Prior Whole Brain Radiotherapy Research Articles

Lorlatinib in the second line and beyond for ALK positive lung cancer: real-world data from resource-constrained settings

BackgroundALK-positive lung cancers are known to have favorable responses with oral tyrosine kinase inhibitors. Lorlatinib is an approved treatment option post first and second-line ALK inhibitors and is now also in first line. We present a retrospective observational study of the safety and efficacy of patients receiving Lorlatinib in second-line and beyond.MethodsWe conducted a retrospective observational study of ALK-positive patients who received Lorlatinib post-progression or intolerance to initial therapy at the Medical Oncology department. The patients who were started on Lorlatinib between January 2018 to December 2019 were included. The patients underwent routine blood and radiological evaluation every two to three months.ResultsA total of 38 patients received Lorlatinib in the specified period. The median age was 48 years (range 23–68), with 53% of patients being male, 37% having comorbidities; the most common being hypertension and diabetes and 79% of patients were of ECOG-PS1. Twenty-two patients (58%) had received two prior TKIs. The most common sites of metastasis before starting Lorlatinib were brain (55%) and bone (53%). All patients except one received prior whole-brain radiotherapy with 4 receiving radiation twice. The median follow-up period was 49 months (95% CI: 46.4–51.6). Eighty-four percent showed disease control with median progression-free survival (PFS) and overall survival (OS) of 16 months (95% CI 5.4–26.6) and 22 months (95% CI 9.9–34.1) respectively. Twelve patients died without documented progression. Five out of twelve with documented progression had brain involvement while six had lung involvement. Twelve out of twenty-four patients who progressed received subsequent chemotherapy. The most common grade 3 and above toxicities were hypercholesterolemia and hypertriglyceridemia. Three (7.8%) patients required dose reduction.ConclusionThis real-world data confirms the efficacy of Lorlatinib in the second line and beyond with adverse effects matching that of registration studies.

RADT-20. STEREOTACTIC RADIOSURGERY FOR 15 OR MORE BRAIN METASTASES

Abstract BACKGROUND Patients with ≥ 15 brain metastases(BM) continue to be treated with whole brain radiation therapy(WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery(SRS), with the aim of evaluating safety, cognitive outcomes, and survival. METHODS Patients who received SRS for ≥ 15 BMs in 1-5 fractions from 2014-2022 using the previously described single isocenter multi-target technique were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System(PROMIS) scores. RESULTS A total of 124 patients treated with LINAC-based SRS were included. The mean and median number of lesions treated per patient was 24.8 and 20, respectively (range 15 – 94). Most common primary histologies were lung(47.6%), melanoma(21.0%), and breast(14.5%). The median SRS dose was 24 Gy(range 18 – 30 Gy). The rate of any grade radiation necrosis (RN) and ≥ grade 3 RN were 15.3% and 3.2% respectively. New onset seizures were seen in 2.4% and alopecia in 2.4%. Median follow-up was 5.1 months(m). When cognitive data were available, 25 of 31 patients had a stable or improved PROMIS score. The 12m local control was 97.6% while overall intracranial control was 20.8%. One-year freedom from neurological death, leptomeningeal disease, and salvage WBRT were 85.6%, 87.6% and 71.7% respectively. Median overall survival(OS) from brain metastases diagnosis was 11.3m(95% CI 7.2m – 15.3m). On univariate analysis, no prior WBRT(p = 0.038), higher KPS(p = 0.002) and systemic therapy after SRS(p < 0.001) predicted for improved OS. CONCLUSIONS We present here the largest study evaluating SRS for patients with ≥ 15 BMs. We found that SRS was safe, had favorable cognitive outcomes, and comparable survival outcomes to contemporary studies evaluating WBRT in this patient population. Our study supports further randomized studies comparing SRS and memory avoidance WBRT approaches for patients with ≥ 15 BMs.

Staged Stereotactic Radiosurgery as a Novel Adaptive Approach to Salvage Previously Irradiated Brain Metastases

We report outcomes specific to a novel 3 fraction (frx) staged stereotactic radiosurgery (St-SRS) regimen designed to salvage metastases previously irradiated and considered to be at high risk of radiation necrosis (RN). A total of 24 patients with 55 metastases treated with our 3 frx St-SRS approach were reviewed. Prior to each frx, patients were re-simulated and planned with a new MRI to allow for treatment adaption. The primary endpoint was the cumulative incidence of local failure (LF) and secondary endpoints included tumor dynamics and RN rates. The median follow up was 9.0 months (range: 2.7-40.1 months) and median age was 59-years (range: 32-84). Primary cancers were of breast (44%), lung (33%), melanoma (22%), and gastro-intestinal (1%) origin. Individual metastases treated with St-SRS had initially failed surgery and post-op cavity hypofractionated SRS (HSRS) for 2/55 (4%), SRS alone for 19/55 (34%), whole brain radiation (WBRT) alone for 6/55 (11%), HSRS for 2/55 (4%), and prior SRS and WBRT exposure for 28/55 (51%). 46/55 (84%) were prescribed 8 Gy, 8 Gy, 4 Gy; 8/55 (14%) had 6 Gy, 6 Gy, 4 Gy and 1/55 (2%) had 8 Gy, 8 Gy, 6 Gy. The median number of weeks between frx was 2.6 (range: 1.0-6.8). The median of the mean and maximum target doses were 9.7 Gy (range: 5.4-11.7 Gy) and 12.4 Gy (range, 7.5-16.0 Gy) respectively. The median prescription isodose line was 62% (range: 50-85%). The mean lesion volume and diameter was 3.8cc (range: 0.05-24.8cc) and 1.6cm (range: 0.2-4.4cm), respectively. The mean percent target volume coverage, Paddick Conformality Index and Gradient Index were 100% (range: 97-100%), 0.7 (range: 0.1-0.9), and 3.2 (range: 2.5-6.7), respectively. The mean volume change between staged frxs was -4.2% (range: -69.3 to +63.1%), and based on the first and last St-SRS MRI was -10.8% (range: -86.6% to +68.7%). The crude LF rate was 27%. The median time to LF was 3.4 months (range: 1.2-7.4 months). Amongst those with a LF, 7/15 (46%) were melanoma, 6/15 (40%) HER2 positive breast cancer, 1/15 (7%) gastrointestinal and 1/15 (7%) non-small cell lung carcinoma. 8/15 (53%) had prior WBRT and SRS exposure, 1/16 (7%) surgery and cavity HSRS, 5/15 (33%) SRS alone and 1/15 (7%) WBRT alone. Only asymptomatic RN events were observed in 4/55 (7%). St-SRS is a promising approach to salvage previously irradiated brain metastases, including prior SRS, with a favorable rate of RN. Tumor volume dynamics between stages can be significant warranting adaptive replanning.

Selected-Lesion SRS as a Novel Strategy in Treatment of Patients with Multiple Brain Metastases

With the increasing use of intracranial SRS (SRS) for treatment of patients with >10-15 brain metastases treatment; debate remains in the literature about how these patients should be treated. While many advocate for treatment of all lesions with either SRS or whole brain radiation therapy (WBRT), several groups are considering selected-lesion SRS (SL-SRS) where only a subset of intracranial lesions are treated. However, the current practice patterns of SL-SRS are not known. A survey of 19 questions was created using open-ended and multiple-choice style questions on SL-SRS practices and indications. The survey was distributed to providers in the US and internationally who perform SRS frequently. Ten out of 50 institutions provided responses reflecting the practices of 16 providers. Descriptive statistics was used to compare answers to each question when applicable including percentages and ranges. SL-SRS was performed at 8/10 institutions, (5 out of 6 US institutions and 3 out of 4 international institutions). Only 2 institutions had established clinical indications for SL-SRS (one in the US and one internationally) and one additional US institution reported clinical trials that require SL-SRS to study efficacy of CNS penetrating targeted therapies. One program reported research protocols for untreated brain metastases that would take priority over SL-SRS (program outside the US). Size of the lesion was cited as the most important factor (90%) when deciding to treat any single lesion. Next, lesion location and focal signs/symptoms were both considered moderately important. 80% ranked distance from prior SRS as the least important factor. Perilesional edema was also less important at most programs (90%). Lesion location and presence of symptoms were also considered important. There were several factors that would encourage providers to consider SL-SRS in a patient. Prior WBRT; progressing systemic disease and CNS-penetrating drug option available; and progressing systemic disease and immunotherapy option available were the most common responses. Most respondents cited "specific request by medical oncology" as well as "cooperative studies in this topic" as factors that might push them towards SL-SRS. Several institutions specified factors beyond the listed options. One institution reported that for patients with >20 lesions, they treated the largest lesions with SRS then follow with WBRT, termed the "pre-WBRT boost." Progression of untreated lesions was the most common reason why providers would bring back patients for additional treatment. The responses to this survey demonstrate that patients with >15-20 intracranial lesions, prior WBRT, and worsening systemic disease with CNS penetrating systemic therapies available are being considered for SL-SRS.

Patient-Reported Cognitive Outcomes and Survival after Stereotactic Radiosurgery for 15 or More Brain Metastases

Overall survival (OS) in metastatic cancer patients has been improving with continued advancements, necessitating greater attention to treatment related toxicities. Patients with ≥ 15 brain metastases (BM) continue to be treated with whole brain radiation therapy (WBRT), despite poor neurocognitive outcomes. We analyzed our institutional experience of treating these patients with stereotactic radiosurgery (SRS), with the aim of evaluating safety, cognitive outcomes, and survival metrics. Patients who received SRS for ≥ 15 BMs in 1-5 fractions from 2014-2022 using the previously described single isocenter multi-target technique were included. Cognitive outcomes were objectively evaluated using serial Patient-Reported Outcome Measurement Information System (PROMIS) scores. Kaplan-Meier method was used for survival analysis and log-rank test was used for intergroup comparisons. A total of 118 patients underwent 124 courses of LINAC-based SRS. The mean and median number of lesions treated per patient was 24.8 and 20, respectively (range 15 - 94). Most common primary histologies were lung (47.6%), melanoma (21.0%), and breast (14.5%). The median SRS dose was 24 Gy (range 18 - 30 Gy) with 87.9% receiving 3 fraction SRS. At the time of SRS, 19.4% patients had received prior WBRT and 24.2% had received at least one prior SRS course. The rate of any grade radiation necrosis (RN) and ≥ grade 3 RN were 15.3% and 3.2% respectively. New onset seizures were seen in 2.4%, alopecia in 2.4%, and subjective cognitive decline in 4% of patients. Median follow-up by reverse Kaplan-Meier method was 17.8 months (m). Cognitive data was available for 38 patients. Mean PROMIS scores at baseline, 3m, 6m and 9m after SRS were 32.0, 31.6, 30.4 and 28.7 out of 40, respectively. When longitudinal trends were available, 25 of 31 patients had a stable or improved PROMIS score. The 12m local control was 97.6%. Cumulative incidence of distant intracranial failure was 79.2%. One year freedom from neurological death, leptomeningeal disease, and salvage WBRT were 85.6%, 87.6% and 71.7% respectively. Median OS from brain metastases diagnosis was 11.3m (95% CI 7.2m - 15.3m) overall, while it was 9.2m (6.5 - 11.8m) after excluding patients who had prior WBRT or SRS (n = 79). One-year survival was 40% from diagnosis and 38.7% from SRS. On Cox regression analysis, prior WBRT (p = 0.002), higher KPS (p = 0.050), systemic therapy after SRS (p<0.001), and controlled extracranial disease (p = 0.007) predicted for improved OS. We present here the largest study evaluating SRS for patients with ≥ 15 BMs. We found that SRS was safe, had favorable cognitive outcomes, and comparable survival outcomes to contemporary studies evaluating WBRT in this patient population. Treatment-naïve patients had a median survival of > 6 months, long enough to benefit from cognitive sparing with SRS. Our study supports further randomized studies comparing SRS and memory avoidance WBRT approaches for patients with ≥ 15 BMs.

Immune Checkpoint Inhibition and Single Fraction Stereotactic Radiosurgery in Non-Small Cell Lung Cancer Brain Metastases: An International Multicenter Study of 395 Patients

Brain metastases most commonly arise from non-small cell lung cancer (NSCLC). In recent years, immune checkpoint inhibitors (ICI) have demonstrated improvements in overall survival (OS) in NSCLC. However, concerns remain about the risk of radiation necrosis (RN) when ICI are administered with stereotactic radiosurgery (SRS). Logistic regression was used to evaluate prognostic factors associated with the development of any grade RN and symptomatic RN. Cumulative incidence of RN was evaluated using competing risks analysis and the Fine and Gray model, where the null hypothesis was rejected for p < 0.05. There were 395 patients with 2,513 brain metastases treated across 11 international institutions included in the analysis. The median follow-up was 14.2 months. Median patient age was 67 years (Interquartile Range [IQR]: 61-73), 53.4% were male, the median Karnofsky Performance Status was 80 (IQR: 80-90), and 88.6% has active extracranial disease at the time of SRS. The median margin dose was 19 Gy (IQR: 18-20), 97.5% of patients were treated on the Gamma Knife ®, 3.8% underwent prior whole brain radiation therapy (WBRT). The median V12 Gy was 5.2 cm3 and 36.5% of patients had a V12 Gy ≥ 10 cm3, anti-PD-1 agents were administered in 91.6% of patients. A V12 Gy ³ 10 cm3 was associated with an increased risk of developing any grade RN; odds ratio (OR): 2.12, p = 0.04 and OR: 2.18; p = 0.03 on univariable and multivariable analysis, respectively. Similarly, a V12 Gy ≥ 10 cm3 was associated with an increased risk of developing symptomatic RN; OR: 3.80, p = 0.003 and OR: 3.95; p = 0.003 on univariable and multivariable analysis, respectively. Receipt of concurrent ICI and prior WBRT were not statistically significant. At 1-year, the cumulative incidence of any grade and symptomatic RN was 4.8% and 3.8%, respectively. The cumulative incidence of any grade RN was 3.8% vs. 5.3% for the concurrent and non-concurrent groups at 1-year, respectively (p = 0.35). The cumulative incidence of symptomatic RN was 3.8% vs. 3.6% for the concurrent and non-concurrent groups at 1-year, respectively (p = 0.95). The risk of any grade and symptomatic RN following SRS and ICI administration for NSCLC brain metastases increases as the V12 Gy exceeds 10 cm3. Concurrent ICI and SRS does not appear to increase this risk. Radiosurgical planning techniques should aim to minimize the V12 Gy.

Leveraging Quantitative Imaging and Machine Learning to Differentiate Radionecrosis from Disease Recurrence in Patients with Brain Metastases

Radiation necrosis can be difficult to non-invasively discern from tumor progression after stereotactic radiosurgery (SRS). In this work, we investigate the utility of radiomics (computerized features) and machine learning to capture per-voxel lesion heterogeneity on routine MRI scans, to differentiate radionecrosis from tumor recurrence in patients with brain metastases treated with SRS. A retrospective analysis was conducted of patients with brain metastases treated with SRS. Eighty-three lesions (n = 56 intact; n = 27 surgical cavity) from 69 patients were identified with median age 68.8 years (range 40.2 - 91.0), of whom 53.6% were male and 33.3% received prior whole-brain radiotherapy (WBRT). Lesion histology included lung (60.2%), renal cell (15.7%), melanoma (10.8%), breast (9.6%), and other (3.6%). Pathologic confirmation was available in 73.5% of lesions. Both intact and resection cavity lesions were included and individually segmented. Image preprocessing and radiomic feature extraction were done using ANTsPy and open-source software. A total of 210 features were extracted from post-contrast T1-weighted (T1w) and T2/FLAIR MRIs. Highly correlated features were removed. Univariate logistic regression was conducted on the remaining T1w and T2/FLAIR features as well as on clinical variables. Multivariate analysis was implemented with various classifiers (Random Forest, Ridge, Lasso, Support Vector Machine [SVM]) on the top-performing features found on univariate logistic regression. Models were assessed using cross-validation to select the best model by area under ROC curve (AUC). Specificity and sensitivity were calculated. On univariate analysis, the top 10 radiomics features consisted of 6 T1w features and 4 T2/FLAIR features (4 GLCM, 3 first order, 1 GLSZM, 1 GLRLM, and 1 shape feature). Age, gender, disease site, prior WBRT, prior fractionated SRS, planning tumor volume, brain-GTV V12 Gy, and immunotherapy before or after SRS were not predictive (AUC less than 62.0%) on univariate analysis compared to radiomic features. Multivariate analysis of top performing radiomic features on both intact and surgical cavities yielded an AUC of 72.0% (standard deviation [SD] ±8.8%). Multivariate analysis of top features on intact lesions alone improved the AUC to 80.5% (SD ±10.8%), with sensitivity of 77.8%, specificity of 72.4%, and positive likelihood ratio of 2.82 in differentiating radionecrosis from recurrence. Radiomics and machine learning tools may improve diagnostic ability of distinguishing radiation necrosis from tumor recurrence after SRS. Further work is needed to deploy this in a larger multi-institutional cohort and prospectively evaluate its efficacy as a decision-support tool to personalize care in patients with brain metastases.

Multi-Institutional Outcomes Following Stereotactic Radiosurgery for Gastrointestinal Brain Metastases

Outcomes following stereotactic radiosurgery (SRS) for gastrointestinal (GI) brain metastases (BM) are poorly defined. We analyzed our multi-institutional database of SRS patients, comparing outcomes between GI and non-GI BM patients after SRS. We retrospectively identified all patients completing an initial SRS course across two institutions from 1/2015-12/2020. Demographic and clinical parameters were manually captured. Intracranial progression (ICP) was defined as any concern on post-SRS imaging for recurrence determined by multidisciplinary consensus. Overall survival (OS) and freedom from ICP (FFICP) were estimated via Kaplan Meier models. Cox proportional hazard models were used to assess associations between ICP and parameters. Among 1383 total patients completing SRS for BM, 102 (7.4%) had GI BM. Among these, 46 (45.1%) were of colorectal (CRC) and 34 (33.3%) esophageal origin. Other GI sites (21.6%) included anal, pancreatic, gastric, GI of unknown origin, and hepatocellular carcinoma. Median follow up was 8.7 mos. GI BM patients were more likely to be younger (mean 59.1 vs 63.5 yrs, p = 0.001), male (56.9% vs 44.3%, p = 0.014 ), have more extracranial metastases (mean 1.9 vs 1.6, p = 0.003), have received systemic therapy (73.5% vs 63.9%, p = 0.049) or resection of BM (45.1% vs 25.0%, p < 0.001) prior to SRS, have larger planned target volumes of all BMs (mean 20.3 ccs vs 15.0 ccs, p = 0.013), and were less likely to receive whole brain radiation therapy (WBRT) prior to SRS (3.9% vs 10.8%, p = 0.028) or systemic therapy after SRS (54.9% vs 68.9%, p = 0.004). Among GI patients, median OS was 28.2 mos (95% CI 16.5-35.3), with no significant differences between GI and non-GI patients (p = 0.220) or among GI subgroups (CRC vs other GI: p = 0.731; esophageal vs other GI: p = 0.478). Median FFICP was significantly worse for GI patients (6.2 mos, 95% CI 4.0-9.6 mos) than for non-GI patients (12.4 mos, 95% CI 10.8-13.9 mos; p = 0.004). After accounting for age, sex, performance status, number of irradiated BMs, extracranial disease burden, extracranial disease control, interval from primary cancer diagnosis to BM diagnosis, resection status, receipt of prior WBRT, and receipt of post-SRS systemic therapy, GI origin was significantly associated with worse FFICP (HR 1.50, 95% CI 1.15-2.02, p = 0.007). FFICP was not significantly different between GI subgroups, with CRC and esophageal patients demonstrating median times to ICP of 5.0 mos (95% CI 3.4-9.6) and 7.2 mos (95% CI 2.7-14.1), respectively. Only 2 GI patients (2.0%) had ICP at site of prior SRS. Across a modern, multi-institutional SRS cohort comparing GI to non-GI primary patients, BMs of GI origin demonstrated inferior FFICP to those of non-GI origin. OS did not vary significantly across GI and non-GI cases. Among GI subtypes, no significant differences were identified across FFICP or OS. These data may help inform treatment decisions and post-SRS surveillance.

Pretreatment Clinical Parameters Associated with Intracranial Progression Burden Following an Initial Stereotactic Radiosurgery Course in a Multi-Institutional Brain Metastases Cohort

While brain metastasis (BM) velocity is a valuable prognostic metric at time of intracranial progression (ICP), pre-SRS risk factors for post-SRS high-burden intracranial progression (ICP) remain poorly characterized. We hypothesized that pre-SRS clinical parameters are associated with subsequent high-burden (ICP), defined as either ≥5 (ICP5) or new/progressive ≥11 BMs (ICP11). All patients completing an initial SRS course for BMs at two institutions from 1/2015-12/2020 were retrospectively identified. Patients with prior whole brain radiation therapy (WBRT) and/or BM resection were eligible. Demographic and clinical parameters were collected. ICP was defined as any radiographic concern for distant and/or in-field progression per multidisciplinary consensus. Overall survival (OS) and freedom from ICP were estimated via the Kaplan Meier method. Cox models assessed association between parameters and freedom from ICP5 and ICP11. We identified 1383 patients completed SRS, with a median follow up of 8.7 months. Patients were 54.8% female, 45.6% with KPS ≥90, and a median of 63.4 years old. Primary tumor types included non-small cell lung (48.7%), breast (14.7%), and melanoma (8.5%). 46.9% had oligometastatic disease (≤5 metastatic foci: including BMs) at SRS, and 53.4% underwent SRS for >1 BM. 10.3% of patients had undergone prior WBRT and 26.1% surgical resection. 555 patients (40.1%) experienced ICP following SRS, of whom 72.6% had 1-4, 11.5% had 5-10, and 15.9% had ≥11 new/progressive BMs. Among patients with ICP, 6-month freedom from ICP was 35.5% (95% CI: 31.1-40.5%) for those with 1-4 BMs at time of ICP, 29.7% (95% CI: 20.4-43.3%) for 5-10 BMs, and 20.5% (95% CI: 13.5-30.1%) for ≥11 BMs (p = 0.016). Respective 12-month OS rates were 56.8% (95% CI: 52.1-61.9%), 46.0% (95% CI: 35.1-60.1%), and 38.7% (95% CI: 29.4-50.9%; p<0.001). Neurologic symptoms at time of ICP were observed in 21.1% of patients with 1-4 BMs, 28.1% with 5-10 BMs, and 50.0% with new/progressive ≥11 BMs (p<0.001). On multivariable analysis, superior freedom from high-burden ICP was associated with the following pre-SRS parameters: oligometastatic burden (ICP5: HR 0.68, 95% CI: 0.47-0.99; ICP11: 0.59; 95% CI: 0.36-0.97), no prior immunotherapy (ICP11: HR 0.57, 95% CI: 0.34-0.57), and a single BM at time of initial SRS (1 vs 2 BM, ICP 5: HR 0.51, 95% CI: 0.31-0.82; ICP11: HR 0.45, 95% CI: 0.24-0.84), while primary tumor type was not associated with ICP5 or ICP11. Pre-SRS parameters including polymetastatic burden, prior receipt of immunotherapy, and >1 BM were associated with post-SRS high-burden ICP. High burden ICP developed earlier following SRS completion and was associated with higher rates of neurologic decline and inferior OS.

Selected-Lesion Stereotactic Radiosurgery (SL-SRS) as a Novel Strategy in the Treatment of Patients With Multiple Brain Metastases.

With the diminishing use of whole-brain radiotherapy (WBRT), there is increasing debate regarding the maximum number of brain metastases that should be treated with stereotactic radiosurgery (SRS). In patients with >10-15 lesions, some groups are proposing a new approach - selected-lesion SRS (SL-SRS) - where only a subset of intracranial lesions are chosen for irradiation. This study is an initial look into this practice. This is a cross-sectional exploratory survey study. A survey of 19 questions was created by the International Radiosurgery Research Foundation (IRRF) using open-ended and multiple-choice style questions on SL-SRS practices and indications with the goal of qualitatively understanding how SL-SRS is being implemented worldwide. The survey was distributed to physiciansin the United States (US) and internationally who are members of the IRRFand who perform SRS frequently.Ten out of 50 IRRF institutions provided responses reflecting the practices of 16 physicians. SL-SRS is being performed at 8/10 institutions. The most common reasons for using SL-SRS included patients with prior WBRT, patients with progressing systemic disease with central nervous system (CNS)-penetrating or immunotherapies available, specific requests from medical oncology, and cooperative studies using this approach. Lesion size was cited as the most important factor when choosing to irradiate any single lesion. The majority of respondents reported 30 mm and 40 mm as size cutoffs (by largest dimension) for treatment of a lesion in eloquent and non-eloquent locations, respectively. Eloquence of lesion location and attributable symptoms were also considered important. Progression of untreated lesions was the most common reason reported for bringing patients back for additional treatment. The responses to this survey show that SL-SRS is being used, allowing for small/asymptomatic brain metastases to be left safely unirradiated. It is currently used in patients who have >10-15 lesions with prior WBRT, those with progression of extracranial disease but with acceptable systemic treatment options, and those with poor functional status. The incorporation of this new approach into clinical trials should be considered for the safe study of the efficacy of new CNS-penetrating systemic therapies.

Pretreatment clinical parameters associated with intracranial progression burden following an initial stereotactic radiosurgery course in a multi-institutional brain metastases cohort.

2013 Background: While brain metastasis (BM) velocity is a valuable prognostic metric at time of intracranial progression (ICP), pre-SRS risk factors for post-SRS high-burden intracranial progression (ICP) remain poorly characterized. We hypothesized that pre-SRS clinical parameters are associated with subsequent high-burden (ICP), defined as either ≥5 (ICP5) or new/progressive ≥11 BMs (ICP11). Methods: All patients completing an initial SRS course for BMs at two institutions from 1/2015-12/2020 were retrospectively identified. Patients with prior whole brain radiation therapy (WBRT) and/or BM resection were eligible. Demographic and clinical parameters were collected. ICP was defined as any radiographic concern for distant and/or in-field progression per multidisciplinary consensus. Overall survival (OS) and freedom from ICP were estimated via the Kaplan Meier method. Cox models assessed association between parameters and freedom from ICP5 and ICP11. Results: We identified 1383 patients completed SRS, with a median follow up of 8.7 months. Patients were 54.8% female, 45.6% with KPS ≥90, and a median of 63.4 years old. Primary tumor types included non-small cell lung (48.7%), breast (14.7%), and melanoma (8.5%). 46.9% had oligometastatic disease (≤5 metastatic foci: including BMs) at SRS, and 53.4% underwent SRS for &gt; 1 BM. 10.3% of patients had undergone prior WBRT and 26.1% surgical resection. 555 patients (40.1%) experienced ICP following SRS, of whom 72.6% had 1-4, 11.5% had 5-10, and 15.9% had ≥11 new/progressive BMs. Among patients with ICP, 6-month freedom from ICP was 35.5% (95% CI: 31.1-40.5%) for those with 1-4 BMs at time of ICP, 29.7% (95% CI: 20.4-43.3%) for 5-10 BMs, and 20.5% (95% CI: 13.5-30.1%) for ≥11 BMs (p = 0.016). Respective 12-month OS rates were 56.8% (95% CI: 52.1-61.9%), 46.0% (95% CI: 35.1-60.1%), and 38.7% (95% CI: 29.4-50.9%; p &lt; 0.001). Neurologic symptoms at time of ICP were observed in 21.1% of patients with 1-4 BMs, 28.1% with 5-10 BMs, and 50.0% with new/progressive ≥11 BMs (p &lt; 0.001). On multivariable analysis, superior freedom from high-burden ICP was associated with the following pre-SRS parameters: oligometastatic burden (ICP5: HR 0.68, 95% CI: 0.47-0.99; ICP11: 0.59; 95% CI: 0.36-0.97), no prior immunotherapy (ICP11: HR 0.57, 95% CI: 0.34-0.57), and a single BM at time of initial SRS (1 vs 2 BM, ICP 5: HR 0.51, 95% CI: 0.31-0.82; ICP11: HR 0.45, 95% CI: 0.24-0.84), while primary tumor type was not associated with ICP5 or ICP11. Conclusions: Pre-SRS parameters including polymetastatic burden, prior receipt of immunotherapy, and &gt; 1 BM were associated with post-SRS high-burden ICP. High burden ICP developed earlier following SRS completion and was associated with higher rates of neurologic decline and inferior OS.

Intracranial and Extracranial Progression and Their Correlation With Overall Survival After Stereotactic Radiosurgery in a Multi-institutional Cohort With Brain Metastases

Clinical trials for metastatic malignant neoplasms are increasingly being extended to patients with brain metastases. Despite the preeminence of progression-free survival (PFS) as a primary oncologic end point, the correlation of intracranial progression (ICP) and extracranial progression (ECP) events with overall survival (OS) is poorly understood for patients with brain metastases following stereotactic radiosurgery (SRS). To determine the correlation of ICP and ECP with OS among patients with brain metastases completing an initial SRS course. This multi-institutional retrospective cohort study was conducted from January 1, 2015, to December 31, 2020. We included patients who completed an initial course of SRS for brain metastases during the study period, including receipt of single and/or multifraction SRS, prior whole-brain radiotherapy, and brain metastasis resection. Data analysis was performed on November 15, 2022. Non-OS end points included intracranial PFS, extracranial PFS, PFS, time to ICP, time to ECP, and any time to progression. Progression events were radiologically defined, incorporating multidisciplinary clinical consensus. The primary outcome was correlation of surrogate end points to OS. Clinical end points were estimated from time of SRS completion via the Kaplan-Meier method, while end-point correlation to OS was measured using normal scores rank correlation with the iterative multiple imputation approach. This study included 1383 patients, with a mean age of 63.1 years (range, 20.9-92.8 years) and a median follow-up of 8.72 months (IQR, 3.25-19.68 months). The majority of participants were White (1032 [75%]), and more than half (758 [55%]) were women. Common primary tumor sites included the lung (757 [55%]), breast (203 [15%]), and skin (melanoma; 100 [7%]). Intracranial progression was observed in 698 patients (50%), preceding 492 of 1000 observed deaths (49%). Extracranial progression was observed in 800 patients (58%), preceding 627 of 1000 observed deaths (63%). Irrespective of deaths, 482 patients (35%) experienced both ICP and ECP, 534 (39%) experienced ICP (216 [16%]) or ECP (318 [23%]), and 367 (27%) experienced neither. The median OS was 9.93 months (95% CI, 9.08-11.05 months). Intracranial PFS had the highest correlation with OS (ρ = 0.84 [95% CI, 0.82-0.85]; median, 4.39 months [95% CI, 4.02-4.92 months]). Time to ICP had the lowest correlation with OS (ρ = 0.42 [95% CI, 0.34-0.50]) and the longest median time to event (median, 8.76 months [95% CI, 7.70-9.48 months]). Across specific primary tumor types, correlations of intracranial PFS and extracranial PFS with OS were consistently high despite corresponding differences in median outcome durations. The results of this cohort study of patients with brain metastases completing SRS suggest that intracranial PFS, extracranial PFS, and PFS had the highest correlations with OS and time to ICP had the lowest correlation with OS. These data may inform future patient inclusion and end-point selection for clinical trials.

Predictors of Radiation Necrosis and Dose/Volume Tolerance of the Brain after Three-Fraction Radiosurgery for Brain Metastases: A Large Single-Institutional Analysis

<h3>Purpose/Objective(s)</h3> Stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (FSRT) is the current standard of care in patients with brain metastases and controlled extracranial disease. Radiation necrosis (RN) is the dose-limiting side-effect of SRS but the dose constraints are poorly defined. FSRT can decrease risk of RN over SRS while maintaining or improving high rates of overall survival (OS). We assessed the survival and risk of RN after FSRT with a goal to identify specific dose/volume constraints associated with grade 3 or higher RN using NTCP modeling. <h3>Materials/Methods</h3> A single-institutional retrospective review of patients treated with 3-fraction FSRT from 2015 to 2020 was performed. Tissue volume (brain + target) around each target lesion was contoured in a consistent manner and volumetric doses per lesion were recorded. RN was defined using biopsy or MRI with perfusion as available and graded using CTCAE version 5.0. Our primary endpoint was grade 3 or higher RN. All statistical analyses were performed using statistical software. <h3>Results</h3> From 2015 to 2020, a total of 439 patients underwent 509 courses of 3-fraction Linac-based FSRT, treating a total of 2394 metastatic lesions (range 1-71, mean = 4.7 and median = 3 lesions per course). 61 patients had ≥10 and 31 patients had ≥15 lesions treated per course. Median RT dose per fraction was 8 Gy (range 5-9 Gy). 11.8% patients received prior whole brain radiation (WBRT). Median follow-up after RT was 8 months (IQR 3-18m). A total of 64 patients (78 lesions) developed RN with 17, 17, 29 and 1 patients developing grade 1, 2, 3 and 4 RN respectively. Grade 3 or higher RN was observed in 5.9% patients. On per lesion analysis, rate of any RN and grade 3 RN was 3.2% and 1.5% respectively. Median time to RN was 11.3m (range 0.7 – 38.4). Of 30 patients with grade 3 or higher RN, 7 (23%) received prior WBRT, 19 (63%) received post-op FSRT to the cavity and 1 (3%) received pre-op FSRT. Most of these patients were managed by steroids, while 25 underwent resection and 6 received bevacizumab. Tissue volume receiving 20 Gy (V20) of <20cc or >20 cc was associated with 2.5% and 10.2% risk of RN respectively, while a V23 of <20 cc or >20 cc was associated with 2.3% vs 12.1% risk of grade 3 or higher RN. Mean V20 in patients who developed Grade 3 or higher RN was statistically higher than the entire cohort (36.9cc vs 14.1cc, p=0.002). Median OS after RT was 10m (1yr and 2yr OS of 45.8% and 30.4%, respectively) while patients who developed RN survived longer compared to rest of the cohort (32m vs 8m, p <0.001). Patients with 15 or more lesions treated per course had similar survival compared to rest of the cohort (8m vs 10m, p = 0.136), after excluding those who received prior WBRT. <h3>Conclusion</h3> In patients receiving 3 fraction FSRT, grade 3 or higher RN was seen in 5.9% patients and 1.5% lesions treated. Risk of RN was significantly lower in patients with V23 of <20 cc. Further studies evaluating the outcomes and RN in patients treated with FSRT compared to SRS or hippocampal avoidance WBRT are warranted.

Imaging-defined necrosis after treatment with single-fraction stereotactic radiosurgery and immune checkpoint inhibitors and its potential association with improved outcomes in patients with brain metastases: an international multicenter study of 697 patients.

Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are commonly utilized in the management of brain metastases. Treatment-related imaging changes (TRICs) are a frequently observed clinical manifestation and are commonly classified as imaging-defined radiation necrosis. However, these findings are not well characterized and may predict a response to SRS and ICIs. The objective of this study was to investigate predictors of TRICs and their impact on patient survival. This retrospective multicenter cohort study was conducted through the International Radiosurgery Research Foundation. Member institutions submitted de-identified clinical and dosimetric data for patients with non-small cell lung cancer (NSCLC), melanoma, and renal cell carcinoma (RCC) brain metastases that had been treated with SRS and ICIs. Data were collected from March 2020 to February 2021. Univariable and multivariable Cox and logistic regression analyses were performed. The Kaplan-Meier method was used to evaluate overall survival (OS). The diagnosis-specific graded prognostic assessment was used to guide variable selection. TRICs were determined on the basis of MRI, PET/CT, or MR spectroscopy, and consensus by local clinical providers was required. The analysis included 697 patients with 4536 brain metastases across 11 international institutions in 4 countries. The median follow-up after SRS was 13.6 months. The median age was 66 years (IQR 58-73 years), 54.1% of patients were male, and 57.3%, 36.3%, and 6.4% of tumors were NSCLC, melanoma, and RCC, respectively. All patients had undergone single-fraction radiosurgery to a median margin dose of 20 Gy (IQR 18-20 Gy). TRICs were observed in 9.8% of patients. The median OS for all patients was 24.5 months. On univariable analysis, Karnofsky Performance Status (KPS; HR 0.98, p < 0.001), TRICs (HR 0.67, p = 0.03), female sex (HR 0.67, p < 0.001), and prior resection (HR 0.60, p = 0.03) were associated with improved OS. On multivariable analysis, KPS (HR 0.98, p < 0.001) and TRICs (HR 0.66, p = 0.03) were associated with improved OS. A brain volume receiving ≥ 12 Gy of radiation (V12Gy) ≥ 10 cm3 (OR 2.78, p < 0.001), prior whole-brain radiation therapy (OR 3.46, p = 0.006), and RCC histology (OR 3.10, p = 0.01) were associated with an increased probability of developing TRICs. The median OS rates in patients with and without TRICs were 29.0 and 23.1 months, respectively (p = 0.03, log-rank test). TRICs following ICI and SRS were associated with a median OS benefit of approximately 6 months in this retrospective multicenter study. Further prospective study and additional stratification are needed to validate these findings and further elucidate the role and etiology of this common clinical scenario.

The Impact of Dose on Treatment Outcomes in Patients Treated for Brain Metastases With a Hypofractionated Technique on Gamma Knife

Purpose: Brain metastases are the most common type of diagnosed central nervous system tumours, occurring in approximately 40% of all cancer patients. Historically, treatment consisted of whole brain radiotherapy (WBRT), however current practice for patients with limited intracranial disease, is to offer stereotactic radiosurgery (SRS). In 2016, our centre acquired a Gamma Knife (GK) unit, designed to treat brain metastases with a stereotactic approach, using an invasive frame based immobilization system. In 2017, a mask based frameless system was introduced, expanding indications for patients and allowing for the treatment of hypofractionated courses on this unit. Given the unique dosimetric characteristics of the GK, our research focused on patients treated for intact brain metastases, with hypofractionated doses, and aimed to report adverse radiation effects and local control. Methods: This was a retrospective study, including all patients with intact brain metastases, treated on the GK unit, with hypofractionated (5 fraction) treatments, between 2017-2020. Hypofractionated treatments are generally given to larger lesions (≥2cm) or those lesions situated in eloquent areas of the brain, such as the motor cortex or brainstem. Patients were excluded if the specific metastases received prior SRS or hypofractionated treatment, however those who received previous whole brain radiotherapy were included. Those without post -treatment imaging follow up were also excluded from the analyses. Competing risk methods were used to determine local control and symptomatic adverse radiation effect (ARE) rates per lesion and Kaplan Meier methods were used to determine survival estimates. The Common Terminology Criteria for Adverse events (CTCAE) v 5.0 was used to determine symptomatic ARE. Results: A total of 146 patients and 299 metastases were identified. The most frequent histologies were lung (38.5%), breast (31.4%) and melanoma (13.7%). 53.4% of patients had a KPS > 70% and the majority had multiple lesions treated at the time of their hypofractionated radiosurgery (62.3%). Only 18% had received prior WBRT. Prescribed doses ranged from 20-27.5Gy with the median being 27.5Gy in 5 fractions prescribed in 54.2% of cases. The median volume of the treated lesions was 2.54cc (range 0.004-24.92cc). Clinical follow-up ranged from 0.5 to 49.9 months, with the median being 13.8 months. The 1 year local control was 84.8%, and on multivariable analyses, 1 year local failure rates increased (8.3% (95% CI, 4.6-13.2) vs 23.5% (95%CI,16.6-31)) with decreasing prescribed doses (27.5Gy vs 20-25Gy) respectively. In terms of adverse radiation effects, there were 32 (10.7%) incidents identified, of which 14 (44%) were symptomatic. For symptomatic AREs, the 1 and 2 year rates were 1.7% (95% CI, 0.7-3.8) and 4.5% (95% CI, 2.4-7.7), respectively. Overall survival for this patient population was 12.7 months, with the 1 and 2 year rates being 51.3% (95% CI 42.6-59.2) and 36.8% (95%, CI 28.5-45.1), respectively. Conclusion: For patients with intact brain metastases, GK hypofractionated treatments are a safe and effective treatment modality. A 27.5Gy prescription dose in 5 fractions is associated with improved local control and a low risk of symptomatic ARE at one year.

Radiation necrosis in renal cell carcinoma brain metastases treated with checkpoint inhibitors and radiosurgery: An international multicenter study

Patients with renal cell carcinoma (RCC) brain metastases are frequently treated with immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS). However, data reporting on the risk of developing radiation necrosis (RN) are limited. RN rates were compared for concurrent therapy (ICI/SRS administration within 4 weeks of one another) and nonconcurrent therapy with the χ2 test. Univariable logistic regression was used to identify factors associated with developing RN. Fifty patients (23 concurrent and 27 nonconcurrent) with 395 brain metastases were analyzed. The median follow-up was 12.1 months; the median age was 65 years. The median margin dose was 20 Gy, and 4% underwent prior whole-brain radiation therapy (WBRT). The median treated tumor volume was 3.32 cm3 (range, 0.06-42.38 cm3 ); the median volume of normal brain tissue receiving a dose of 12 Gy or higher (V12 Gy) was 8.42 cm3 (range, 0.27-111.22 cm3 ). Any-grade RN occurred in 17.4% and 22.2% in the concurrent and nonconcurrent groups, respectively (P = .67). Symptomatic RN occurred in 4.3% and 14.8% in the concurrent and nonconcurrent groups, respectively (P = .23). Increased tumor volume during SRS (odds ratio [OR], 1.08; 95% confidence interval [CI], 1.01-1.19; P = .04) was associated with developing RN, although V12 Gy (OR, 1.03; 95% CI, 0.99-1.06; P = .06), concurrent therapy (OR, 0.74; 95% CI, 0.17-2.30; P = .76), prior WBRT, and ICI agents were not statistically significant. Symptomatic RN occurs in a minority of patients with RCC brain metastases treated with ICI/SRS. The majority of events were grade 1 to 3 and were managed medically. Concurrent ICI/SRS does not appear to increase this risk. Attempts to improve dose conformality (reduce V12) may be the most successful mitigation strategy in single-fraction SRS.

NQPC-5 Does high-dose methotrexate-based chemotherapy for relapsed primary CNS lymphoma increase a risk of leukoencephalopathy with prior whole brain radiotherapy?

Backgrounds: Standard care for primary central nervous system lymphoma (PCNSL) comprises high-dose (HD) methotrexate (MTX) -based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). HD-MTX administration following WBRT has been suggested to increase a risk of leukoencephalopathy. However, given that there are no other agents with efficacy similar to or better than MTX, patients with relapsed PCNSL may often be treated with regimens containing HD-MTX if the initial MTX treatment achieved a long-term complete remission. Here, we retrospectively analyzed prevalence and an extent of white mater damages in association with prior WBRT in patients with relapsed PCNSL treated with HD-MTX based therapy. Patients & methods: Among 79 patients with relapsed/refractory PCNSL in a total of 162 patients with newly-diagnosed PCNSL treated in our institution from April, 2000 to February, 2021, 35 patients were identified with evaluable KPS, MMSE, and Fazekas scale data at both baseline and follow-up periods. Of the 35 patients, 22 were treated with chemotherapy at a relapse (10 with prior WBRT, while 12 without WBRT), and were included in this preliminary study. Results: In the WBRT group (male/female: 5/5), median age was 65 years (range, 45–73), initial median KPS was 70 (40–90), and median WBRT dose was 27 Gy (23.4–40). Median progression-free survival (mPFS) was 11.8 months, and median overall survival (mOS) was not reached. In the non-WBRT group (M/F 8/4), median age 75 (62–84), initial mKPS 80 (50–90), mPFS 16.2 m, and mOS not reached. Initial KPS and MMSE score tended to be worse in WBRT group, presumably due to enrichment of patients with poorer performance status and more comorbidities. A decline in the Fazekas score was not associated with MMSE deterioration.Conclusions: The preliminary analysis was not informative enough, and further extensive imaging analysis will be exploited.

Efficacy and Safety of a Second Course of Stereotactic Radiation Therapy for Locally Recurrent Brain Metastases: A Systematic Review.

Simple SummaryApproximately 30% of patients diagnosed with cancer will ultimately develop brain metastases. Many improvements have been made in systemic and local cancer treatments, which have increased overall survival but also, as a consequence, the number of patients who present with local recurrence following intracranial stereotactic radiotherapy. The management of these recurrences remains controversial. The aim of our review is to evaluate the efficacy and tolerance of a second course of stereotactic radiotherapy. Recent advances in cancer treatments have increased overall survival and consequently, local failures (LFs) after stereotactic radiotherapy/radiosurgery (SRS/SRT) have become more frequent. LF following SRS or SRT may be treated with a second course of SRS (SRS2) or SRT (SRT2). However, there is no consensus on whenever to consider reirradiation. A literature search was conducted according to PRISMA guidelines. Analysis included 13 studies: 329 patients (388 metastases) with a SRS2 and 135 patients (161 metastases) with a SRT2. The 1-year local control rate ranged from 46.5% to 88.3%. Factors leading to poorer LC were histology (melanoma) and lack of prior whole-brain radiation therapy, large tumor size and lower dose at SRS2/SRT2, poorer response at first SRS/SRT, poorer performance status, and no controlled extracranial disease. The rate of radionecrosis (RN) ranged from 2% to 36%. Patients who had a large tumor volume, higher dose and higher value of prescription isodose line at SRS2/SRT2, and large overlap between brain volume irradiated at SRS1/SRT1 and SRS2/SRT2 at doses of 18 and 12 Gy had a higher risk of developing RN. Prospective studies involving a larger number of patients are still needed to determine the best management of patients with local recurrence of brain metastases

Stereotactic radiosurgery for brain metastases from small cell lung cancer without prior whole-brain radiotherapy: A meta-analysis

ObjectivesAssess upfront Stereotactic radiosurgery (SRS) effectiveness for small cell lung cancer (SCLC) brain metastases (BM). Where possible, a comparison with whole-brain radiotherapy (WBRT) was performed. MethodsFollowing PRISMA and MOOSE guidelines, eligible studies were identified on Medline, Embase, Cochrane Library, and proceedings of annual meetings between inception and July 01, 2020. ResultsNine observational studies with 1638 patients were included. The median overall survival (OS) was 8.3 months (95% CI 7.1–9.5 months, I2 = 0%). OS rate at 12 months was 39% (95% CI 31–44%, I2 = 0%). The relative risk between SRS and WBRT for the OS at 12 months was 1.33 (95% CI 1.13–1.51, P = 0.0001). The projected OS for 6, 12, 18- and 24-months comparing SRS with WBRT was 67% vs. 57%, 39% vs. 29%, 22% vs. 15% and 15% vs 9%, favoring SRS (P < 0.001). The LC rate at 12 months was 93% (95% CI 91–94%, I2 = 0%). The distant brain failure rate (DBFR) at 12 months was 41% (95% CI 33–48%, I2 = 52%, P = 0.08). The SRS or WBRT as salvage treatment after upfront SRS was 32% and 19%, respectively. The freedom from neurologic death at 12 months was 87% (95% CI 84–89%). ConclusionBased on the pooling of a large sample of retrospective studies our meta-analysis suggests that for high selected SCLC patients with limited BM upfront SRS produces favorable lesion control and survival outcomes. These findings support the design of randomized clinical trial to confirm the role of SRS in this clinical scenario.

LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

AbstractBackground:Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer.Methods:Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was &gt;3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions.Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test.Results:Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699).Conclusion:In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.