Post Stereotactic Radiosurgery Research Articles

Bilateral Multiple Orbital Metastases Successfully Treated with Standalone Stereotactic Radiosurgery: Clinical Image

Bilateral orbital metastases are extremely rare, and no previous literatures have reported bilateral multiple orbital metastases treated with stereotactic radiosurgery (SRS). We present the impressive images of a patient with history of metastatic leiomyosarcoma with newly diagnosed bilateral multiple orbital metastases. The pre-SRS MRI showed a right and two left orbital metastatic lesions. The patient underwent SRS, and the post-SRS MRI at 2-month following SRS showed a decrease in size of the treated lesions. The PET scan at 5 months after the treatment showed no avid F-fluorodeoxyglucose uptakes in the three orbital metastases. The presenting symptoms are all improved after the treatment without no adverse effects from the SRS. Our interesting images show the presence of multiple lesions in the orbital spaces with excellent treatment responses post SRS. This is the first report of a patient who has bilateral and multiple orbital metastases that were successfully treated with standalone SRS.

Sustaining consistent cobalt-60 dose rate enhances radiosurgical outcomes in brain arteriovenous malformation management

Background and purposeThe impact of cobalt-60 dose rate (Co-60 DR) on outcomes of stereotactic radiosurgery (SRS) for brain arteriovenous malformations (AVMs) remains fully elucidated. This study explored the association between Co-60 DR and SRS outcomes in AVM treatment. Materials and methods772 AVM patients from 1990 to 2020 were included. High DR was defined as ≥ 2.4 Gy/min. AVM patients were categorized into 3 cohorts based on the nidus volume: small (<5 mL), medium (≥5 mL and < 10 mL), and large (≥10 mL). The primary endpoint was AVM obliteration; secondary endpoints included post-SRS hemorrhage. ResultsCumulative obliteration rates of the large AVM were significantly increased in the high DR group than those in the low DR group (84 % vs. 45 % at 5 years, log-rank test; p = 0.011). Multivariable analysis showed that the obliteration rate was significantly elevated for the high DR group in the large AVM cohort with an adjusted hazard ratio (HR) of 1.78 (95 % confidence interval [CI]: 1.00–3.17, p = 0.049). Post-SRS hemorrhage rates of the entire cohort were significantly decreased in the high DR group than in the low DR group (2.5 % vs. 5.3 % at 5 years, log-rank test; p = 0.035). Multivariable analysis revealed post–SRS hemorrhage was reduced in the high DR group with an adjusted HR of 0.47 (95 % CI: 0.24–0.92, p = 0.026). ConclusionHigh DR may lead to increased efficiency for large AVMs and decreased post-SRS hemorrhage in all AVM cases. Sustaining a higher Co-60 DR could potentially yield favorable outcomes for SRS for AVMs.

Ga68] DOTATATE PET/MRI-guided radiosurgical treatment planning and response assessment in meningiomas.

Our purpose was to determine the utility of [68Ga]-DOTATATE PET/MRI in meningioma response assessment following radiosurgery. Patients with meningioma prospectively underwent postoperative DOTATATE PET/MRI. Co-registered PET and gadolinium-enhanced T1-weighted MRI were employed for radiosurgery planning. Follow-up DOTATATE PET/MRI was performed at 6-12 months post-radiosurgery. Maximum absolute standardized uptake value (SUV) and SUV ratio (SUVRSSS) referencing superior sagittal sinus (SSS) blood pool were obtained. Size change was determined by Response Assessment in Neuro-Oncology (RANO) criteria. Association of SUVRSSS change magnitude and progression-free survival (PFS) was evaluated using Cox regression. Twenty-seven patients with 64 tumors (26% World Health Organization [WHO]-1, 41% WHO-2, 26% WHO-3, and 7% WHO-unknown) were prospectively followed post stereotactic radiosurgery (SRS) or stereotactic body radiotherapy (SBRT; mean dose: 30 Gy, modal dose 35 Gy, mean of 5 fractions). Post-irradiation SUV and SUVRSSS decreased by 37.4% and 44.4%, respectively (P < .0001). Size product decreased by 8.9%, thus failing to reach the 25% significance threshold as determined by RANO guidelines. Mean follow-up time was 26 months (range: 6-44). Overall mean PFS was 83% and 100%/100%/54% in WHO-1/-2/-3 subcohorts, respectively, at 34 months. At maximum follow-up (42-44 months), PFS was 100%/83%/54% in WHO-1/-2/-3 subcohorts, respectively. Cox regression analyses revealed a hazard ratio of 0.48 for 10-unit reduction in SUVRSSS in the SRS cohort. DOTATATE PET SUV and SUVRSSS demonstrated marked, significant decrease post-radiosurgery. Lesion size decrease was statistically significant; however, it was not clinically significant by RANO criteria. DOTATATE PET/MR thus represents a promising imaging biomarker for response assessment in meningiomas treated with radiosurgery. NCT04081701.

Imaging Findings Post-Stereotactic Radiosurgery for Vestibular Schwannoma: A Primer for the Radiologist.

Noninvasive tumor control of vestibular schwannomas through stereotactic radiosurgery allows high rates of long-term tumor control and has been used primarily for small- and medium-sized vestibular schwannomas. The posttreatment imaging appearance of the tumor, temporal patterns of growth and treatment response, as well as extratumoral complications can often be both subtle or confusing and should be appropriately recognized. Herein, the authors present an imaging-based review of expected changes as well as associated complications related to radiosurgery for vestibular schwannomas.

Endothelial marker profiles in cerebral radiation-induced vasculopathy: A comparative immunohistochemical analysis.

Radiation therapy results in radiation-induced vasculopathy, characterized by alterations in the vascular architecture stemming from radiation exposure. The exact molecular pathways and associated pathologies of this condition have yet to be comprehensively understood. This study aimed to identify specific markers' roles in cerebral vascular endothelial injury pathogenesis after radiosurgery and explore their unique expression patterns in diverse pathologies post-stereotactic radiosurgery. A retrospective cohort study was conducted to assess the expression profiles of endothelial markers via immunohistochemical analysis in 25 adult patients (13 males and 12 females) who had undergone neurosurgical resection for various central nervous system pathologies following stereotactic radiosurgery or radiotherapy from 2001 to 2015. Our findings revealed strong immunohistochemical expression of ICAM-1 and E-selectin across various disease states, while MMP-9, PAI-1, and eNOS exhibited moderate expression levels. In contrast, VCAM-1 and P-Selectin had the weakest expression across all groups. Notably, while individual markers showed significant variations in expression levels when comparing different diseases (P < .001), no substantial differences were found in the overall immunohistochemical expression patterns across the 5 distinct pathologies studied (P = .407, via 2-way ANOVA). Despite the varied long-term effects of radiotherapy on the vascular endothelium, a common thread of inflammation runs through the pathology of these conditions. The distinct patterns of marker expression identified in our study suggest that different markers play unique roles in the development of radiation-induced vasculopathy. These findings offer insights that could lead to the development of novel preventive strategies and treatments.

Predictors of radiation-induced changes in arteriovenous malformation patients undergoing radiosurgery: Insights from a Malaysian linear accelerator cohort.

Radiation-induced changes (RICs) post-stereotactic radiosurgery (SRS) critically influence outcomes in arteriovenous malformation (AVM) treatments. This study aimed to identify predictors of RICs, described the types and severity of RICs, and assessed their impact on patient's functional outcomes to enhance risk assessment and treatment planning for AVM patients. This retrospective study analyzed 87 AVM patients who underwent SRS at Hospital Kuala Lumpur between January 2015 and December 2020. RICs were identified through detailed magnetic resonance imaging evaluations, and predictive factors were determined using multiple logistic regression. Functional outcomes were assessed with the modified Rankin scale (mRS). Among the cohort, 40.2% developed RICs, with radiological RICs in 33.3%, symptomatic RICs in 5.7%, and permanent RICs in 1.1%. Severity categorization revealed 25.3% as Grade I, 13.8% as Grade II, and 1.1% as Grade III. Notably, higher Pollock-Flickinger scores and eloquence location were significant predictors of RIC occurrence. There was a significant improvement in functional outcomes post-SRS, with a marked decrease in non-favorable mRS scores from 8.0% pre-SRS to 1.1% post-SRS (P = 0.031). The study identified the eloquence location and Pollock-Flickinger scores as predictors of RICs post-SRS. The significant reduction in non-favorable mRS scores post-SRS underscores the efficacy of SRS in improving patient outcomes. Their results highlighted the importance of personalized treatment planning, focusing on precise strategies to optimize patient outcomes in AVM management, reducing adverse effects while improving functional outcomes.

Stereotactic Radiosurgery as an Effective and Safe Treatment Modality in Central Nervous System Lymphoma, a Single Institution Experience

CNS lymphoma (CNSL) is an aggressive liquid cancer with the potential for rapid progression. Standard treatment regimens for CNSL have included chemotherapy and whole brain radiotherapy (WBRT). WBRT carries a high risk of leukoencephalopathy (LE) manifesting as cognitive decline and is identifiable on brain MRI as fluid attenuation inversion recovery (FLAIR) changes. Stereotactic radiosurgery (SRS) can precisely deliver higher biologically effective doses of radiation, while minimizing damage to surrounding healthy brain tissue. SRS offers enhanced local control in CNSL with minimal risk of LE. Patients undergoing SRS at an NCI-designated comprehensive cancer center from 2000 to 2022 were prospectively enrolled into a database. Twenty-nine consecutive patients diagnosed with relapsed primary CNSL (59%) or secondary CNSL (41%) were included in this study. Median age at diagnosis was 70 (range 23-91) years and 14 were female. Follow up MRI imaging was obtained at 1-, 3-, 6- and 12-months post-procedure. Measurement of tumor volumes was performed at treatment and each subsequent follow-up by image co-registration and tumor segmentation. Pre and post SRS brain MRIs were independently reviewed by a neuro-radiologist to score the grade of LE for each patient. Progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan-Meier analyses and Log-rank tests using statistical software. Twenty-nine patients treated for 50 tumors were studied. Twenty-four patients were treated for a single tumor, and 5 for multiple tumors. Six patients underwent repeat SRS treatment for 10 out-of-field recurrences and 1 patient for an in-field recurrence. Of the 35 SRS procedures performed, 32 (88%) were single session delivery and 3 were hypofractionated. Stereotactic immobilization was achieved with frame (57%) or thermoplastic mask (43%). Median prescribed dose was 14 Gy (range 10-21) to the 50% isodose line (range 40-100). Median coverage, selectivity and gradient index were 0.97, 0.69, and 2.9 respectively. Median follow-up time was 4.5 months (range 0.5-64). Twenty-six (52%) tumors completely responded to treatment with no residual enhancement, while the rest decreased in volume. No tumor failed to respond to treatment. Median time to best volumetric response was achieved in 2.9 months (range 1-6.1) and median volume of best response was zero cc (range 0-1.19). The median OS of the cohort was 7.0 months (95% CI 5.1-8.9), while the median PFS was 5.0 months (95% CI 1.2-8.8). Median score of LE was zero, and only one patient experienced grade 3 MRI FLAIR changes. With a median time to response of 2.9 months, a 100% initial response rate and a single in-field failure, our analysis demonstrates a rapid and effective response of CNSL to SRS. Distant failures were controlled with repeat SRS. The absence of LE in the treated patients provides further evidence for safety and tolerability of SRS in CNSL.

Performance sensitivity analysis of brain metastasis stereotactic radiosurgery outcome prediction using MRI radiomics

Recent studies have used T1w contrast-enhanced (T1w-CE) magnetic resonance imaging (MRI) radiomic features and machine learning to predict post-stereotactic radiosurgery (SRS) brain metastasis (BM) progression, but have not examined the effects of combining clinical and radiomic features, BM primary cancer, BM volume effects, and using multiple scanner models. To investigate these effects, a dataset of n = 123 BMs from 99 SRS patients with 12 clinical features, 107 pre-treatment T1w-CE radiomic features, and BM progression determined by follow-up MRI was used with a random decision forest model and 250 bootstrapped repetitions. Repeat experiments assessed the relative accuracy across primary cancer sites, BM volume groups, and scanner model pairings. Correction for accuracy imbalances across volume groups was investigated by removing volume-correlated features. We found that using clinical and radiomic features together produced the most accurate model with a bootstrap-corrected area under the receiver operating characteristic curve of 0.77. Accuracy also varied by primary cancer site, BM volume, and scanner model pairings. The effect of BM volume was eliminated by removing features at a volume-correlation coefficient threshold of 0.25. These results show that feature type, primary cancer, volume, and scanner model are all critical factors in the accuracy of radiomics-based prognostic models for BM SRS that must be characterised and controlled for before clinical translation.

SURG-10. PERMANENT CARRIER-EMBEDDED CESIUM-131 BRACHYTHERAPY FOR THE SALVAGE TREATMENT OF PREVIOUSLY IRRADIATED, RECURRENT BRAIN METASTASES

Abstract BACKGROUND Salvage of recurrent, previously-irradiated brain metastases (rBrM) is a significant clinical challenge. High local failure is seen following salvage resection without adjuvant re-irradiation, while re-irradiation is associated with high radionecrosis rates. Salvage surgery plus intraoperative Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced integral brain dose versus re-irradiation. METHODS A prospective registry of consecutively treated patients with post-stereotactic radiosurgery (SRS) rBrM was analyzed. Following resection, cavities were implanted with commercially-available, collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60Gy at 5mm from the cavity. RESULTS Twenty patients underwent 24 operations with Cs131 implantation in 25 cavities. Previous SRS occurred a median of 358d preoperatively (range=56-1334). Median maximum preoperative diameter was 3.0cm (range=1.1-6.3) and enhancing volume was 9.5cm3 (range=0.6-69.7). Gross- or near-total resection was achieved in 60%. A median of 16 Cs131 seeds (range=6-30), with a median activity of 3.5U/seed were implanted. Maximal preoperative diameter and enhancing volume were weakly associated with the number of implanted seeds (correlation coefficients=0.50, 0.41, respectively). There was one postoperative wound dehiscence in a multiply resected and irradiated patient with hydrocephalus. With median follow-up of 1.6 years for survivors, 2 tumors recurred (one in-field, one marginal) resulting in 9.8% 1-year progression incidence (95%CI=0.0-23.2). Radiographic seed migration was identified in 7/25 cavities (28%) on scans ranging from 1.9-11.7 months post-implantation, without clinical sequelae. CONCLUSIONS With &amp;gt;1 year of follow-up, intraoperative brachytherapy with Cs131 implants was associated with a high rate of local control and a favorable toxicity profile. Modest correlation between preoperative tumor geometry and implanted tiles with high associated cost suggests a need to optimize planning criteria. A randomized trial of salvage resection with or without Cs131 is ongoing (NCT04690348) to assess the incremental benefit of brachytherapy.

5 Year Survivors from Brain Metastases Treated with Stereotactic Radiosurgery: Biology, Improving Treatments or Just Plain Luck?

<h3>Purpose/Objective(s)</h3> Improvements in therapies have led to an increasing number of long-term survivors of brain metastases. This population has not been well characterized. The present series compares a population of 5-year survivors of brain metastases to a generalized brain metastasis population to assess for factors attributable to long term survival. <h3>Materials/Methods</h3> A single institution retrospective review was performed to identify 5-year survivors of brain metastases who have received stereotactic radiosurgery (SRS). Electronic medical records were queried to characterize this population based on clinical, demographic and treatment data. A historical control population of 747 patients with brain metastases was used to assess for similarities and differences between the long-term survivor population and the general population treated with upfront SRS. Statistical analysis was performed with SAS version 9.4 using the 2-sample t test, chi squared test, and Fine Gray competing risk analysis using death as a competing risk. <h3>Results</h3> From 9/99 to 2/17 a total of 2422 patients were treated with SRS for brain metastases at a single institution, where 95 patients (3.9%) were found to have survived over 57 months. In the historical control population, 25 of 747 patients (3.3%) lived beyond 57 months. In the long-term survivor cohort, primary tumors were from lung (53%), melanoma (19%), breast (12%), renal cell (9.5%) and other histology (7.4%). Median survival of the long-term survivor cohort was 85 months, with mean number of 2.2 (SD=2.0) metastases treated and 2% receiving WBRT prior to SRS. Two-sample t-test test found no difference between long term survivors and controls with regards to age (p=0.2), primary cancer distribution (p=0.7), number of metastases (p=0.9), insurance type (p=0.1) or median income level (p=0.3). 22% of long-term survivors were receiving systemic therapy at last follow-up, and 52% showed no evidence of clinical disease at the last follow-up. Cumulative incidence of neurologic death at 6, 8 and 10 years for the long-term survivor cohort was 5%, 15%, and 15%, respectively. In the historical controls, cumulative incidence of neurologic death reached a plateau at 34% after 4.9 years. 61% of long-term survivors received further SRS (median 2, range 2-9, IQR 2.3), while 7% received post SRS WBRT. 5-year survivors received more additional SRS (P<0.0001), while historical controls received more post SRS WBRT (P=0.0008). <h3>Conclusion</h3> Five-year survivors of brain metastasis represent a diverse histologic population, suggesting that biologically, for each cancer type, a small population of oligometastatic and indolent cancers exist. While neurologic death of this long-term survivors is lower than in historical controls, these patients can still, die of neurologic death.

MMAP-10 ADVERSE RADIATION EFFECT AFTER STEREOTACTIC RADIOSURGERY AND IMMUNOTHERAPY/TARGETED THERAPY FOR MELANOMA BRAIN METASTASES

BACKGROUNDSafety of immunotherapy (IO) and targeted therapy (TT) with stereotactic radiosurgery (SRS) in melanoma brain metastases (MBM) treatment remains incompletely understood. We aim to identify whether timing of IO/TT in relation to SRS impacts rates of adverse radiation effect (ARE) in MBM. METHODSRetrospective review of patients with MBM treated with SRS and IO/TT within three months prior and one year after SRS, from 2011-2021 at a single institution with at least two months MRI follow-up, identified 108 patients with 939 unique MBM meeting criteria. ARE was confirmed on independent imaging review. Concurrent IO/TT was defined as receiving IO/TT within 4 weeks before or after SRS. Data analysis was performed with the univariate cox proportional hazard model and Kaplan-Meier method. RESULTSMedian radiographic follow-up from time of SRS was 16months. IO/TT was initiated prior to SRS for 681 (72.5%) metastases and after SRS for 258 (27.5%) metastases. 837 (89.1%) metastases received concurrent IO/TT. Most common IO agents were ipilimumab (n=416), nivolumab (n=448), and pembrolizumab (n=203). Most common TT agents were dabrafenib (n=548), trametinib (n=540), and vemurafenib (n=81). 2-year local progression-free survival (PFS), distant intracranial PFS, and overall survival were 94.1%, 33.3%, and 55.2%, respectively. 55 (5.9%) metastases in 33 (30.6%) patients experienced ARE. Median time to ARE was 5mo (IQR 4-9mo). Of those who experienced ARE, 22 (66.7%) patients were symptomatic and treated with steroids; 12 (36.4%) patients underwent surgical intervention. ARE rates were not impacted by concurrent vs nonconcurrent IO/TT (5.5% vs 4.9%, p=0.34) nor IO/TT initiation pre vs post SRS (6.0% vs 5.4%, p=0.61). CONCLUSIONIO/TT in conjunction with SRS resulted in low ARE rates as compared to historical controls in the pre-IO/TT era. Timing of IO/TT in relation to SRS may not significantly impact ARE rates in MBM treatment.

Salvage resection plus cesium-131 brachytherapy durably controls post-SRS recurrent brain metastases.

BackgroundSalvage of recurrent previously irradiated brain metastases (rBrM) is a significant challenge. Resection without adjuvant re-irradiation is associated with a high local failure rate, while reirradiation only partially reduces failure but is associated with greater radiation necrosis risk. Salvage resection plus Cs131 brachytherapy may offer dosimetric and biologic advantages including improved local control versus observation, with reduced normal brain dose versus re-irradiation, however data are limited.MethodsA prospective registry of consecutive patients with post-stereotactic radiosurgery (SRS) rBrM undergoing resection plus implantation of collagen-matrix embedded Cs131 seeds (GammaTile, GT Medical Technologies) prescribed to 60 Gy at 5 mm from the cavity was analyzed.ResultsTwenty patients underwent 24 operations with Cs131 implantation in 25 tumor cavities. Median maximum preoperative diameter was 3.0 cm (range 1.1–6.3). Gross- or near-total resection was achieved in 80% of lesions. A median of 16 Cs131 seeds (range 6–30), with a median air-kerma strength of 3.5 U/seed were implanted. There was one postoperative wound dehiscence. With median follow-up of 1.6 years for survivors, two tumors recurred (one in-field, one marginal) resulting in 8.4% 1-year progression incidence (95%CI = 0.0–19.9). Radiographic seed settling was identified in 7/25 cavities (28%) 1.9–11.7 months post-implantation, with 1 case of distant migration (4%), without clinical sequelae. There were 8 cases of radiation necrosis, of which 4 were symptomatic.ConclusionsWith > 1.5 years of follow-up, intraoperative brachytherapy with commercially available Cs131 implants was associated with favorable local control and toxicity profiles. Weak correlation between preoperative tumor geometry and implanted tiles highlights a need to optimize planning criteria.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11060-022-04101-9.

Real-world outcomes in advanced renal cancer patients treated with stereotactic radiosurgery for intracranial metastases.

e16516 Background: The proportion of metastatic renal cancer (mRC) patients with intracranial involvement is 8%, and 2% develop brain secondaries exclusively [1]. Although renal cancer is generally regarded as relatively radioresistant, studies have shown patients treated with stereotactic radiosurgery (SRS) demonstrate a local progression free survival (PFS) rate of 79-84% at 1 year and median overall survival (OS) of 9.6 – 13.9 months [2,3]. We evaluate the outcomes of patients with mRC who have received SRS to intracranial metastases at two tertiary centres in the North West of England. Methods: Patients who received SRS from January 2017 to July 2019 at Royal Preston Hospital, and from May 2016 to March 2021 at the Christie were retrospectively identified from the database of the respective hospitals. Clinical records were used to obtain demographics, therapies received and follow up data. Results: A total of 41 patients were identified. 31 patients (76%) were male and the average age at treatment was 59.6 years. 5 patients received treatment on &gt;1 occasion, but only the first episode was considered for analysis. 80.4% had a performance status of 0-1 and most patients had clear cell histology. 19 patients (46.3%) had lesions treated bilaterally. The median follow up time was 11 months. Prescribed doses ranged between 18Gy to 30Gy in 1-5 fractions. 11 patients (26.8%) progressed during the follow up period, with a median time to progression of 5 months. The longest time to progression was 17 months, in a patient who received Nivolumab following SRS. 28 patients (68.3%) died during the follow up period with a median time to death of 9.1 months. Median OS was 11 months, with 19 out of the 28 patients (67.9%) dying within the first year. The 1 year survival rate was 52.6% and 2 year survival rate was 16.2%. A range of systemic agents were used pre and post SRS including immunotherapy. 6 patients (23%) commenced immunotherapy following SRS (nivolumab +/- ipilimumab), with OS ranging from 6 – 49 months (average 25.5 months). Conclusions: We found that outcomes in this cohort of patients treated with SRS were comparable to previous findings. A subgroup who commenced Nivolumab following SRS demonstrated an average survival of over 2 years.[Table: see text]

107P Application of contrast clearance analysis (CCA) to assess viable tumour in non-small cell lung cancer (NSCLC) brain metastases post-stereotactic radiosurgery (SRS)

Brain metastases are a frequent complication in NSCLC. SRS is a non-invasive precision brain metastases treatment. Magnetic resonance imaging (MRI) with contrast-enhanced sequences forms the mainstay of brain metastasis imaging. On MRI post-SRS it can be difficult to differentiate viable tumour from post-treatment change such as radionecrosis. MRI technique CCA aims to distinguish vascular tumour from non-vascular post-treatment change with delayed contrast enhanced images (Zach Neuro Onc 2015). Retrospective review of patients in Royal Marsden Hospital with CCA scan from 1/1/2018 – 1/9/2021. 54 patients, with median of 65 years (range 32 - 89); 87% adenocarcinoma, 5.6% squamous cell carcinoma and 7.5% NSCLC “other”. Patients received up to 7 lines of systemic treatment. Twenty patients had targeted treatments (ALK, EGFR or ROS1). 51 patients received SRS (range 1-6), 10 patients whole brain radiotherapy (WBRT), 23 patients surgical resection (range of 1-2) and 2 patients partial brain radiotherapy. CCA imaging was performed during systemic treatment (47 patients) and during monitoring off treatment (30 patients). During these periods there was a median of 1 CCAs (range 1-7). Systemic therapy continued for median of 7 months from CCA. In 47% CCA concluded viable tumour was present, 53% CCA concluded post SRS changes. Recommended action was monitoring (49 cases), surgery (7 cases), SRS (12 cases), systemic therapy change (6 cases), WBRT (1 case). In the 7 cases where patients underwent resection of presumed tumour, 4 patients had viable tumour and 3 radionecrosis on histology. CCA was performed an average of 30 days prior to surgery. Two cases of radionecrosis, reported in 2017, were reclassified on retrospective review. CCA provided evidence to proceed to brain management. Patients were maintained on systemic therapy for multiple lines of therapy. There was not complete concordance with histology; recent recommendations to perform CCA within 14 days of surgery and evolving expertise in reporting means concordance is likely higher. Prospective validation including impact on patient outcome is warranted.

Synchronous glioblastoma and brain metastases: illustrative case.

BACKGROUNDRadiosurgical treatment of brain metastases is usually performed without brain tissue confirmation. While it is extremely rare for glioblastoma to develop concurrently in patients with brain metastases, they can look radiographically similar, and recognition is important because it alters management and prognosis. The synchronous presence of brain metastases and glioblastoma has not been published to date in the literature, making this a rare illustrative case.OBSERVATIONSA 70-year-old female had lung biopsy-proven metastatic lung adenocarcinoma and multiple brain metastases. Her treatment course included initial carboplatin, pemetrexed, and bevacizumab followed by maintenance nivolumab, and she underwent stereotactic radiosurgery to the multiple brain metastases. During interval radiological surveillance, one lesion in the right temporal lobe was noted to slowly progress associated with development of significant perilesional edema causing midline shift despite repeated stereotactic radiosurgical treatments. Biopsy of this lesion revealed glioblastoma, IDH wildtype.LESSONSGlioblastomas and brain metastases have similar radiological features, so the possibility of incorrect diagnosis needs to be considered for all lesions with interval growth poststereotactic radiosurgery. Biopsy and/or resection/laser ablation should be considered prior to reirradiation.

Yield of Surveillance Imaging in Long-Term Survivors of Brain Metastasis Treated With Stereotactic Radiosurgery

Although patients with brain metastasis treated with stereotactic radiosurgery (SRS) in the definitive or post-operative setting have high rates of local control, surveillance imaging is necessary to assess for central nervous system (CNS) recurrence. Guidelines recommend magnetic resonance imaging (MRI) of the brain every three months for surveillance in asymptomatic patients post-SRS. However, optimal frequency and duration of surveillance imaging in long-term survivors is unknown. Our objective is to define the yield and cost of surveillance MRIs in long-term (> 1 year) survivors following SRS.We identified a cohort of patients with brain metastases treated with SRS in the definitive or postoperative setting at a single institution from 8/2014 to 9/2019. Eligible patients had at least one-year of follow-up with absence of CNS disease failure up to and including the first MRI of the brain after 12 months from SRS. Each post-treatment MRI of the brain was assessed for disease progression or new lesions. CNS disease-free survival was time from SRS to last follow-up, death or CNS failure. Delay to diagnosis and cost per patient were estimated using hypothetical MRI schedules of 2, 3, 4 and 6 months from 1-year post-treatment while CNS disease-free. Delay to diagnosis was calculated as time from actual CNS progression to hypothetical imaging date. Medicare reimbursement median cost of $498 per MRI brain with and without contrast was used for this analysis.A total of 373 patients treated with SRS for brain metastasis were identified at our institution. 61 patients met eligibility criteria for inclusion in this study (median follow-up 2.50 years, median age at treatment 60 years). The median CNS disease-free survival in this population was 2.37 years from date of SRS. 15 patients (24.6%) had CNS progression at median time of 2.26 years. Of the 15 patients, 3 patients were symptomatic at recurrence. Median frequency of MRI after one year post SRS was 5.9 months. Per patient, $1156 was spent annually on MRIs of the brain after 12 months with average annual yield of 17.0%. The cost per diagnosis of CNS progression was $6806. A 2-month, 3-month, 4-month and 6-month MRI schedule had a respective estimated delay to diagnosis of 0.69 months, 1.13 months, 1.44 months and 3.19 months. The respective mean total cost of each MRI schedule per patient from one-year post-treatment while CNS disease-free was $4662, $3053, $2229 and $1380.Patients with metastatic disease to the brain treated definitively or postoperatively with SRS without evidence of CNS recurrence at one year have a low rate of CNS failure and relatively good prognosis. Based strictly on limiting delay of diagnosis, a 2-month MRI Brain schedule is optimal in this population, albeit with a relatively small increase in financial cost over the patient's lifespan. We propose a multi-institutional study of long-term survivors with brain metastasis to strengthen these findings.B.J. Rich: None. D. Kwon: None. Y.S. Soni: None. D.L. John: None. J.B. Bell: None. G. Azzam: None. E.A. Mellon: None. R. Yechieli: Support and guide school in strategic and management related matters; Toras Chaim Toras Emes, Miami FL.C. Benjamin: None. R. Benveniste: None. R.J. Komotar: None. M. Ivan: None. J. Morcos: None. T. Diwanji: None.

Concurrent vs. Sequential Stereotactic Radiosurgery and Immune Checkpoint Inhibition in Melanoma Brain Metastases: An International Cooperative Group Study

Multiple single institution retrospective studies have suggested that managing melanoma brain metastases (MBM) with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is associated with improved overall survival (OS) when administered concurrently (within 4 weeks) rather than sequentially (ICI and SRS administered more than 4 weeks apart). However, there is a paucity of data quantifying the risk of developing radiation necrosis (RN) in this setting.The International Radiosurgery Research Foundation approved the analysis. The Kaplan Meier method and log-rank test were used to compare OS and local control (LC) at 1- and 2-years post SRS. Factors associated with the development of RN and OS were further analyzed using logistic and Cox proportional hazards regression models. The null hypothesis was rejected for P < 0.05.There were 254 patients with 1,322 MBM treated across 10 international institutions. The median follow-up was 12.9 months, median age was 63 years (interquartile range [IQR]: 51-73 years), BRAF mutation was present in 46.6% of patients, active extracranial disease was present in 70% of patients, and the median Karnofsky Performance Status (KPS) was 90. SRS/ICI was administered concurrently in 46.5% of patients. All patients were treated on the stereotactic radiosurgery platform. The median margin dose was 20 Gy (IQR: 18-21 Gy), median number of fractions was 1 (range: 1-4), mean total brain metastasis volume was 3.4 cc and the mean V12 Gy was 8.7 cc. Radiation necrosis occurred in 14.2% of patients (5.9% Grade 1; 5.1% Grade 2; 2.8% Grade 3; 0.4% Grade 4). Overall survival at 1-year was 77.4% vs. 72.1%, and at 2-years was 63.1% vs. 46.1% (P = 0.048) for concurrent and sequential therapy, respectively. Local control at 1-year was 91.5% vs. 84.6%, and at 2-years was 84.9% vs. 75.6% (P = 0.12) for concurrent and sequential therapy, respectively. On multivariate logistic regression total treated brain metastasis volume (odds radio [OR]: 1.11; 95% confidence interval [CI]: 1.03-1.20; P = 0.008) was associated with a higher risk of development of RN; however, sequential therapy (OR: 0.97; 95% CI: 0.46-2.06; P = 0.94), and V12 (OR: 0.98; 95% CI: 0.95-1.01; P = 0.22) were not statistically significant. On multivariate cox regression, sequential therapy (hazard ratio [HR]: 1.58; 95% CI: 1.05-2.42; P = 0.03) and KPS (HR: 0.96; 95% CI: 0.94-0.98; P < 0.001) were prognostic factors for OS, while the presence of extracranial disease (HR: 1.03; 95% CI: 0.66-1.59; P = 0.90) and age (HR: 1.01; 95% CI: 1.00-1.02; P = 0.25) were not prognostic.In appropriately selected patients with MBM, concurrent administration of SRS/ICI may be associated with improved OS without an increased risk of RN when compared to sequential therapy. The risk of RN appears to increase with irradiated brain volume; therefore, hypofractionated SRS may be considered in patients with high volume disease. Prospective data are needed to further evaluate these findings.E.J. Lehrer: None. J. Gurewitz: None. T.D. Malouff: ASTRO Bylaws Committee. K. Bernstein: None. D. Kondziolka: None. P. Bonney: None. S.I. Patel: Independent Contractor; Alberta Health Services. Research Grant; Alberta Cancer Foundation. Travel Expenses; University Hospital Foundation. Chair; Alberta Health Services. Co-Director; Alberta Health Services. Manage and screen wish applications; Make-A-Wish Foundation (Northern Alberta Chapter). J.D. Palmer: Research Grant; Varian Medical Systems, The Kroger Company. Consultant; Huron Consulting. Speaker's Bureau; Varian Medical Systems, Depuy Synthes. Advisory Board; Novocure. Member of panel; NCCN.K. Fakhoury: None. C.G. Rusthoven: Employee; SURVIVEiT (nonprofit cancer patient advocacy). Research Grant; Takeda. Advise regarding patient-facing medical content; SURVIVEiT.D. Mathieu: None. C. Deibert: None. P. Picozzi: None. B. Jones: None. C. Lee: None. S. Sharma: None. A. Niranjan: None. J.P. Sheehan: Neuropoint Alliance. M. Ahluwalia: None. D.M. Trifiletti: None.

Stereotactic Radiosurgery With vs. Without Prior Embolization for Brain Arteriovenous Malformations: A Propensity Score Matching Analysis

Objective: Whether partial embolization could facilitate the post-stereotactic radiosurgery (SRS) obliteration for brain arteriovenous malformations (bAVMs) remains controversial. We performed this study to compare the outcomes of SRS with and without prior embolization for bAVMs.Methods: We retrospectively reviewed the Beijing Tiantan AVMs prospective registration research database from September 2011 to October 2014. Patients were categorized into two groups, combined upfront embolization and SRS (Em+SRS group) and SRS alone (SRS group), and we performed a propensity score matching analysis based on pre-embolization baseline characteristics; the matched groups each comprised 76 patients.Results: The obliteration rate was similar between SRS and Em+SRS (44.7 vs. 31.6%; OR, 1.754; 95% CI, 0.905–3.401; p = 0.096). However, the SRS group was superior to the Em+SRS group in terms of cumulative obliteration rate at a follow-up of 5 years (HR,1.778; 95% CI, 1.017–3.110; p = 0.033). The secondary outcomes, including functional state, post-SRS hemorrhage, all-cause mortality, and edema or cyst formation were similar between the matched cohorts. In the ruptured subgroup, the SRS group could achieve higher obliteration rate than Em+SRS group (56.5 vs. 31.9%; OR, 2.773; 95% CI, 1.190–6.464; p = 0.018). The cumulative obliteration rate at 5 years was also higher in the SRS group (64.5 vs. 41.3%; HR, 2.012; 95% CI, 1.037–3.903; p = 0.038), and the secondary outcomes were also similar between the matched cohorts.Conclusion: Although there was no significant difference in the overall obliteration rate between the two strategies, this study suggested that pre-SRS embolization may have a negative effect on post-SRS obliteration. Furthermore, the obliteration rates of the SRS only strategy was significantly higher than that of the Em+SRS strategy in the ruptured cohort, while no such phenomenon was found in the unruptured cohort.

Investigating diffusion patterns of brain metastases pre- and post-stereotactic radiosurgery: a feasibility study

Purpose. Metastatic complications are responsible for 90% of cancer-associated mortality. Magnetic resonance imaging (MRI) can be used to observe the brain’s microstructure and potentially correlate changes with metastasis occurrence. Diffusion weighted imaging (DWI) is an MRI technique that utilizes the kinetics of water molecules within the body. The aim of this study is to use DWI to characterize diffusion changes within brain metastases in cancer patients pre- and post-stereotactic radiosurgery (SRS). Methods. We retrospectively analyzed 113 metastases from 13 patients who underwent SRS for brain metastasis recurrence. Longitudinal apparent diffusion coefficient (ADC) maps were registered to Gd-T1 images and CT, and clinical metastasis ROIs from all SRS treatments were retrospectively transferred onto these ADC maps for analysis. Metastases were characterized based on pre-SRS diffusion pattern, primary cancer site, and post-SRS outcome. ADC values were calculated pre- and post-SRS. Results.ADC values were significantly elevated (980.2 × 10−6 mm2 s−1 and 1040.3 × 10−6 mm2 s−1 pre- and post-SRS, respectively) when compared to healthy brain tissue (826.8 × 10−6 mm2 s−1) for all metastases. Three identified pre-SRS patterns were significantly different before SRS and within 6 months post-SRS. No significant differences were observed between different primaries pre-SRS. Post-SRS, Lung metastases ADC decreased by 86.2 × 10−6 mm2 s−1, breast metastases increased by 116.7 × 10−6 mm2 s−1, and genitourinary metastases showed no significant ADC change. SRS outcomes showed ADC variability pre-treatment but no significant differences pre- and post-SRS, except at 6–9 months post-SRS where progressing metastases were elevated when compared to other response groups. Conclusion. This study provided a unique opportunity to characterize diffusion changes in brain metastases before their manifestation on standard Gd-T1 images and post-SRS. Identified patterns may improve early detection of brain metastases as well as predict their response to treatment.

MLTI-05. Adjuvant re-irradiation improves local control of surgically resected recurrent brain metastases

BackgroundThe efficacy of salvage resection (SR) of recurrent brain metastases (BrM) post-stereotactic radiosurgery (SRS) is not well described. We sought to characterize the impact of adjuvant post-salvage radiation therapy (PSRT) in this setting and identify tumor-specific variables that influence local control.MethodsRetrospective analysis of post-SRS recurrent BrM that underwent SR between 2003–2020 at Memorial Sloan Kettering Cancer Center was performed. Cases with histologically-viable malignancy were included and stratified by receipt of adjuvant PSRT within 60 days of SR (PSRT cohort) vs. observation (observation cohort). Resection-site outcomes were described using cumulative incidences and univariate and multivariate competing risks regression accounting for clustering.ResultsOne-hundred fifty-five recurrent BrM in 135 patients were included. Thirty-nine (25.2%) of the post-operative cavities were treated with adjuvant PSRT, and the remaining 116 (74.8%) cavities were initially observed. Gross- or near-total resection was associated with significantly improved local control compared to subtotal resection (p=0.007). Adjuvant PSRT was associated with a reduced rate of LR at 6 months [18.0% (95%CI: 9.8–33.1%) vs. 35.9% (95%CI: 27.9–46.2%) with initial observation] and 12 months [28.8% (95%CI: 17.0–48.8%) vs. 43.9% (95%CI: 36.2–53.4%)]. On multivariate analysis, adjuvant PSRT (p=0.095), low tumor-viability within the resected BrM (p=0.17), and first-time resection (p=0.035) all independently trended towards improved local control. BrM size at SR (≥3cm vs. <3cm, p=0.48), primary malignancy (p=0.35), and specific PSRT modality (whole or partial brain radiation vs. SRS, p=0.43) were not associated with differences in LR rate. Radiation necrosis (RN) was significantly increased in the PSRT cohort (HR 4.55, 95%CI: 1.26–16.39, p=0.02), though the total percentage with symptomatic RN remained low (PSRT cohort 5.1% vs observation cohort 0.9%).ConclusionsLocal control after SR of a recurrent BrM may be optimized with gross- or near-total resection and adjuvant post-operative re-irradiation, with low symptomatic RN.