Wednesday 12 June
11:45

Wednesday 12 June

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B46
11:45 - 13:00

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
Segovia Break Out