Repeat stereotactic radiosurgery as salvage therapy for locally recurrent brain metastases previously treated with radiosurgery

OBJECTIVEThere are a variety of salvage options available for patients with brain metastases who experience local failure after stereotactic radiosurgery (SRS). These options include resection, whole-brain radiation therapy, laser thermoablation, and repeat SRS. There is little data on the safety and efficacy of repeat SRS following local failure of a prior radiosurgical procedure. This study evaluates the clinical outcomes and dosimetric characteristics of patients who experienced tumor recurrence and were subsequently treated with repeat SRS.METHODSBetween 2002 and 2015, 32 patients were treated with repeat SRS for local recurrence of ≥ 1 brain metastasis following initial SRS treatment. The Kaplan-Meier method was used to estimate time-to-event outcomes including overall survival (OS), local failure, and radiation necrosis. Cox proportional hazards analysis was performed for predictor variables of interest for each outcome. Composite dose-volume histograms were constructed for each reirradiated lesion, and these were then used to develop a predictive dosimetric model for radiation necrosis.RESULTSForty-six lesions in 32 patients were re-treated with a second course of SRS after local failure. A median dose of 20 Gy (range 14–22 Gy) was delivered to the tumor margin at the time of repeat SRS. Local control at 1 year was 79% (95% CI 67%–94%). Estimated 1-year OS was 70% (95% CI 55%–88%). Twelve patients had died at the most recent follow-up, with 8/12 patients experiencing neurological death (as described in Patchell et al.). Eleven of 46 (24%) lesions in 11 separate patients treated with repeat SRS were associated with symptomatic radiation necrosis. Freedom from radiation necrosis at 1 year was 71% (95% CI 57%–88%). Analysis of dosimetric data revealed that the volume of a lesion receiving 40 Gy (V40Gy) was the most predictive factor for the development of radiation necrosis (p = 0.003). The following V40Gy thresholds were associated with 10%, 20%, and 50% probabilities of radiation necrosis, respectively: 0.28 cm3 (95% CI 3%–28%), 0.76 cm3 (95% CI 9%–39%), 1.60 cm3 (95% CI 26%–74%).CONCLUSIONSRepeat SRS appears to be an effective salvage option for patients with brain metastases experiencing local failure following initial SRS treatment. This series demonstrates durable local control and, although rates of radiation necrosis are significant, repeat SRS may be indicated for select cases of local disease recurrence. Because the V40Gy is predictive of radiation necrosis, limiting this value during treatment planning may allow for a reduction in radiation necrosis rates.

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Gamma Knife versus Frameless Linear Accelerator Based Stereotactic Radiosurgery for Brain Metastases: Clinical Outcomes and Factors Associated with Local Failure and Radiation Necrosis

10.21203/rs.3.rs-885725/v1 ◽

2021 ◽

Author(s):

Gregory S. Alexander ◽

Jill S. Remick ◽

Emily S. Kowalski ◽

Kai Sun ◽

Yannick Poirer ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Clinical Outcomes ◽

Gamma Knife ◽

Linear Accelerator ◽

Radiation Necrosis ◽

Univariate Analysis ◽

Local Failure ◽

Rank Test ◽

Chi Square Analysis

Abstract BackgroundSingle-fraction stereotactic radiosurgery (SF-SRS) for the treatment of brain metastases can be delivered with either a Gamma-Knife platform (GK-SRS) or with a frameless linear accelerator (LA-SRS) which vary based on patterns of prescribing, patient setup and radiation delivery. Whether these differences affect clinical outcomes is unknown. MethodsPatients treated for metastatic brain cancer treated with SF-SRS from 2014-2020 were retrospectively reviewed and clinical outcomes were recorded on a per lesion basis. Covariates between groups were compared using a Chi-square analysis for dichotomous variables and t-test for continuous variables. Median follow up was calculated using the reverse Kaplan Meier (KM) method. Primary endpoints of local failure (LF) and symptomatic radiation necrosis (RN) were estimated using the KM method with salvage WBRT used as a censoring event. Outcome estimates were compared using the log-rank test. Multivariate analysis (MVA) and Cox proportional hazards modeling were used for statistical analyses. Propensity score (PS) adjustments were used to reduce the effects confounding variables.ResultsOverall, 119 patients with 287 lesions were included for analysis which included 57 patients (127 lesions) treated with LA-SRS compared to 62 patients (160 lesions) treated with GK-SRS. On both multivariate and univariate analysis, there was no statistically significant differences between GK-SRS and LA-SRS for LF, RN, or the combined endpoint of either LF or RN (multivariate p-value=0.17).ConclusionsIn our retrospective cohort, we found no statistically significant differences in the incidence of RN or LF in patients treated with GK-SRS when compared to LA-SRS.Trial Registration: Retrospectively registered

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Staged Stereotactic Radiosurgery for Large Brain Metastases: Local Control and Clinical Outcomes of a One-Two Punch Technique

Neurosurgery ◽

10.1093/neuros/nyx355 ◽

2017 ◽

Vol 83 (1) ◽

pp. 114-121 ◽

Cited By ~ 11

Author(s):

Ammoren Dohm ◽

Emory R McTyre ◽

Catherine Okoukoni ◽

Adrianna Henson ◽

Christina K Cramer ◽

...

Keyword(s):

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Radiation Necrosis ◽

Treatment Options ◽

Radiation Therapy Oncology Group ◽

Local Failure ◽

Median Dose ◽

Kaplan Meier ◽

Dosimetric Analysis

Abstract BACKGROUND Treatment options are limited for large, unresectable brain metastases. OBJECTIVE To report a single institution series of staged stereotactic radiosurgery (SRS) that allows for tumor response between treatments in order to optimize the therapeutic ratio. METHODS Patients were treated with staged SRS separated by 1 mo with a median dose at first SRS of 15 Gy (range 10-21 Gy) and a median dose at second SRS of 14 Gy (range 10-18 Gy). Overall survival was evaluated using the Kaplan-Meier method. Cumulative incidences were estimated for neurological death, radiation necrosis, local failure (marginal or central), and distant brain failure. Absolute cumulative dose–volume histogram was created for each treated lesion. Logistic regression and competing risks regression were performed for each discrete dose received by a certain volume. RESULTS Thirty-three patients with 39 lesions were treated with staged radiosurgery. Overall survival at 6 and 12 mo was 65.0% and 60.0%, respectively. Cumulative incidence of local failure at 6 and 12 mo was 3.2% and 13.3%, respectively. Of the patients who received staged therapy, 4 of 33 experienced local failure. Radiation necrosis was seen in 4 of 39 lesions. Two of 33 patients experienced a Radiation Therapy Oncology Group toxicity grade > 2 (2 patients had grade 4 toxicities). Dosimetric analysis revealed that dose (Gy) received by volume of brain (ie, VDose(Gy)) was associated with radiation necrosis, including the range V44.5Gy to V87.8Gy. CONCLUSION Staged radiosurgery is a safe and effective option for large, unresectable brain metastases. Prospective studies are required to validate the findings in this study.

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MLTI-06. Surgical resection plus stereotactic radiosurgery versus SRS alone for large brain metastases: a comparative study

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab071.055 ◽

2021 ◽

Vol 3 (Supplement_3) ◽

pp. iii14-iii14

Author(s):

Enrique Gutierrez ◽

Aristotelis Kalyvas ◽

Conrad Villafuerte ◽

Barbara-Ann Millar ◽

Tatiana Conrad ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Surgical Resection ◽

Proportional Hazards ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Hazards Model ◽

Kaplan Meier ◽

Large Brain

Abstract Purpose Large brain metastases (BRM) are challenging to manage. Therapeutic options include Stereotactic Radiosurgery (SRS) or surgery (S) with adjuvant SRS. We sought to compare overall survival (OS), radionecrosis (RN), local failure (LF), pachymeningeal (PMD) and leptomeningeal (LMD) disease in patients treated with SRS vs. S+SRS. Methods We reviewed a prospective registry database from 2009 to 2020 and identified all patients with BRM (≥4cc in volume) treated with SRS or S+SRS. WBRT or SRS re-targeting the index lesion were censoring events. Survival percentages were calculated using the Kaplan-Meier method. Differences between groups were tested using the Cox proportional hazards model. Results 383 patients were identified, 128 and 255 were treated with S+SRS and SRS, respectively. Median ages in the S+SRS and SRS groups were 62.2 (23.6–98.5) and 60.2 (20.2–97.4) (P 0.33). OS at 12 and 24 months was 69% and 41% vs 55% and 20% for the S+SRS and SRS groups, respectively hazard ratio (HR) 1.64 (1.23–2.18) (P<0.001). LF requiring salvage surgery at 12 and 24 months were 3% and 5% vs 8% and 10% for S+SRS and SRS groups, respectively (P 0.067). RN at 12 and 24 months were 9% and 17% vs 15% and 21% for S+SRS and SRS groups, respectively 1.32 HR (0.77–2.29) (P =0.32). PMD disease at 12 and 24 months were 16% and 21% vs 3% and 7% for S+SRS and SRS groups, respectively HR 0.26(0.12–0.56) (P < 0.001). LMD at 12 and 24 months were 4% and 6% vs 2% and 4% for S+SRS and SRS groups, respectively HR 0.73(0.25–2.17) (P 0.57). Conclusion Surgical resection plus SRS correlated with improved OS and a trend towards a decreased incidence of LF compared to SRS alone. However, patients treated with S experienced an increased incidence of PMD.

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Potential role for LINAC-based stereotactic radiosurgery for the treatment of 5 or more radioresistant melanoma brain metastases

Journal of Neurosurgery ◽

10.3171/2014.12.jns141919 ◽

2015 ◽

Vol 123 (5) ◽

pp. 1261-1267 ◽

Cited By ~ 8

Author(s):

Jessica M. Frakes ◽

Nicholas D. Figura ◽

Kamran A. Ahmed ◽

Tzu-Hua Juan ◽

Neha Patel ◽

...

Keyword(s):

Brain Metastases ◽

Metastatic Melanoma ◽

Stereotactic Radiosurgery ◽

Proportional Hazards Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Local Failure ◽

Time To Failure ◽

Kaplan Meier ◽

Melanoma Brain Metastases

OBJECT Linear accelerator (LINAC)-based stereotactic radiosurgery (SRS) is a treatment option for patients with melanoma in whom brain metastases have developed. Very limited data are available on treating patients with ≥ 5 lesions. The authors sought to determine the effectiveness of SRS in patients with ≥ 5 melanoma brain metastases. METHODS A retrospective analysis of metastatic melanoma treated with SRS in a single treatment session for ≥ 5 lesions was performed. Magnetic resonance imaging studies were reviewed post-SRS to evaluate local control (LC). Disease progression on imaging was defined using the 2009 Response Evaluation Criteria in Solid Tumors (RECIST). Survival curves were calculated from the date of brain metastases diagnosis or the date of SRS by using the Kaplan-Meier (KM) method. Univariate and multivariate analysis (UVA and MVA, respectively) were performed using the Cox proportional-hazards model. RESULTS The authors identified 149 metastatic brain lesions treated in 28 patients. The median patient age was 60.5 years (range 38–83 years), and the majority of patients (24 [85.7%]) had extracranial metastases. Four patients (14.3%) had received previous whole-brain radiotherapy (WBRT), and 11 (39.3%) had undergone previous SRS. The median planning target volume (PTV) was 0.34 cm3 (range 0.01–12.5 cm3). Median follow-up was 6.3 months (range 1–46 months). At the time of treatment, 7% of patients were categorized as recursive partitioning analysis (RPA) Class I, 89% as RPA Class II, and 4% as RPA Class III. The rate of local failure was 11.4%. Kaplan-Meier LC estimates at 6 and 12 months were 91.3% and 82.2%, respectively. A PTV volume ≥ 0.34 cm3 was a significant predictor of local failure on UVA (HR 16.1, 95% CI 3.2–292.6, p < 0.0001) and MVA (HR 14.8, 95% CI 3.0–268.5, p = 0.0002). Sixteen patients (57.1%) were noted to have distant failure in the brain with a median time to failure of 3 months (range 1–15 months). Nine patients with distant failures received WBRT, and 7 received additional SRS. Median overall survival (OS) was 9.4 and 7.6 months from the date of brain metastases diagnosis and the date of SRS, respectively. The KM OS estimates at 6 and 12 months were 57.8% and 28.2%, respectively, from the time of SRS treatment. The RPA class was a significant predictor of KM OS estimates from the date of treatment (p = 0.02). Patients who did not receive WBRT after SRS treatment had decreased OS on MVA (HR 3.5, 95% CI 1.1–12.0, p = 0.03), and patients who did not receive WBRT prior to SRS had improved OS (HR 0.11, 95% CI 0.02–0.53, p = 0.007). CONCLUSIONS Stereotactic radiosurgery for ≥ 5 lesions appears to be effective for selected patients with metastatic melanoma, offering excellent LC. This is particularly important for patients as new targeted systemic agents are improving outcomes but still have limited efficacy within the central nervous system.

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Stereotactic radiosurgery with concurrent lapatinib is associated with improved local control for HER2-positive breast cancer brain metastases

Journal of Neurosurgery ◽

10.3171/2018.10.jns182340 ◽

2020 ◽

Vol 132 (2) ◽

pp. 503-511 ◽

Cited By ~ 8

Author(s):

Shireen Parsai ◽

Jacob A. Miller ◽

Aditya Juloori ◽

Samuel T. Chao ◽

Rupesh Kotecha ◽

...

Keyword(s):

Breast Cancer ◽

Epidermal Growth Factor Receptor ◽

Brain Metastases ◽

Local Control ◽

Radiation Necrosis ◽

Growth Factor Receptor ◽

Local Failure ◽

Her2 Breast Cancer ◽

Epidermal Growth ◽

Breast Cancer Brain Metastases

OBJECTIVEWith increasing survival for patients with human epidermal growth factor receptor 2-positive (HER2+) breast cancer in the trastuzumab era, there is an increased risk of brain metastasis. Therefore, there is interest in optimizing intracranial disease control. Lapatinib is a small-molecule dual HER2/epidermal growth factor receptor inhibitor that has demonstrated intracranial activity against HER2+ breast cancer brain metastases. The objective of this study was to investigate the impact of lapatinib combined with stereotactic radiosurgery (SRS) on local control of brain metastases.METHODSPatients with HER2+ breast cancer brain metastases who underwent SRS from 1997–2015 were included. The primary outcome was the cumulative incidence of local failure following SRS. Secondary outcomes included the cumulative incidence of radiation necrosis and overall survival.RESULTSOne hundred twenty-six patients with HER2+ breast cancer who underwent SRS to 479 brain metastases (median 5 lesions per patient) were included. Among these, 75 patients had luminal B subtype (hormone receptor-positive, HER2+) and 51 patients had HER2-enriched histology (hormone receptor-negative, HER2+). Forty-seven patients received lapatinib during the course of their disease, of whom 24 received concurrent lapatinib with SRS. The median radiographic follow-up among all patients was 17.1 months. Concurrent lapatinib was associated with reduction in local failure at 12 months (5.7% vs 15.1%, p < 0.01). For lesions in the ≤ 75th percentile by volume, concurrent lapatinib significantly decreased local failure. However, for lesions in the > 75th percentile (> 1.10 cm3), concurrent lapatinib did not significantly improve local failure. Any use of lapatinib after development of brain metastasis improved median survival compared to SRS without lapatinib (27.3 vs 19.5 months, p = 0.03). The 12-month risk of radiation necrosis was consistently lower in the lapatinib cohort compared to the SRS-alone cohort (1.3% vs 6.3%, p < 0.01), despite extended survival.CONCLUSIONSFor patients with HER2+ breast cancer brain metastases, the use of lapatinib concurrently with SRS improved local control of brain metastases, without an increased rate of radiation necrosis. Concurrent lapatinib best augments the efficacy of SRS for lesions ≤ 1.10 cm3 in volume. In patients who underwent SRS for HER2+ breast cancer brain metastases, the use of lapatinib at any time point in the therapy course was associated with a survival benefit. The use of lapatinib combined with radiosurgery warrants further prospective evaluation.

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Timing of Adjuvant Fractionated Stereotactic Radiosurgery Impacts Local Control of Resected Brain Metastases

Practical Radiation Oncology ◽

10.1016/j.prro.2021.01.011 ◽

2021 ◽

Author(s):

Diana A. Roth O‘Brien ◽

Phillip Poppas ◽

Sydney M. Kaye ◽

Sean S. Mahase ◽

Anjile An ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Local Control ◽

Fractionated Stereotactic Radiosurgery

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The incidence and predictors of new brain metastases in patients with non–small cell lung cancer following discontinuation of systemic therapy

Journal of Neurosurgery ◽

10.3171/2021.9.jns212150 ◽

2021 ◽

pp. 1-11

Author(s):

Dennis London ◽

Dev N. Patel ◽

Bernadine Donahue ◽

Ralph E. Navarro ◽

Jason Gurewitz ◽

...

Keyword(s):

Lung Cancer ◽

Brain Metastases ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Systemic Therapy ◽

Recurrent Events ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Small Cell ◽

Small Cell Lung

OBJECTIVE Patients with non–small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy. METHODS A prospectively collected registry of patients undergoing radiosurgery for brain metastases was analyzed. Of 606 patients with NSCLC, 63 met the inclusion criteria of discontinuing systemic therapy for at least 90 days and undergoing active surveillance. The risk factors for the development of new tumors were determined using Cox proportional hazards and recurrent events models. RESULTS The median duration to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase (RTK) pathways (e.g., KRAS, EGFR) were more likely to develop new tumors (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33–3.81, p = 2.5 × 10−3; HR 2.51, 95% CI 1.45–4.34, p = 9.8 × 10−4, respectively). CONCLUSIONS The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or RTK pathway mutations have a higher rate of new metastases and should be followed more closely.

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Use of radiomics for the prediction of local control of brain metastases after stereotactic radiosurgery

Neuro-Oncology ◽

10.1093/neuonc/noaa007 ◽

2020 ◽

Vol 22 (6) ◽

pp. 797-805 ◽

Cited By ~ 5

Author(s):

Andrei Mouraviev ◽

Jay Detsky ◽

Arjun Sahgal ◽

Mark Ruschin ◽

Young K Lee ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Clinical Features ◽

Characteristic Curve ◽

Response Prediction ◽

Response Assessment ◽

Local Failure ◽

Post Contrast ◽

Axial Diameter ◽

Fluid Attenuated Inversion Recovery

Abstract Background Local response prediction for brain metastases (BM) after stereotactic radiosurgery (SRS) is challenging, particularly for smaller BM, as existing criteria are based solely on unidimensional measurements. This investigation sought to determine whether radiomic features provide additional value to routinely available clinical and dosimetric variables to predict local recurrence following SRS. Methods Analyzed were 408 BM in 87 patients treated with SRS. A total of 440 radiomic features were extracted from the tumor core and the peritumoral regions, using the baseline pretreatment volumetric post-contrast T1 (T1c) and volumetric T2 fluid-attenuated inversion recovery (FLAIR) MRI sequences. Local tumor progression was determined based on Response Assessment in Neuro-Oncology‒BM criteria, with a maximum axial diameter growth of >20% on the follow-up T1c indicating local failure. The top radiomic features were determined based on resampled random forest (RF) feature importance. An RF classifier was trained using each set of features and evaluated using the area under the receiver operating characteristic curve (AUC). Results The addition of any one of the top 10 radiomic features to the set of clinical features resulted in a statistically significant (P < 0.001) increase in the AUC. An optimized combination of radiomic and clinical features resulted in a 19% higher resampled AUC (mean = 0.793; 95% CI = 0.792–0.795) than clinical features alone (0.669, 0.668–0.671). Conclusions The increase in AUC of the RF classifier, after incorporating radiomic features, suggests that quantitative characterization of tumor appearance on pretreatment T1c and FLAIR adds value to known clinical and dosimetric variables for predicting local failure.

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MLTI-15. A CASE SERIES OF PRE-OPERATIVE GAMMA-KNIFE RADIOSURGERY FOR RESECTABLE BRAIN METASTASES

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.074 ◽

2019 ◽

Vol 1 (Supplement_1) ◽

pp. i17-i17

Author(s):

Tatsuya Takezaki ◽

Haruaki Yamamoto ◽

Naoki Shinojima ◽

Jun-ichiro Kuroda ◽

Shigeo Yamashiro ◽

...

Keyword(s):

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Gamma Knife ◽

Systemic Treatment ◽

Radiation Necrosis ◽

Gamma Knife Radiosurgery ◽

Case Series ◽

Phase 3 ◽

Optimal Sequence ◽

Median Margin

Abstract Recent advances in the systemic treatment of various cancers have resulted in longer survival and higher incidence of brain metastases. Phase 3 trials in north America and in Japan have demonstrated that stereotactic radiosurgery will be a standard adjuvant modality following surgery for resectable brain metastases. However, we don’t know the optimal sequence of this combination therapy. We hypothesized that pre-operative stereotactic radiosurgery for resectable brain metastases provides favorable rates of local control, overall survival, leptomeningeal dissemination and symptomatic radiation necrosis. We have experienced 4 cases of resected brain metastases within 1–7 days after Gamma-knife surgery (median margin dose:22Gy) and have been following their clinical course. We will show the repressive cases.

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31. RADIATION NECROSIS IN STEREOTACTIC RADIOSURGERY AND CHECKPOINTS INHIBITORS FOR BRAIN METASTASES FROM LUNG ADENOCARCINOMA

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.019 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii5-ii5

Author(s):

James Jurica ◽

Shraddha Dalwadi ◽

David Baskin ◽

Eric Bernicker ◽

Brian Butler ◽

...

Keyword(s):

Overall Survival ◽

Multivariate Analysis ◽

Brain Metastases ◽

Lung Adenocarcinoma ◽

Stereotactic Radiosurgery ◽

Median Survival ◽

Radiation Necrosis ◽

Concomitant Treatment ◽

Prognostic Assessment ◽

Graded Prognostic Assessment

Abstract PURPOSE Treatment with stereotactic radiosurgery (SRS) and immune checkpoint inhibitors (ICI) is increasingly common for brain metastases (BM) from lung adenocarcinoma. Rates of radiation necrosis (RN) with SRS in the setting of ICIs is an ongoing area of research. We investigated rates of RN in patients with BM from lung adenocarcinoma treated with SRS with or without concurrent ICIs. METHODS We identified 39 patients at a single institution who underwent SRS treatment for BM from lung adenocarcinoma. Of these, 19 (49%) received SRS without ICIs and 20 (51%) patients received ICIs within a month of SRS. The rate of RN, defined by MRI features and histology when available, was compared between each group using multivariate analysis. Kaplan Meier survival estimates were calculated based on overall survival and compared to median survival predicted by the graded prognostic assessment. RESULTS Overall survival for all patients from diagnosis of brain metastases was 16.6 months (range 3.6–45.9) and median survival predicted by the graded prognostic assessment was 13.7 months (range 6.9–26.5). In total 11 (28%) patients developed MRI and/or histologic evidence for RN during the follow-up period; 5 of 20 (25%) from the SRS with ICI group and 6 of 19 (31%) from the SRS without ICI group. In multivariate analysis, ICI treatment had no significant impact on rates of RN between groups (OR 0.72 [95% CI: 0.17–2.93]; p=0.65) while bevacizumab treatment was associated with a decreased RN risk (OR 0.88 [95% CI: 0.43–0.99]; p=0.02). CONCLUSION Retrospective analysis of patients with BM from lung adenocarcinoma treated with SRS suggested that administration of ICIs does not increase risk for development of RN. Further, concomitant treatment with bevacizumab may decrease risk of RN. These findings suggest that patients with BM from lung adenocarcinoma can be treated with combination therapy without increased risk of neurologic toxicity.

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