Wednesday 12 June
Time Segovia Plenary Segovia Break Out El Pardo I
07:30
07:30-09:00
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A41
BREAKFAST SEMINAR
QUALITY SRS/SRT: WHAT'S REQUIRED

BREAKFAST SEMINAR
QUALITY SRS/SRT: WHAT'S REQUIRED

Moderators: Guilherme BULGRAEN DOS SANTOS (BRAZIL), Alexis DIMITRIADIS (Physicist) (London, UK), Anderson PASSARO (Medical Physicist) (São Paulo, BRAZIL)
07:30 - 07:50 Task Force Recommendations (AAPM/ASTRO). Steven GOETSCH (Medical Physicist) (Solana Beach, USA)
07:50 - 08:10 The ISRS Accreditation Program. Ian PADDICK (Physicist) (London, UK)
08:10 - 08:30 QA perspectives in the management of respiratory motion. Andrea GIRARDI (Medical Physicist) (Brussels, BELGIUM)
08:30 - 08:50 Emerging QA techniques. Fang-Fang YIN (Medical Physicist/Professor) (Durham, NC, USA)

07:30-09:00
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B41
BREAKFAST SEMINAR
EMERGING SBRT INDICATIONS

BREAKFAST SEMINAR
EMERGING SBRT INDICATIONS

Moderators: Sebastiao CORREA (RADIO-Oncologist) (São Paulo, BRAZIL), Richard POPPLE (Medical Physicist) (Birmingham, USA), Ben SLOTMAN (Professor and Chairman) (AMSTERDAM, THE NETHERLANDS)
07:30 - 07:50 Cervical. Yoshiya Josh YAMADA (New York, USA)
07:50 - 08:10 SBRT in the management of inoperable pancreatic cancer. Marta SCORSETTI (Director Department) (Rozzano-Milan, ITALY)
08:10 - 08:30 SBRT and liver. Lorenzo LIVI (Full Professor, Head of Radiation Oncology Unit) (Florence, ITALY)
08:30 - 08:50 Kidney. David PRYOR (Radiation Oncologist) (Brisbane, AUSTRALIA)

07:30-09:00
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C41
BREAKFAST SEMINAR
VASCULAR DISORDERS

BREAKFAST SEMINAR
VASCULAR DISORDERS

Moderators: Leonardo FRIGHETTO (Neurosurgeon) (Porto Alegre, BRAZIL), Bruce POLLOCK (Physician) (Rochester, USA), Bruno SANTOS (Neurosurgeon) (Aracaju, BRAZIL)
07:30 - 08:00 Management of Unruptured AVMs in the Post ARUBA Era. Steven CHANG (Member) (Stanford, USA)
08:00 - 08:30 Large AVMs: Strategies and Outcomes. Isaac YANG (Associate Professor) (Los Angeles, USA)
08:30 - 09:00 Endovascular Combination Therapy: Best Practices. Eduardo WAJNBERG (BRAZIL)

09:00
09:00-10:15
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A42
PLENARY SESSION
NOVEL TECHNOLOGIES & TECHNIQUES - PART I

PLENARY SESSION
NOVEL TECHNOLOGIES & TECHNIQUES - PART I

Moderators: Matthew FOOTE (Co-Director) (Brisbane, AUSTRALIA), Marc LEVIVIER (Chef de Service) (Lausanne, SWITZERLAND), Charles Ambroise. VALERY (directeur unité GK) (Paris, FRANCE)
09:00 - 09:15 Liquid Biopsy and Implications for SRS/SBRT. John SUH (Radiation Oncologist) (Cleveland, USA)
09:15 - 09:30 DTI & SRS for Behavioral Disorders. Alessandra GORGULHO (Director of Research Affairs) (Sao Paulo, BRAZIL)
09:30 - 09:45 Brain Radiosurgery Without a Bunker. John ADLER (neurosurgery) (Région de la baie de San Francisco, USA)
09:45 - 10:00 MR-LINAC Technology. David JAFFRAY (Speaker) (Toronto, CANADA)
10:00 - 10:15 #17783 - When the machine is challenging the expert : Intuitive inverse planning.
When the machine is challenging the expert : Intuitive inverse planning.

Background : Inverse doseplanning are nowadays far to be competing with the quality of doseplanning elaborated by expert with an experience of thousands of planning for Gamma Knife radiosurgery (GKS). A new inverse planning (IP) method based on « efficient convex optimization algorithms » is supposed to provide high quality doseplans in real-time.

Material and Method : Have been recruited 86 patients treated by single dose GKS for vestibular schwannomas (VS). The planning elaborated by the first author with an experience of 27 years and more than 15000 doseplanning is serving as a reference. The constraints determined by the planner lead the IP for a first real-time planning. Interactive additional constraints are proposed by the planner in order to optimize the plan and a second optimized plan is calculated by the IP. The primary endpoint is the Paddick index. Coverage, selectivity and gradient indexes, dose at the organ at risk, 12 Gy isodose line volume are compared among the three plans (expert, IP run 1 and IP run 2). The statistical analyses is planned on a non-inferiority trial design.

Results: After a single run of the IP, the Paddick index of the IP is already demonstrating to be non-inferior to the one of the expert. For the expert and the IP respectively, the median conformity index was 0,99 and 0,98, the median selectivity index 0,92 and 0,90, the median gradient index was 2,95 and 2,84, the median dose at the modulus of the cochlea was 2,83 Gy and 2,86 Gy, the median number of shot 14,31 and 24,13, the median beam-on time was 46,20 min and 26,77 min.

Conclusion: These preliminary results are showing that the “Intuitive Plan” IP based on « efficient convex optimization algorithms » is providing, in real-time, high quality doseplans with excellent conformity, selectivity and gradient indexes with specially optimized beam-on time. If the new IP proposed here is truly able to compete in real -ime with the quality of the plans of an expert with long years of experience, this would allow customers with limited experience to provide immediately there patients with high quality GKS. Moreover, for more experienced users, it may also help to save both time spent planning and beam-on time, while being able to interact intuitively with the dosimetry.

Jean REGIS (MARSEILLE), Hamdi HUSSEIN, Louise MERLY, Castillo LAURA, Anne BALOSSIER, Giorgio SPATOLA

10:15 - 10:45 COFFEE BREAK -POSTERS & EXHIBITION
10:45
10:45-11:15
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A44
PARALLEL SESSION
NOVEL TECHNOLOGIES & TECHNIQUES - PART II

PARALLEL SESSION
NOVEL TECHNOLOGIES & TECHNIQUES - PART II

Moderators: John ADLER (neurosurgery) (Région de la baie de San Francisco, USA), Marc LEVIVIER (Chef de Service) (Lausanne, SWITZERLAND), Sergio MORENO-JIMENEZ (Chief) (Mexico city, MEXICO)
10:45 - 10:55 #17633 - a44-1 Procedural aspects of stereotactic radiosurgery for ablation of ventricular tachycardia.
a44-1 Procedural aspects of stereotactic radiosurgery for ablation of ventricular tachycardia.

Purpose

Authors present procedural aspects based on case report series of cardiac radiosurgery in a patient with malignant ventricular tachycardia.

Material and methods

Patients with stable chronic heart failure (NYHA II, III) with decreased left ventricular ejection fraction, recurrent therapies for VT from Implantable Cardioverter Defibrillator (ICD) and failure of catheter ablation were treated by radiosurgical ablation. Stereotactic radiosurgery system CyberKnife was used. The location of the critical part of the arrhythmogenic substrate was determined by electroanatomic mapping during catheter ablation procedure. The ICD lead was used as a surrogate for compensation of respiratory movements. No additional margin for Planning Target Volume (PTV) was added. We evaluated dosimetric aspects and and radiation-induced events.

 

Results

From January 2014 until March 2017, ten patients (9 males/1 female), mean age 66 years (range 64-80) received radiosurgical ablation 25Gy in one fraction. Mean PTV, treatment duration,  isodose line with prescribed dose, conformality index, and homogeneity index were 22.15 ccm (range 14.2-29.6), 68 min (range 45-80), 80% (range 66-84), 1.28 (range 1.15-1.78) and 1.24 (range 1.19-1.52), respectively. Nine correlation models have to be often created, median one per 12 minutes (range 2-15 min), to reach precision better than 3 mm (average correlation error 1,1 mm). Only one type of acute radiation-related toxicity was observed: nausea occurred in four patients with the target volume localized in the inferior wall of the left ventricle, close to the stomach. All four patients showed a good response to setron-based antiemetic drugs administered for three days. One patient (number 5 in apendix) with known mitral regurgitation presented with progression of regurgitation and changes in valvular morphology 17 month after radiosurgery (possible grade 3 late radiation related toxicity). No other late radiation-related toxicity events were observed and three patients suffered non-arrhythmic deaths during long follow up.

Conclusion

Stereotactic radiosurgery of recurrent ventricular tachycardia is feasible and seems a viable option as a bail-out procedure after failed catheter ablation of VT.

Jakub CVEK (OSTRAVA, CZECH REPUBLIC), Radek NEUWIRTH, Lukas KNYBEL, Otakar JIRAVSKY, Lukas MOLENDA, Josef KAUTZNER, Marek SRAMKO, Petr PEICHL
11:05 - 11:15 #17738 - a44-3 Laser interstitial thermal therapy (LITT) in the diagnosis and treatment of suspected radiation-induced inflammation vs recurrence after SRS.
a44-3 Laser interstitial thermal therapy (LITT) in the diagnosis and treatment of suspected radiation-induced inflammation vs recurrence after SRS.

Brain metastases show very high rates of response to stereotactic radiosurgery (SRS.) However, a substantial fraction of treated lesions will enlarge and/or become more conspicuous, as early as 4 months or as late as 3 years or more, following SRS.  Management of these lesions is complicated by difficulty in definitively distinguishing radiation-induced inflammation (radionecrosis) from tumor recurrence / progression on imaging.  Surgical resection of a lesion can provide a histologic diagnosis and therapeutic benefit in such cases, but has dangers in patients who are poor surgical candidates. Conversely, stereotactic biopsy can provide a diagnosis with minimal risk, but does not provide needed therapeutic relief. Laser Interstitial Thermal Therapy (LITT), which combines minimally invasive laser thermal ablation with real time in vivo MRI-based temperature monitoring, has now emerged as a successful treatment approach for the management of radiographically progressive metastatic lesions post-SRS, which might otherwise have few remaining options. LITT proves effective against both radiation-induced inflammation and recurrent metastatic disease. Furthermore, ample evidence suggests LITT opens the blood-brain barrier (BBB) for a period of time after treatment, improving otherwise poor access for other modalities, including immune-based platforms. Therefore, LITT is well-suited to intracranial lesions, proffering a novel treatment platform on its own, while simultaneously potentiating therapies that otherwise provide limited efficacy in the brain. Unfortunately, LITT remains handicapped by a small radius of treatment (lesions larger than 3cm provide a challenge) and a lack of treatment specificity for tumor versus normal tissue. Despite these limits, LITT has reshaped our multi-disciplinary treatment algorithm for radiographic progression as applied in our Center for Brain Metastasis. We present our current clinical experience with LITT in more than 50 cases of radiographically progressing post-SRS metastatic lesions. We also highlight our research efforts to enhance the technology with a novel nanotechnology platform.

Peter FECCI (Durham, USA), Scott FLOYD, Jordan TOROK, John KIRKPATRICK
10:45 - 11:15 #17740 - A44-4 Molecular profiling of high dose irradiated tissues identifies differential gene expression profiles between conventional and high dose “flash” protons.
A44-4 Molecular profiling of high dose irradiated tissues identifies differential gene expression profiles between conventional and high dose “flash” protons.

Recent studies have highlighted an enhanced therapeutic index of ultra-high dose rate, or FLASH, irradiation compared to conventional radiation treatment modalities (Favaudon et al., 2014). However, the molecular correlates of response remain unknown and may aid to delineate the molecular underpinnings of efficacy and toxicity.  While previous studies have focused on experimental aspects of electron FLASH we sought to test proton FLASH in a preclinical setting. To this end, a clinical Varian ProBeam irradiated the entire thoracic region of sex and age matched mice to a dose range of 15-20 Gy at FLASH (40 Gy/sec), Conventional (1 Gy/s) and pulsed-FLASH (FLASH dose split into 10 doses at 1 second intervals) dose rates. Upon sacrifice after 24 hours, the lungs were harvested for histology and genetic expression profiling using Agilent mouse genome arrays. We observed 15 and 20-fold fewer differentially expressed genes in FLASH and pulsed-FLASH respectively when compared to the conventionally treated samples. To systematically assess the response pathways, we conducted Gene Set Enrichment Analysis (GSEA) on all expression profiles and observed down regulation of cell cycle and mitotic pathways in all treatment groups. Notably, split-flash induced immune and inflammatory signaling pathways such as JAK-STAT. We observed up to a 30% reduction in lung fibrosis, as well as reduced incidence of skin dermatitis and improved overall survival in FLASH- vs conventionally-treated mice. These findings highlight that flash modalities induce a unique subset of pathways which are not present in conventional proton therapy. Future work will seek to further validate our preliminary results of differential expression profiles and to provide insight into the mechanism of action of FLASH radiation and its impact on potential therapeutic opportunities.

Angel KU VILLANUEVA, Swati GIRDHANI, Eric ABEL, Isabel JACKSON, John ELEY, Zeljko VUJASKOVIC, Renate PARRY, Sengupta DEBANTI (Palo ALto, USA)

10:45-11:45
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B44
PARALLEL SESSION
OVERVIEW OF CURRENT TREATMENT TECHNIQUES FOR GLIOMAS

PARALLEL SESSION
OVERVIEW OF CURRENT TREATMENT TECHNIQUES FOR GLIOMAS

Moderators: Jing LI (Radiation Oncologist) (Houston, USA), Marcos MALDAUN (Neurosurgical Oncology) (São Paulo - SP, BRAZIL), José Marcus ROTTA (Presidente) (BRAZIL)
10:45 - 10:55 Advancements of Immunotherapy for GBMs. Samuel CHAO (Radiation Oncologist) (Cleveland, USA)
10:55 - 11:05 What are the target and margin? John KIRKPATRICK (Professor - Radiation Oncology & Neurosurgey) (Durham, NC, USA)
The rationale for radiosurgery the contrast-enhancing lesion alone in recurrent malignant gliomas
11:05 - 11:15 Radiosurgery and Stereotactic Radiotherapy for Gliomas. Luis LARREA (Director) (Valencia, SPAIN)
11:15 - 11:25 Multimodality Approach for Glioma Management. Tony WANG (Associate Professor of Radiation Oncology) (New York, USA)
11:25 - 11:35 20 Years of Leading Edge GBM Radiosurgery: An Update. Christopher DUMA (Speaker) (Newport Beach, USA)

10:45-11:15
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C44
Oral Session
OCULAR DISORDERS

Oral Session
OCULAR DISORDERS

Moderators: Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL), Andrey GOLANOV (Head of the Department) (Moscow, RUSSIA), Bruno SANTOS (Neurosurgeon) (Aracaju, BRAZIL)
10:45 - 10:55 #16743 - c44-1 Relative survival rates and complications in uveal melanoma patients after C LINAC stereotactic radiosurgery.
c44-1 Relative survival rates and complications in uveal melanoma patients after C LINAC stereotactic radiosurgery.

Uveal melanoma (iris, ciliary body, choroid) is the most frequent intraocular malignant tumor in adults.

Long term analysis of 168 patients with intraocular uveal melanoma treated by stereotactic radio surgery (SRS) at linear accelerator in Slovakia by "One-day session" radiosurgery at C LINAC. The median tumor volume at baseline was 0.3cm3 with range from 0.05 to 2.6cm3. The therapeutic dose was 35.0Gy by 99% of DVH (dose volume histogram). Average overall survival after stereotactic irradiation was 1st year after SRS 96.4%, 2nd year 83%, in 5 years 82.7%. Survival rates at 5-year interval and the rates of secondary enucleating due to complications after one-day session linear accelerator irradiation were comparable to those achieved with other irradiation techniques used for treatment uveal melanoma. Radiation complications can lead to visual acuity reduction or secondary enucleation of the eye globe. Radiation-induced optic neuropathy (RION) is a severe ocular complication developing in high-risk patients with uveal melanoma after SRS. We analysed association between the secondary enucleation and the presence of secondary glaucoma or hemophtalmus as well as of the radiation-induced optic neuropathy after SRS. Secondary enucleation was necessary 16.7% patients due to secondary glaucoma. The presence of RION was significantly associated with a higher dose on the optic nerve (P=0.0123 in invariable and 0.0049 in multivariable analysis, respectively). Importantly, the overall survival of patients who underwent secondary enucleation was not different from the survival of patients without enucleation (P=0.7501).

Alena FURDOVA (Bratislava SLOVAKIA, SLOVAKIA), Miron SRAMKA, Gabriel KRALIK, Martin CHORVATH
10:55 - 11:05 #17733 - c44-2 Gamma-Knife radiosurgery as an eye salvage treatment of intraocular retinoblastoma: three-year results of a pilot study.
c44-2 Gamma-Knife radiosurgery as an eye salvage treatment of intraocular retinoblastoma: three-year results of a pilot study.

Background: In some cases of chemoresistant or recurrent intraocular retinoblastoma (Rb) external beam radiotherapy (RT) is the only way to save the eye. Due to severe complications conventional RT currently has very limited use. To the best of our knowledge there is no information concerning Gamma-knife radiosurgery (GKRS) in the management of Rb.

Purpose: To present the three-year experience of single fraction GKRS of Rb as an alternative to enucleation.

Methods: Since June 2015 fifteen eyes of 14 patients aged from 12 to 114 months (mean 35) with Rb Group B (n=4), Group C (n=1) and Group D (n=10) were treated with GKRS. All patients previously were treated with all kinds of chemotherapy including systemic, intra-arterial, and intravitreal, different kinds of focal ophthalmological treatment. Due to different reasons there were no capabilities to preserve the eye using conventional approaches.

Three types of dosimetric plans were used and will be presented – single PTV for the whole vitreous cavity (3 eyes), PTV for single retinal or vitreous tumor (8 eyes), and double PTVs for double retinal tumors or retinal and vitreous lesions (4 eyes). In cases of massive vitreous Rb (4 patients) irradiation dose of 20-22 Gy at 50% isodose was prescribed along the inner MRI/CT contour of the eye globe and the lens. The retinal tumors were treated with 22-24 Gy at 50% isodose. Doses for critical structures of the eye and orbit have been also taken into consideration, and will be presented.

Results: Fourteen eyes were preserved. Complete tumor regression was achieved in 11 eyes. In 3 eyes more than 50% regression was seen. One eye was enucleated because of suspicion of tumor progression. Complications were analysed according to time after chemotherapy. Vitreous hemorrhage occurred in 4 patients and was successfully managed conservatively or surgically with intraocular Melphalan irrigation. In 5 eyes mild to moderate optic neuropathy and/or retinopathy developed. In 3 eyes retinal detachment occurred. One eye developed eccentric opacities of posterior lens capsule. No signs of iridocyclitis, keratopathy, and damage of orbital tissues, bones, or brain were seen. Follow-up was from 4 to 41 months (mean 12.5).          

Conclusions: The three-year experience of GKRS for Rb showed that it may be a reasonable treatment approach as an alternative to enucleation in selective cases. 

Andrey YAROVOY, Vera YAROVAYA (Moscow, RUSSIA), Andrey GOLANOV, Valery KOSTJUCHENKO, Karina DZICCOEVA
11:05 - 11:15 #17781 - c44-3 Outcomes of gamma-knife radiosurgery of posterior uveal melanoma unsuitable for other eye-sparing treatment modalities.
c44-3 Outcomes of gamma-knife radiosurgery of posterior uveal melanoma unsuitable for other eye-sparing treatment modalities.

Currently a wide spectrum of eye-sparing treatment modalities for posterior uveal melanoma (PUM) are in use but they have limited indications.

Purpose: to present the results of gamma-knife radiosurgery (GKRS) of PUM unsuitable for other eye-sparing treatment modalities.

 Methods: Since 2012 sixteen consecutive patients aged from 15 to 78 years with PUM were included into the study and treated with GKRS. These tumors were not indicated to other eye-sparing modalities available in our clinic – ruthenium-106 brachytherapy, transretinal excision, transscleral excision, or laser treatment, because of the size or/and location. Majority of patients refused to remove the eye. Two patients had the only eye. Tumor thickness was from 5.5 to 9.6 mm, mean 7.7 mm, basal diameter from 9.4 to 21.4 mm, mean 15.0 mm. Four tumors were juxtapapillar. GKRS irradiation doses were 35-40 Gy on 50% isodose curve.

Results: Partial tumor regression was achieved in all cases. There were no cases of complete regression. Regression after GKRS was much slower than after brachytherapy. Two peripapillar tumors progressed and the eyes were enucleated.  Two patients underwent endoresection of irradiated tumors 2 years after GKRS because of very limited response. One eye was removed because of phthisis bulbi. Vision increased in 3 patients, decreased in 5. One patient developed liver metastasis and died in 2 years after treatment. Thirteen eyes (81%) were preserved. The follow up was from 12 to 82 months, mean 39 months.

Conclusion: GKRS is an effective treatment option for PUM not suitable for brachytherapy or surgical excision and can save the eye and vision in selective cases.

Andrey YAROVOY (Moscow, RUSSIA), Andrey GOLANOV, Valery KOSTJUCHENKO, Vera YAROVAYA, Amina CHOCHAEVA

11:15
11:15-11:45
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A45
PARALLEL SESSION
EXPANDING APPLICATION OF SBRT: HEAD AND NECK -- OLIGOMETASTASES

PARALLEL SESSION
EXPANDING APPLICATION OF SBRT: HEAD AND NECK -- OLIGOMETASTASES

Moderators: Ana BOTERO (Radiation Oncologist) (Pembroke Pines, USA), Miguel A. CELIS (DIRECTOR) (MEXICO, MEXICO), Sebastiao CORREA (RADIO-Oncologist) (São Paulo, BRAZIL)
11:15 - 11:25 #17814 - a45-1 Stereotactic Body Radiotherapy (SBRT) for head and neck cancers in previously unirradiated medically unfit patients.
a45-1 Stereotactic Body Radiotherapy (SBRT) for head and neck cancers in previously unirradiated medically unfit patients.

Background

SBRT has been established as an option for treatment of recurrent cancers of the head and neck (H&N) in previously irradiated patients. There has been limited data published on using SBRT palliatively for patients who have not undergone previous radiation therapy (RT).

Material and Methods

From August 2011 to August 2018, 66 patients with cancers of the H&N who had not received previous RT were treated with SBRT. Median age was 80 years (range, 25-98). 40 patients were men and 26 were women. 45 patients had newly diagnosed H&N cancers and 21 had recurrences previously treated by surgery. All were not considered to be candidates for curative treatment via surgery or conventionally fractionated chemoRT due to extent of primary of disease, presence of metastases or performance status. Median KPS was 70 (range, 50-90). Median SBRT dose was 40 Gy (range, 24-40). All but two patients underwent 5 fraction regimens. Median number of days between first and last fraction of SBRT was 15. Median PTV volume was 82 cubic centimeters. 32 patients received concurrent systemic therapy with SBRT (6 chemotherapy, 20 cetuximab, 4 chemotherapy and cetuximab, 2 nivolumab) and 34 patients received no systemic therapy.

Results

Median follow-up was 16 months (range, 1-89). Overall survival was 44% with a median survival of 10 months (range, 1-47). Local control was 68%, with 21 patients failing in-field at a median of 4.3 months. An additional 4 patients experienced marginal failure, with the majority of the recurrence occurring outside of the SBRT PTV.  Regional and distant control were 73% and 76%, respectively. No collected variables had a significant effect on control or survival using univariate and multivariate analysis, including age, gender, race, KPS, smoking, alcohol, stage, dose, time elapsed during SBRT, PTV volume or use of concurrent systemic therapy. Only two patients (3%) experienced grade 3+ toxicity, which included one grade 3 dysphagia and one grade 3 anorexia.  

Conclusion

SBRT is a viable option for control and palliation in previously unirradiated patients with H&N cancers who are not candidates for curative treatment. Rates of control, survival and toxicity are all similar to those reported in previously irradiated patients.

Emile GOGINENI (New York, USA), Zaker RANA, Prashant VEMPATI, Jessie KARTEN, Anurag SHARMA, Douglas FRANK, Doru PAUL, Nagashree SEETHARAMU, Maged GHALY
11:25 - 11:30 #17813 - a45-2 Safety and efficacy of repeat stereotactic body radiotherapy (SBRT) for local recurrence of head and neck cancer after initial SBRT.
a45-2 Safety and efficacy of repeat stereotactic body radiotherapy (SBRT) for local recurrence of head and neck cancer after initial SBRT.

Background

SBRT has been established as an option for treatment of recurrent cancers of the head and neck (H&N) in previously irradiated patients. There has been limited data published on effective means of salvaging patients who fail SBRT. Here we report on the safety and efficacy of repeat SBRT (RSBRT).

Material and Methods

From October 2012 to May 2018, 9 patients with local relapse of primary H&N cancer who failed first course of SBRT (FSBRT) were retreated with RSBRT. Median age at RSBRT was 67 years (range, 51-90). 7 patients were men and 2 were women. FSBRT doses were 25 Gy in 1 patient, 35 Gy in 3 patients and 40 Gy in 5 patients, all in 5 fractions. 3 patients received concurrent chemotherapy (CT) and 2 patients received concurrent cetuximab (CET) with first course of SBRT. Maximum toxicity grades were between 0 and 2 for FSBRT using CTCAE version 5.0. Local recurrences were diagnosed by CT and/or PET scans showing increasing size and/or avidity and confirmed pathologically via biopsy. Median interval between FSBRT and RSBRT was 9 months (range, 5-27). RSBRT doses were 35 Gy in 4 patients and 40 Gy in 5 patients, all in 5 fractions. Median PTV volume of RSBRT was 34.7 cubic centimeters (range, 8.6-90.2). The median percentage volume of overlap between the two SBRT courses was 64% (range, 26-100). 4 patients received concurrent CT, 4 patients received concurrent CET and 1 patient received concurrent nivolumab with RSBRT.

Results

 

Median follow-up (FU) from completion of RSBRT was 8 mo (range, 5-36). Overall survival rates were 78% at 6 mo and 57% at 12 mo. Local failure occurred in 4 patients, with one additional experiencing marginal failure, as the majority of recurrent tumor occurred outside of the PTV in this patient. Median time to recurrence was 4 mo (range, 2-13). 4 patients had not developed recurrence until their death or last FU at a median of 12 mo (range, 6-36). 9, 3 and 2 patients experienced grades 1, 2 and 3 toxicities, respectively. Grade 3 toxicities included fatigue in one patient and hearing loss in another, an expected side effect given that the cochlea fell within the PTV for both courses of SBRT.  No patient experienced grade 4 or 5 toxicities.

Conclusion

Repeat SBRT was well-tolerated, with rates of grade 3+ toxicity similar to those previously reported on H&N SBRT. Repeat SBRT is a viable option for those who fail initial SBRT.

Emile GOGINENI (New York, USA), Zaker RANA, Adam RIEGEL, Luis MADURO, Michael WOTMAN, Mihaela MARRERO, Edward GABALSKI, Lucio PEREIRA, Doru PAUL, Nagashree SEETHARAMU, Maged GHALY
11:30 - 11:35 #17815 - a45-3 Using the G8 screening tool to predict quality adjusted survival for elderly head and neck cancer patients treated with stereotactic body radiotherapy (SBRT).
a45-3 Using the G8 screening tool to predict quality adjusted survival for elderly head and neck cancer patients treated with stereotactic body radiotherapy (SBRT).

Background

The G8 has been a useful prognostic tool at baseline in order to predict elderly patients’ ability to tolerate surgery, chemotherapy and conventionally fractionated radiation. Studies have identified that patients with lower baseline scores, with the most common cutoff being 14, will be unable to complete curative treatment and should be considered instead for palliative measures. There has been limited data on how patients with lower baseline scores will respond to SBRT in terms of ability to tolerate treatment, local control (LC) and overall survival (OS). Additionally, while the G8 has been used as a predictor of prognosis at baseline, there has been little published on its use at follow-up (FU) after treatment.

Material and Methods

From December 2012 to November 2016, 171 patients with cancers of the H&N were treated with palliative SBRT. Median age and KPS were 75 years and 70 respectively. G8 scores were captured for all patients at baseline, 4-6 weeks FU after SBRT and 2-3 month FU. Factors influencing changes in baseline G8 score were compared through repeated measures ANOVA and the impact of change in score on OS and LC were calculated through Kaplan-Meier analysis.

Results

Median FU was 17.0 mo. Median baseline G8 was 10.5 (range, 4.5-16.0). OS was 40.4% with a median survival (MS) of 18.4 months. There were no significant differences in patients with baseline scores <=14 vs >14 in LC (71.0% vs 86.0%, p=0.104) or OS (38.3% vs 54.5%, p=0.171). Patients who saw a decrease in their G8 score at 2-3 month FU (n=69) had an OS of 8.7% with a MS of 8.6 months. This was significantly lower than patients who had a stable or increase in their G8 score at 2-3 month FU (n=102) with an OS of 61.8% and MS of 35.9 months (p<.001). Change in G8 score did not significantly affect local, regional or distant control, which were 74%, 67% and 60%, respectively. Grade 3 toxicity occurred in 9% of patients and there were no grade 4 or 5 toxicities.

Conclusion

Patients who are not candidates for curative treatment who have low baseline G8 scores still benefit from palliative SBRT, with high rates of LC.  Decline in G8 scores from baseline at 4-6 weeks and 2-3 months FU significantly predict worse OS compared to patients with stable or increasing G8 scores.  

Emile GOGINENI (New York, USA), Michael WOTMAN, Zaker RANA, Jessie KARTEN, Adam RIEGEL, Luis MADURO, Dev KAMDAR, Doru PAUL, Nagashree SEETHARAMU, Maged GHALY
11:35 - 11:45 Results of Oligometastases with SBRT. Daniel TRIFILETTI (Assistant Professor) (Jacksonville, USA)

11:15-13:00
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C45
Oral Session
MENINGIOMAS

Oral Session
MENINGIOMAS

Moderators: Gus BEUTE (Neurosurgeon) (Tilburg, THE NETHERLANDS), Waltter KRAVCIO (NEUROSURGEON) (PANAMA, PANAMA), Dennis SHRIEVE (Professor and Chair) (Salt Lake City, USA)
11:15 - 11:25 #17630 - c45-1 Optic nerve sheath meningiomas multisession radiosurgery. Preliminary results from a prospective study.
c45-1 Optic nerve sheath meningiomas multisession radiosurgery. Preliminary results from a prospective study.

Objective. Optic nerve sheath meningiomas are rare benign neoplasms of the meninges surrounding the optic nerve. These can be a significant cause of visual impairment. Traditional treatment options for optic nerve sheath meningiomas (ONSM) include observation, surgery and radiotherapy, but to date none of these has become the clear treatment of choice.

The aim of this study is to evaluate the safety, especially in term of visual sparing, and the effectiveness of multisession radiosurgery for ONSM.

Materials and methods. This is a prospective single center. Patients suffering for ONSM which underwent a multisession radiosurgery have been considered.

Inclusions criteria are a ONSM diagnosis, visual impairment at presentation, progression of visual dysfunction during the observation period, disease progression. Adulthood and the informed consent signature are also required. Due to the histological diagnosis imply an invasive and hazardous procedure, no biopsies will be performed and the diagnosis will be exclusively radiological.

Results. According to the study protocol 50 patients underwent a mRS in the period between February 2011 and November 2018. All, had a 25 Gy treatment delivered in five fraction (five consecutive days), prescribed to the 77-91 % isodose line (median 82%). The mean age at the treatment time was 51 years old (range 18-82; median 51 yrs). The mean treatment volume was 2.5 cc (range 0.5-9.5; median 1.8 cc). The mean dose to the treated optic nerve ranged between 8.3 and 28.5 Gy (median 24.4 Gy); the maximum point dose ranged between 20.1 and 32.5 Gy (median 29.4 Gy). The mean dose to the optic chiasm ranged between 1.5 and 21.9 Gy (median 4.6 Gy).

After a mean follow-up period of 35 months (range 4-80: median 30 months) only one patients (2%) developed  a visual worsening. Eight patients (16 %) improved and 41 were stable along the follow-up period.

The toxicity rate was always very low and no patients required medication due to complication related to the treatment.

None of the treated meningioma showed a radiological progression

Conclusions. Multisession radiosurgery for ONSMs was found to be safe and effective. Twenty-five Gy delivered in 5 fractions is an effective treatment modality for these kind of tumors. The treatment schedule controlled the tumors while sparing visual function.

Marcello MARCHETTI (Milano, ITALY), Valentina PINZI, Cecilia IEZZONI, Laura FARISELLI
11:25 - 11:35 #17642 - c45-2 Hypofractionated stereotactic radiosurgery for large-sized skull base meningiomas: a preliminary report on 31 patients.
c45-2 Hypofractionated stereotactic radiosurgery for large-sized skull base meningiomas: a preliminary report on 31 patients.

Purpose: Although stereotactic radiosurgery (SRS) has been proved to be effective and safe in the treatment of intracranial meningiomas, concerns are raised in the use of SRS for large-sized tumors with involvement of the skull base, which frequently encroach onto adjacent critical neurovascular structures. Here we investigated the role of hypofractionated SRS as a therapeutic option for large-sized skull base meningiomas.

Materials and Methods: Between November 2011 and December 2014, thirty-one consecutive patients (median age 55 years, 9 men and 22 women) had been treated with hypofractionated SRS using the CyberKnife for large-sized skull base meningiomas > 10 cm3 in volume (median volume 18.9 cm3, range 11.6-58.2 cm3). All patients harbored middle or posterior skull base tumors, most frequently of cavernous sinus (n=7, 22.6%), petroclival (n=6, 19.4%), or medial tentorial edge (n=6, 19.4%) locations. Most of them (n=27, 87.1%) did not receive any prior therapy and 4 patients received prior partial resection of the tumor. SRS was delivered in five daily fractions (range 3-5 fractions) with a median cumulative dose 27.8 Gy (range 22.6-27.8 Gy).

Results: With a median follow-up of 33 months (range 9-61 months), tumor control was achieved in 28 of 31 patients (90.3%). Treatment response on MRI included partial response (volume decrease > 20%) in 17 patients (54.8%), stable in 11 (35.5%), and progression (volume increase > 20%) in 3 (9.7%). Neurological symptoms improved in 10 patients (32.2%), unchanged in 20 (64.5%), and worsened in 1 (3.2%). Three patients underwent a craniotomy for their progressive tumors, which disclosed a histological diagnosis of atypical meningioma in all of them.

Conclusions: Our preliminary results suggest a promising role of hypofractionated SRS for large-sized skull base megningiomas in terms of both tumor control and functional outcomes, representing a reasonable therapeutic option in select patients.

Young Hyun CHO (SEOUL, KOREA), Hyuk-Jin OH, Kyoungjun YOON, Eun Suk PARK, Do Hee LEE, Do Hoon KWON
11:35 - 11:45 #17675 - c45-3 Long-term outcome of low dose (≦12 Gy) gamma knife radiosurgery for skull base meningiomas.
c45-3 Long-term outcome of low dose (≦12 Gy) gamma knife radiosurgery for skull base meningiomas.

 Objective: The optimal doses of radiosurgery for skull base meningioma have been reported 13 - 15 Gy. We have been intended to perform low dose radiosurgery for treating close to critical structure of skull base. We evaluate long-term efficacy of low dose (≦12 Gy) gamma knife radiosurgery (GKS).

Methods:Between January 1994 and May 2013, the authors treated WHO grade  Ⅰmeningiomas in 295 patients using low dose radiosurgery. Median treatment volume was  6.9 cm3, median prescribed marginal dose was 12 Gy (range 8 -12 Gy) . 22 patients with large volume tumors were treated by two-staged radiosurgery (volume fractions).

Results:  The mead duration of follow-up was 8.7 years (range 0.5 - 21 years). Local tumor growth control was 85%, Actuarial local control rates at 5, 15, and 15 years were 92%, 82%, and 74%, respectively. 5% were aggressive change of tumors. Univariative analysis revealed without preGKS surgery and below 60 years old were positive factor and sex, tumor volume, treatment dose, staged surgery were not significant for tumor control. The clinical outcome was improved in 15% and unchanged in 69% of patients. The radiation induced neuropathy occurred 7.1% (21 patients). The trigeminal neuralgia considering most devastating symptoms was improved or disappeared in 40% (4/10patients), but new trigeminal neuralgia was occurred in 4.4%(13 patients).

Conclusion:The low dose GKS (≦12 Gy) for skull base meningiomas can achieve long-term tumor growth control with low morbidity with a long-term follow-up period of > 8.5 years.But the aggressive change was still difficult to control; this not related radiosurgery however this may be natural course. 

Yoshiyasu IWAI, Hiroshi UDA (Osaka, JAPAN), Kazuhiro YAMANAKA, Kenichi ISHIBASHI
11:45 - 11:55 #17684 - c45-4 Gamma knife radiosurgery as primary treatment for convexity meningiomas: clinical results at long-term follow-up in a series of 206 lesions.
c45-4 Gamma knife radiosurgery as primary treatment for convexity meningiomas: clinical results at long-term follow-up in a series of 206 lesions.

Object. Surgical resection has been for many years the treatment of choice for intracranial convexity meningiomas. To date Gamma Knife Radiosurgery (GKRS) has gained a clinical validation for the treatment of small, deep-seated tumors or in case of patients not eligible for surgery. Nevertheless, its role in the treatment of convexity meningiomas is still debated, due to the lack of clinical evidence. The present study aims to assess safety and efficacy of GKRS, as primary treatment for convexity meningiomas.

Methods. One-hundred-fifty-nine patients (107 females and 52 males; mean age: 59.7 years) harboring convexity meningiomas underwent GKRS as primary treatment, between January 2001 and December 2014. The total number of lesions was 206, with an average volume of 2.28 cm(median 1.35 cm3). Median margin dose was 15 Gy.

Results.The mean clinical and radiological follow-up (FU) were 65.1 and 56.1 months, respectively. At last FU 89.3% of lesions were stable or reduced in size. The actuarial 3-, 5- and 10-year progression-free survival were 94%, 92% and 76%, respectively. The actuarial 3-, 5- and 10-year local tumor control were 97%, 94% and 87%, respectively. Permanent complications after GKRS were reported in 6 cases (3.8%). Failure rate of GKRS was 10.7%. No treatment-related deaths were recorded.

Conclusion. GKRS demonstrated to be a safe and effective treatment for intracranial convexity meningioma providing high tumor control rates with low treatment-related morbidity. GKRS may represent a valuable alternative to surgery as primary treatment for patients harboring small lesions, or for whom are not eligible for surgery.

Filippo GAGLIARDI (MILAN, ITALY), Michele BAILO, Giuseppe BARISANO, Nicola BOARI, Antonella DEL VECCHIO, Angelo BOLOGNESI, Pietro MORTINI
11:55 - 12:05 #17696 - c45-5 Optimized hypofractionated SRS regimens for perioptic lesions based on low alpha/beta ratio of the optic pathway.
c45-5 Optimized hypofractionated SRS regimens for perioptic lesions based on low alpha/beta ratio of the optic pathway.

Objectives:

Theoretically, hypofractionation can only be justified if there is a positive difference between alpha/beta ratio of the lesion and the alpha/beta ratio of the surrounding organs at risk. For the visual system 3 different alpha/beta ratios have been published so far, two of them negative, stressing the theoretical model. The knowledge of the alpha/beta ratio of the optic pathway is essential to calculate radiobiological dose parameters, such as the single fraction equivalent dose (SFED), from which optimized hypofractionated SRS (HF-SRS) regimens for perioptic lesions can be derived.

 

Material and methods

The alpha/beta ratio of the optic pathways was estimated from a meta-analysis of 429 studies published between 2000 and June 2018. We included 15 studies with fraction sizes between 1 and 31, considering the following inclusion criteria: frequency of radiation induced optical neuropathy, RION between >0% and <10%, follow up period of at least 24 months, no tumor progression, no prior radiation and detailed dosimetric analysis for the visual system. Additionally we included results from our center on 68 HF-SRS treatments and 161 single fraction treatments for perioptic lesions.

 

Results

The Fraction Equivalent (FE) plot method revealed an alpha/beta ratio of the optic pathway of 1.03 Gy, confidence interval [-0.38 – 1.60]. Based on this result and published alpha/beta ratios of brain tumors, optimized HF-SRS regimens were derived from SFED calculations. An increased SFED of up to 10% for perioptic meningiomas and of more than 25% for malignant tumors can be reached with optimized HF-SRS schedules, maintaining the same low risk of radiation induced optic neuropathy.

 

Conclusion

A significant benefit from HF-SRS can be achieved, because of the relatively low alpha/beta ratio of the optic system of 1.03 Gy. HF-SRS schedules can be optimized based on the knowledge of alpha/beta ratios and SFED calculations.

Herwin SPECKTER (Santo Domingo, DOMINICAN REPUBLIC), Jairo SANTANA, Jose BIDO, Giancarlo HERNANDEZ, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Peter STOETER
12:05 - 12:15 #17701 - c45-6 Atypical Meningiomas: pattern of post radiotherapy recurrences in relation to the irradiated area.
c45-6 Atypical Meningiomas: pattern of post radiotherapy recurrences in relation to the irradiated area.

Purpose:

In radiotherapy for macroscopic (residual) disease in atypical meningioma (AM), target volume definition and prescribed doses vary. Insight into the recurrence pattern of these tumors is needed for optimal target definition. The purpose of this study is to describe the patterns of recurrence after postoperative or salvage radiotherapy in our patients with AM.

 

Patients and methods:

Twenty-nine consecutive patients with AM referred to our department from 2005 through 2016 were retrospectively studied. Fractionated stereotactic radiotherapy (FSRT) was performed on a dedicated linac. The CTV was defined as the macroscopic tumor and included adjacent tissues that contained residual microscopic disease. CTV-PTV margin was 2mm. Prescribed doses were mostly 25-35Gy in 5 -7 fractions or 54-60Gy in 30 fractions, depending on the size of the PTV. The MRI scans that showed recurrent disease were registered with the planning CT and MRI scans to characterize the recurrences as in-field, marginal or distant. The relation of the recurrences with the dura was determined. 

 

Results

In total the included patients received 73 surgeries and 56 FSRT treatments. Median follow-up after FSRT was 11.2 years. In 72.4% of the patients a recurrence was diagnosed after FSRT. We found 26 in-field, 6 marginal and 7 distant recurrences; all were connected to the dura. First recurrence after first radiotherapy appeared after a median time of 3.3 years. Median survival after first radiotherapy was 8.7 years.

 

Conclusion

AM frequently recurs and multiple surgeries and radiation treatments may be needed. Most post radiotherapy recurrences of AM originate in or close to the irradiated dura and not in other adjacent tissues.  The high rate of in-field recurrence suggests high doses are needed. The high frequency of marginal recurrences suggests that radiation should be directed not only at the macroscopic tumor, but also at the adjacent dura.


Mônica Helena SCHURING-PEREIRA (Rotterdam, THE NETHERLANDS), Mirjam MAST, Jan VAN SANTVOORT, Rishi NANDOE TEWARIE, Rogier HAGENBEEK, Sjoerd VAN DUINEN, Ruud WIGGENRAAD
12:15 - 12:25 #17718 - c45-7 Hypofractionated SRS versus single session SRS for perioptic lesions. A single center study of 245 patients.
c45-7 Hypofractionated SRS versus single session SRS for perioptic lesions. A single center study of 245 patients.

Objectives:

Hypofractionated radiosurgery (HFSRS) of lesions in the sellar region is still controversially discussed as an alternative to single session SRS.

 

Material and methods

According to our protocol, HFSRS is performed when it is technically impossible to limit the maximum point dose to the anterior visual pathway (AVP) to 12 Gy. Between 2011 and 2018 a total of 72 patients with perioptic lesions (mean distance lesion-to-AVP=0.3mm, 69% in direct contact) were treated with HFSRS and 173 with single fraction (mean margin dose was 15.5 Gy, mean distance lesion-to-AVP=2.0mm, 30% in direct contact). In the HFSRS group, 7 treatments were performed with a 5 day course with a mean margin dose of 5x6.93 Gy, 56 treatments with 4x5.32 Gy, and 9 treatments with 3x6.31 Gy. Exact delineation of the optic pathways was performed on high resolution 3D T1 images and additionally since 2016 by applying FGATIR sequences.

  

Results

After a mean imaging follow-up period (FUP) of 23m [2-72m], local control was achieved in all lesions treated with HFSRS, except for 1 lesion (caused by pituitary apoplexy). An overall mean reduction in volume of 3.05%/m was observed. Mean FUP for ophthalmologic evaluation was 28m [2-79m]. Improved vision was observed in 10 cases; 1 case was confirmed for radiation induced optic neuropathy (RION) after delivery of 4x5.60 Gy as maximum optic point dose. All treatments were well tolerated and concluded satisfactorily. Spatial frame displacement during HFSRS course was measured <0.3mm using CT images. In the group of single session SRS, after a mean imaging FUP of 27m [4-78m], local control was achieved in all but 7 lesions, with an overall mean reduction of 1.52%/m. Mean FUP for ophthalmologic evaluation was 36m [7-81m]. 1 case was confirmed for RION, after delivery of 10.2 Gy as maximum optic point dose. For all patients dose volume histograms were analyzed for both nerves, both tracts and chiasm.

 

Conclusion

According to our preliminary results, HFSRS can be considered as an efficient and relatively safe alternative to treat lesions even contacting the AVP, benefiting from a low alpha/beta ratio of 1.03 Gy (study submitted to ISRS 2019) of the visual pathway.

Herwin SPECKTER (Santo Domingo, DOMINICAN REPUBLIC), Jairo SANTANA, Jose BIDO, Giancarlo HERNANDEZ, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Peter STOETER
12:25 - 12:35 #17728 - c45-8 Radiosurgical decompression for skull base meningiomas causing compressive ophthalmic neuropathy.
Radiosurgical decompression for skull base meningiomas causing compressive ophthalmic neuropathy.

Background & Purpose: Skull base meningiomas frequently need complex and technically demanding surgery risking morbidities. Radiosurgery is a strong alternative but considered as a controversial option especially for tumors causing compressive ophthalmic neuropathy. To reduce the risk of radiation toxicity, we applied hypofractionated stereotactic radiosurgery (hSRS) in treating these tumors and reviewed our outcomes.

 Methods and Materials: Nineteen patients with compressive ophthalmic neuropathy (CN II = 9; CN III/IV/VI = 12) caused by meningiomas received hSRS between 2011 and 2014. All tumors were located at the skull base (cavernous sinus = 8; petroclival = 3; clinoidal = 8). hSRS was delivered in five daily fractions with a median marginal dose of 27.1 Gy (≈14 Gy in a single fraction, assuming an α/β of three) to a tumor volume of 13.1 ± 12.2 cm3. The mean follow-up periods was 27 months.

 Results: All tumors except one shrank after treatment, with a mean volume decrease of 26.1 % (range 4-48 %). In nine patients with compressive optic neuropathy, vision improved in 66.7 % (n = 6), was unchanged in 33.3 % (n = 3). Ophthalmoplegia improved in 66.6 % of eyes (n = 8), was unchanged in 25 % (n = 3), and worsened in 8.3 % (n = 1). One patient with histologically proven atypical meningioma experienced tumor progression and aggravation in neurological symptom.

 Conclusion: Our results suggest a promising role of hSRS for skull base meningiomas causing compressive ophthalmic neuropathy in terms of both tumor control and functional outcomes.

Eun Suk PARK, Hyuk-Jin OH, Eun Jung LEE, Kyoung Jun YOON, Young Hyun CHO (SEOUL, KOREA)
12:45 - 12:55 #17799 - c45-10 Risk of carotid artery stenosis or occlusion after radiosurgery of cavernous sinus meningiomas.
c45-10 Risk of carotid artery stenosis or occlusion after radiosurgery of cavernous sinus meningiomas.

Introduction: Stereotactic radiosurgery (SRS) is an accepted treatment option for patients with cavernous sinus meningiomas (CSM).  The risk of stenosis or occlusion of the internal carotid artery (ICA) after SRS of CSM has never been reported.

Methods: Retrospective review of 154 patients (41 men/113 women) having single-fraction SRS from 1990-2015.  Inclusion criteria included no prior history of radiation and a minimum of 12 months of MRI follow-up after SRS.  Pre-SRS grading of ICA involvement was based on the method of Hirsch et al (1993): Grade I (n=62), tumor touches or partially encircles ICA; Grade II (n=57), tumor encircles but does not narrow lumen of ICA; Grade III (n=35), tumor encircles and narrows the ICA.  The median treatment volume was 8.3 cm3 (range, 0.7-42.2).  The median tumor margin dose was 15 Gy (range, 12-20).

Results: The median MRI follow-up after SRS was 8.1 years (range, 1-24.9).  No Grade I patient developed ICA narrowing.  Three Grade II patients (5.3%) had asymptomatic ICA stenosis.  Five Grade III patients (14.3%) progressed to ICA occlusion (4 asymptomatic, 1 symptomatic).  The median time after SRS to stenosis or occlusion was 4.9 years (range, 2.8-7.6).  The 5-year and 10-year risk of ICA stenosis was 4.3% and 7.1% for Grade II patients.  The 5-year and 10-year risk of ICA occlusion was 10.3% and 18.1% for Grade III patients.  The 5-year and 10-year risk of symptomatic ICA occlusion was 0.7% for the entire group, and 3.3% for Grade III patients.  Multivariate analysis found younger patient age (RR 0.92, 95% CI 0.86-0.99, p=0.03) and higher carotid grade (RR 5.4, 95% CI 1.7-17.1, p=0.004) to be associated with ICA stenosis or occlusion.   

Conclusion: ICA stenosis or occlusion was not uncommon after SRS for CSM if the tumor encircles the artery at the time of procedure, although it was typically not symptomatic. 

Bruce POLLOCK (Rochester, USA), Michael LINK, Scott STAFFORD, Ian PARNEY, Robert FOOTE

11:45
11:45-13:00
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A46
PARALLEL SESSION
FUNCTIONAL RADIOSURGERY UPDATE

PARALLEL SESSION
FUNCTIONAL RADIOSURGERY UPDATE

Moderators: Daniel BENZECRY ALMEIDA (BRAZIL), Antonio DE SALLES (Professor - Chief) (Sao Paulo, BRAZIL), David MATHIEU (Professor) (Sherbrooke, CANADA)
11:45 - 12:00 Imaging of Mind Function & Resting State fMRI. Constantin TULEASCA (Resident) (Lausanne, SWITZERLAND)
12:00 - 12:15 Facial Pain Syndromes. K Singh SAHNI (Chief, Department Of Neuroscience.) (RICHMOND, VA.USA., USA)
12:15 - 12:30 Movement Disorders. Jean REGIS (PROFESSEUR) (MARSEILLE, FRANCE)
12:30 - 12:45 Evolution of Gamma Knife Capsulotomy for Intractable Obsessive-Compulsive Disorder. Miguel EURIPEDES (Chairman of the Department of Psychiatry and Full Professor) (São Paulo - SP, BRAZIL)
12:45 - 13:00 History in the Context of Behavioral Disorder Surgery. Michael SCHULDER (Vice Chair, Neurosurgery) (Lake Success, NY, USA)

11:45-13:00
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B46
Oral Session
METASTASES #3

Oral Session
METASTASES #3

Moderators: Lily ANGELOV (Staff Neurosurgeon) (Cleveland, USA), Kita SALLABANDA (Asoc.Prof.) (Madrid, SPAIN), Leonardo VIEIRA (Doctor) (Recife, BRAZIL)
11:45 - 11:55 #17636 - b46-1 Cranial radiosurgery using ELEKTA Unity MR-LINAC. Preliminary results on patient-specific End-to-End QA for a multiple brain metastases case.
b46-1 Cranial radiosurgery using ELEKTA Unity MR-LINAC. Preliminary results on patient-specific End-to-End QA for a multiple brain metastases case.

The ELEKTA Unity MR-linac combines a 1.5T magnet with a linac. The added value for cranial radiosurgery by such a system that combines diagnostic quality MR images taken before and during radiosurgery, is expected to be high. The aim of this work is to present preliminary results regarding patient-specific End-to-End QA for a multiple brain metastasis case treated with Unity. Spatial and dosimetric accuracy are evaluated in 3D, following a full clinical patient treatment workflow.

An RTsafe polymer gel filled phantom was created using anonymized planning CT scans of a real patient. Three arbitrary brain metastases (size ~ 10 mm) were delineated on the real patient planning CT scans A Monaco treatment plan was then created. The RTsafe polymer gel filled phantom was then irradiated as if it is the real patient following the clinical workflow: set up on a head frame and a thermoplastic mask, image guidance using the Unity MR scanning capabilities and treatment delivery with Unity. Immediately after the termination of the treatment delivery, without changing the set-up, the irradiated phantom was MR-scanned using a MR pulse sequence that derived 3D T2-maps of the phantom (spatial resolution of 1x1x2 mm^3). The high-dose areas within the patient-specific phantom exhibit low T2-values and therefore apear dark in the MR scans. A co-registration was followed between: a) the real patient planning CT scans were the RStructure file is superimposed and b) the 3D T2-maps of the irradiated patient-specific phantom. A bone-to-bone registration process was used. 

After the corregistration process and by blending the registered images, a direct inspection of the spatial coincidence between: a) the three PTVs structures and b) the corresponding  high dose areas (low T2 - dark areas), revealed a superb spatial accuracy of dose delivery. For a quantitative spatial and dosimetric analysis, the 3D T2-maps were converted to 3D relative dose maps. 1D, 2D and 3D intercomparison between the TPS calculations and the corresponding polymer gel measurements, revealed a truly satisfying 3D dosimetric precission. The spatial accuracy of dose delivery was also quantitatively verifyied. 

By the use of the proposed End to End QA methodology, it was demonstrated that the ELEKTA Unity MR-linac is capable for multiple brain metastases treatments with superb geometric and dosimetric performance

Evangelos PAPPAS (ATHENS, GREECE), Georgios KALAITZAKIS, Thomas MARIS, Dimitris MAKRIS, Efstathios EFSTATHOPOULOS, Ioannis SEIMENIS
11:55 - 12:05 #17669 - b46-2 Rapid Rescue Radiosurgery (RRR) in the acute management of critically located brain metastases: a two-center short-term outcome analysis.
b46-2 Rapid Rescue Radiosurgery (RRR) in the acute management of critically located brain metastases: a two-center short-term outcome analysis.

Background: The management of metastatic lesions in the eloquent brain remains a major challenge. Adaptive hypofractionated gamma knife radiosurgery may be applied in next-to emergency situations to treat life- and function-threatening intracranial metastases deemed not indicated for microsurgery or other treatment; debulking or even ablative effects might be achieved within days to weeks post therapy. The application of this treatment modality in defined acute settings has been termed Rapid Rescue Radiosurgery (RRR). We report the expeditious effects of RRR during treatment and 4 weeks after treatment completion with focus on tumour ablation, salvage/rescue of organs at risk and toxicity.

Methods: 39 patients with 50 brain metastases, treated over 7 days in three separate Gamma Knife radiosurgery sessions (GKRS 1 - 3) between November 2013 and December 2018, were retrospectively analyzed in terms of tumour volume reduction, salvage of organs at risk and radiation induced toxicity under the period of treatment (GKRS 1 to GKRS 3) and at first follow up MRI (4 weeks after GKRS 3). The Leksell® Coordinate Frame G was mounted prior each GKRS. All patients were treated using the Leksell Gamma Knife® Perfexion™ (Karolinska University Hospital, Stockholm, Sweden) and Leksell Gamma Knife® Model C (Bezmialem Vakif University Medical School, Istanbul, Turkey).

Results:  Frame mounting prior each GKRS was well tolerated. Mean peripheral doses at GKRS 1, GKRS 2 and GKRS 3 were 7.7, 8.0, and 8.3 Gy, respectively (range 6.0-9.5 Gy) at the 35-50% isodose lines. In the surviving group at first follow-up (n=38), mean tumor volume reduction was -6% at 1 week (GKRS 1- GKRS 3) and -53% % 4 weeks after GKRS 3. Six patients died prior to first follow-up due to extracranial disease; however, further neurologic deterioration post RRR was not reported in this subgroup of patients.

Conclusions: In this study, RRR proved effective in terms of debulking, rapid tumour volume reduction and preservation/rescue of neurological function. Radiation induced toxicity was not reported in this short term follow-up. RRR should be considered when microsurgery and other therapies are not feasible, yet an acute intervention remains necessary.  However, the true potential of this procedure lies on a set of synergic radiation-modulated immune responses aiming to achieve long-lasting systemic effect.

Georges SINCLAIR, Georges SINCLAIR (Reading, UK, UK), Georges SINCLAIR, Hamza BENMAKHLOUF , Kerime AKDUR, Mustafa Aziz HATIBOGLU
12:05 - 12:15 #17705 - b46-3 Stereotactic radiosurgery for brain metastases from renal-cell carcinoma.
b46-3 Stereotactic radiosurgery for brain metastases from renal-cell carcinoma.

BACKGROUND: Brain metastases (BM) is a significant problem in patients with metastatic renal-cell carcinoma (RCC). Local and systemic therapies including stereotactic radiosurgery (SRS) are rapidly evolving, necessitating reassessments of outcomes for modern patient management.

PURPOSE: The study purpose was to evaluate the impact of gamma knife radiosurgery (GKRS) alone on the overall survival and intracranial recurrence rates in brain metastasis patients from RCC.

PATIENTS AND METHODS: The RCC patients with BM treated with SRS were reviewed. 74 patients were identified with BM treated between 2010 and 2015.  A total of 309 BM were treated with SRS with 1 to 24 BMs treated per session (median, 2 BMs). The median (range) of volume was 4,47 cc (0,3-19,8). The median (range) SRS treatment dose was 20 (15-24) Gy.

RESULTS: The median overall survival was 10 months (95% CI 6,5-13,3). Survival after 1-year was 43,2% for all patients. Survival was not statistically different between patients with < 5 BM versus ≥ 5 BM (P = 0,4583). Local control after 12 months was achieved in 87,1% patients. Progression-free survival after 12 months was 48,4%. Аccording to multivariate analysis, favorable prognostic factors were  KPS >70 and total target volume BMs <5 cm3.

CONCLUSION: SRS is effective in controlling BM in patients with RCC. Over half of treated patients survive  one  year, and no differences in survival were noted in patients with ≥ 5 BM metastases in comparison with those, who had < 5 BM. Factors predicting better survival were high functional status and low total target volume BMs

Andrey GOLANOV (Moscow, RUSSIA), Sergey BANOV, Elena VETLOVA, Alexandra DALECHINA, Valery KOSTJUCHENKO, Natalia ANTIPINA, Ivan OSINOV, Amayak DURGARYAN
12:15 - 12:25 #17744 - b46-4 Hypofractionated Stereotactic Radiosurgery and Radiotherapy to Large Resection Cavity of Metastatic Brain Tumors.
b46-4 Hypofractionated Stereotactic Radiosurgery and Radiotherapy to Large Resection Cavity of Metastatic Brain Tumors.

- OBJECTIVE: To evaluate the efficacy of postoperative fractionated stereotactic radiosurgery (FSRS) and hypo-fractionated stereotactic radiotherapy (SRT) to large surgical cavities after gross total resection of brain metastases.

- METHODS: A retrospective analysis of 41 patients who had received tumor-bed FSRS (5 fractions) or SRT (10 fractions) after resection of brain metastasis between 2005 and 2015 was performed. All resection cavities were treated with a frameless linear accelerator-based system. Patients who underwent subtotal resection, single-dose SRS to the resection cavity, or were treated with a fractionation schedule other than 5 or 10 fractions, were excluded.

- RESULTS: Twenty-six patients were treated with 5 fractions and 15 patients with 10 fractions. The median planning target volume was 19.78 cm3 (12.3 - 28 cm3) to the 5-fraction group and 29.79 cm3 (26.3 - 47.6 cm3) to the 10-fraction group (P [ 0.020). The 1-year and 2-year local control rates for all patients were 89.4% and 77.1%, respectively, and 89.6% and 78.6% were free from distant intracranial progression, respectively. No difference was observed in local control or freedom from distant intracranial progression between the 5-fraction or 10-fraction groups. The median overall survival was 28.27 months (95% confidence interval, 19.42 - 37.12) for all patients. No patient developed necrosis at the resection cavity.

- CONCLUSIONS: Fractionation offers the potential to exploit the different biological responses between neoplastic and normal tissues to ionizing radiation. The use of 5 daily doses of 5-6 Gy or 10 daily doses of 3 Gy is a good strategy to have a reasonable local control and avoid neurotoxicity.

Leonardo CONRADO (Salvador, BRAZIL), Tania KAPREALIAN, Alisson R. TELES, Stephen TENN, Nader POURATIAN
12:25 - 12:35 #17838 - b46-5 Immune checkpoint inhibitors and stereotactic radiosurgery in melanoma brain metastases.
b46-5 Immune checkpoint inhibitors and stereotactic radiosurgery in melanoma brain metastases.

Background: “On demand” Stereotactic Radiosurgery (SRS) is increasingly used in combination with immune checkpoint therapy (ICT) to control melanoma brain metastases (MBM). However, little is known about potential interactions between ICT and RS in terms of toxicity and efficacy.

Goal: The goal of this retrospective study was to analyze results of a cohort of patients treated for MBM from January 2014 to December 2016 in our institution.

Methods: From an institutional database, we identified consecutive patients with MBM, treated with GK and receiving concurrent ICT with anti-CTLA4 or anti-PD1 within the 12 weeks of SRS procedure.

Results:  Sixty-two patients presenting 296 lesions were included, and 52 patients (84%) had ongoing ICT at the time of irradiation. Median follow-up time was 18 months (13-22). Minimal median dose delivered was 18 Gy. Median volume per lesion and total tumor volume were 0.219 cm3 and 2.1 cm3 respectively. The 1-year control rate per irradiated lesion was 89%. Thirty-one patients (44.3%) developed distant brain metastases after a median time of 6 months after GK. At the time of analysis, 34 patients had died. Median overall survival (OS) was 14 months. Median OS in subgroups treated with Ipilimumab, Nivolumab, multiples immunotherapy were respectively: 11 months, 15 months and 13.5 months and was not reached for Pembrolizumab subgroup. In multivariate analysis, positive predictive factors for local control were: delay since the initiation of immunotherapy more than 1 month (p=0.009) and previous brain irradiation (p=0.009). Total tumor volume <2.1 cm3 was a positive predictive factor for both OS (p=0.003) and intracranial disease control (p=0.038).  Predictive factors of toxicity were: female gender (p=0.001) and previous treatment with MAPK (p=0.05).

Conclusion: Combination of GK and ICT in MBM is safe and shows favorable outcomes.  A long duration of ICT before SRS seems to improve local control.

 

Charles VALERY (Paris), Charlotte FENIOUX, Aymeric AMELOT, Pierre-Yves BORIUS, Idriss TROUSSIER, Iannis LAMPROGLOU, Philippe SAIAG, Philippe MAINGON, Jean-Jacques MAZERON, Philippe CORNU
12:35 - 12:45 #17859 - b46-6 Hypofractionated stereotactic radiosurgery for resected brain metastases.
b46-6 Hypofractionated stereotactic radiosurgery for resected brain metastases.

Background: After resection of brain metastases, stereotactic radiosurgery (SRS) to the surgical cavity reduces local recurrence with minimal cognitive impairment. For large surgical cavities, reduced single-fraction doses required to minimize toxicity can compromise local control. Hypofractionated stereotactic radiosurgery (HF-SRS) may better balance tumor control with toxicity.

Materials/Methods: Patients treated with adjuvant HF-SRS following resection for brain metastases at Duke University Medical Center between 2012 and 2016 were included. The gross target volume was contoured per consensus guidelines with 2mm margin to obtain the planning target volume.  All patients were treated with image-guided SRS using a linear accelerator with high-resolution collimation. Patient demographics, primary disease characteristics and treatment details were recorded. Rates of local control (LC), distant brain failure (DBF), radionecrosis (RN) and overall survival (OS) were calculated.  

Results: 86 patients with a total of 91 lesions that were resected and treated with HF-SRS were identified. The median age and KPS were 61 and 80, respectively. The majority of patients were female (n=49, 57%), had extracranial metastases at the time of HF-SRS (n=53, 62%) and a single brain metastases (n=55, 64%). The most common histology was NSCLC (n=36, 42%) followed by breast (n=18, 21%) and melanoma (n=10, 12%). The median pre-operative maximum tumor dimension was 3.3 cm (range 0.8-6.2). All patients were treated in five fractions, the majority with a fraction size of 5 Gy (n=81, 89%). Median follow up was 10.7 months. The 2-yr LC and DBF rates were 69% and 63%, respectively. Subsequent brain irradiation was utilized in 38 patients. Median OS was 13.8 months and 2-yr OS was 38%. One case of symptomatic RN was observed.

Conclusions: Post-operative HF-SRS delivered in five fractions has an excellent safety profile and reasonable probability of local control. Close surveillance is warranted given the high risk of DBF in this setting.

Jordan TOROK (Durham, NC, USA), Andrew FAIRCHILD, Justus ADAMSON, Zhanerke ABISHEVA, Scott FLOYD, Michael MORAVAN, Peter FECCI, Fang-Fang YIN, John KIRKPATRICK

13:00 - 14:30 LUNCH (exhibition area), VISIT OF THE EXHIBITION & POSTERS
13:15
13:15-14:15
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B47
BRAINLAB SPONSORED SESSION
Novalis Circle Symposium: Clinical and Technical Innovations in Spine SRS Treatments

BRAINLAB SPONSORED SESSION
Novalis Circle Symposium: Clinical and Technical Innovations in Spine SRS Treatments

13:15 - 13:30 Value of SRS over Conventional Fractionation for Bone Metastases. Yoshiya Josh YAMADA (New York, USA)
13:30 - 13:45 Commissioning and Clinical Implementation of Elements Spine SRS. Niko PAPANIKOLAOU (Professor and chief) (San antonio, USA)
13:45 - 14:00 Clinical Experience Utilizing Elements Spine SRS. Pablo CASTRO PENA (Radiation Oncologist) (Cordoba, ARGENTINA)
14:00 - 14:15 Review of 6D Setup and Monitoring for Spine SRS Treatment. Amol GHIA (Associate Professor) (Houston, USA)

13:15-14:15
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C47
ACCURAY SPONSORED SESSION
Cyberknife Radiosurgery for Intramedullary Arteriovenous Malformations

ACCURAY SPONSORED SESSION
Cyberknife Radiosurgery for Intramedullary Arteriovenous Malformations

13:15 - 14:15 Cyberknife Radiosurgery for Intramedullary Arteriovenous Malformations. Iris GIBBS (Professor) (Stanford, USA)

14:30
14:30-15:00
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A48
PANEL 1
PITUITARY TUMORS POINT - COUNTERPOINT

PANEL 1
PITUITARY TUMORS POINT - COUNTERPOINT

Moderator: Manoel PAIVA (NEUROSURGEON/CHIEF DEPARTMENT) (SAO PAULO, BRAZIL)
14:30 - 14:37 The Case for SRS. Bruce POLLOCK (Physician) (Rochester, USA)
14:37 - 14:44 The Case for SRT. Daniel TRIFILETTI (Assistant Professor) (Jacksonville, USA)
14:44 - 15:00 Panelist. Yoshiaysu IWAI (Neurosurgery, Radiosurgery) (Osaka, JAPAN), Alessandra GORGULHO (Director of Research Affairs) (Sao Paulo, BRAZIL)

14:30-15:00
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B48
PANEL 2
SPINE POINT - COUNTERPOINT

PANEL 2
SPINE POINT - COUNTERPOINT

14:30 - 14:37 The Case for SRS. Amol GHIA (Associate Professor) (Houston, USA)
14:37 - 14:44 The Case for SRT. Yoshiya Josh YAMADA (New York, USA)
14:44 - 14:55 Panelist: Stereotactic radiosurgery for patients with asymptomatic spine metastasis: observation versus early intervention. Lily ANGELOV (Staff Neurosurgeon) (Cleveland, USA), Moon-Jun SOHN (Stererotactic radiosurgery using Dedicated LINAC plateform) (Goyang, KOREA)
14:55 - 15:00 Panelist: Stereotactic radiotherapy for intramedullary spinal lesions. Yoshimasa MORI (Director) (Kawasaki, JAPAN), Samuel RYU (Professor) (Stony Brookn NY, USA)

14:30-15:30
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C48
Oral Session
PHYSICS #3

Oral Session
PHYSICS #3

Moderators: Batista DELANO (BRAZIL), Steven GOETSCH (Medical Physicist) (Solana Beach, USA), Uriel NOVICK (Chief Medical Physicist) (CABA, ARGENTINA)
14:30 - 14:39 #17885 - c48-1 C48-1 Commissioning tests on a Gamma Knife Icon using an RTSafe humanoid phantom.
C48-1 Commissioning tests on a Gamma Knife Icon using an RTSafe humanoid phantom.

The RTsafe avatar phantom is a novel water based humanoid phantom, modelled on a patient’s CT scan, with a highly detailed skull anatomy created by virtue of its 3D printed construction. During the commissioning of three Gamma Knife Icon units, a variety of tests were devised using these phantoms:

Point dose measurements with ionisation chambers (PTW Semiflex 31010 and Pinpoint 3D 31014) were performed for single (16mm) shot plans and compared with the Leksell GammaPlan (LGP) calculated dose using the TMR10 algorithm. 2D measurements using EBT3 film and 3D measurements using gel dosimetry allowed End-to-End testing for complex multi-isocentric plans.
It was possible to mount the Leksell G frame on the rigid outer surface of the phantom. This allowed measurement of the degradation of stereotactic accuracy due to frame distortion. The four mounting pins were torqued to values between 20 and 90cNm in 10cNm steps. For each torque setting, separate CT and CBCT scans were acquired. Correction of the location of a reference isocentre was investigated when a treatment plan based on the stereotactic (fiducialised) CT was co-registered with a pre-treatment CBCT.

Results
Point dose measurements for the single shot plans demonstrated a mean error of -8.0% and -6.1% for Semiflex and Pinpoint respectively when compared to the TMR10 algorithm, but reduced to -3.4% when planned in the heterogenous phantom with Convolution. Local gamma pass rates for 5%/1mm were >95% for 2D film studies. 3D gel dosimetry yielded acceptable correlation between LGP and measured dose when assessed via DVH comparison and gamma index analysis.
Comparison between targeting using conventional stereotactic CT and CBCT showed a mean agreement of 0.25mm over a wide range of torque settings.

Conclusion
The RTsafe phantom has demonstrated its versatility for use in commissioning the Gamma Knife Icon

Ian PADDICK (London, UK), Ben EARNER, Thomas BURROWS, Alexis DIMITRIADIS
14:39 - 14:48 #16789 - c48-2 A high-precision, registration accuracy and full-system test for adaptive SRS.
c48-2 A high-precision, registration accuracy and full-system test for adaptive SRS.

A novel full-system test (FST) phantom and method have been developed to demonstrate and quality assure the geometric accuracy of image co-registration and overall shot delivery in the context of SRS using Gamma Knife® Icon™.  The method uses eight Vernier scale bars to achieve sub-voxel precision co-registration accuracy measurements and pin-located radiochromic films to determine overall shot delivery precision.  A Procrustes superimposition analysis method was used to assess residual registration errors and decouple these from focal precision errors which also contribute to the observed shot position full-system test error.

 

Validation tests demonstrated that artificially applied randomly generated synthetic registration errors of < 0.15 mm could be accurately detected and quantified.  Cross-validation of full-system test results with the manufacturer standard focal precision test demonstrated that both approaches measure similar focal precision errors, to within < 0.1 mm, and that registration and focal precision components of the full-system geometric error can be successfully decoupled using our Vernier registration analysis approach. 

 

CBCT co-registration errors were shown to be of comparable magnitude to the focal precision errors, demonstrating that CBCT registration based in-mask treatments can achieve sub-voxel inter-fraction geometric accuracy, rivalling traditional frame-based immobilisation.  Whilst real patient treatments also exhibit intra-fraction motion, the use of IFMM monitoring has been shown to restrict this error to the same order as the inter-fraction motion errors reported here. This novel full-system geometric test method and phantom design concept is in principle applicable in principle to any SRS technique involving high (sub-voxel) image co-registration performance, enhancing confidence in rigid registration based positional correction for these critical applications.

Michael NIX, Gavin WRIGHT (Leeds, UK), Peter BOWNES, Peter FALLOWS, Wayne SYKES
14:48 - 14:56 #16886 - c48-3 Interfractional Patient Motion and Adaptive Planning in Fractionated Gamma Knife Radiotherapy.
c48-3 Interfractional Patient Motion and Adaptive Planning in Fractionated Gamma Knife Radiotherapy.

Introduction:

The Gamma Knife Icon allows adaptive, fractionated radiotherapy (a-gkFSRT) of cerebral lesions in a stereotactic environment using cone-beam computer tomography (CBCT) (re)positioning and thermoplastic mask fixation. Interfractional patient motion is countered with translational table movement and rotation of the treatment plan/shots, resulting in an updated dose calculation. Here, we analyzed interfractional patient motions and the corresponding plan adaptions.

Material and Methods:

We recorded a total of 439 fractions for 36 patients (15 male and 21 female) that underwent a-gkFSRT for intracranial lesions (meningioma, brain metastasis resection cavities, primary metastases, vestibular schwannoma and pituitary adenoma). For each fraction, we analyzed the mean interfractional patient motion and compared the resulting deviation after adaptive planinng. Furthermore, a subset of 198 fractions were analyzed in terms of plan quality of the daily plan adaption. Finally we analyzed the largest patient motions and the resulting deviations after plan adaption.

Results:

For all 439 fractions, the interfractional translation shifts were 0.05±0.55mm, -0.39±0.59mm and -0.08±1.37 mm in x-, y- and z-direction, respectively. The interfractional rotational differences were -0.15±0.98°, -0.09±0.62° and -0.15±0.93° around the x-, y- and z-axis. When analyzing 198 selected fractions, we found a deviation between planned and delivered fraction doses of -0.05±0.15% for the Dmin to the target, 0.08±0.40% for Dmax to the target, 0.00±0.06% for target volume coverage, 0.00±0.00% for PCI and 0.24±0.37% for gradient. Of note, even the largest interfractional patient shift (>2mm or >2°) did not result in clinically relevant deviations of dose distribution after plan adaption with only minimal deviations in gradient (<0.72%) and Dmin to an organ-at-risk (‑11.55%). 

Conclusion:

Interfractional patient shifts in a-gkFSRT are in submillimeter ranges and do not require patient repositioning. Daily plan adaption results in plans that are almost identical to the reference treatment plan, even in case of major interfractional positioning shifts.

Florian STIELER (Mannheim, GERMANY), Beate SCHWEIZER, Frederik WENZ, Frank Anton GIORDANO, Sabine MAI
14:56 - 15:04 #17708 - c48-4 Pre-treatment CBCT image verification for frame-based SRS on Gamma Knife Icon.
c48-4 Pre-treatment CBCT image verification for frame-based SRS on Gamma Knife Icon.

The Icon-model Gamma Knife (GK) introduced on-board CBCT for GK SRS.  Intended to facilitate mask-based SRS, Icon also provides an opportunity for QA of conventional frame-based patients via pre-treatment image verification.

Stereotactic definition of planning MR images for our frame patients is based upon conventional fiducial marker localisation.  Pre-treatment CBCT is performed routinely for these cases.  Within Leksell GammaPlan (LGP) pre-treatment CBCT is co-registered to planning MRI.  Since both should share a common stereotactic space, LGP-reported co-registration translations and rotations are ideally zero.  In practice non-zero values result from definition and co-registration uncertainties, but excessive non-zero values could indicate frame slippage or fiducial box displacement.

Analysis of 501 co-registrations from 470 patients fitted with one of four frames (n = 126, 121, 126 and 128, respectively) between Dec-15 and Jan-19 is presented.  CBCT was co-registered against a 120-slice 0.8x0.8x1.5mm voxel MPRAGE (n=465) or a 52-slice 0.4x0.4x1.0mm voxel CISS (n=33) acquired on a Siemens Avanto (n=483) or Aera (n=18).

Overall mean(S.D.) X/Y/Z translations and rotations were 0.16(0.39)/0.11(0.26)/0.67(0.34)mm and 0.15(0.31)/-0.05(0.22)/0.26(0.16)deg, respectively.  Mean differences of 0.00/0.21/0.38mm and 0.42/0.01/0.19deg MPRAGE-vs-CISS were significant (p<0.01) for Y,Z rotations and X,Z translations, as were Avanto-vs-Aera mean differences of -0.10/0.00/0.06mm and -0.20/0.03/0.38deg for X,Z rotations.   Single factor ANOVA indicated significant (p<0.01) mean differences in translations and Z rotation between frames.  No correlation to LGP-reported definition errors was found.

Pre-treatment CBCT offers valuable verification of MR fiducial-based stereotactic definition integrity beyond the LGP-reported definition errors.  Three cases of frame slippage were identified by this process, all characterised by excessive (>2 S.D.) values for at least two of the translation/rotation values as compared to the overall data.  More detailed analysis of our data has indicated dependence upon sequence, scanner and frame and these factors should be considered when interpreting pre-treatment CBCT verifications on Icon.

Gavin WRIGHT (Leeds, UK), Peter FALLOW, Paul HATFIELD, Nick PHILLIPS, Peter BOWNES
15:04 - 15:12 #17754 - c48-5 Comparison of initial setup accuracy of the ExacTrac system using the mask-base fusion method or the localizer and target positioner method for intracranial frameless stereotactic radiosurgery.
c48-5 Comparison of initial setup accuracy of the ExacTrac system using the mask-base fusion method or the localizer and target positioner method for intracranial frameless stereotactic radiosurgery.

Aim

The recent upgrade of the BrainLab Exactrac system (v6.2) removes the need for the use of a Frameless Localizer and Target Positioner (TarPo) at CT, allowing for treatment prepositioning based on a fusion of an internally stored CT of the frameless SRS mask base. The redundancy of the TarPo gives way for the use of the Frameless Radiosurgery Positioning Array at CT, allowing it to be contoured and its attenuation accounted for in iPlan dosimetry. We report on the initial setup accuracy of the mask base fusion (MBF) feature compared to the TarPo localisation (TL) method using ExacTrac <v.6.2 for patients receiving stereotactic radiosurgery (SRS) or fractionated SRS (fSRS) for intracranial tumours.

Methods

94 SRS (39 TL, 55 MBF) and 72 fSRS (40 TL, 34 MBF) patients were retrospectively analysed. The median initial image corrections in 6-degrees of freedom (DOF) were compared between TL (n=79) and MBF (n=79) for both SRS and fSRS (first fraction only) patients with a Wilcoxon-Rank test (p<0.05). Systematic and random error was calculated for all 6DOF using the daily initial corrections of all fractions of the fSRS patients.

Results

The median initial corrections for the TL method and MBF method respectively were: lateral shift -0.52mm vs -0.97mm (p=0.06), longitudinal shift 0.18mm vs 1.11mm (p=0.001), vertical shift 0.80mm vs -1.56mm (p <0.001), lateral angle -0.03deg vs -0.21deg (p=0.18), longitudinal angle 0.43deg vs 0.05deg (p=0.03) and vertical angle -0.15deg vs 0.07deg (p=0.37). The systematic error for positioning accuracy of fSRS was 1.5mm or less for all directions regardless of setup method, except the vertical shift (6.1mm using TL and 2.2mm using MBF). The random error for both methods was 0.9mm or less for all directions.

Conclusion

The initial setup accuracy is comparable between the TL and MBF methods. The longitudinal shift, vertical shift and longitudinal angle corrections are greater with the MBF method, but are less than 2mm or 0.5deg making them clinically inconsequential to the image verification process. An advantage of the MBF method is the redundancy of the TarPo allows for the Frameless Radiosurgery Positioning Array to be placed at CT and contoured, with attenuation then accounted for in the planning dosimetry, reducing the dose variation produced by the array during SRS delivery.

Katrina WOODFORD (Melbourne, AUSTRALIA), Gishan RATNAYAKE, Sashendra SENTHI, Jeremy D RUBEN, Vanessa PANETTIERI
15:12 - 15:20 #17766 - c48-6 Using Cone Beam Computer Tomography for stereotactic space verification within frame-based Leksell Gamma Knife Icon radiosurgery.
c48-6 Using Cone Beam Computer Tomography for stereotactic space verification within frame-based Leksell Gamma Knife Icon radiosurgery.

Leksell Gamma Knife Icon (Elekta AB) includes a cone-beam CT (CBCT) to define the stereotactic space without the need for an invasive frame. The aim of this study was to analyze the differences between the stereotactic frame - based coordinates and the CBCT - determined coordinates.

We performed CBCT before frame-based stereotactic Gamma Knife radiosurgery for 212 patients as an additional quality assurance (QA) procedure within radiosurgery treatment. The rotational and translational shifts, maximum shot displacement,delivered maximum doses for critical structures and coverage of the tumors were recorded. The factors investigated were z-coordinates of the right and left posterior pins, tumor localization, Leksell stereotactic coordinates of the tumor, tumor volume,  mean and maximum definition errors for the MR study. The statistical analysis was performed by the R statistical package.

The maximum shot displacement in anatomy was more than 1 mm for 32 patients. Planned tumor coverage was no less than 99% but the delivered one was less 95% in 12 cases. The z-coordinate of the tumor (p=0.036), volume of the tumor (p=0.045) were associated with differences of  the coverage. The x-coordinate of the tumor (p=0.029) and the mean definition error (p=0.024) on MR images were associated with maximum shot displacement.

The understanding of the differences between the stereotactic frame - based and the CBCT 3D stereotactic space is an important aspect of Gamma Knife Icon radiosurgery.

The differences between radiological and mechanical isocenters in case of frame-based radiosurgery are often assumed to be 0.2 - 0.5 mm. But the uncertainty of target and the structure localization could lead to more than 5% reduction of the prescribed dose coverage of the tumor.  The method of stereotactic space definition (frame or CBCT) that obtains more accurate results should be determined as well as the clinical significance of the demonstrated shifts are supposed to be defined

Valery KOSTJUCHENKO (Moscow, RUSSIA), Irina BANNIKOVA, Alexandra DALECHINA, Andrey GOLANOV, Sergey BANOV, Angelika ARTEMENKOVA, Ivan OSINOV
15:20 - 15:28 #17796 - c48-7 Preliminary report of stereotactic radiotherapy using mask system of Leksell Gamma Knife Icon.
c48-7 Preliminary report of stereotactic radiotherapy using mask system of Leksell Gamma Knife Icon.

Object: Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment. This provides exceptional accuracy and precision of radiosurgery, making it a possibility for many more disease types and many more patients to be treated. We have consistently selected mask fixation, except 3 AVM patients, who needed digital angiography after frame fixation for dose planning.

Methods: We retrospectively analyzed 566 patients (702 times) who underwent Gamma Knife Icon using mask fixation between September 25th, 2017 and December 31th, 2018 at Rakusai Shimizu Hospital. The most common disease was brain metastases (384 patients), followed by meningioma (78), vestibular schwannoma (24), AVM (17), trigeminal neuralgia (15) and others (48). Patients with small, few, newly diagnosed, and non-eloquent area tumors were treated in a single session. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule. If the tumor number was large, we selected a multisession schedule. Therefore, 209 patients were treated in a   single session, 377 with fractionation, and 116 with multiple sessions. For higher accuracy, we changed the upper limit of the HDMM system from 1.5mm to 1.0mm for malignant tumors and 0.5mm for benign tumors.

Results: We selected fractionated schedules as follows; 7.0 Gy x 5Fr (5-10 ml), 4.2Gy x 10Fr (10-20ml), 3.7Gy x 10Fr (20-30ml), 3.2Gy x 10Fr (30ml-) for malignant tumors, and 2.7Gy x 10Fr for benign tumors. Compared with frame fixation, almost all of patients (97%) who had previously experienced the frame fixation felt more comfortable.

Conclusions: Although these results are limited to short periods, survival rated, local control rates and qualitative survival rated in patients unsuitable for SRS, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges. Further examination is needed for comparison with staged Gamma Knife radiotherapy, Cyber-Knife and Novalis radiotherapies

Takuya KAWABE (Kyoto, JAPAN), Manabu SATO

15:00
15:00-15:30
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A49
PANEL 3
VESTIBULAR SCHWANNOMA POINT-COUNTERPOINT

PANEL 3
VESTIBULAR SCHWANNOMA POINT-COUNTERPOINT

15:00 - 15:10 Earlier is Better. Marc LEVIVIER (Chef de Service) (Lausanne, SWITZERLAND)
15:10 - 15:20 Watch and Wait. Oystein TVEITEN (Consultant neurosurgeon) (Bergen, NORWAY)
15:20 - 15:30 Panelist. Gus BEUTE (Neurosurgeon) (Tilburg, THE NETHERLANDS), Manoel PAIVA (NEUROSURGEON/CHIEF DEPARTMENT) (SAO PAULO, BRAZIL), Isaac YANG (Associate Professor) (Los Angeles, USA)

15:00-15:30
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B49
PARALLEL
STANDARDISATION IN RADIOSURGERY

PARALLEL
STANDARDISATION IN RADIOSURGERY

Moderators: Felipe ERLICH (Radiation Oncologist) (Rio de Janeiro, BRAZIL), Patrick HANSSENS (Radiation Oncologist) (Tilburg, THE NETHERLANDS), Crystian SARAIVA (Medical Physicist) (São Paulo, BRAZIL)
15:00 - 15:10 Contouring: How do we improve what we see? Caroline CHUNG (Associate Professor, Radiation Oncology) (Houston, USA)
15:10 - 15:20 #17857 - b49-2 The impact of the variability of target delineation on the resulting treatment planning and dose distributions in GK radiosurgery – a multicentre analysis.
b49-2 The impact of the variability of target delineation on the resulting treatment planning and dose distributions in GK radiosurgery – a multicentre analysis.

Objective

The aim of this study was to quantify the multiobserver variability in treatment planning for six common radiosurgery targets in relation to the variability in target contouring.

Material and methods

Twelve experienced Gamma Knife® centers participated in the study providing contours of targets and organs-at-risk together with the treatment plan for six common targets in radiosurgery.

The agreement volume index (AVI), defined as the ratio of the common to the encompassing volume for each target, was calculated. This metric was calculated for each volume within the X Gy isodose  (VXGy).  The correlation between the variability in the dosimetric and contouring parameters was assessed by plotting the AVI's of contours and volumes within the prescription isodose as well as for a broad range of VXGy. Variability in contouring and resulting dose distributions were also estimated by calculating the conformity of the plans to the average target.

Results and discussion

Analysis of prescription isodoses showed lower variability in treatment plan dosimetry for the cavernous sinus meningioma, pituitary adenoma and medium metastasis (AVI's of 0.28, 0.40 and 0.28, respectably) than in the contouring.  Variability between the plans and contours were similar for small metastasis (AVI = 0.37)  and the vestibular schwannoma (AVI = 0.48) but larger for the large metastasis (AVI = 0.52) . Absolute differences in dose at the voxel level also showed high variability for all cases, in the order of 5-15 Gy. Clinically, the coverage pass-rate to the average target ranged between 50% (cavernous sinus meningioma) and 83% (Vestibular schwannoma) across all the treatment plans.

Conclusions

The treatment plan dosimetry variability was as large as the contouring variability for this highly conformal treatment with enough range in dose coverage to have potential implications on tumor control.

Helena SANDSTRÖM (Stockholm, SWEDEN), Caroline CHUNG, Hidefumi JOKURA, Iuliana TOMA-DASU
15:20 - 15:30 Variations in dose According to Planning Philosophy. Ian PADDICK (Physicist) (London, UK)

15:30
15:30-16:20
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A491
Oral Session
GLIOMAS

Oral Session
GLIOMAS

Moderators: Samuel CHAO (Radiation Oncologist) (Cleveland, USA), Christopher DUMA (Speaker) (Newport Beach, USA), Rodrigo GUIMARAES (BRAZIL)
15:30 - 15:40 #17650 - a491-2 Interplay of focal radiation therapy with targeted cellular therapy in glioblastoma.
a491-2 Interplay of focal radiation therapy with targeted cellular therapy in glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common primary adult brain tumor and carries a devastating prognosis. We have shown that mesenchymal stem cell (MSC) therapies offer a new treatment paradigm for therapy delivery; however, it is unknown if radiosurgery can promote or inhibit MSC activity.

AIMS: Study the modulatory effect of single-dose, focused ionizing radiation (IR) on MSC migratory patterns.

METHODS AND RESULTS: To confirm IR-induced cytotoxicity, MTT assay of the radiated patient-derived glioblastoma brain tumor initiating cells (BTICS) showed decreased viability after 2 Gy, 8 Gy and 20 Gy IR at 48 hours and further (p=0.006). MSCs were transduced with an iRFP lentiviral vector, and ex vivo implantation of MSCs was carried out on organotypic slices of normal mouse brain to evaluate engraftment and migration in the setting of IR delivery, groups of 0 Gy, 2 Gy, 5 Gy and 10 Gy were compared via confocal microscopy using 3D time lapse, daily qualitative evaluation of migratory patterns showed a trend to longer migratory distances with increasing dose of IR compared to control.

Additionally, to assess IR effects on MSC migration, transwell assays were performed, in quadruplicate, using conditioned media from radiated patient-derived glioblastoma BTICs; after 12 hours incubation, migration was assessed by directly counting DAPI-labeled nuclei via fluorescence microscopy. Reduced MSC transwell migration was found after 10 Gy IR compared to the control, 2 Gy IR and 5 Gy IR groups (p=0.008, p=0.002, and p=0.010, respectively). Finally, in an in vivo murine model, IR to orthotopic glioblastoma tumor, followed by intracardiac injection of MSC, resulted in MSC homing in irradiated and non-irradiated tumor.

CONCLUSION: MSC migration to BTIC-conditioned media decreases when BTICs are exposed to high dose IR in vitro, and migration of MSCs seems to likewise follow a positive relationship with the delivery of IR on an ex vivo, and in vivo mouse model. This suggests that radiosurgery could ‘prime’ the tumor microenvironment if delivered prior to MSC delivery. Further efforts to synergize IR with the MSC payload are underway.

Daniel TRIFILETTI (Jacksonville, USA), Henry RUIZ-GARCIA, Rachel SARABIA ESTRADA, Hugo GUERRERO-CAZARES, Anna HARRELL, Sujan MONDAL, Keila ALVARADO-ESTRADA, Alfredo QUINONES-HINOJOSA
15:40 - 15:50 #17678 - a491-3 Bioengineering TRAIL for synergy with focal irradiation in glioblastoma.
a491-3 Bioengineering TRAIL for synergy with focal irradiation in glioblastoma.

INTRODUCTION: Glioblastoma (GBM) is the most common primary adult brain tumor. We have shown that mesenchymal stem cell (MSC) therapies offer a new treatment paradigm for therapy delivery; however, the ideal payload has not been identified. We believe that TRAIL (tumor necrosis factor-related apoptosis inducing ligand), a cancer cell-death triggering protein, could synergize with current existing therapies, including focal irradiation.

AIMS: Design and produce a regulable expression vector for exploring the boosting effect of glioblastoma focal radiation priming on TRAIL-secreting MSC therapy.

METHODS AND RESULTS: To study the synergy of focal radiation and TRAIL therapy, 8 Gy of ionizing radiation was delivery to an in vitro patient-derived GBM model. TRAIL receptors levels (DR4 & DR5) increased at 48 hours after irradiation when compared to non-irradiated GBM using RT-qPCR (p<0.01). Thereafter, we designed a secretable version of TRAIL aiming to enable MSCs TRAIL secretion.  The original gene was modified by adding a novel tag to assure its secretion to the extracellular compartment. We also included a tetracycline-inducible TRAIL expression system to allow for on-demand TRAIL release, increasing the safety of the protein secretion. Structural and functional validation was carried, and TRAIL protein was proven on the conditioned media. To generate stable MSCs able to secrete TRAIL, a lentiviral vector was produced and successfully tested on three different primary adipose MSC cell lines. Further work is being carried out to test the final synergism of radiation, MSC and TRAIL therapies. 

CONCLUSION: We have showed that GBM TRAIL receptors increase after 48 hours of focal radiation and that TRAIL-secreting MSCs can be bioengineered for possible synergy with radiation. Consequently, appropriate use of modern radiation delivery techniques such as SRS could possess a boosting effect on targeted cellular therapies. Our novel TRAIL-secreting adipose MSCs will help allow us to further study this system.

Henry RUIZ-GARCIA, Natanael ZARCO, Virginea DE ARAUJO-FARIAS, Anna HARRELL, Hugo GUERRERO-CAZARES, Rachel SARABIA ESTRADA, Alfredo QUINONES-HINOJOSA, Daniel TRIFILETTI (Jacksonville, USA)
15:50 - 16:00 #17657 - a491-4 Stereotactic radiosurgery in combination with high-dose methotrexate as a first-line treatment for primary central nervous system lymphoma: a single institution experience.
a491-4 Stereotactic radiosurgery in combination with high-dose methotrexate as a first-line treatment for primary central nervous system lymphoma: a single institution experience.

Objective: Primary central nervous system lymphoma (PCNSL) is a rare cancer accounting for less than 4% of primary brain and central nervous system tumors. High-dose methotrexate (HD-MTX) is the gold standard for newly diagnosed PCNSL. However, stereotactic radiosurgery (SRS) may be efficacious as a co-adjuvant treatment. The purpose of this study is to determine the effectiveness of HD-MTX in combination with SRS in the treatment of PCNSL.

Methods: This is a prospective, observational cohort study evaluating the treatment of histologically confirmed PCNSL with HD-MTX in a dose of 3.5 g/m2 and treatment with HD-MTX, plus SRS. Strict inclusion and exclusion criteria were employed. Primary outcomes were measured by survival rate. Secondary outcomes were assessed by the tumor's responsiveness to treatment and reduction in size as noted on imaging, the Karnofsky Performance Status (KPS), the activities of daily living (ADL) and mini-mental state examination (MMSE).

Results: Between January 2010 and January 2018, 82 cases were evaluated. Included in this evaluation were 44 chemotherapy and 38 chemotherapy, plus SRS, patients. The follow-up period was 12 to 96 months (mean: 54.8 months). Patients were treated with SRS prescription doses ranging from 12 Gy to 16 Gy (median: 14 Gy). The median survival rate from initial diagnosis was 38.4 months in the chemotherapy group and 52.6 in the chemotherapy, plus SRS, group (p-value: 0.005). All lesions showed a complete response after SRS when evaluated using magnetic resonance imaging after one to three weeks (mean range: 2.2 weeks). No significant side effects related to SRS were observed. During follow-up period, the good ADL preservation was achieved for 22.4 months from SRS. Patients with KPS >90 at SRS demonstrated longer ADL preservation (36 months from SRS). No significant difference in MMSE between two groups was found.

Conclusions: SRS in combination with HD-MTX as a first-line treatment provided better prognosis and not worse neurocognition state. This noninvasive treatment modality should be considered as an option for patients with PCNSL. A newly registered study (SRS-PCNSL*) is underway.

*SRS-PCNSL: Upfront Stereotactic Radiosurgery in Combination with Methotrexate Based Chemotherapy in the Treatment of Newly Diagnosed Primary Central Nervous System Lymphoma 

Hao LONG (Guangzhou, CHINA)
16:00 - 16:10 #18092 - a491-6 Fractionated Radiosurgery plus Check Point Blockade is a Novel Paradigm for Treating Glioblastoma Multiforme.
a491-6 Fractionated Radiosurgery plus Check Point Blockade is a Novel Paradigm for Treating Glioblastoma Multiforme.

Purpose: We have shown that fractionated radiosurgery (fSRS) with simultaneous differential dosing of 32 Gy (to enhancing tumor) and 24 Gy (to flair abnormality) in 4 fractions improved the local control of recurrent glioblastoma (GBM).  Although immunotherapy improved outcome in many tumor types, CHECKMATE 143 showed no benefit of adding checkpoint inhibitors to the standard GBM treatment. We carried out experiments to develop a new strategy of in-situ vaccination effect against the local tumor by fSRS combined with immune checkpoint inhibitor. 

Materials and Method: Orthotopic GL261 glioma cells implanted to the forebrain in immunocompetent B57 mice. The tumor diameter becomes 2-3 mm on day 10 post-implantation. Total of 46 tumor-bearing mice were randomized to treatment groups of 1) untreated control, 2) anti-PD-1 (aPD1) mouse nivolumab 10 mg/kg i.p. on days 10, 12, and 14 post-implantation, 3) RS 10 Gy on day 10 post-implantation, and 4) combination of RS and aPD1. Survival time was measured. The brains at time points of 11, 15, 30 days, and death. The whole brain samples were prepared for multiplex IHC, flow cytometry, and western blot and gene expression assay by RNA extraction to examine the dynamics in immune effector cells and the signatures. The mice were imaged with 9.4 Tesla MRI scan to measure the tumor size and to identify the predictive imaging markers.

Results: Median survival time was 22.5 days in untreated control, 30 days by aPD1 monotherapy, and 36 days RS 10 Gy alone. After RS and aPD-1 together, the median survival was not reached up to 60 days with 75% of mice being alive with a complete pathological response at the end of the study duration. IHC and gene expression arrays showed that tumor growth by itself induced a dramatic increase in both the CD8+ T-cells and tumor-infiltrating phagocytic cells, associated with increased INF-γ level in the tumor tissue and serum, and elevated expression of CD86 (a marker of dendritic cells/macrophages). Therapy with aPD1 alone did not cause any significant change.  All these increases were completely abrogated by 10 Gy radiation. However, CD8+ cells and CD86 were increased again by the combined RS and aPD1. The expression of IFN-γ was sustained in the mice that were cured of the tumor. MRI scan showed increased permeability and T2 kurtosis parameter in the responders.

Conclusion: Combined RS and aPD1 significantly improved GBM tumor control and survival. CD8+ and CD86+ cells play a major role with increased INF-γ level. The findings indicate that the local anti-tumor immune response against GBM may be a unique mechanism, distinct from the abscopal (distant) effects.

Samuel RYU (Stony Brookn NY, USA), Alex STESSIN, Mariano CLAUSI, Timothy DUONG, Stella TSIRKA

15:30-16:20
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B491
Oral Session
PITUITARY TUMORS

Oral Session
PITUITARY TUMORS

Moderators: Gustavo ADOLPHO (BRAZIL), Benjamin JONKER (Neurosurgeon) (Sydney, AUSTRALIA), Manoel PAIVA (NEUROSURGEON/CHIEF DEPARTMENT) (SAO PAULO, BRAZIL)
15:30 - 15:40 #17659 - a491-1 Follow-up studies of Gamma Knife radiosurgery for non-functioning pituitary adenomas.
a491-1 Follow-up studies of Gamma Knife radiosurgery for non-functioning pituitary adenomas.

OBJECTIVE

  The aim of this study was to evaluate the long term clinical outcomes of Gamma Knife surgery(GKS) for non-functioning pituitary adenomas (NFPAs) and the role of GKS in the management of NFPAs. 

 METHODS  

Between January 2000 and December 2010,204 patients with residual or recurrent NFPAs after surgery undergoing GKS were enrolled in this study.The median age of the patients was 48 years old (mean 48 years,range 14 to 79 years).The median tumor volume was 3.3 ml (mean 5.2 ml, range 0.326.4 ml).The median margin dose was 14Gy (mean 14 Gy,918Gy).The median maximum dose was 31Gy (mean 30Gy,2040Gy).The median duration of follow up was 86 months (mean 88 months,range 12-213 months).

Duaring the same period,52 patients with NFPAs without prior surgery undergoing GKS were enrolled in this study.The mean age of the patients was 55 years old.The mean tumor volume was 5.0 ml.The mean margin dose was 14Gy.The mean maximum dose was 31Gy.The mean duration of follow up was 41 months.

 RESULTS

Of these 204 patients with adjuvant GKS,the latest follow-up MR imaging studies demonstrated tumor regression in 102 patients(50%),tumor stable in 81 patients(40%),and tumor enlargement in 21 patients(10%).The tumor control rate of this cohort was 90%.37 patients(18%) developed new onset hypopituitarism.5 patients(2.5%) presented new or worsening visual dysfunction without tumor growth.

Of these 52 patients with primary GKS,the latest follow-up MR imaging studies demonstrated that the tumor control rate of this cohort was 88%.5 patients(10%) developed new onset hypopituitarism.6 patients(12%) presented worsening visual dysfunction all due to tumor growth.

CONCLUSION  

GKS provided a high tumor control and low complication rate for NFPAs.We recommended that early GKS should be considered the routine adjuvant treatment for residual NFPAs after subtotal surgical resection.

Shibin SUN (Beijing, CHINA)
15:40 - 15:50 #17665 - a491-2 Long-term outcome of gamma knife radiosurgery for patients with nonfunctioning pituitary adenomas.
a491-2 Long-term outcome of gamma knife radiosurgery for patients with nonfunctioning pituitary adenomas.

Purpose: We evaluated the treatment results of gamma knife radiosurgery for nonfunctioning pituitary adenomas.

Material and methods: Between January 1994 and December 2014, we treated and followed up 134 patients with nonfunctioning pituitary adenomas. All the tumors were treated by neurosurgery prior to radiosurgery, 3 patients (2.2%) received conventional radiation therapy before radiosurgery. Tumor volume ranged from 0.27 to 15.1 ml (median: 2.17 ml). Radiosurgical dose ranged from 8 to 16 Gy (median: 12 Gy) for the tumor margin. The median follow-up was 9 years (1 to 22 years).

Results: Tumor growth control rate was 95% at 5-years, 94% at 10-years and 91% at 15 years. 3 patients (2.2%) suffered out-of filed recurrences. The actuarial endocriopathy needed hormonal replacement therapy was 4% at 5-years, 7% at 10-years and 15% at 15 years. 3 patients (2.2%) suffered the permanent cranial neuropathy. The suprasellar extension was significant factors of poor tumor control (p=0.049) and high incidence of endocrinopathy (p=0.014). Cystic enlargement was occurred in 8%, but all lesions were decreased or unchanged in size during follow-up periods. New cranial neuropthy was occurred 2.2% during 42 to 144 months after radiosurgery.

Conclusion: Gamma knife radiosurgery is very useful for nonfunctioning pituitary adenomas in the standpoint of long-term tumor growth control. We recommend early adjuvant radiosurgery for the residual tumor after enough tumor debulking or regrowth after surgery.

Yoshiaysu IWAI (Osaka, JAPAN), Kenichi ISHIBASHI, Kazuhiro YAMANAKA
15:50 - 16:00 #17697 - a491-3 Plasticity of the visual cortex to visual pathway injuries before and after SRS of suprasellar tumors.
a491-3 Plasticity of the visual cortex to visual pathway injuries before and after SRS of suprasellar tumors.

Objectives:

To demonstrate that lesions of the visual pathways due to suprasellar tumors are accompanied by alterations of the visual cortex and to see if these alterations are reversible after treatment of tumors by Gamma Knife radiosurgery.

Methods:

In 36 patients with perioptic tumors and defects of their visual fields and in an age-matched control group, magnetic resonance imaging was performed before and after Gamma Knife radiosurgery. T1 weighted images were evaluated by voxel-based morphometry and correlated to the degree of visual field defects.

Results:

In patients, grey matter density and cortical thickness were reduced in all parts of the occipital cortex, reaching significance (p<0.05) in the left superior and middle occipital gyri, with correlation to visual field defects. Follow-up scans showed further reduction in all occipital areas.

Conclusions:

As in other peripheral lesions of the optic system, damage of the optic nerves, chiasm and tracts due to compression by suprasellar tumors affects the visual cortex and induces a reduction of grey matter density which - in contrast to some clinical recuperation - does not recuperate after successful Gamma Knife radiosurgery. However, a follow-up study in a prospective design including only patients without previous operations, which might have injured these structures in an irreversible way, is needed to confirm this conclusion or show under which conditions exceptional recuperations of the visual cortex are possible. In addition, the unexpected finding of a more general affection of cortical thickness in patients with pituitary tumors could be looked into more closely in order to identify and possibly prevent any predisposing factors.

Herwin SPECKTER (Santo Domingo, DOMINICAN REPUBLIC), Jairo SANTANA, Jose BIDO, Giancarlo HERNANDEZ, Diones RIVERA, Luis SUAZO, Santiago VALENZUELA, Peter STOETER
16:00 - 16:10 #17888 - a491-4 Gamma knife radiosurgery in patients with Crooke’s cell adenoma.
a491-4 Gamma knife radiosurgery in patients with Crooke’s cell adenoma.

Background: Crooke’s cell adenoma, which is known to be clinically aggressive, is a very rare subtype of pituitary neoplasm. They could secreting adreno-corticotropic hormone or endocrinologically silent. Gamma knife radiosurgery (GKRS) for this subtype of adenoma is extremely rare. We aim to evaluate the effect of GKRS on endocrine remission and tumor control.

Patients and methods: A total of seven patients (3M/4F, median age at GKRS, 54 years, range, 21 to 65 years) with a pathology-confirmed Crooke’s cell adenoma treated with GKRS at University of Virginia Gamma Knife Center constituted this study. The median time interval between TSR and GKRS was 3 months. The median margin dose was 25Gy (range, 18Gy to 25Gy). Median treated adenoma volume was 3.12cc. The median follow-up was 74 months (range, 54 to 120 months).

Results: The tumor control was achieved in all patients. All but one achieved endocrine remission. The median time interval to cortisol normalization off of anti-hormone secreting medication was 9 months (range, 0 to 24 months). Newly developed or worsening endocrinopathy occurred in 3 patients at the time interval of 6, 15, and 18 months, respectively. The CN III neuropathy developed in 1 patient. Two patients required bilateral adrenalectomy at 44 months and 50 months following GKRS, respectively.

Conclusion: This study suggests that Crooke’s cell adenoma is truly an aggressive entity. GKRS represents a safe and effective treatment option. Large number of patients from a multicenter study is warranted to further elucidate the effectiveness of GKRS. A multimodality treatment in this patient cohort is necessary.

Zhiyuan XU (Charlottesville, USA), David SCHLESINGER, Sheehan JASON

15:30-16:20
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C491
Oral Session
VESTIBULAR SCHWANNOMA #2

Oral Session
VESTIBULAR SCHWANNOMA #2

Moderators: Yuri ANDRADE SOUZA (BRAZIL), Laura FARISELLI (director) (milano, ITALY), Randy JENSEN (Professor) (Salt Lake City, USA)
15:30 - 15:40 #17545 - c491-1 Efficiency Index comparison of linac-based and Gamma Knife-based radiosurgery of vestibular schwannoma treatment plans.
c491-1 Efficiency Index comparison of linac-based and Gamma Knife-based radiosurgery of vestibular schwannoma treatment plans.

Background: The Efficiency Index (EI) was recently proposed as a plan quality descriptor for stereotactic radiosurgery (SRS) plans, combining conformity, gradient and mean dose to the target in a single value (EI=Intergal DoseTV / Integral Dose50%PIV) 1. It has theoretical limits between 0-100%, and the values achieved clinically have been quantified to range from 37.7% to 58.0 (mean: 49.0%) for a group of 100 Gamma Knife (GK) plans.

Methods: This study aims to compare the achieved EIs between two similar groups of linac-based and GK-based SRS plans with a scope of assessing the utility of this index in linac-based SRS. A group of 20 consecutive vestibular schwannoma treatments with useful hearing were collected from each platform database making a total of 40 plans. The average target volumes were 2.77 and 2.18cc for linac and GK respectively. The linac plans included a 1mm treatment margin in the target volume whereas the GK plans did not. Linac cases were treated with a Varian TrueBeam, micro-MLC collimator single isocentre VMAT technique. GK cases were treated with an Elekta Perfexion using multiple isocentres.

Results: The average EIs achieved were 39.8% (range: 23.5-52.8%) and 51.3% (range: 36.4-56.7%) for linac and GK plans respectively. In both groups a higher score was seen with improvements in conformity and gradient. The differences in EIs seen between the two groups are attributed to differences in conformity (Mean Conformity Index: 0.87 vs 0.88), differences in gradient (Mean Gradient Index: 3.69 vs 2.71) and differences in mean dose to the target (15.5 vs 17.3 Gy). A trend for lower EIs was observed in smaller target volumes, mainly due to the poor gradients achieved in these plans.

Conclusion: The EI is a useful metric for both linac and GK plan quality assessment, and its score increases with improvements to qualities that are considered clinically relevant.

1.         Dimitriadis A, Paddick I: A novel index for assessing treatment plan quality in stereotactic radiosurgery. J Neurosurg 129:118–124, 2018

Alexis DIMITRIADIS (London, UK), Hany ATTALLAH, Ronald BEANEY, Ian PADDICK
15:40 - 15:50 #17691 - c491-2 Radiomic: prediction of acoustic neuroma response to the cyberknife treatment.
c491-2 Radiomic: prediction of acoustic neuroma response to the cyberknife treatment.

Aim: The aim of the study was to use a radiomic approach to evaluate the possibility to predict the response of an acoustic neuroma to Cyberknife® radiotherapy analyzing pre-treatment MR images. Materials:  38 patients presenting an acoustic neuroma treated with Cyberknife® at our institute were selected. Comparing the pre and post-radiotherapy images , acquired after at least 2 years, the radiotherapist divided the patients according to the volumetric treatment outcome (stability, reduction, increasement). This classification was used by the machine learning algorithm as a reference value. All images were acquired on two 1.5T machines with contrast enhanced T1-weighted sequences in axial plane. Semi-automatic tumor segmentation was carried out by a radiotherapist  on MR images using the level tracing effect of the 3DSlicer image analysis software.  After the segmentation a resampling step was done to harmonize the images acquired on the scanners. Sequentially, 1135 shape-based, intensity-based and texture-based features were extracted using IBEX, an open software infrastructure platform. An evolutionary machine learning algorithm (a TWIST system based on KNN algorithm) was used to subdivide the dataset into training and test set and select features yielding the maximal amount of information. After the features extraction, a predictive model based on a training-testing crossover procedure was developed. The best neural network obtained was a 2-layers feed forward back propagation algorithm with 37 input variables containing the maximal amount of information.
Results: The neural network was used twice inverting the training/testing set. In the first analysis the sensitivity was 71.43%, while the specificity was 100%, with a global accuracy of 85.71%. In the second analysis the sensitivity was 83.33% and the specificity 88.24%, with a global accuracy of 85.78%. The mean value of the global accuracy was 85.75%.
Conclusions: The obtained results show that Machine Learning coupled with Radiomics has a great potential in distinguishing, before radiosurgery,  patients with volume reduction from patients without.

Isa BOSSI ZANETTI (Milano, ITALY), Natascha Claudia D'AMICO, Enzo GROSSI, Giovanni VALBUSA, Deborah FAZZINI, Achille BERGANTIN, Irene REDAELLI, Anna Stefania MARTINOTTI, Cecilia IEZZONI, Giuseppe SCOTTI, Laura FARISELLI, Sergio PAPA, Giancarlo BELTRAMO
15:50 - 16:00 #17854 - c491-3 Short-term volumetric tumor response as predictor for long-term tumor control after Gamma Knife radiosurgery of vestibular schwannoma.
c491-3 Short-term volumetric tumor response as predictor for long-term tumor control after Gamma Knife radiosurgery of vestibular schwannoma.

Introduction

Gamma Knife radiosurgery (GKRS) is an effective treatment strategy for vestibular schwannomas (VSs), obtaining long-term tumor control rates of 90%. Currently, predicting long-term tumor control is not possible, making lifelong follow-up mandatory and prospective studies on tumor control difficult to conduct. Therefore, predicting tumor control at earlier stages would be beneficial. We explored the predictability of long-term tumor control employing short-term volumetric tumor responses.

Methods

All VS patients with minimum follow-up of 3 years were included. Tumor volumes were obtained from follow-up MRIs. Tumor volume reduction (TVR) was calculated at 6, 12, 24 and 36 months following GKRS. Correlations between TVRs and long-term tumor control were evaluated.

Results

We included 795 patients, of which 96 showed loss of tumor control. The median follow-up time was 61 months. TVRs at 6, 12, 24, and 36 months were based on MRIs from 186, 693, 541 and 399 patients, respectively. Cox regression analyses indicate that TVRs at 6, 24 and 36 months are significantly related to tumor control, indicating a proportional correlation. Kaplan-Meier analyses, when stratifying the cohort in 4 groups based on the TVRs, confirmed this relation: tumors with pronounced TVRs in the first years following GKRS had significantly lower risks of treatment failure, as compared to increasing tumors. For example, if tumor volumes were stable or decreasing between 6 and 24 months after GKRS, loss of long-term tumor control was observed rarely compared to tumors with increasing volumes in this follow-up period: 5-year tumor control probabilities are 97.5% and 67.1%, and the 10-year probabilities are 92.0% and 67.1%, respectively.

Conclusions

Results from this research clearly indicate that TVRs at 6, 24 and 36 months following treatment are predictive for long-term tumor control in GKRS-treated VS. These findings can help in determining an individual follow-up schedule for VS patients and make prospective studies on long-term tumor control more feasible.

Patrick LANGENHUIZEN (Tilburg, THE NETHERLANDS), Svetlana ZINGER, Sieger LEENSTRA, Patrick HANSSENS, Peter DE WITH, Jeroen VERHEUL
16:00 - 16:10 #17864 - c491-4 Role Of Bevacizumab As A Prophylactic And Rehabilitative Treatment Modality In Cases Of Sporadic And Syndromic Vestibular Schwannoma: Fifty Shades Of Grey.
c491-4 Role Of Bevacizumab As A Prophylactic And Rehabilitative Treatment Modality In Cases Of Sporadic And Syndromic Vestibular Schwannoma: Fifty Shades Of Grey.

Objectives:

Detection of vestibular schwannoma (VS) in young patient demands specific attention considering it’s relatively aggressive course and natural

history of the disease. Patients with syndromic variants such as neurofirbromatosis type 2 (NF2) suffer from multiple tumors including bilateral VS,

meningioma, ependymomas, and peripheral nerve sheath tumors. Such patients may suffer from unprecedented complications following radio

surgical treatment such as poor tumor control and functional outcome.

Methods:

Authors describe their own experience with Bevacizumab as a preventive and rehabilitative treatment option in two such patients who suffered from

complications of radiosurgery in the immediate post-procedure period. Literature is reviewed for the indications, dosage, safety profile, and

complications profile on short and long-term of Bevacizumab in vestibular schwannomas.

Results:

One middle-aged patient of sporadic vestibular schwannoma suffered rapid onset facial paresis within one month of GKRS. After a failed attempt

with steroids, the patient regained partial improvement following Bevacizumab treatment. Another young female of phenotypic NF2 syndrome

suffered rapid onset hearing deficit within two weeks of GKRS, which improved to pre GKRS level with the early introduction of Bevacizumab.

Bevacizumab has shown its efficacy both as a prophylactic and rehabilitative treatment modality for syndromic patients of VS.

Conclusions:

Though not a wonder drug, Bevacizumab is a valuable adjunct in crossroad situations. It has a proven role as a prophylactic treatment option to

retard the growth of VS and spinal ependymomas with no role on meningiomas. As a rehabilitative treatment option, Bevacizumab may be used in

steroid-resistant cases to prevent radiosurgery-induced complications. Long-term studies are warranted to confirm the dosing schedules, regimens,

and complication profile.

Manjul TRIPATHI (Chandigarh, INDIA)
16:10 - 16:20 #17646 - c491-5 Observation or stereotactic radiosurgery for newly diagnosed vestibular schwannomas: A systematic review and meta-analysis.
c491-5 Observation or stereotactic radiosurgery for newly diagnosed vestibular schwannomas: A systematic review and meta-analysis.

Introduction: Vestibular schwannomas are benign tumors with a slow growth rate. There exists controversy regarding whether patients should receive upfront observation, radiotherapy including SRS or FSRT, or surgery at the time of diagnosis. For patients declining resection, this systematic review evaluates the risks and benefits between observation and SRS upon diagnosis of VS.

Methods: Published studies on VS were systematically reviewed for clinical series including patients with newly/recently diagnosed unilateral VS. Studies that included patients with previous treatment for the VS or focused on patients with neurofibromatosis were excluded. Review articles and systematic reviews were excluded but reviewed for relevant references that would otherwise meet search criteria.

Results: Most patients electing observation underwent their first surveillance scan 6 months after initial      diagnosis. Follow up was similar for patients receiving radiosurgery. Observation alone conferred a radiographic tumor control rate of 65% and serviceable hearing in 71.3% by the end of the follow up period in the reviewed studies, and 34% of patients initially opting for observation ultimately opted for treatment. The follow up period varied between studies. Initial radiosurgery resulted in a tumor control rate of 97% and serviceable hearing rate of 73.8% at by the end of the follow up period. Radiosurgery resulted in improved tumor control at the end of the follow up period (p < 0.0001), and serviceable hearing did not statistically differ (p = 0.69).

Conclusion: Based on the available published data, observation after initial diagnosis is appropriate for many patients with VS without symptomatic brainstem compression. However, initial observation does risk early progressive hearing dysfunction if the tumor grows and patients with serviceable hearing at diagnosis may benefit from early therapy. Long term follow up is critical, and an algorithm to better risk-stratify patients with newly diagnosed VS is underway.

Janet LEON, Eric LEHRER, Jennifer PETERSON, Laura VALLOW, Henry RUIZ-GARCIA, Austin HADLEY, Steven HERCHKO, Larry LUNDY, Kaisorn CHAICHANA, Prasanna VIBHUTE, Jason SHEEHAN, Daniel TRIFILETTI (Jacksonville, USA)

16:20 - 17:00 COFFEE BREAK - POSTERS & EXHIBITION
17:00
17:00-17:45
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A493
ISRS GENERAL ASSEMBLY

ISRS GENERAL ASSEMBLY

17:00-18:00
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C493
REDE D'OR SPONSORED SESSION

REDE D'OR SPONSORED SESSION

17:00 - 18:00 Moderator. Karina MOUTINHO (neurosurgery) (Santa Paula, BRAZIL)
17:00 - 17:20 The Challenges of Radiosurgery in Brain Metastases. Felipe ERLICH (Radiation Oncologist) (Rio de Janeiro, BRAZIL)
17:20 - 17:40 The Challenges of Radiosurgery in treatment of oligometastatic disease. Allisson Barcelos BORGES (Radiation Oncologist) (Brasilia-DF, BRAZIL)
17:40 - 18:00 The Oncologia D’Or Changing the Radiotherapy and Radiosurgery Scenario. Karina MOUTINHO (neurosurgery) (Santa Paula, BRAZIL)

17:45
20:00 - 23:30 CONGRESS DINNER - Casa Das Canoas, Tijuca Forest - (Upon Registration)