GKSRS is currently underutilised as an adjuvant treatment in the management of residual or recurrent ependymoma in the U.K., despite being clinically commissioned by the National Health Service since 2016.


Cormac GAVIN, Ramez IBRAHIM, Debapriya BHATTACHARYYA, Geza MEZEI, John YIANNI, Paul VAUGHAN, Katharine HUNT, Matthias RADATZ, Julian CAHILL (Sheffield, United Kingdom)
14:10 - 14:20 #29924 - OP56 Thirteen-Year Single Center Experience Of Pilocytic Astrocytomas Irradiation.
OP56 Thirteen-Year Single Center Experience Of Pilocytic Astrocytomas Irradiation.

Purpose:

Pilocytic astrocytomas (PA) are the most common gliomas (WHO I) in children. According to lots of trials in different countries Stereotactic Radiation Therapy (SRT) and  Radiosurgery (SRS) provide tumor growth control if surgical removal is not possible or in case of recurrence. In this paper, we have summarized our own experience with radiation treatment of PA, which composes the largest series available.

 

Materials and  Methods:

The study included 410 consecutive patients who received radiation treatment at the N. N. Burdenko National Medical Research Center of Neurosurgery between April 2005 and January 2018. There were 225 female and 185 male patients. The study group consisted of 110 adults and 300 children (including those under the age of 18). The median age was 10.8 years (Q1-Q3: 5.4-19.3 years). Histopathological verification was performed in 307 cases (74.8%). In 103 patients (25.2%) the diagnosis was established according to clinical and neuroimaging data (MRI, CT-perfusion and PET). The indication for the radiation treatment was a residual tumor after surgery (204 pts, 49.7%) or recurrence after previous removal or chemotherapy (206 pts, 50.3%). Standard fractionation was used most frequently (292 cases, 71.2%). Hypofractionation and radiosurgery were used in 61 (14.9%) and 57 (13.9%) cases, respectively.

 

Results:

The median follow-up period was 68 months (range - 3-300 months) from the diagnosis establishment. 391 patients (95.4%) were available for the follow-up. The median follow-up period after irradiation was 45 months (range - 3-162 months). The 5-year PFS was 97,5% and 5-year OS was 99%. Undesirable events occurred in 77 (19.7%) patients: pseudoprogression – in 67 patients (89.5%), tumor progression – in 8 patient (4 local and 4 distant repalses), brain stem necrosis and intratumoral hemorrhage – in 1 case each.  In cases where radiotherapy was delayed until disease progression, the tumor volume was larger and the patients' state was worse than when irradiation was performed immediately if there was a residual after surgery.

Conclusion:

Stereotactic irradiation is the effective method of treatment for PA in patients with residual tumors, patients with PA relapse and patients with progressive disease. The treatment should be indicated as early as possible after partial resection. The most common adverse event after irradiation is pseudoprogression.


Yury TRUNIN, Andrey GOLANOV (Moscow, Russia), Alexander KONOVALOV, Igor PRONIN, Mikhail GALKIN, Marina RIZHOVA, Lyudmila SHISHKINA, Alexander TURKIN, Natalya SEROVA, Natalya ANTIPINA, Ruslan ZAGIROV, Elena IGOSHINA
14:20 - 14:30 #30196 - OP57 SBRT for recurrent skull base malignancies.
OP57 SBRT for recurrent skull base malignancies.

Purpose: Using SBRT for reirradiation of skull base malignancies is one of the most challenging tasks due to the strict requirements on patient immobilization and the high complexity of treatment planning. We present our experience and outcomes of the SBRT treatment for skull base recurrences.

Methods: Forty-three recurrent skull base patients were treated with SBRT between December 2014 and April 2020. All patients were immobilized using a three-point customized cushion/mask/bite-block system. High quality volumetric modulated arc therapy conformal plans were generated in Pinnacle or RayStation treatment planning system. Clinical goals for critical structures were customized for each patient based on prescription dose, distances from nearby organ-at-risk (OAR) structures to target, OAR tolerance, as well as the patient specific prior radiation treatment history. Patients were treated on Varian Truebeam STx with Exactrac and CBCT imaging guidance. Dosimetry was summarized and the outcome included overall survival, local control and toxicities.

Results: Forty-two percent of cases (n=18) were of squamous cell histology. Median follow up was 18.2 months (range 7.8-60.6 months). Twenty-seven percent (n=12) of patients received induction systemic therapy, 58% (n=25) received concurrent and 23% (n=10) received adjuvant therapy. The median SBRT dose was 45Gy (40-45Gy in 5 fractions (n=40) or 36Gy in 4 fractions (n=3)). Median primary target volume was 17.7 cm3 (range 1.5-58.5 cm3). The median target coverage was 95% (range 79%-100%) and target mean dose was 105% (range 101.9%-114.1%) of prescription dose. Brainstem achieved maximum dose of 11Gy or ALARA for 60% (n=26) of the patients, while 4 patients had brainstem abutting target and received brainstem dose V21Gy < 0.5 cm3. Other OARs (optic pathway, carotid, cochlea, temporal lobe) also achieved clinical goals. The use of 2mm PTV margin seemed adequate for skull base SBRT based on our previous report of intra-fractional positional accuracy using Exactrac/CBCT imaging system. The two-year survival and local control were 71.8% and 75.4%, respectively. There were no Grade 3+ acute toxicities. Two patients presented Grade 3+ late toxicities, including one Grade 3 toxicity associated with temporal lobe necrosis, and one Grade 4 osteoradionecrosis.

Conclusion: with the combination of improved immobilization, high quality conformal treatment planning and advanced image guidance, our optimized SBRT workflow for skull base reirradiation showed excellent outcomes with acceptable toxicities.


He WANG (Houston, USA), Kevin DIAO, Christopher GOODMAN, Xin WANG, Jack PHAN
14:30 - 14:40 #29454 - OP58 Phase I trial of sulfasalazine combined with stereotactic radiosurgery for recurrent glioblastoma: Study protocol for NCT04205357.
OP58 Phase I trial of sulfasalazine combined with stereotactic radiosurgery for recurrent glioblastoma: Study protocol for NCT04205357.

Background

Sulfasalazine (SAS), a well-known anti-inflammatory drug has shown tumor selective radiosensitizing properties in preclinical studies. The antioxidant glutathione (GSH) produced at high levels in glioma cells normally protects against radiation injury by scavenging the reactive oxygen species produced during radiation therapy (RT). SAS blocks the uptake of cysteine through the xCT-channel, a rate-limiting step for glioma cell GSH production. We have previously shown that tumor growth slowed down and overall survival (OS) was prolonged when SAS was combined with gamma knife surgery (GKS) in a glioma animal model compared to either treatment alone. Our hypothesis is that SAS potentiates the efficacy of SRS in glioblastoma (GBM) patients with a low risk of side effects. This open-label, single-arm trial aims to evaluate the maximum tolerated dose (MTD) and the preliminary efficacy of SAS combined with GKS in first or second relapse of GBM following standard of care.

Methods

The trial is designed as a standard 3 + 3 phase 1-dose escalation study with 3-6 patients in each dose-cohort. The trial will enroll 12-24 patients for treatment with oral SAS (1.5, 3.0, 4.5 or 6.0 g/day) 3 days prior to single session GKS with 12 Gy prescription dose to the tumor margin. The dose will be escalated depending on the absence/presence of severe toxicity in the previous cohort of treated patients. If more than 1 patient in a cohort of 3 or 6 patients (≥33%) experiencing grade 3 or higher toxicity levels, the study will be terminated and the dose will be defined as MDT. Toxicity is graded using the Common Toxicity Criteria for Adverse Events (CTCAE) v5.0 recorded the first 30 days. Primary end-point is to establish the recommended dose for efficacy testing in phase II/III trials. Secondary end-points are assessments of 1) intratumoral GSH production evaluated with GSH-spectroscopy before and after SAS treatment, 2) late adverse radiation effects utilizing 11C-MET-MRI-PET 3) changes in KPS/quality of life (FACT-Br), 4) need for steroidal treatment, 5) progression free survival (PFS) utilizing Response Assessment in Neuro-Oncology criteria and 6) OS. PFS and OS will be compared with historical controls treated between 2018-2022.

 

Discussion: Due to the dismal prognosis for GBM patients, novel treatment modalities are urgently needed. The trial will establish the recommended dose for SAS repurposed as a radiosensitizer for a future phase 2/3 trial. Our proposed treatment may ultimately lead to increased effect of radiation therapy for these highly radioresistant tumors.


Bente Sandvei SKEIE (Bergen, Norway), Per Øyvind ENGER, Jan Ingemann HEGGDAL, Maziar BEHBAHANI, Goplen DOROTA, Shahin SAROWAR
14:40 - 14:50 #30106 - OP59 - WITHDRAWN - Call for expert consensus on guidelines for the treatment of recurrent glioblastoma.
OP59 - WITHDRAWN - Call for expert consensus on guidelines for the treatment of recurrent glioblastoma.

Background and Objective: Possible management strategies for recurrent glioblastomas of the brain include surgery, chemotherapy, radiotherapy, and combined treatments.  Over several treatment approaches, reoperation and reirradiation have shown promising results.  Indications for surgical resection rather than stereotactic radiosurgery are still debated.  We hereby conduct an expert consensus to provide guidelines for the treatment of recurrent glioblastomas.

Methods: To aggregate expert opinions in an anonymous fashion we adopt the conventional e(lectronic)-Delphi method.  This takes place over a series of rounds where communication occurs through electronic exchange.  First, a questionnaire is formulated upon a set of assumptions and solutions or options.  We search PubMed, MEDLINE, and EMBASE from 2000 to 2022 for studies reporting on surgical resection and/or stereotactic radiosurgery for recurrent glioblastomas of the brain.  Two independent reviewers select studies and abstract data.  We list the variables considered to define the treatment modality and design the questionnaire.  Second, an expert panel is identified and invited to provide opinions.  Members are recruited based on their grounded expertise in both neuroradiosurgical and neurosurgical fields.  Representative members of intercontinental and international stereotactic radiosurgical and neurosurgical societies join efforts to elaborate a pragmatic worldwide set of guidelines.  Based on predetermined criteria, responses are analyzed and ranked.  A second questionnaire is developed employing the results and feedback from the first round.  Responses are again collected and assessed for consensus.  The process terminates when an acceptable degree of consensus is reached. 

Results: Three rounds are usually sufficient to achieve consensus with the largest adjustments usually occurring between the first and second rounds.  Consensus is generally reached at the end of the third round for the majority of the items originally posed.  Results bring out discrepancies among intercontinental healthcare backgrounds, featuring thorough reasons for treatment choices.  Guidelines are advanced in the shape of the items gaining consensus.  

Conclusions: The proposed expert consensus document highlights adherence and divergencies among experts on the treatment of recurrent glioblastoma.  Taking into account clear items of agreement between members, we postulate a pragmatic worldwide set of guidelines.   Across social and cultural heterogeneities of healthcare environments, we aim to provide universal determinants to best select patients for surgery or stereotactic radiosurgery, through a decision-making process embodying a multidisciplinary neuro-oncology team.  Larger prospective studies are still warranted to provide a higher level of evidence.


Lucio DE MARIA (Brescia, Italy), Fabio GHITTI, Giorgio SPATOLA, Karol MIGLIORATI, Mario BIGNARDI, Stefano Maria MAGRINI, Oscar VIVALDI, Alberto FRANZIN, Alessandro LA CAMERA, Marco Maria FONTANELLA
14:50 - 15:00 #29776 - OP60 Preoperative Radiation in Glioblastoma undirectly regulates p53 expression improving survival in a preclinical model.
OP60 Preoperative Radiation in Glioblastoma undirectly regulates p53 expression improving survival in a preclinical model.

Glioblastoma (GBM) is the most common and devastating primary brain tumor in adults. The current standard of care includes maximal safe resection followed by concurrent radiation and temozolomide-based chemotherapy.

Near uniform recurrence forces us to pursue alternative approaches to improve patient outcomes. Neoadjuvant irradiation is used in other cancer types to reduce the tumor burden before resection, however, its role in the preoperative setting has not been evaluated in the treatment of primary brain tumors.

In this preclinical study, we evaluated if preoperative irradiation before surgical resection improves survival.  39 immunocompromised adult athymic nude female rats were orthotopically engrafted with a patient-derived glioma cell line and randomized to receive different treatments: not treated (NT); tumor resection only (RE),  tumor resection followed by radiotherapy (RERT), and radiotherapy prior to tumor resection (RTRE). The rats received 30 Gy hyperfractionated stereotactic irradiation in 5 fractions of 6 Gy. RNAseq was performed from the samples of at least 2 rats per group. Kaplan-Meier analysis showed a significant survival benefit of the  RTRE group of 3.43 weeks over the RERT group (P-value <0.0001). RNA expression analysis showed 2,451 differentially expressed genes. Among the genes of interest, we found upregulation of miR186, which is a well-known antioncogenic micro-RNA, and downregulation of metallothionein 1E (MT1E), a gene that has been related to a decrease in the activity of the tumor suppressor gene p53. Moreover, the small nucleolar RNA, SNORD60, appears downregulated. The reduction on SNORD60 drives a reduction in cholesterol trafficking which could be associated with less angiogenesis.

This study demonstrates in principle the benefits of neoadjuvant therapy in GBM, and highlights the importance of epigenetic regulation in the treatment outcomes, suggesting these non-coding RNAs as potential new druggable targets. Further clinical studies are required and underway to determine the impact of these novel radiation strategies in patients.


Beatriz Irene FERNANDEZ-GIL (Jacksonville, USA), Andrea OTAMENDI-LOPEZ, Carla VAZQUEZ-RAMOS, Paula SCHIAPPARELLI, Hugo GUERRERO-CAZARES, Steven HERCHKO, Henry RUIZ-GARCIA, Mark JENTOFT, Alfredo QUINONES-HINOJOSA, Daniel TRIFILETTI, Rachel SARABIA-ESTRADA
RED 2 ROOM

Wednesday 22 June

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C36
14:00 - 15:00

ORAL PRESENTATION
Vascular

Moderators: Francesco INSERRA (Consultant Neurosurgeon) (Catania, Italy), Vincent LUBRANO (Toulouse, France)
14:00 - 14:10 #28866 - OP49 Comparison of single-session, neo-adjuvant, and adjuvant embolization GKRS for AVM.
OP49 Comparison of single-session, neo-adjuvant, and adjuvant embolization GKRS for AVM.

Purpose

Gamma knife radiosurgery (GKRS) has been established as an effective treatment option for intracranial arteriovenous malformations (AVMs), especially with small or medium nidi located in eloquent or deep regions. GKRS and embolization are increasingly being used in combination for larger, complicated AVMs and especially for ruptured AVMs. The aim of the present study was to compare outcomes of single-session, neo-adjuvant, and adjuvant embolization GKRS for AVM.

 

Methods

A database of 453 patients with AVMs, who underwent GKRS between January 2007 and December 2017 in a single institution, was retrospectively reviewed.  This study excluded patients who had less than 2 years of follow-up, were less than 10 years, or who had been previously treated by repeat or volume-staged GKRS, resection or embolization before the study period. Obliteration rate and incidence of latent period hemorrhage and delayed cyst formation were assessed during the follow-up.

 

Results

In total, 228 patients were enrolled in this study. The neo-embolized, adjuvant embolized, and non-embolized group consisted of 29 (12.7%), 19 (8.3%), and 180 (78.9%) patients, respectively. Statistically significant differences were detected among the three groups with history of previous hemorrhage (75.9% vs 89.5% vs 43.9%) and presence of aneurysm (48.3% vs 52.6% vs 15.0%). Regarding obliateration, the difference was not significant among the three groups, but in the Kaplan-Meier curve, there was a point (38 months) where the curve crossed over. The cumulative incidences of latent period hemorrhage and delayed cyst formation were not significantly different among the groups.The Cox regression model for factors regarding time to obliteration demonstrated neo-embolization showed a significant inverse correlation after 38 months from GKRS. In univariate analyses, those with a higher nidus volume VRAS, Pollock-Flickinger score, and SM grade before GKRS showed a significant inverse correlation for obliteration. 

 

Conclusions

Although the current study demonstrated similar results regarding obliteration, latent-period hemorrhage, and cyst formation in patients who underwent GKRS with and without embolization, except for the long-term results in the neo-embolization group, the embolized group included more AVMs with history of previous rupture and intranidal/flow-related aneurysms, which have a lower chance of obliteration and a high probability of repeat hemorrhage. GKRS with either neo- and adjuvant embolization appears to be a beneficial approach for the treatment of AVMs with more complex angioarchitecture that are at risk for hemorrhage during the latency period. Further studies involving a larger number of cases and continuous follow-up are necessary to confirm our conclusions.

 


Myung Ji KIM (Seoul, Korea), Jung HYUN HO, Jin Woo CHANG, Won Seok CHANG
14:10 - 14:20 #30154 - OP50 Long term risk of radionecrosis after gamma knife radiosurgery for cerebral AVMs: could previous endovascular treatments play a decisive role? A preliminary data report.
OP50 Long term risk of radionecrosis after gamma knife radiosurgery for cerebral AVMs: could previous endovascular treatments play a decisive role? A preliminary data report.

Background: Radionecrosis is a phenomenon that typically occurs many years after gamma-knife radiosurgery (GKRS) for brain arteriovenous malformations (bAVM). Late post-radiosurgery complications (LPRC) are characterized by massive perilesional edema, cyst formation and encapsulated hematoma and are distinct from radiation-induced changes (RICs) noted in the first 1 to 2 years after GKRS.

Objective: To determine the incidence of late occurrence of radionecrosis after gamma knife radiosurgery for bAVMs previously treated with several endovascular treatments. A secondary goal is evaluating the role of radiation-induced changes as predictor of late post-radiosurgery complications risk.

Methods: From 2008 to 2016, 209 bAVMs were treated with GKRS at Niguarda Hospital and 36 out of 209 bAVMs underwent at least two endovascular treatments in addition to Radiosurgery. The median MRI follow-up after radiosurgical treatment was 54 months (range 36-180).

Results: Radionecrosis/permanent RICs was observed in 13 Patients (13,8%) at a median of 93,4 months after GKRS (range, 51-125). 5 out of 13 Patients (2,4%) developed cystic formations, massive edema and encapsulated hematoma. All patients were symptomatic at the time of LPRC detection. Patients undergone at least two endovascular procedures prior GKRS (OD=6,718;p=0,001) and having RICs of high grade (OD= 5,289; p= 0,0001) were more likely to develop LPRC. Statistically significant differences were found in the pluri-endovascular treatments group in terms of SM grade distribution (p=0,031), median target volume (p=0,0001), median 12-Gy volume (p=0,004), lobar location (p=0,018) and latent period hemorrhage (p=0,037).

Conclusions: LPRC are correlated with previous several endovascular treatments and early RICs. These results highlight the need of a defined multidisciplinary strategy for the treatment of bAVMs, especially for large and incidentally found asymptomatic ones.


Giada VALENTE, Mariangela PIANO (Milan, Italy), Guglielmo PERO, Amedeo CERVO, Antonio MACERA, Marco PICANO, Andrea ROMI, Marco CENZATO, Edoardo BOCCARDI, Filippo LEOCATA, Alessandro LA CAMERA
14:20 - 14:30 #29450 - OP51 Preoperative flow analysis of arteriovenous malformations and obliteration response after stereotactic radiosurgery.
OP51 Preoperative flow analysis of arteriovenous malformations and obliteration response after stereotactic radiosurgery.

Objectives:
 
Morphological and angioarchitectural features of cerebral arteriovenous malformations have been widely described and associated with outcomes; however, few studies have addressed the quantitative analysis of AVM flow.  The authors examined AVM flow and transit time on angiograms using a direct visual analysis and a computer-based method and correlated with obliteration response after Gamma Knife stereotactic radiosurgery.
 
 
Methods:
A retrospective analysis was conducted at a single institution using a prospective registry patients managed from January 2013 to December 2019: 71 patients were analyzed using a visual method and 38 using a computer-based method. After comparison and validation, obliteration response was correlated to flow analysis, demographic, angioarchitectural, and dosimetric data.
 
 
Results:
AVM volume was 1.84cc (range, 0.64-5.64), 32 (45.1%) of which were in critical functional locations, and the mean marginal dose was 18.8 Gy (16-22). Twenty-six (36%) were classified as high flow, 36 (52%) as moderate flow, and 9 (12%) as low flow AVMs. Complete obliteration was achieved in 44 (62%) patients at the time of the study; mean time to obliteration were 27 months for low flow, 34 months for moderate flow, and 47 months for high flow AVMs. Univariate and multivariate analysis of factors affecting obliteration included volume, age, Pollock-Flickinger score, and low flow. Adverse radiation effects were identified in 5 (7%) of patients, and 67 (94%) remained free of any functional deterioration during follow-up time.
 
Conclusions:
AVM flow analysis and categorization in terms of venous drainage and transit time are useful predictors of probability and time to obliteration. We think that a more quantitative understanding of flow can help to guide stereotactic radiosurgery treatment and set accurate outcome expectations.
 
 

Juan Diego ALZATE (New York, USA), Assaf BERGER, Kenneth BERNSTEIN, Joshua SILVERMAN, Reed MULLEN, Tanxia QU, Peter K NELSON, Maksim SHAPIRO, Douglas KONDZIOLKA
14:30 - 14:40 #30094 - OP52 Long-term outcome of Gamma Knife radiosurgery for symptomatic brainstem cavernous malformation.
OP52 Long-term outcome of Gamma Knife radiosurgery for symptomatic brainstem cavernous malformation.

Objective: To analyze the long-term outcome of Gamma Knife radiosurgery (GKS) for symptomatic brainstem cavernous malformation (s-BSCM).

Methods: Forty five patients (14 males, 31 females) were treated with GKS for s-BSCM from January 1998 to December 2011. All patients were followed up for more than 5 years and their clinical data were analyzed retrospectively. All patients had a history of symptomatic bleeding once or more before GKS. These hemorrhages caused neurological deficits including cranial nerve deficits, hemiparesis, hemisensory deficits, spasticity, or chorea. The mean target volume of s-BSCM was 1.82 cm3 and the median prescribed marginal dose of radiation was 13 Gy. The mean clinical and imaging follow-up period was 9.31 years (range, 5.1 – 19.4 years).

Results: The 45 patients had 69 hemorrhagic events before GKS. During follow-up period after GKS, 35 patients had no hemorrhagic event, six patients had one episode of symptomatic hemorrhage, and four patients had two episodes. The calculated annual hemorrhage rate was 40.06% at pre-GKS, 3.3% at 2 years after GKS, 1.48% at 5 years after GKS, and 4.64% at >5 years after GKS. In this study of 45 patients, symptomatic radiation-induced complications developed in only one patients (2.2%). No patients had died at the last follow-up.

Conclusions: GKS for s-BSCM is safe and effective alternative to surgical resection for reducing the rate of recurrent hemorrhage. Because the annual hemorrhage rate increases more than 5 years after GKS, clinicians should monitor patients closely to determine their subsequent treatment.  


Jin Wook KIM (Ras Al Khaimah, United Arab Emirates), Kawngwoo PARK, Hyun-Tai CHUNG, Sun Ha PAEK
14:40 - 14:50 #30139 - OP53 Pediatric intracranial arteriovenous malformations: results after radiosurgical treatment.
OP53 Pediatric intracranial arteriovenous malformations: results after radiosurgical treatment.

Intracranial arterovenous malformations (AVM) often cause hemorrhage in pediatric population. Treatment options include microsurgical resection, endovascular embolization, staged or single fraction radiosurgery (SRS), or a combination of them, with the goal of eliminating the risk of hemorrhage. In case of AVM located in eloquent or deep area, SRS can represent the only feasible approach. Nevertheless, different aspects of SRS for pediatric AVM are under debate, in particular for unruptured AVM. The goal of this analysis is to evaluate efficacy and safety of SRS for childhood

A retrospective chart review was performed to identify patients treated for AVM at our institution. Patients with age less than or equal to 18 years at the time of SRS, and at least 2 years of radiologic follow-up or AVM obliteration were selected for analysis. Statistical analyses were performed to determine obliteration rates and clinical outcome.

From 2011 to 2021 we identify 14 pediatric patients. Median age at the moment of SRS was 15,5 years (range 11-18 years) and the most common presentation were seizure and motor deficits in 21,4% of patients respectively. The median treated nidus volume and radiosurgical margin dose were 2 cc (range 0.2 – 5.4 cc) and 18 Gy (range 17-19 Gy), respectively. One patient was treated by means of volume staged radiosurgery. At a median follow-up of 31 months (range 18-74 months), the overall AVM obliteration rates was 57%. Post-SRS neurological events were not registered. Four patients (28.5%) with neurological deficits at diagnosis improved after SRS. Two patients (14%) had hemorrhage after 2 and 3 years from SRS. 

SRS was successful in majority of patients with minimal morbidity. SRS for AVM can be a safe and viable method in pediatric patients when surgery and/or embolization cannot be achieved.


Valentina PINZI (Milan, Italy), Marcello MARCHETTI, Francesco GHIELMETTI, Laura FARISELLI
14:50 - 15:00 #30054 - OP54 “Gamma-knife” radiosurgery in eyes with diffuse choroidal hemangioma (Sturge-Weber syndrome) as a rescue treatment.
OP54 “Gamma-knife” radiosurgery in eyes with diffuse choroidal hemangioma (Sturge-Weber syndrome) as a rescue treatment.

Purpose: to present the results of Gamma-knife radiosurgery (GKRS) of diffuse choroidal hemangioma (DCH) in patients with Sturge-Weber syndrome

Methods: Four patients (4 eyes) with DCH were managed with GKRS. There were 2 males and 2 females aged 6, 15, 16 and 32 y.o. All patients were presented with port-wine stains of the face. Visual acuity (VA) before treatment was poor in every case due to exudative total retinal detachment and varied from 0.002 to 0.006 (mean 0.005).  The choroidal thickness was from 5.1 mm to 7.3 mm (mean 5.8mm). The height of the retinal detachment was measured from 2.5 to 6.6 mm (mean 4.95mm). GKRS was proposed as the last opportunity to save the eye and provide any VA degree. The dosimetry plans included double PTVs of 18 Gy sparing critical structures – optic nerve and central retina. Optic nerve received 8.9-20Gy (mean 14.24Gy), central retina – 13-28.8Gy (mean 20.5Gy).

Results: Tumor activity control was achieved in all cases. The choroidal thickness reduced to 3.2-4.5mm (mean 3.8 mm) within 3 months, to 2.1-4.4mm within 6 months. Choroidal thickness decreased by 44% on average (34-50%).   Retinal detachment resolution was seen in every treated eye that provided the VA of 0.02 – 0.4 (mean 0.15). No tumor progression was detected and no additional treatment was required. All eyes under follow-up are stable from 3 to 40 months. Irradiation “tracks” corresponding to the planning are seen on the eye fundus examination and will be presented. No complications were detected within follow-up period.

Conclusion:

There is no effective conventional treatment of DCH in patients with Sturge-Weber syndrome. GKRS may be used as the single opportunity to save the eye and provide any kind of vision. Further investigation is needed.


Vera YAROVAYA (Moscow, Russia), Andrey GOLANOV, Andrey YAROVOY, Valery KOSTJUCHENKO, Roman LOGINOV, Arina LESTROVAYA
BLUE 2 ROOM
15:00

Wednesday 22 June

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A37
15:00 - 16:10

ORAL PRESENTATION
Body SRS/SBRT (2)

Moderators: Stefano ARCANGELI (Milan, Italy), Anna BRUYNZEEL (Amsterdam, The Netherlands)
15:00 - 15:10 #29394 - OP61 Induction chemotherapy and ablative 5-fraction stereotactic magnetic resonance-guided adaptive radiation therapy for patients with initially inoperable adenocarcinoma of the pancreas.
OP61 Induction chemotherapy and ablative 5-fraction stereotactic magnetic resonance-guided adaptive radiation therapy for patients with initially inoperable adenocarcinoma of the pancreas.

Background: Emerging data suggest ablative radiation therapy (A-RT) substantially improves long-term local control (LC) for inoperable pancreatic ductal adenocarcinoma (PDAC) and potentially overall survival (OS).  However, routine delivery of ablative dose has been limited by conventional image guidance and daily variability in nearby gastrointestinal organs-at-risk. 

Materials/Methods: A single institution retrospective analysis was performed of inoperable non-metastatic PDAC patients who received induction chemotherapy then 5-fraction ablative stereotactic magnetic resonance image-guided adaptive radiation therapy (A-SMART) on a 0.35T-MR Linac from 2018-2021 without fiducial markers and in breath hold.  Elective volume coverage was used in 80.6% of patients and became routine in late 2019 including a margin around the gross tumor volume (GTV), celiac artery, and superior mesenteric artery.  RECIST 1.1 and CTCAE v5 criteria were used to evaluate response and toxicity, respectively.

Results: 62 patients were evaluated with median age 66 years (range 35-91) and nearly all ECOG 0-1 (96.8%).  Tumor location was the head of pancreas (88.7%), otherwise the body (11.3%). Median tumor size was 3.8 cm (range 1.5-6.9).  Locally advanced disease was common (72.6%), otherwise borderline resectable (22.6%) or medically inoperable (4.8%).  Median CA19-9 at diagnosis was 168.7 U/mL (range, 1.2-12,868.6).  All patients received induction chemotherapy for a median 4.2 months (range, 0.2-13.3), usually FOLFIRINOX (69.4%) otherwise gemcitabine/nab-paclitaxel (24.2%) or gemcitabine alone (6.5%).  Median prescribed dose was 50 Gy (range 40-50) and median biologically effective dose (BED10) was 100 Gy10. Therapy after A-SMART included surgery (22.6%), irreversible electroporation (9.7%), and/or chemotherapy (51.6%).  13/14 resected patients had negative margins (92.9%).  Median follow-up was 18 months (range 6-44 months) from diagnosis.  Median and 2-year estimated LC was not reached and 87.7%, respectively.  Median and 2-year estimated progression-free survival (PFS) was 16 months and 25.7%, respectively.  Median and 2-year estimated OS was 23 months and 45.5%, respectively.  No significant LC/OS difference was observed between surgery versus no surgery after A-SMART.  % CA19-9 change after induction chemotherapy was a statistically significant prognostic factor for OS (hazard ratio 1.005; 95% confidence interval 1.001-1.009; P=0.008).  Acute/late grade 3+ toxicity rates were 4.8%/4.8%, respectively.

 

Conclusions:  To our knowledge, this is the first analysis of 5-fraction A-SMART for inoperable PDAC in which all patients first received chemotherapy.  This novel strategy appears to substantially improve the therapeutic ratio, achieve long-term OS for a subset of patients even without subsequent surgery, and allow for a potentially lengthy chemotherapy-free interval after A-SMART. 


Michael CHUONG (Miami, USA), Roberto HERRERA, Adeel KAISER, Muni RUBENS, Rupesh KOTECHA, Matthew HALL, Antonio UCAR, Fernando DE ZARRAGA, Santiago APARO, Horacio ASBUN, Ramon JIMENEZ, Raj NARAYANAN, Sarah JOSEPH, Domenech ASBUN, Tino ROMAGUERA, Diane ALVAREZ, James MCCULLOCH, Alonso GUTIERREZ, Kathryn MITTAUER
15:10 - 15:20 #29975 - OP62 Impact of stereotactic body radiation therapy on the prognosis of unresectable pancreatic cancer. clinical results and prognostic factors on 142 patients.
OP62 Impact of stereotactic body radiation therapy on the prognosis of unresectable pancreatic cancer. clinical results and prognostic factors on 142 patients.

For resectable pancreatic tumors surgery is the gold standard of care, however more than 50% of patients are unresectable at the time of diagnosis. In patients with bordeline resectable/locally advanced pancreatic cancer, the integration of chemotherapy and chemo-radiation treatment, also as neoadjuvant treatment, is the current therapeutic option. The standard fractionation of the radiotherapy treatment is associated with a significant toxicity rate and with a disappointing overall survival. Higher local control related to the high doses employed, short overall treatment time and sequential integration with systemic therapy, represent the crucial advantages of SBRT over conventional CRT.

Methods

After multidisciplinary board evaluation, patients with inoperable pancreatic cancer with maximum tumor diameter 5cm, N0 and M0 were treated with SBRT. Prescription dose was 45Gy in 6 fractions. Radiotherapy treatment plan was based on 3 phases 4D contrast enhanced simulation CT-scan and if necessary image registration of PET-CT or MRI. ITV of the lesion and Organs at risk were contoured on the simulation CT- scan in all phases of the breath. Primary end-point was freedom from local progression (FFLP). Secondary end-points were overall survival, progression-free survival, and toxicity. Local control was defined according to RECIST v1.1 criteria. Acute and late toxicity was scored according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.

Results

Between January 2011 and June 2021, 142 patients with pancreatic cancer were treated with SBRT at Humanitas Cancer Center. Median age was 71 years (range 41-91 years). 14 patients (9.8%) presented a borderline resectable disease and 128 patients (90.2%) a locally advanced disease. 76 patients (53.5%) received induction CHT before SBRT, for a median time of 5 months (range 3 - 10 months). FFLP was 81.9%, 69.1% and 58.5% at 1, 2 and 3 years, respectively. Median OS was 11.6 months and 1-2-3 years OS rates were 45.4% (95%CI 37.0 – 53.5), 16.1% (95%CI 10.5 – 22.9) and 9.8% (95%CI 5.4 – 15.7), respectively. CHT administered before SBRT (HR 0.59, 95%CI 0.41–0.84, p=0.004) and CHT post-SBRT (HR 0.63, 95%CI 0.43–0.92, p=0.019) were significantly correlated with OS. No case of Grade 3 toxicity was detected.  

Conclusions

SBRT is an effective and safe local therapy for selected patients with inoperable pancreatic cancer. Since OS was improved in patients pre-treated with induction CHT, our results suggest that the treatment for these patients must be multimodal and the stereotactic treatment may be a promising therapeutic option in this multi-modality context. 


Luciana DI CRISTINA (Milano, Italy), Tiziana COMITO, Maria MASSARO, Maria Ausilia TERIACA, Beatrice MARINI, Lorenzo LO FARO, Antonio Marco MARZO, Giacomo REGGIORI, Pasqualina GALLO, Marta SCORSETTI
15:20 - 15:30 #29803 - OP63 Stereotactic Body Radiation Therapy (SBRT) in patients with hepatocellular carcinoma (HCC): a monocenter experience.
OP63 Stereotactic Body Radiation Therapy (SBRT) in patients with hepatocellular carcinoma (HCC): a monocenter experience.

Aims

Despite the proved efficacy of Stereotactic Body Radiation therapy (SBRT) in hepatocellular carcinoma (HCC), this treatment is not included in major international guidelines at any stage, mainly due to the absence of prospective randomized studies. SBRT is commonly reserved for patients with unresectable disease, or in cases of lesions located near large vessels, just below the diaphragm, or larger than 4 cm. The aim of this study was to analyze the results of a large monocentric group of HCC patients treated with SBRT, assessing the impact of this approach on the clinical outcome.

Material and methods

All HCC patients treated with SBRT between 2010 to 2020 at our Institution were retrospectively assessed. Patients with up to 4 liver lesions, any maximum diameter and no extrahepatic metastases were included in our analysis. The gross tumour volume (GTV) coincided with the clinical target volume (CTV). The internal target volume (ITV) was generated by the CTV considering all the different respiratory phases to CT-scans. The Planning target volume (PTV) consisted of ITV plus an isotropic margin of 5 mm. Patients were treated with a dose of 40-75 Gy in 3-10 fractions using the technique of modulated arc volumetric therapy in its RapidArc form and flattening filter-free beams. Local control (LC) and overall survival (OS) were calculated. 

Results

Overall, 133 patients for a total of 245 lesions were included. The details are described in Table 1. At a median follow-up of 19 months (range 3–100), 56 patients were alive (42.1%).  One- and 2-years rates of LC were 87.9% (95% CI 81.1–92.4) and 79.5% (95% CI 69.0–86.8).  In terms of OS, the 1- and 2-years rates were 78.6% (95% CI 69.8–97.6) and 48% (95% CI 37.2–58). In multivariate analysis, previous liver surgery (HR 0.74, 95% CI 0.27-0.85; p 0.012) HBV-related infection (HR 1.61, 95% CI 2.19-11.46; p 0.0001) and radiological response after SBRT (HR 0.29, 95% CI 1.13-1.57; p 0.0006) were significantly correlated with prolonged OS. No association was found between LC and patients/disease characteristics in Cox proportional-hazard regression analysis. Globally, SBRT was well tolerated with no grade 4 or 5 toxicity.

Conclusions

Our analysis confirms the efficacy of SBRT in the treatment of HCC patients with an acceptable toxicity profile.


Lorenzo LO FARO (Milan, Italy), Ciro FRANZESE, Tiziana COMITO, Maria Ausilia TERIACA, Elena CLERICI, Piera NAVARRIA, Antonio Marco MARZO, Luciana DI CRISTINA, Giacomo REGGIORI, Stefano TOMATIS, Marta SCORSETTI
15:30 - 15:40 #29445 - OP64 Pattern of failure after stereotactic body radiotherapy (SBRT) for liver metastases: impact of local control.
OP64 Pattern of failure after stereotactic body radiotherapy (SBRT) for liver metastases: impact of local control.

Introduction

Only 30% of patients with liver metastases (LM) may be suitable for surgery due to unfavourable location, comorbidities or extrahepatic disease burden. Patients treated with stereotactic radiotherapy (SBRT) reported excellent local control (LC) and low toxicity rate although data on global disease control are missing. The aim of this preliminary analysis was to assess patterns of failure in a cohort of patients treated with SBRT for LM.

Method

Data from patients treated between 2018 and 2020 at our Institution with SBRT to LM receiving at least an EQD2 of 50 Gy (α/β=10) as per ESTRO consensus were collected. Failure patterns following SBRT and rates of local control (LC), intrahepatic relapse (excluding treated site, IHR), extrahepatic relapse (EHR), and overall survival (OS) were evaluated.

Results

Forty-three patients received liver SBRT due to oligometastatic (20,46%) and oligoprogressive (23,54%) disease. Most common primary tumors were breast (n=18,42%) and colon (n=10,23%) cancer. SBRT was performed using Cyberknife real-time tumor tracking(n=30,70%) or abdominal compression-assisted VMAT (n=13,30%) delivering 35-60 Gy in 3-5 fractions, corresponding to median EQD2 of 94 (50-150) Gy. Twelve (28%) patients were chemotherapy-naïve, while the remaining patients received 1(20,46%), 2(5,12%) or ≥3(6,14%) chemotherapy lines. Median follow-up was 12 months. Patterns of failure are reported in Table 1. One-year LC, IHR, EHR and OS were 80%,51%,49% and 87% respectively. At multivariate analysis LC was significantly correlated with EQD2≥94Gy(p=0.009) and ≥3 chemotherapy lines(p=0.04). IHR and EHR were significantly associated with local failure (p=0.0013) and intrahepatic progression (p=0.03), respectively. A significant correlation between OS and local relapse was shown (p=0.026).

Conclusion

In our experience, improved LC using high BED in non-heavily pretreated patients was correlated to reduced risk of IHR and to improved OS. IHR was the dominant mode of failure in patients treated with SBRT for LM,and was correlated to further progression at extrahepatic sites. Our findings suggest that IHR may result from uncontrolled macroscopic LM rather than ubiquitous micrometastatic dissemination, and preceed further systemic spread at distant sites. Our findings support the use of SBRT as an efficient tool to block stepwise metastatic spread from uncontrolled isolated LM to liver, and from liver to distant site, thus extending global disease control.

 


Viola SALVESTRINI, Mauro LOI (Firenze, Italy), Pierluigi BONOMO, Daniela GRETO, Vanessa DI CATALDO, Niccolò BERTINI, Lucia ANGELINI, Manuele ROGHI, Marianna VALZANO, Ludovica ZISCA, Andrea ALLEGRA, Raffaella DORO, Laura MASI, Lorenzo LIVI
15:40 - 15:50 #29933 - OP65 Stereotactic body radiotherapy (SBRT) in locally advanced pancreas cancer. Institutional Experience.
OP65 Stereotactic body radiotherapy (SBRT) in locally advanced pancreas cancer. Institutional Experience.

 Stereotactic body radiotherapy (SBRT) in locally advanced pancreas cancer. Institutional Experience

Introduction: SBRT would allow local control for LAPC with acceptable toxicity in a short time.

Objective: to assess early and late toxicities and clinical response in patients treated with SBRT.

Methods: we enrolled 74 patients with LAPC treated with neoadjuvant, concomitant or adjuvant chemotherapy plus SBRT. The treatment dose was 25-37.3 Gy, 3-5 daily fractions, utilizing IMRT and VMAT, a 6-MV photon beam and Linac Novalis IGRT-ExaTrac accelerator. GTV and OARs were delineated in CT and PET-CT fused images. OARs were contoured according RTOG criteria. The treatment planning was done in Eclipse V15.6. Acute (≤ 3 m) and late (> 3 m) toxicities were classified according to the CTCAE V.5.0.

Results: of 74 LAPC patients, mean follow up 9.8 m, 58 (78.4 %) received SBRT in pancreatic tumor as primary treatment, 11 (14.9 %) were operated first, and SBRT was delivered for relapse; 4 patients (5.4 %) were rescued with SBRT because recurrence after conventional radiotherapy and 1 (1.3 %) received SBRT twice. Median overall survival from SBRT was 10.3 months. Thirty seven patients (50.0 %) did not have any early toxicity and two patients (2.8 %) had G3 gastrointestinal toxicity. Twenty five patients (65.8 %) did not have any late toxicity and two patients (5.2 %) had ≥ G3 gastrointestinal toxicity. Relive of pancreatic pain was observed in 53/58 patients after SBRT (91.4 %). Overall survival at 12 and 18 months was 45 % and 37 % respectively.

Conclusion: we suggest that SBRT is a feasible and safe option for patients with pancreatic cancer with a good rate of relieve of pancreatic pain. Keywords: Pancreas cancer. VMAT. IMRT. Stereotactic body radiation therapy.


Maria Veronica VERA MERINO (Cordoba, Argentina)
15:50 - 16:00 #30180 - OP66 An evaluation of total internal motions of locally advanced pancreatic cancer during SBRT using Calypso® Extracranial Tracking, and its possible clinical impact on motion management.
OP66 An evaluation of total internal motions of locally advanced pancreatic cancer during SBRT using Calypso® Extracranial Tracking, and its possible clinical impact on motion management.

Background: The primary goal of this study was to determine the total extent of locally advanced pancreatic cancer’s internal motions, using Calypso® Extracranial Tracking intrafractional real-time, fiducial-based motion management system (Varian Medical Systems, Palo Alto, CA, USA). Secondary goal was to indicate possible clinical advantages of continuous intrafractional fiducial-based tumor motion tracking during SBRT.

Methods: Thirty-four patients were treated with SBRT for locally advanced pancreatic cancer on Varian EDGE® linear accelerator using Calypso® Extracranial Tracking for motion management. Planning MSCTs in free breathing and in deep breath hold, as well as 4D CTs were performed. 4D CT’s reconstructed maximum intensity projection scans and ITVs were chosen for comparison as they present respiratory movements of the lesion predominantly. The data from Calypso® Extracranial Tracking and 4D CTs were used to calculate and compare the movements of the lesions in the cranio-caudal, anterior-posterior and left-right directions. The volumes of the 4D CT-based ITV and the volumes of the Calypso®-based ITV were compared as well. All measurements were done in free breathing.

Results: Significantly larger medians of tumor excursions were found with Calypso® Extracranial Tracking than with 4D-CT in following directions: cranio-caudal: 29 mm vs. 19 mm (p < 0.001), anterior-posterior: 14 mm vs. 9 mm (p < 0.001), and left-right: 11 mm vs. 9 mm (p < 0.039), respectively. The median volume of the Calypso®-based ITV was significantly larger than that of the 4D-CT based ITV: 146.4 cm3 vs. 69.7 cm3, respectively (p < 0.001).

Conclusions: Beside known respiratory-induced internal motions, locally advanced pancreatic cancer in free breathing seems to have significant additional motions (e.g. peristaltic). Those motions should be taken into account during all alternative respiratory motion management or motion mitigation techniques, as they possibly underestimate the overall movements of the lesion. Only direct and continuous intrafractional fiducial-based motion tracking during SBRT seems to provide complete coverage of the target lesion with the prescribed isodose, which could also allow for safe tumor dose escalation.


Hrvoje KAUČIĆ (Zagreb, Croatia), Domagoj KOSMINA, Hrvoje ŠOBAT, Dragan SCHWARZ, Vanda LEIPOLD, Ivana ALERIĆ, Mihaela MLINARIĆ, Adlan ČEHOBAŠIĆ, Iva ANDRAŠEK, Asmir AVDIĆEVIĆ, Ana MIŠIR KRPAN
16:00 - 16:10 #29926 - P147 Stereotactic body radiation therapy for adrenal gland metastases: results and impact on hormonal production.
P147 Stereotactic body radiation therapy for adrenal gland metastases: results and impact on hormonal production.

BACKGROUND

In recent years SBRT has emerged as a valid alternative to invasive treatments in the oligometastatic setting, guaranteeing excellent local control and limited side effects. Nevertheless the literature regarding treatment of adrenal gland metastases is still based on retrospective data.

MATERIALS AND METHODS

We included in the present trial patients affected by adrenal gland metastases from solid primary cancers. Dose prescription was 45 Gy delivered in 3 consecutive fractions. Clinical Target Volume (CTV) was delineated as the visible tumor on the 4D-CT simulation images. Planning Target Volume (PTV) was obtained with isotropic expansion of 5 mm from CTV. Primary end-point was to evaluate local control (LC) of the treated lesion. Secondary end-points were acute and late toxicity as well as endocrine setting, progression free survival (PFS), and overall survival (OS). In-field and out-field progression were recorded.

RESULTS

Thirty-six patients were enrolled from 2017 to 2020. Most common primary tumor was located in the lung (58.3%), followed by skin (11.1%) and kidney (8.3%). Median diameter of the treated lesions was 4.1 cm (range 2.2–6.7), and median volume was 25cc (range 3–69.4). With a median follow-up of 9.5 months (range 3–41.3), LC rates at 1 and 2 years were 94.7% (95%CI 68.1–99.2) and 88.4% (95%CI 60.8-97.0). Median LC was not reached. PFS rates at 1 and 2 years were 50.5% (95%CI 29.2–68.5) and 29.8% (95%CI 10.1–52.7%). Median PFS time was 14.7 months. OS at 1 and 2 years were 62.9% (95%CI 42.7–77.6) and 44.1% (95%CI 23.7–62.7). Median OS was 23.4 months. At univariate analysis, non-oligorecurrence was associated with worse OS (HR 4.33, 95%CI 1.23–15.2; p=0.022). Regarding hormonal production from the adrenal glands only a mild variation was shown after the treament.

CONCLUSION

SBRT is confirmed to be a feasible and effective technique with minimal toxicities and acceptable alteration of the hormonal production.


Damiano DEI, Damiano DEI (Milano, Italy), Ciro FRANZESE, Maria Ausilia TERIACA, Marco BADALAMENTI, Tiziana COMITO, Nicola LAMBRI, Lucia PAGANINI, Pietro MANCOSU, Stefano TOMATIS, Marta SCORSETTI
SILVER ROOM

Wednesday 22 June

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B37
15:00 - 16:10

ORAL PRESENTATION
Brain Metastases (2)

Moderators: Michaela MAY (Neurosurgeon) (Prague, Czech Republic), Pierina NAVARRIA (MD) (Rozzano, Italy)
15:00 - 15:10 #30134 - OP73 RADIONECROSIS VERSUS PROGRESSION IN BRAIN TUMORS: RESULTS OF A PROMISING MRI TOOLS.
OP73 RADIONECROSIS VERSUS PROGRESSION IN BRAIN TUMORS: RESULTS OF A PROMISING MRI TOOLS.

Introduction

Distinguish between radiation necrosis (RN) and tumor progression, in patients with irradiated primary or metastatic brain tumors, is a diagnostic challenge. Also the use of new MRI sequences, like diffusion, perfusion-weighted and spectroscopy, or PET with new amino acid tracers, is not always able to differentiate these two entities.

To overcome this crucial problem, encouraging results have been obtained using the analysis of delayed contrast extravasation MRI to calculate high resolution maps, called “treatment response assessment maps” (TRAMs).

Aim of this exploratory analysis is to assess TRAM ability in differentiate between radiation effect and tumor progression in a small cohort of brain tumor patients treated with radiation therapy (RT).

 

Materials and methods

Thirty-four patients irradiated for primary and metastatic brain tumors were evaluated.

12patients have primary brain tumors, 22patients have brain metastases from different solid tumors.

Distinguish by histological subtypes and type of treatment, the 12patients with primary brain tumors were: 8glioblastoma, 2anaplastic astrocitoma, 1pleomorphic xanthoastrocytoma WHO grade II, and 1anaplastic xanthoastrocytoma WHO grade III, treated with surgery followed by RT and concomitant and\or adjuvant chemotherapy with temozolomide. Among brain metastatic patients, primary tumor was: 18non-small cell lung cancer, 2malignant melanoma, 1breast cancer and 1renal cell carcinoma.All of them were treated with stereotactic radiosurgery at the dose of 20-24Gy in 1fr, or with hypofractionated stereotactic radiotherapy at the dose of 27-30Gy in 3fr.

All images were uploaded and elaborate into the image workstation ([Brainlab AG, Olof-Palme-Straße 9,  81829 Munich]).

TRAMs were calculated by subtracting T1 MRI images acquired 5 minutes after contrast injection from the T1 MRI images acquired 60-105 minutes later. On TRAMs, radiation effects appeared as red areas whereas persistent tumoral lesion appeared as blue areas.

 

Results

From February 2021, 34 patients have been evaluated, in a prospective study, with this novel MRI modality. During their follow-up, 13patients(38%) showed a clinicoradiologic suspicion of a persistent tumoral lesion or progressive disease, and 21(62%) a suspicion of RN. For 14patients a brain MET-PET has been performed. TRAMs analysis have shown a fair agreement with clinicoradiologic diagnosis, perfusion-weighted MRI, and PET imaging. Moreover, 7patients underwent surgical resection, with histopathological confirm of persistent disease in 4 and radionecrosis in 3.

 

Conclusions

These preliminary results show the ability of TRAMs evaluation in distinguish between RN and progressive disease. The recruitment of new patients continues, and further evaluations are ongoing to evaluate sensitivity and positive predictive value of TRAMs analysis.


Pierina NAVARRIA (Rozzano, Italy), Luisa BELLU, Elena CLERICI, Federico PESSINA, Letterio Salvatore POLITI, Giovanni SAVINI, Marco MARZO, Marta SCORSETTI
15:10 - 15:20 #30206 - OP74 Stereotactic Laser Ablation (SLA) followed by consolidation stereotactic radiosurgery (cSRS) as treatment for brain metastasis that recurred locally after initial radiosurgery (BMRS).
OP74 Stereotactic Laser Ablation (SLA) followed by consolidation stereotactic radiosurgery (cSRS) as treatment for brain metastasis that recurred locally after initial radiosurgery (BMRS).

Introduction: The optimal treatment paradigm for brain metastasis that recurs locally after initial radiosurgery (BMRS) remains an area of active investigation.  Here, we report outcomes for patients with BMRS treated with stereotactic laser ablation (SLA, also known as laser interstitial thermal therapy, LITT) followed by consolidation radiosurgery (cSRS).

 

Methods: Clinical outcomes of 20 patients with 21 histologically confirmed BMRS treated with SLA followed by consolidation SRS and > 6 months follow-up were collected retrospectively across three participating institutions.

 

Results: Consolidation SRS (5 Gy x 5 or 6 Gy x 5) was carried out 16-73 days (median of 26 days) post-SLA in patients with BMRS. There were no new neurological deficits after SLA/cSRS. While 3/21 (14.3%) patients suffered temporary Karnofsky Performance Score (KPS) decline after SLA, no KPS decline was observed after cSRS. There were no 30-day mortalities or wound complications. Two patients required re-admission within 30 days of cSRS (severe headache that resolved with steroid therapy (n=1) and new onset seizure (n=1)).  With a median follow-up of 228 days (range: 178-1367 days), the local control rate at 6 and 12 months (LC6, LC12) was 100%.  All showed diminished FLAIR volume surrounding the SLA/cSRS treated BMRS at the six-month follow-up; none of the patients required steroid for symptoms attributable to these BMRS.  These results compare favorably to the available literature for repeat SRS or SLA-only treatment of BMRS.

 

Conclusions: This multi-institutional experience supports further investigations of SLA/cSRS as a treatment strategy for BMRS.


Clark CHEN (Minneapolis, USA)
15:20 - 15:30 #30125 - OP75 How to dose-stage large or high risk brain metastases - an alternative two-fraction radiosurgical treatment approach.
OP75 How to dose-stage large or high risk brain metastases - an alternative two-fraction radiosurgical treatment approach.

Objective: We evaluate the clinical outcome in patients with large, high-risk brain metastases (BM) treated with different dose-strategies of two-fraction dose-staged Gamma Knife radiosurgery (GKRS).

Methods142 patients from two centers, who had been treated with two-fraction dose-staged GKRS between June 2015 and January 2020, were analyzed. Depending on the changes in marginal dose between the first and second GKRS treatments, the study population was divided into three treatment groups: dose-escalation, dose-maintenance and dose-deescalation.

ResultsIn our study population, 166 large, high-risk BM were treated with the two-fraction dose-staged GKRS treatments. The median volume decreased significantly between the first and second GKRS and to last FU.  We could show that the outcome was influenced by different dose strategies and primary tumor origin. Of note, the vast majority of dose-staged BM did not show any significant post-radiosurgical complications. 

ConclusionsIn patients with large or high-risk BM, all three dose-staged GKRS treatment strategies represent effective local treatment methods with excellent local tumor control rates. Complication rates are acceptable and in line with previously reported single-fraction, but also with dose-staged radiosurgical complication rates. Depending on the primary tumor origin and initial treatment volume, different dose-strategy options are available.


Anna CHO, Brigitte GATTERBAUER, Sergey ILYALOV, Josa Maria FRISCHER (Vienna, Austria)
15:30 - 15:40 #30132 - OP76 Local control outcomes after re-irradiation of brain metastases with stereotactic radiosurgery.
OP76 Local control outcomes after re-irradiation of brain metastases with stereotactic radiosurgery.

Introduction

Brain metastases (BM) can be treated with stereotactic radiosurgery (SRS) to achieve long term control. In the event of local progression beyond 6 months from first SRS, BM can be re-treated with salvage SRS. Factors such as patient fitness and local control duration (LCD) should be considered when deciding on salvage SRS. Short LCD after first SRS might predict poor response to salvage SRS. We report the outcomes of salvage SRS at our centre, and evaluate if LCD after first SRS predicts outcomes after salvage SRS.

Method

Patients who had BM re-treated with salvage SRS were included in this study.  Statistical analysis was performed with SPSS Version 26. Kaplan-Meier analysis was performed to compare LCD after first SRS and salvage SRS.

Results

20 patients had 27 BM re-treated with SRS. Median age was 62 years at first SRS and 62.5 years at salvage SRS. All patients were ECOG PS 0 or 1. 15 patients had 1 BM retreated, 3 patients had 2 BM retreated, and 2 patients had 3 BM retreated. Median BM volume was 1.8ml at first SRS and 1.1ml at salvage SRS.  At first SRS, 14 BM (51.9%) were treated with 22Gy but at salvage SRS only 5 BM (18.5%) received 22Gy. Other doses at salvage SRS were 15Gy (7.4%), 18Gy (29.6%) and 27Gy in 3 fractions (40.7%)

Median LCD after first SRS was 336 days. In comparison median LCD after salvage SRS was 732 days which was significantly longer (log rank p = 0.034). At the time of analysis, of the 27 re-treated BM, 10 experienced further local progression while the remaining 17 were censored; 9 BM due to 8 patient deaths and 8 BM were stable at the time. As continuous variables, first LCD and salvage LCD were moderately correlated (Pearson’s correlation = 0.444, p = 0.020) but on Cox regression first LCD was not significantly associated with salvage LCD (HR = 0.997, 95% CI 0.994 – 1.001, p = 0.107)

Conclusion

Salvage LCD is not inferior but in fact significantly longer than first LCD despite lower salvage SRS dose. First LCD is not a predictor for salvage LCD therefore salvage SRS should be considered even if first LCD was relatively short provided the patient is otherwise suitable for re-treatment. Our sample is relatively small resulting therefore we aim to repeat analysis with a larger cohort.  


Joon Wee HO (Nottingham, United Kingdom), Luis AZNAR-GARCIA, Poulam PATEL, Judith CHRISTIAN
15:40 - 15:50 #29912 - OP77 Immune checkpoint inhibitor and MR-guided radiation “booster shot” in situ tumor vaccination in patients with limited metastatic carcinoma: interim analysis of a single-arm phase 2 trial.
OP77 Immune checkpoint inhibitor and MR-guided radiation “booster shot” in situ tumor vaccination in patients with limited metastatic carcinoma: interim analysis of a single-arm phase 2 trial.

Background:  Radiation therapy (RT) and immune checkpoint inhibitors (ICIs) can be synergistic, although abscopal responses are uncommon.  We hypothesized that stereotactic body radiation therapy (SBRT) delivered to two lesions sequentially – effectively delivering a radiation “booster shot” after initial in situ RT tumor "vaccination" – with concurrent ICI may potentiate a clinically meaningful immune response.

Methods:  Patients with metastatic carcinoma who experienced progression in 1-5 lesions while previously receiving ICI monotherapy were enrolled in a single arm phase 2 trial (NCT04376502). Eligible patients had 3+ measurable lesions, 2 of which sequentially received SBRT separated by 1 week (#1: 40 Gy/5 fractions; #2: 30 Gy/5 fractions) on a 0.35T MR Linac using soft tissue tracking and automatic beam gating.  The same ICI was continued until disease progression or unacceptable toxicity.  The primary objective was to evaluate best overall response rate (ORR) in non-irradiated lesion(s) and was evaluated using Simon’s two-stage design.  

Results:  In this interim analysis, 9 patients with non-small cell lung cancer (NSCLC) (78%) or melanoma (22%) completed SBRT typically with concurrent pembrolizumab (44%) or nivolumab (33%).  SBRT was most commonly delivered to lung (22%), adrenal gland (22%), and liver (17%) metastases.  Median follow up was 10.7 months (range, 4.6-22.2) from enrollment.  8 patients (89%) were alive at the time of analysis.  Best ORR in non-irradiated lesions was complete response (CR), partial response (PR), stable disease (SD), and progressive disease (PD) in 0, 1 (11%), 4 (44%), and 4 (44%) patients, respectively; 5 (55%) achieved clinical benefit with PR/SD.  Best ORR in irradiated lesions was CR, PR, SD, or PD in 2 (22%), 4 (44%), 3 (33%), and 0 patients, respectively. One NSCLC patient who initially progressed on pembrolizumab achieved a PR at a non-irradiated site (left adrenal) and CR at both irradiated sites (lung, right adrenal).  He experienced distant progression (solitary brain metastasis) 6.5 months after SBRT, was salvaged with stereotactic radiosurgery, and remains on pembrolizumab without further progression now 21.7 months after SBRT.  Seven patients (77.8%) experienced distant progression after a median 3.7 months (range, 1.8-6.5) from SBRT.  No grade 2+ toxicity occurred.  

Conclusions:  Despite experiencing disease progression on immunotherapy, SBRT “revaccination” while continuing the same immunotherapy appears to achieve a favorable response at both irradiated and non-irradiated sites without causing significant toxicity.  These early results suggest that this novel treatment strategy provides clinically meaningful benefit and could delay the need to change systemic therapy.  


Michael CHUONG (Miami, USA), Surya CHUNDRU, Noah KALMAN, Federico ALBRECHT, Paul KAYWIN, Guilherme RABINOWITS, Carolina ROJAS, Minesh MEHTA, Rupesh KOTECHA
15:50 - 16:00 #30222 - OP78 Neuroinflammatory Changes of the Normal Brain Tissue in Cured Mice Following Combined Radiation and anti-PD-1 Blockade Therapy for Glioma.
OP78 Neuroinflammatory Changes of the Normal Brain Tissue in Cured Mice Following Combined Radiation and anti-PD-1 Blockade Therapy for Glioma.

The efficacy of combining radiation therapy with immune checkpoint inhibitor blockade to treat brain tumors is currently the subject of multiple investigations and holds significant therapeutic promise.  However, the long-term effects of this combination therapy on the normal brain tissue are unknown. Here, we examined mice that were intracranially implanted with murine glioma cell line, and treated with a combination of 10 Gy cranial irradiation (RT) and anti-PD-1 checkpoint blockade (aPD-1). This combination treatment cured 75% of the mice over 90 days of study duration. We examined the contralateral normal brain in the long-term survivors after the combined treatment. Post-mortem analysis of the cerebral hemisphere contralateral to tumor implantation showed that neural stem cells were well preserved in subventricular zone.  In addition, we observed a drastic reduction in the number of mature oligodendrocytes in the subcortical white matter. Importantly, this observation was evident specifically in the combined (RT + aPD-1) treatment group but not in the single treatment arm of either RT alone or aPD-1 alone. Elimination of microglia with a small molecule inhibitor of colony stimulated factor-1 receptor (PLX5622) prevented the loss of mature oligodendrocytes. These results identify for the first time a unique pattern of normal tissue changes in the brain secondary to combination treatment with radiotherapy and immunotherapy. The results also suggest a role for microglia as key mediators of the adverse treatment effect.


Samuel RYU (Stony Brook, USA)
16:00 - 16:10 #30204 - P058 Dose-Adapted Single-Isocenter Multitarget Stereotactic Radiosurgery: A Prospective Study.
P058 Dose-Adapted Single-Isocenter Multitarget Stereotactic Radiosurgery: A Prospective Study.

Purpose: We evaluated the efficacy and safety of simultaneous stereotactic radiosurgery for multiple lesions using a single isocenter and a volume-and critical structure-adapted dosing strategy in patients with 4 to 10 brain metastases.

Study Design: Adult patients with 4 to 10 brain metastases were enrolled on this prospective single-institution trial. The primary endpoint was overall survival. Secondary endpoints were local recurrence, distant brain failure, neurologic death, and rate of adverse events. Exploratory objectives were neurocognition, quality of life, dosimetric data, salvage rate, and radionecrosis. Dose was prescribed in a single fraction per RTOG 90-05 or as 5 Gy × 5 fractions for lesions ≥3 cm diameter, lesions involving critical structures, or single-fraction brain V12Gy >20 mL.

Results: Forty patients were treated on the study. The median age was 61 years, median Karnofsky performance status 90, and median number of brain lesions was 6. We used the graded prognostic assessment to estimate expected survival, and twenty-two patients lived longer than expected after SRS, with 1 living patient who had not reached that milestone at the time of publication. Median overall survival was 8.1 months with a 1-year overall survival of 35.7%. The 1-year local recurrence rate was 5% (10 of 204 of evaluable lesions) in 12.5% (4 of 32) of the patients. Distant brain failure was observed in 19 of 32 patients with a 1-year rate of 35.8%. There were no grade 3-5 treatment-related adverse events. Radionecrosis was observed in only 5 lesions, with a 1-year rate of 1.5%. Rate of neurologic death was 20%. Neurocognition and quality of life did not significantly change 3 months after SRS compared with pretreatment.

Conclusions: These results suggest that single-isocenter multitarget stereotactic radiosurgery using adapted dose for target volume and critical structures is an effective and safe treatment for patients with 4 to 10 brain metastases.


Grace KIM, Scott FLOYD (Durham, USA), Evan BUCKLEY, James HERNDON, Karen ALLEN, Tykeytra DALE, Justus ADAMSON, Lam LAY, William GILES, Anna RODRIGUES, Zhiheng WANG, Jordan TOROK, Junzo CHINO, Peter FECCI, John SAMPSON, Carey ANDERS, Fang Fang YIN, John KIRKPATRICK
RED 2 ROOM

Wednesday 22 June

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C37
15:00 - 16:10

ORAL PRESENTATION
Functional

Moderators: Luca ATTUATI (Consultant) (Milan, Italy), Andrei BRINZEU (MD) (Lyon, France)
15:00 - 15:10 #29974 - OP67 Effect on Gait and balance of VIM bilateral Gamma Knife Radiosurgery versus bilateral deep brain stimulation in severe essential tremor.
OP67 Effect on Gait and balance of VIM bilateral Gamma Knife Radiosurgery versus bilateral deep brain stimulation in severe essential tremor.

Introduction: Patients suffering of severe essential tremor (ET) are frequently experiencing gait and balance problems compared to healthy controls. Bilateral VIM neurosurgical therapies are known to carry a risk of gait and balance worsening in patients presenting with ET. This risk clearly identified in old radiofrequency ablation series is not clearly evaluated in bilateral Radiosurgery (SRS) or deep brain stimulation (DBS).

Material and method: In Marseille Functional Neurosurgery department gait and balance have been prospectively evaluated in all the patients operated bilaterally for essential tremor. The assessment was performed relying on multiparametric automated optoelectronic walk analyses before & 12 , 17 and 48 months after. Were evaluated 19 patients with bilateral DBS in on and off condition and 28 patients with bilateral SRS.

Results: The tremor score after DBS and SRS was decreased respectively of 56 & 72%. The improvement of the quality of life score was respectively of 77% and 83%. After DBS we observed a trend for recurrence with a tremor reduction of 56% and 50% respectively at 1 and 4 years after DBS. On the short term (1 year) we observed no gait & balance worsening both after DBS and SRS. However, in patients stimulated (DBS) more than 4 years we observed a significant decline in gait and balance features both in off and on condition and two patients (10,5%) experience falls after 4 years. Out of a patient with hyper-response (3,6%) bilateral SRS induced no Gait and balance worsening.

Conclusion: Both DBS and SRS are sparing gait and balance performances in ET patients at 1 year. On the long run DBS patients are experiencing gait and balance worsening. Large patient cohort followed on the long run are still required for confirmation of these results.


Mira VALENTIN, Boutin EMMANUELLE, Tatiana WITJAS, Axel CRETOL, Romain CARRON, Jean Philippe AZULAY, Vaugoyeau MARIANNE, Jean REGIS (MARSEILLE)
15:10 - 15:20 #29996 - OP68 Central lateral thalamotomy for neuropathic pain using Gamma Knife radiosurgery: a single-center retrospective study.
OP68 Central lateral thalamotomy for neuropathic pain using Gamma Knife radiosurgery: a single-center retrospective study.

Background: Neuropathic pain is a disabling disorder with limited effective treatments. The medial thalamus is a site of pain-related affective-motivational dimension cerebral processing. Lesioning the medial thalamus has been used as a potential treatment for neuropathic pain. Within the medial thalamus, the central lateral nucleus has been considered as a putative target for stereotactic lesion.

 

Objective: To study the safety and efficacy of central lateral thalamotomy using Gamma Knife radiosurgery (GKRS) for the treatment of neuropathic pain.

 

Methods: We retrospectively reviewed all patients with neuropathic pain who were treated with central lateral thalamotomy using GKRS. We report on characteristics including pain etiology, adverse events, changes in pain scores using the Visual Analogue Scale and Barrow neurological Institute pain intensity score.

 

Results: Twenty-one patients underwent central lateral thalamotomy using GKRS between 2014 and 2021. Pain reduction occurred in 12 patients (57%) after a median period of 3 months (range 0.5-12 months) and persisted in seven patients (33%) at the last assessments, at a median follow-up of 28 months (range 8-81 months). Meaningful pain reduction occurred more frequently in patients with trigeminal deafferentation pain compared to all other patients (P = .005). Rates of pain reduction at 1, 2, 3, and 5 years were 48%, 48%, 19%, and 19%, respectively. No patient had treatment-related adverse events.

 

Conclusions: Central lateral thalamotomy using GKRS is remarkably safe. Pain reduction following this procedure occurs in a subset of patients and is more frequent in those with trigeminal deafferentation pain; however, pain recurs frequently over time.


Piero PICOZZI, Andrea FRANZINI (Milano, Italy), Pierina NAVARRIA, Elena CLERICI, Pessina FEDERICO
15:20 - 15:30 #29476 - OP69 Stereotactic radiosurgery for epilepsy related to hypothalamic hamartomas.
OP69 Stereotactic radiosurgery for epilepsy related to hypothalamic hamartomas.

Hypothalamic hamartoma (HH) is a dysplastic lesion fused with the hypothalamus and manifest clinically by epilepsy, precocious puberty and behavioral disorders. Up to 50% of patients become free of seizures after surgery, but various complications occur in 1/4 of them.  Radiofrequency thermocoagulation, laser interstitial thermal therapy, and stereotactic radiosurgery (SRS) are alternative treatment options.

OBJECTIVE: To define indications for SRS in patients with HH and to clarify the irradiation parameters.

METHODS: Twenty-two patients with HH and epilepsy underwent SRS at the Moscow Gamma-knife Center with sufficient FU-data available for retrospective outcome evaluation in 19 of them. The median age at the time of treatment was 11.5 years (1.3 - 25.8) and the diameter of irradiated lesion ranged between 5.5 to 40.9 mm. In 8 cases (36%), the lesion volume exceeded 3 cm3. The average prescribed dose was 18 Gy +/- 2.0, the average prescribed isodose – 48% +/- 4.2. The median FU was 14.8 months (3.4 - 96.1).

RESULTS: Three patients were free of every seizures at the last check (Engel IA - 15.8%). One patient (5.3%) improved dramatically after treatment with compete resolution of generalized convulsions and experienced only rare emotional seizures (Engel IB). Eleven patients (57.8%) reported a marked decrease in frequency of seizures. The severity and frequency of seizures did not change in 4 patients (21.1%). The best results were achieved in cases with an average target dose above 20-22 Gy, minimal target dose more than 7-10 Gy, at least 70-80% of the lesion volume covered by prescribed dose, and in patients with HH almost total covered by dose above 12 Gy. None of the patients had any complications after SRS.

CONCLUSIONS: Careful patient selection for SRS makes it an effective option to treat epilepsy in patients with HH. The best candidates for SRS are children with seizure age at onset older than 1 year, the lesion volume less than 3 cm3, and if the area of HH-fusion with the hypothalamus does not exceed 150 mm2. SRS is safe and free of treatment related neurological, endocrine or visual disturbances. Repeat SRS may be helpful in cases with incomplete results after first procedure.


Aleksandr SAVATEEV, Andrey GOLANOV (Moscow, Russia), Dmitrij SAUSHEV, Ivan OSINOV, Valerij KOSTJUCHENKO
15:30 - 15:40 #29963 - OP70 Increased Gray Matter Density in the Right Mesencephalic Tegmentum Is Associated With Better Engel Classes I and II After Radiosurgery for Hypothalamic Hamartomas.
OP70 Increased Gray Matter Density in the Right Mesencephalic Tegmentum Is Associated With Better Engel Classes I and II After Radiosurgery for Hypothalamic Hamartomas.

Objective:

Hypothalamic hamartomas (HH) are disabling congenital lesions, responsible for gelastic seizures frequently associated with catastrophic epilepsies, epileptogenic encephalopathy, cognitive and psychiatric severe comorbidities. Stereotactic radiosurgery is well-established minimally invasive therapeutic approach. 

Methods:

Here, we used voxel-based morphometry (VBM), as depicted on pretherapeutic standard structural magnetic resonance neuroimaging. We assessed whether gray matter density (GMD) correlates with seizure outcome. Were examined 24 patients (10 males, 14 females; mean age 12.7 years, median 9, range 5.9-50), treated in Marseille University Hospital, France, between May 2001 and August 2018.

Results:

Most relevant anatomical area predicting postoperative Engel class I and II versus III and IV was mesencephalic tegmentum. Higher pretherapeutic GMD in this area was associated with better outcome in terms of seizure cessation. The only other statistically significant clusters were right cerebellar lobule VIIIb and VIIIa. Lower pretherapeutic GMD in both clusters correlated with better Engel class outcome. Grey matter density decreased with age in the left medio-dorsal thalamus. 

Conclusions:

Seizure cessation was associated with higher GMD in mesencephalic tegmental area, acknowledged to be involved in the neural control of explosive vocal behavior in animals. This area is connected by the mamillo-tegmental bundle to the lateral tuberal nucleus area of the hypothalamus, where HH are known to rise. In the future, the detection of more gray matter in this “laugh” tegmental area, based on pretherapeutic routine structural neuroimaging might help in patient selection for minimally invasive radiosurgery for HH.


Constantin TULEASCA (Lausanne, Switzerland), Hussein HAMDI, Chauvel PATRICK, Lepine ANNE, Bartolomei FABRICE, Jean RÉGIS
15:40 - 15:50 #30130 - OP71 Brain structural MRI predicts outcome of radiosurgical treatment in trigeminal neuralgia.
OP71 Brain structural MRI predicts outcome of radiosurgical treatment in trigeminal neuralgia.

Introduction. To determine structural magnetic resonance imaging (MRI) alterations occurring in trigeminal neuralgia (TN) patients who do not respond to radiosurgical treatment or experience pain recurrence after initial temporary response.

Methods. Thirty patients with idiopathic or classic TN, who underwent Gamma Knife radiosurgery and were followed for at least 24 months, were retrospectively analysed. Patients’ structural pre-treatment MRI, and their pre- and post-operative clinical features were investigated. More specifically, according to the Barrow National Institute (BNI) pain intensity scale at 6 months after treatment, patients were classified as initial “responders” and “non-responders”. In reference to responders’ patients, any change from the best class after GKSRS to a lower outcome class over time was considered as a “recurrence”. 15 age- and sex-matched healthy controls without any pain condition were also enrolled. Cortical thickness and subcortical gray matter (GM) atrophy were assessed in TN patients relative to controls, and among patient subgroups according to treatment outcomes (initial responders/non-responders, recurrence/long-lasting pain relief). MRI predictors of poor treatment outcomes were also explored.

Results. Cortical thinning of temporal, prefrontal, cingulate and somatosensory areas bilaterally were found in TN patients relative to controls. No significant cortical thickness and GM volume differences were found when TN initial (6 months after treatment) responder and non-responder patients were compared. Patients who experienced TN recurrence after initial pain relief were characterized by thicker parahippocampal and temporal lobe cortex bilaterally and higher volume of right amygdala and hippocampus compared to patients with long-lasting pain relief at last follow-up. Furthermore, baseline cortical thinning of right parahippocampal, left fusiform, left middle temporal cortex values and disease duration were associated with poor outcome (including non-responder patients and those who experienced TN recurrence) after treatment at last follow-up (R2= 0.57, p < 0.001).

Conclusions. This study supports the role of central nervous system as a strong modulator of pain in trigeminal neuralgia. Our findings, in fact, provides novel insights into TN brain structural alterations, which might contribute to TN development and its maintenance.


Luigi ALBANO (Milan, Italy), Federica AGOSTA, Silvia BASAIA, Antonella CASTELLANO, Roberta MESSINA, Lina Raffaella BARZAGHI, Andrea FALINI, Pietro MORTINI, Massimo FILIPPI
15:50 - 16:00 #29317 - OP72 Therapeutic use of Linac-based stereotactic body radiosurgery (SRS) in the management of malignant spasticity: preliminary results from a prospective trial.
OP72 Therapeutic use of Linac-based stereotactic body radiosurgery (SRS) in the management of malignant spasticity: preliminary results from a prospective trial.

Background: spasticity is a clinical event characterized by increased muscle contraction, sometimes painful, secondary to central nervous system damage. It leads to high rate of nursing procedures, hospital admissions, costs and quality of life impairment with problems in sleeping, breathing, and speaking. Standard treatment for systemic spasticity is represented by oral or intrathecal baclofen. In the case of focal spasticity, available treatment options are intramuscular botulinum toxin, alcoholic or surgical neurolysis or even selective neurotomies or rhizotomies. However, these surgical procedures are characterized by prolonged surgical sessions and may have infective, anesthetic and surgical complications. They requires an experienced team, costs are relatively high, and the learning curve is slow. The aim of the present study is to evaluate the therapeutical effectiveness of linac-based stereotactic radiosurgery (SRS) in the treatment of malignant spasticity.

Material and methods: patients with spasticity to the lower limbs unresponsive to systemic therapies were treated with linac-based SRS to the spinal nerves responsible for the spasms within a prospective observational trial (n° 51262). Treatment dose was 45 Gy in a single fraction delivered with VMAT technique. The primary end-point was the reduction of the muscular resistance to passive movement measured with the Modified Ashworth Scale (MAS). Secondary end-points were toxicity, quality of life, and spinal nerves radiological features (fractional anisotropy, diffusivity).

Results: from December 2020, the first 4 patients were treated at our Institution. The first patient was treated at the bilateral nerves L4-S1 and had a complete spasms resolution the day after SRS administration that lasts 10 months after treatment. The second was treated at bilateral levels L3-L5 and had a progressive reduction up to 40% of the spasms over 4 months (fig. 1). The third patient was treated at the bilateral L4-5 and left S1. After 2 months, she had a MAS reduction (2 versus 3), however she died of thromboembolism 6 months after SRS. Patient 4 had MAS 3 and was treated at the bilateral L3-4. Few days after SRS administration he had a complete response to treatment with MAS 0, which lasted 3 months after treatment. No acute treatment-related toxicities or spasticity relapse were reported.

Conclusion: this is the first clinical report on linac-based SRS for the treatment of malignant spasticity. These preliminary results with a short follow-up documented a clinical activity of SRS that will be explored in a larger population to better assess effectiveness, toxicity, and duration of the response.


Luca NICOSIA (ITALY, Italy), Elena ROSSATO, Renato AVESANI, Federico FERRARI, Francesco CUCCIA, Niccolò GIAJ-LEVRA, Vanessa FIGLIA, Rosario MAZZOLA, Francesco RICCHETTI, Michele RIGO, Fabio MARCHIORETTO, Massimo ZAMPERINI, Antono DE SIMONE, Ruggero RUGGIERI, Filippo ALONGI
16:00 - 16:10 #29332 - P100 Image-guided LINAC radiosurgery for trigeminal neuralgia: 10 years follow-up.
P100 Image-guided LINAC radiosurgery for trigeminal neuralgia: 10 years follow-up.

 668 patient with Trigeminal Neuralgia (TN) have been treated  at the CDI Cyberknife Center (Milan)during the last 12 years using LINAC image-guided radiosurgery. Long term follow-up  ( 10 years) is available  for 84 patients.

Methods

Patients with typical TN and severe medically-refractory pain were treated with image-guided robotic radiosurgery (Cyberknife) by a single neurosurgeon (PR) . Treatment was delivered in single session .Pre-operative imaging included thin cuts( 0,5 mm) pre- and post-contrast stereotactic head CT and volumetric post-contrast MR(MPRAGE) integrated by FIESTA( later CISS) images. A 6 mm retrogasserian/mid-cisternal target was identified and received 60 Gy prescribed  to the 80% idodose( max dose  calls were made or further clinical evaluations performed if needed. Visual analogue scores( VAS, 0-10) and Barrow Neurological Institute(BNI) scale(I-V) have been used to assess the pain level before the treatment and during the follow-up. VAS scores >7 and BNI grade IV-V ,both indicating severe pain, were required to undergo the treatment.  BNI facial numbness scale (I-IV) was used to assess the development of sensory disturbances following the treatment. 

Results

Pain relief rate in 343 patients was 92% after 6 month, 87% after 1 year and 76% after 3 years.  5 and 10 years follow-up is available for 84 patients, with relief rates of 74% and 72% respectively. 15 patients within this group required a second treatment  due to lack of efficacy of the first treatment(4) or pain relapse (11). The rate of sensory complications at 5 and 10 years was, respectively, 9,5%( 8 Patients) and 5,9%(5 patients).

Overall pain relief rate 10 years after  image-guided LINAC radiosurgery for TN was satisfactory in over 2/3 of the patients treated. 

Conclusions 

Long-term follow-up confirms the efficacy and safety of image-guided  LINAC radiosurgery for TN. Second treatments are useful to achieve long-term pain relief in patients not responding to or relapsing after a first treatment. Aside from sensory complications, no other neurological complications have been found.Sensory complications  in the patients receiving 2 treatments delivering 60 Gy to the same 6 mm target led to the reduction of second treatment dose to 45 Gy.This lower dose was later observed to induce a much lower rate of sensory complications without affecting pain relief rates


Pantaleo ROMANELLI, Giancarlo BELTRAMO, Livia BIANCHI, Alfredo CONTI (Bologna, Italy)
BLUE 2 ROOM
16:10 COFFEE BREAK AND EXHIBITION
16:30

Wednesday 22 June

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A39
16:30 - 17:30

ORAL PRESENTATION
Spinal & Oligo-metastases

Moderators: Marcello MARCHETTI (physician) (Milano, Italy), Kita SALLABANDA (Medical Direcor) (Madrid, Spain)
16:30 - 17:30 #29572 - OP79 Mature local control and reirradiation rates comparing spine stereotactic body radiotherapy to conventional palliative external beam radiotherapy.
OP79 Mature local control and reirradiation rates comparing spine stereotactic body radiotherapy to conventional palliative external beam radiotherapy.

Purpose: Stereotactic body radiotherapy (SBRT) improves complete pain response for painful spinal metastases compared to conventional external beam radiotherapy (cEBRT). We report mature local control and reirradiation rates in a large cohort of patients treated with SBRT vs. cEBRT enrolled previously in the Canadian Clinical Trials Group Symptom Control (SC).24 phase II/III trial.

Methods/Materials: 137/229 (60%) patients randomized to 24 Gy in 2 SBRT fractions or 20 Gy in 5 cEBRT fractions were retrospectively reviewed. By including all treated spinal segments, we report on 66 patients (119 spine segments) treated with SBRT, and 71 patients (169 segments) treated with cEBRT. The primary outcomes were MR-based local control and reirradiation rates for each treated spine segment.

Results: The median follow-up was 11.3 months (IQR:5.3-27.7 months), and median OS in the SBRT and cEBRT cohorts were 21.6 and 18.9 months (p=0.428), respectively. The cohorts were balanced with respect to radioresistant histology and presence of “Mass” (paraspinal and/or epidural disease extension). Risk of local failure after SBRT vs. cEBRT at 6, 12 and 24 months were 2.8% vs. 11.2%, 6.1% vs. 28.4% and 14.8% vs. 35.6%, respectively (p<0.001). cEBRT (HR:3.48, 95%CI:1.94-6.25, p<0.001) and presence of “Mass” (HR:2.07, 95%CI:1.29-3.31, p=0.002) independently predicted local failure on multivariable analysis. The 1-year reirradiation rates and median times to reirradiation after SBRT vs. cEBRT, were 2.2% vs 15.8% (p=0.002) and 22.9 months vs. 9.5 months respectively. Radioresistant histology (HR:2.66, 95%CI:1.43-4.94, p=0.002) and cEBRT (HR:2.34, 95%CI:1.14-4.78, p=0.002) independently predicted for reirradiation. 8/12 iatrogenic vertebral compression fractures (VCFs) were after SBRT and 4/12 after cEBRT; Grade 3 toxicities were isolated to the SBRT cohort (5/12).

Conclusions: Risk of local failure and reirradiation is lower with SBRT compared to cEBRT for spinal metastases. Although the iatrogenic VCF rates were within expectations, Grade 3 VCF were isolated to the SBRT cohort.


K. Liang ZENG, Sten MYREHAUG, Hany SOLIMAN, Zain A. HUSAIN, Chia-Lin TSENG, Jay DETSKY, Mark RUSCHIN, Eshetu G. ATENAFU, Christopher D WITIW, Jeremie LAROUCHE, Leodante DA COSTA, Pejman Jabehdar MARALANI, Wendy R PARULEKAR, Arjun SAGHAL (Toronto, Canada)
16:30 - 17:30 #30146 - OP80 Selection criteria for Stereotactic Body Radiation Treatment of spinal metastases.
OP80 Selection criteria for Stereotactic Body Radiation Treatment of spinal metastases.

Purpose or Objective

Stereotactic Body Radiotherapy (SBRT) is widely used for treatment of uncomplicated spine metastases to palliate symptoms and prolong disease control. However, criteria for patient selection are not available. The aim of this study is to identify determinants of local failure and progression-free interval in patients treated with SBRT to spinal metastases.

Materials and Methods

Data from consecutive patients treated with Cyberknife-based spine SBRT between January 2019 and March 2020 were retrospectively collected. Dose was expressed as Biological Effective Dose for α/β=10 (BED10). Kaplan-Meyer method was used to calculate Local Control (LC) and Disease Free Survival (DFS) from date of SBRT to event. Univariate (UVA) and Multivariate analysis (MVA) were performed using log-rank and Cox model, respectively. 

Results

Sixty-two patients accounting for 70 spinal metastases were included. Median age was 66 (range 32-87) years. Disease was metastatic at diagnosis in 21 patients (34%) : an active primary tumor was present in 17 patients (27%). Among treated sites, most represented primary malignancies were prostate (n=28, 40%) and breast (n=21, 30%). Dose regimens consisted of 25-30 Gy in 5 fractions and 21-30 Gy in 3 fractions in respectively 61 (87%) and 9 (13%) cases, resulting in a median BED of 43.2 (range 37.5-60) Gy10. Concurrent chemotherapy (including cytotoxic or targeted agents) was administered in 43% of cases (n=30). After a median follow up of 10 months (range 1-24 months), 9 local relapses and 40 distant progressions were observed. One year LC was 87% (Fig.1): non-prostate primary tumor ( p=0.003, Fig.2) and concurrent chemotherapy (p=0.006, Fig.3) were associated to poorer LC at UVA, and an independent correlation was confirmed at MVA (respectively p=0.017 and p=0.024). One-year DFS was 43% (Fig.4). UVA showed a correlation between impaired DFS and active primary tumor (p=0.003), metastatic dissemination at diagnosis (p=0.02) and non-prostate primary tumor (p=0.009), although only an active primary tumor site was independently associated to DFS at MVA (p=0.007, Fig.5). Only G2 acute pain or nausea were observed. No late toxicity, in particular vertebral fracture, was reported.

Conclusion

Spine SBRT results in high LC rates and durable progression-free survival with low incidence of mild toxicity. Clinical nomograms based on patient-related characteristics may help to select candidates for this approach.


Michele AQUILANO (Firenze, Italy), Mauro LOI, Sara LUCIDI, Giulio FRANCOLINI, Gabriele SIMONTACCHI, Daniela GRETO, Isacco DESIDERI, Pierluigi BONOMO, Andrea Gaetano ALLEGRA, Lucia ANGELINI, Laura MASI, Raffaella DORO, Ivano BONUCCI, Vanessa DI CATALDO, Monica MANGONI, Lorenzo LIVI
16:30 - 17:30 #29328 - OP81 Monitoring patient movement during stereotactic body radiotherapy of spinal metastases.
OP81 Monitoring patient movement during stereotactic body radiotherapy of spinal metastases.

Aim: This study aims to evaluate, minimize and correct any intrafractional patient movement during stereotactic vertebral radiotherapy using a low dose non-invasive technique without prolonging treatment times.

Method: 38 patients with 41 volumes were included in this study spanning from September 2018 until May 2021. Three different workflows were assessed during this period. Any deviations on kV-CBCT (Varian) were corrected in 6 degrees of freedom and checked with ExacTrac stereoscopic imaging before delivery of stereotactic body radiotherapy (SBRT).  Our departmental protocol allows a tolerance of 1mm/1° for spinal SBRT. kV-CBCT was repeated after SBRT to determine intrafractional motion. Each fraction was delivered with 2-4 VMAT arcs per treatment on a Varian TrueBeam™ linear accelerator and additional ExacTrac images were performed according to the workflow.

In workflow 1, positioning was with CBCT and ExacTrac before SBRT whereas in workflow 2 additional ExacTrac images were performed between the arcs. In workflow 3, ExacTrac imaging was between and during arcs when the gantry reached the 0° position. When the ExacTrac deviation exceeded 1mm/1°, patient positioning was corrected and ExacTrac imaging was repeated for verification. A total of 564 kV-CBCTs and 727 ExacTrac images were collected. 1280 images were suitable for the evaluation of patient positioning.

Results: Workflow 3 (96.7% of images within tolerance), achieved a significant improvement compared to the results recorded in workflow 1 (84.8%) and 2 (82.5%). Treatment time for workflow 3 was 13 min compared to workflow 1 (12 min) and 2 (12 min). All three workflows recorded acceptable surface dose according to radiation protection standards.

Conclusion: The study demonstrated that the use of additional intrafractional low dose ExacTrac images during SBRT of spinal metastases reduced the number of out-of-tolerance measurements and optimized treatment delivery within a standard treatment timeslot.


Madeleine VAN NIEKERK (Aarau Switzerland, Switzerland), Tessa LAZEROMS, Susanne ROGERS, Viktor GAJDOS, Ismail OEZDEN, Emely KESSLER, Oliver RIESTERER
16:30 - 17:30 #29458 - OP82 Assess critical tasks in postoperative spine stereotactic radiation therapy in presence of high density implants using a robotic radiotherapy device.
OP82 Assess critical tasks in postoperative spine stereotactic radiation therapy in presence of high density implants using a robotic radiotherapy device.

Purpose
High density materials that are used in stabilization hardware potentially pose an issue regarding postoperative radiation therapy. This work investigates radiation therapy workflow steps in situations where hybrid implants consisting of titanium and carbon-fiber-composites (CFP-T) were used for stabilization and the radiation therapy is delivered using a robotic device.

Methods
To investigate the quality of the image registration and delineation, these tasks were carried out using CT images from two patients with CFP-T implants in place. Treatment plans were created on an anthropomorphic phantom equipped with CFP-T spine stabilization to assess the accuracy of the calculated dose distributions. The phantom allows to measure the dose distribution near to the high density material using radiochromic film. Furthermore, a regular machine QA end-to-end (E2E) test was modified to test the image guidance procedure for the anthropomorphic phantom.

Results
It was possible to delineate the patient cases with the CFP-T implants according to international consensus.
The gamma passing rates of the comparison between the calculated and measured dose distributions were above 97% using the following criteria: 5% (of the maximal dose), 1 mm with 20% dose threshold. The modified E2E test was as accurate as the unmodified standard tests (targeting accuracy < 0.95 mm).

Conclusion
No critical impediments regarding postoperative spine irradiations in presence of CFP-T implants were identified in this work.