Stereotactic Radiosurgery Cohort Research Articles

Outcomes of adjuvant radiation treatment following subtotal resection of world health organization grade II meningiomas.

Existing literature on adjuvant radiation after subtotal resection (STR) of WHO II meningiomas is limited by heterogenous patient cohorts, combining adjuvant and salvage radiation, gross total resection (GTR) and STR, primary radiation treatment vs. re-treatment, or grade II and III meningiomas, all of which have different expected outcomes. Tumor control estimates in a large homogenous patient cohort are needed to accurately counsel patients. A retrospective review of patients that had immediate post-operative imaging-confirmed residual WHO grade II meningioma followed by either adjuvant intensity-modulated radiation therapy (IMRT) or stereotactic radiosurgery (SRS) between 1996 and 2020 was conducted. Kaplan-Meier survival analysis and log-rank test was used to assess progression-free survival (PFS). Thirty-nine patients met inclusion criteria (IMRT = 32; SRS = 7). Overall, the 3-, 5-, and 10-year PFS was 81.1%, 61.2%, and 44.6%, respectively. Median follow-up time was 37 months. When comparing IMRT and SRS cohorts, baseline characteristics did not differ significantly between groups, but significantly larger residual tumor volumes were treated with IMRT (22.2 cm3 vs. 6.3 cm3, p = 0.004). PFS was not significantly different between IMRT and SRS at 3 years (81.1% vs. 80.0%) or 5 years (65.5% vs. 40%) (p = 0.19). There was no significant difference in radiation necrosis between groups (IMRT = 3/32 patients vs. SRS = 0/7 patients, p = 0.32). Our homogenous patient cohort displayed acceptable control rates at 3 years using SRS or IMRT as adjuvant therapy. No significant difference in PFS or radiation necrosis was noted between patients treated with adjuvant IMRT versus SRS.

RBIO-04. OUTCOMES OF RADIOSURGERY FOR WHO GRADE 2 MENINGIOMAS: THE ROLE OF KI-67 INDEX IN GUIDING THE TUMOR MARGIN DOSE

Abstract The management of WHO grade 2 meningiomas is complicated by their diverse clinical behaviors. Stereotactic radiosurgery (SRS) can be an effective management option. Literature on SRS dose selection is limited, but suggests a higher dose is better for tumor control. We aimed to characterize the predictors of post-SRS outcomes that can help guide planning and management. We reviewed a cohort of consecutive patients with pathologically-proven WHO grade 2 meningiomas who underwent SRS at a single institution between 2011 and 2023. Ninety-nine patients (median age 62 years) underwent SRS, eleven of whom received hypofractionated SRS in 5 fractions. Twenty-two patients had received prior irradiation. The median follow-up was 49 months. The median overall survival (OS) was 119 months (95%CI 92–NA) with estimated 5- and 10-year survival of 83% and 27% respectively. The median progression-free survival (PFS) was 40 months (95%CI 32–62) with 3- and 5-year rates at 54% and 35% respectively. The median locomarginal PFS was 63 months (95%CI 51.8-NA) with 3- and 5-year rates at 65% and 52%. Nine (9%) patients experienced adverse events, 2 CTCAE grade 3 and 7 grade 2, consisting of worsening neurologic deficit from edema. In the single-session SRS cohort, Ki-67 was a significant predictor of both OS and intracranial PFS. Tumors with Ki-67 >10% had ~10 times risk of locomarginal progression compared to Ki-67 ≤10% (p<0.001). In tumors with Ki-67 >10%, margin dose ≥14 Gy was associated with significantly better tumor control, but not for tumors with Ki-67 ≤ 10%. Other significant predictors of tumor control were prescription dose, tumor volume, and location. The management of WHO grade 2 meningiomas requires a multi-modality approach. This study demonstrated the value of a targeted SRS approach in patients with limited disease, and further establish predictive biomarkers that can guide planning through a personalized approach.

Vestibular Schwannoma Koos Grade II International Study of Active Surveillance Versus Stereotactic Radiosurgery: The VISAS-K2 Study.

This study assessed the efficacy and safety of stereotactic radiosurgery (SRS) in comparison with watchful waiting for managing Koos grade II vestibular schwannomas (VS). A retrospective, multicentric analysis was conducted, focusing on patients with Koos grade II VS who either received SRS (SRS group) or were observed (observation group). To ensure comparability between groups, propensity score matching was used, including factors such as demographic characteristics, tumor dimensions, and hearing assessments. The primary end points examined were tumor control, maintenance of serviceable hearing, and neurological outcomes. A total of 92 patients were equally matched across both cohorts, with a median follow-up of 37 months for the SRS group and 27.5 months for those observed. The SRS cohort exhibited superior tumor control over observation across 3, 5, and 8 years, achieving a 100% control rate vs 47.9%, 40.1%, and 34.3% for the observation group at these time intervals, respectively (P < .001). Serviceable hearing preservation rates were comparable between the 2 groups throughout 3, 5, and 7 years (72.9% for SRS vs 65.4% for observation at 3 years; P = .86). Moreover, SRS management correlated with a lower incidence of vestibular symptoms (odds ratio = 0.11, P = .002), with no significant disparity in the deterioration of cranial nerve (CN) V or CN VII functions. Notably, the likelihood of experiencing any CN impairment was significantly diminished in the SRS cohort (odds ratio = 0.47, P = .04). For patients with Koos grade II VS, SRS offers superior tumor control rate and a lower risk of CN dysfunction without sacrificing hearing preservation.

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.

Clinical outcomes of melanoma brain metastases treated with nivolumab and ipilimumab alone versus nivolumab and ipilimumab with stereotactic radiosurgery.

Upfront dual checkpoint blockade with immune checkpoint inhibitors (ICI) has demonstrated efficacy for treating melanoma brain metastases (MBM) in asymptomatic patients. Whether the combination of stereotactic radiosurgery (SRS) with dual checkpoint blockade improves outcomes over dual-checkpoint blockade alone is unknown. We evaluated clinical outcomes of patients with MBM receiving ICI with nivolumab and ipilimumab, with and without SRS. 49 patients with 158 MBM receiving nivolumab and ipilimumab for untreated MBM between 2015 and 2022 were identified at our institution. Patient and tumor characteristics including age, Karnofsky Performance Status (KPS), presence of symptoms, cancer history, MBM burden, and therapy course were recorded. Outcomes measured from initiation of MBM-directed therapy included overall survival (OS), local control (LC), and distant intracranial control (DIC). Time-to-event analysis was conducted with the Kaplan-Meier method. 25 patients with 74 MBM received ICI alone, and 24 patients with 84 MBM received concurrent SRS. Median follow-up was 24months. No differences in age (p = 0.96), KPS (p = 0.85), presence of symptoms (p = 0.79), prior MBM (p = 0.68), prior MBM-directed surgery (p = 0.96) or SRS (p = 0.68), MBM size (p = 0.67), or MBM number (p = 0.94) were seen. There was a higher rate of nivolumab and ipilimumab course completion in the SRS group (54% vs. 24%; p = 0.029). The SRS group received prior immunotherapy more often than the ICI alone group (54% vs. 8.0%; p < 0.001). There was no significant difference in 1-year OS (72% vs. 71%, p = 0.20) and DIC (63% v 51%, p = 0.26) between groups. The SRS group had higher 1-year LC (92% vs. 64%; p = 0.002). On multivariate analysis, LC was improved with combination therapy (AHR 0.38, p = 0.01). In our analysis, patients who received SRS with nivolumab and ipilimumab had superior LC without increased risk of toxicity or compromised immunotherapy treatment completion despite the SRS cohort having higher rates of prior immunotherapy. Further prospective study of combination nivolumab and ipilimumab with SRS is warranted.

Analysis of upfront resection or stereotactic radiosurgery for local control of solid and cystic cerebellar hemangioblastomas.

The purpose of this study was to identify rates of and risk factors for local tumor progression in patients who had undergone surgery or radiosurgery for the management of cerebellar hemangioblastoma and to describe treatments pursued following tumor progression. The authors conducted a retrospective single-center review of patients who had undergone treatment of a cerebellar hemangioblastoma with either surgery or stereotactic radiosurgery (SRS) between 1996 and 2019. Univariate and multivariate regression analyses were performed to examine factors associated with local tumor control. One hundred nine patients met the study inclusion criteria. Overall, these patients had a total of 577 hemangioblastomas, 229 of which were located in the cerebellum. The surgical and SRS cohorts consisted of 106 and 123 cerebellar hemangioblastomas, respectively. For patients undergoing surgery, tumors were treated with subtotal resection and gross-total resection in 5.7% and 94.3% of cases, respectively. For patients receiving SRS, the mean target volume was 0.71 cm3 and the mean margin dose was 18.0 Gy. Five-year freedom from lesion progression for the surgical and SRS groups was 99% and 82%, respectively. The surgical and SRS cohorts contained 32% versus 97% von Hippel-Lindau tumors, 78% versus 7% cystic hemangioblastomas, and 12.8- versus 0.56-cm3 mean tumor volumes, respectively. On multivariate analysis, factors associated with local tumor progression in the SRS group included older patient age (HR 1.06, 95% CI 1.03-1.09, p < 0.001) and a cystic component (HR 9.0, 95% CI 2.03-32.0, p = 0.001). Repeat SRS as salvage therapy was used more often for smaller tumor recurrences, and no tumor recurrences of < 1.0 cm3 required additional salvage surgery following repeat SRS. Both surgery and SRS achieve high rates of local control of hemangioblastomas. Age and cystic features are associated with local progression after SRS treatment for cerebellar hemangioblastomas. In cases of local tumor recurrence, salvage surgery and repeat SRS are valid forms of treatment to achieve local tumor control, although resection may be preferable for larger recurrences.

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.

Choice of radiotherapy modality for the combined treatment of non-small cell lung cancer with brain metastases: whole-brain radiation therapy with simultaneous integrated boost or stereotactic radiosurgery.

To compare Whole-brain radiation therapy with simultaneous integrated boost (WBRT+SIB) to stereotactic radiosurgery (SRS)for non-small cell lung cancer (NSCLC)with brain metastases (BMs)in terms of overall survival (OS), intracranial progression-free-survival(iPFS), toxicity and objective response rate (ORR). A retrospective review was performed in our hospital of 90 patients diagnosed with NSCLC- BM who received either SRS (n = 48) or WBRT+SIB (n = 42) from January 2016 to January 2022. 76 (84.44%) patients received systemic drug therapy after radiotherapy, including chemotherapy(n=53), targeted therapy(n=40), immunotherapy(n=23), and anti-vascular drug therapy(n=45). OS and iPFS were estimated by the Kaplan-Meier method and compared using the log-rank test. Univariate and Multivariate analysis of the prognostic factors was performed using the Cox proportional hazard regression model. The WBRT+SIB cohort had a longer median iPFS (20.0 versus (VS) 12.0 months, P = 0.0069) and a similar median OS (32.0 vs 28.0 months, P = 0.195) than the SRS cohort. Intracranial objective response rates in WBRT +SIB and SRS cohorts were 76.19% and 70.09%, respectively (P = 0.566). Disease control rates were 88.09% and 83.33%, respectively (P = 0.521). Multivariate analysis showed that WBRT+SIB is the only factor affecting iPFS(hazard ratio (HR):0.597 {95%confidence interval(CI):0.370-0.966}, P=0.035). Sex, Liver metastasis and Lymph node metastasis are risk factors for NSCLC-BM. In the context of systemic drug therapy, WBRT+SIB may have better intracranial local control than SRS in NSCLC-BM patients.

Combination of EGFR-Directed Tyrosine Kinase Inhibitors (EGFR-TKI) with Radiotherapy in Brain Metastases from Non-Small Cell Lung Cancer: A 2010-2019 Retrospective Cohort Study.

Traditionally, brain metastases have been treated with stereotactic radiosurgery (SRS), whole-brain radiation (WBRT), and/or surgical resection. Non-small cell lung cancers (NSCLC), over half of which carry EGFR mutations, are the leading cause of brain metastases. EGFR-directed tyrosine kinase inhibitors (TKI) have shown promise in NSCLC; but their utility in NSCLC brain metastases (NSCLCBM) remains unclear. This work sought to investigate whether combining EGFR-TKI with WBRT and/or SRS improves overall survival (OS) in NSCLCBM. A retrospective review of NSCLCBM patients diagnosed during 2010-2019 at a tertiary-care US center was performed and reported following the 'strengthening the reporting of observational studies in epidemiology' (STROBE) guidelines. Data regarding socio-demographic and histopathological characteristics, molecular attributes, treatment strategies, and clinical outcomes were collected. Concurrent therapy was defined as the combination of EGFR-TKI and radiotherapy given within 28 days of each other. A total of 239 patients with EGFR mutations were included. Of these, 32 patients had been treated with WBRT only, 51 patients received SRS only, 36 patients received SRS and WBRT only, 18 were given EGFR-TKI and SRS, and 29 were given EGFR-TKI and WBRT. Median OS for the WBRT-only group was 3.23 months, for SRS + WBRT it was 3.17 months, for EGFR-TKI + WBRT 15.50 months, for SRS only 21.73 months, and for EGFR-TKI + SRS 23.63 months. Multivariable analysis demonstrated significantly higher OS in the SRS-only group (HR = 0.38, 95% CI 0.17-0.84, p = 0.017) compared to the WBRT reference group. There were no significant differences in overall survival for the SRS + WBRT combination cohort (HR = 1.30, 95% CI = 0.60, 2.82, p = 0.50), EGFR-TKIs and WBRT combination cohort (HR = 0.93, 95% CI = 0.41, 2.08, p = 0.85), or the EGFR-TKI + SRS cohort (HR = 0.46, 95% CI = 0.20, 1.09, p = 0.07). NSCLCBM patients treated with SRS had a significantly higher OS compared to patients treated with WBRT-only. While sample-size limitations and investigator-associated selection bias may limit the generalizability of these results, phase II/III clinicals trials are warranted to investigate synergistic efficacy of EGFR-TKI and SRS.

477 Stereotactic Radiosurgery With Versus Without Prior Onyx Embolization for Brain Arteriovenous Malformations

INTRODUCTION: Investigations of the combined effects of neoadjuvant Onyx embolization and stereotactic radiosurgery (SRS) on brain arteriovenous malformations (AVM) have not accounted for initial angioarchitectural features prior to neuroendovascular intervention. METHODS: The International Radiosurgery Research Foundation AVM databases from 1987–2018 were retrospectively reviewed. Patients were categorized, based on AVM treatment approach, into Onyx embolization and SRS (OE+ SRS) or SRS alone (SRS-only) cohorts and then propensity score-matched in a 1:1 ratio. Primary outcome was AVM obliteration. Secondary outcomes were post-SRS hemorrhage, all-cause mortality, radiologic and symptomatic radiation-induced changes (RIC), and cyst formation. Comparisons were analyzed using crude rates and cumulative probabilities adjusted for competing risk of death. RESULTS: The matched OE + SRS and SRS-only cohorts each comprised 53 patients. Crude rates (37.7% vs. 47.2% for OE + SRS vs. SRS-only cohorts, respectively; OR = 0.679, p = 0.327) and cumulative probabilities at 3, 4, 5, and 6 years (33.7%, 44.1%, 57.5%, and 65.7% for OE + SRS cohort vs. 34.8%, 45.5%, 59.0%, and 67.1% for SRS-only cohort, respectively; SHR = 0.961, p = 0.896) of obliteration were similar between the matched cohorts. The secondary outcomes of the matched cohorts were also similar. Asymptomatic and symptomatic embolization-related complication rates in the matched OE + SRS cohort were 18.9% and 9.4%, respectively. CONCLUSIONS: Pre-SRS AVM embolization with Onyx does not appear to negatively influence outcomes after SRS. Our analyses, based on de novo nidal characteristics, thereby refute previous studies that found detrimental effects of Onyx embolization on SRS-induced AVM obliteration. However, given the risks incurred by nidal embolization using Onyx, this neoadjuvant intervention should be employed judiciously in multimodal treatment strategies involving SRS for appropriately selected large-volume or angioarchitecturally high-risk AVMs.

P03.03.A STEREOBRAIN: Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4-10 brain metastases - a non-randomized controlled trial

Abstract Background Since the JLGK0901 study described non-inferiority of stereotactic radiosurgery (SRS) of 5-10 compared to 2-4 brain metastases in 2014, it has been widely discussed if SRS should replace whole brain radiotherapy (WBRT) in 5 - 10 brain metastases though lacking randomized evidence. At our department, WBRT has been the treatment of choice in 4-10 brain metastases until 2017. This paradigm was entirely changed to include patients within the STEREOBRAIN trial (DRKS00014694). We designed this prospective controlled single arm trial to systematically introduce SRS to 4 to 10 brain metastases comparing this new treatment regimen with the former approach. We aimed at showing a survival benefit of this novel treatment paradigm. Material and Methods Inclusion criteria were 4-10 brain metastases, largest diameter 2.5 cm, all histologies except SCLC, germ cell tumors, lymphoma, and ECOG ≤ 2. The retrospective WBRT cohort was identically selected from consecutive patients from 2012 to 2017 in a 1:2 fashion. At a significance level of 5%, a total number of 99 events (deaths) across the two groups allows to detect an increase in median OS from 6 months (retrospective WBRT cohort) to 11 months (SRS) considered clinically relevant (and corresponding to a hazard ratio of 0.55 assuming exponential distributions of survival times within groups) with a power of 80%. Propensity-score matching was performed to take confounders into account given the inherent bias caused by different treatment periods. Multiple brain mets SRS was performed using a single-isocenter technique. Results Patients were recruited from 2017 - 2020 and end of F/U was July 1st 2021. Forty patients were recruited to the SRS cohort and 70 patients were eligible within the WBRT cohort (81 events altogether). Median follow-up, OS and intracranial progression free survival were 21.6 months (95%-CI 19.8-NA), 10.4 months (95%-CI 9.3-NA) and 7.1 months (95%-CI 3.9-14.2) for the SRS-cohort, and 61.4 months (95% 54.6-NA), 6.5 months (95%-CI 4.9-10.4) and 5.9 months (95%-CI 4.1-8.8) for the WBRT-cohort, respectively. The Cox-model yielded a trend for improved survival within the SRS-cohort, HR 0.65 (95%-CI 0.4-1.1); p=0.076. After optimal propensity score matching, OS was significantly superior for the SRS-cohort (HR 0.53 (95%-CI 0.32-0.86), p=0.01). No grade III toxicities were observed in the SRS-cohort. Conclusion Despite all limitations of a historical control and missing the target number of events, there was a clear signal of improved survival with SRS compared to WBRT for patients with 4-10 metastases. Whether adapted WBRT (hippocampal sparing, simultaneous integrated boost) or SRS is to be preferred needs to be investigated in the future.

Factors correlating with survival following adjuvant or definitive radiosurgery for large brain metastases.

We sought to identify variates correlating with overall survival (OS) in patients treated with surgery (S) plus adjuvant stereotactic radiosurgery (SRS) versus definitive SRS for large (&gt;4 cc) brain metastases (BrM). We used univariate (UVA) and multivariate analyses (MVA) to identify survival correlates among eligible patients identified from a prospective registry and compared definitive SRS to S+ adjuvant SRS cohorts using propensity score-matched analysis (PSMA). Secondary outcomes were measured using the cumulative incidence (CI) method. We identified 364 patients; 127 and 237 were treated with S+SRS and definitive SRS, respectively. On UVA, SRS alone [HR1.73 (1.35,2.22) P &lt; .001), BrM quantity [HR 1.13 (1.06-1.22) (P &lt; .001)]; performance status (PS) [HR 2.78 (1.73-4.46) (P &lt; .001)]; extracranial disease (ECD) [HR 1.82 (1.37,2.40) (P &lt; .001)]; and receipt of systemic treatment after BrM therapy, [HR 0.58 (0.46-073) (P &lt; .001)] correlated with OS. On MVA, SRS alone [HR 1.81 (1.19,2.74) (P &lt; .0054)], SRS target volume [HR 1.03 (1.01,1.06) (P &lt; .0042)], and receipt of systemic treatment [HR 0.68 (0.50,0.93) (P &lt; .015)] correlated with OS. When PSMA was used to balance ECD, BrM quantity, PS, and SRS target volume, SRS alone remained correlated with worsened OS [HR 1.62 (1.20-2.19) (P = 0.0015)]. CI of local failure requiring resection at 12 months was 3% versus 7% for S+SRS and SRS cohorts, respectively [(HR 2.04 (0.89-4.69) (P = .091)]. CI of pachymeningeal failure at 12 months was 16% versus 0% for S+SRS and SRS. SRS target volume, receipt of systemic therapies, and treatment with S+SRS instead of definitive SRS correlated with improved survival in patients with large BrM.

Stereotactic Radiosurgery Compared With Active Surveillance for Asymptomatic, Parafalcine, and Parasagittal Meningiomas: A Matched Cohort Analysis From the IMPASSE Study.

The optimal management of asymptomatic, presumed WHO grade I meningiomas remains controversial. To define the safety and efficacy of stereotactic radiosurgery (SRS) compared with active surveillance for the management of patients with asymptomatic parafalcine/parasagittal (PFPS) meningiomas. Data from SRS-treated patients from 14 centers and patients managed conservatively for an asymptomatic, PFPS meningioma were compared. Local tumor control rate and new neurological deficits development were evaluated in the active surveillance and the SRS-treated cohorts. There were 173 SRS-treated patients and 98 patients managed conservatively in the unmatched cohorts. After matching for patient age and tumor volume, there were 98 patients in each cohort. The median radiological follow-up period was 43 months for the SRS cohort and 36 months for the active surveillance cohort (P = .04). The median clinical follow-up for the SRS and active surveillance cohorts were 44 and 36 months, respectively. Meningioma control was noted in all SRS-treated patients and in 61.2% of patients managed with active surveillance (P < .001). SRS-related neurological deficits occurred in 3.1% of the patients (n = 3), which were all transient. In the active surveillance cohort, 2% of patients (n = 2) developed neurological symptoms because of tumor progression (P = 1.0), resulting in death of 1 patient (1%). Up-front SRS affords superior radiological PFPS meningioma control as compared with active surveillance and may lower the risk of meningioma-related permanent neurological deficit and/or death.

Comparison of Active Surveillance to Stereotactic Radiosurgery for the Management of Patients with an Incidental Frontobasal Meningioma-A Sub-Analysis of the IMPASSE Study.

Simple SummaryMeningioma, a type of brain tumor, is a common incidental finding on brain imaging. The best management approach for patients with an incidental meningioma remains unclear. This retrospective multi-center study investigated the outcomes of patients with an incidental meningioma in a frontobasal location, who were managed with active surveillance (n = 28) compared to stereotactic radiosurgery (SRS) (n = 84). Within 5 years of follow-up, SRS improved the radiological control of incidental frontobasal meningiomas (0% vs. 52%), but no symptoms occurred in either group. In the active surveillance cohort, 12% underwent an intervention for tumor growth. The findings of this study provide information to enable shared decision making between clinicians and patients with incidental frontobasal meningiomas.Meningioma is a common incidental finding, and clinical course varies based on anatomical location. The aim of this sub-analysis of the IMPASSE study was to compare the outcomes of patients with an incidental frontobasal meningioma who underwent active surveillance to those who underwent upfront stereotactic radiosurgery (SRS). Data were retrospectively collected from 14 centres. The active surveillance (n = 28) and SRS (n = 84) cohorts were compared unmatched and matched for age, sex, and duration of follow-up (n = 25 each). The study endpoints included tumor progression, new symptom development, and need for further intervention. Tumor progression occurred in 52.0% and 0% of the matched active surveillance and SRS cohorts, respectively (p < 0.001). Five patients (6.0%) treated with SRS developed treatment related symptoms compared to none in the active monitoring cohort (p = 0.329). No patients in the matched cohorts developed symptoms attributable to treatment. Three patients managed with active surveillance (10.7%, unmatched; 12.0%, matched) underwent an intervention for tumor growth with no persistent side effects after treatment. No patients subject to SRS underwent further treatment. Active monitoring and SRS confer a similarly low risk of symptom development. Upfront treatment with SRS improves imaging-defined tumor control. Active surveillance and SRS are acceptable treatment options for incidental frontobasal meningioma.

Stereotactic radiosurgery versus active surveillance for asymptomatic, skull-based meningiomas: an international, multicenter matched cohort study.

The optimal management of asymptomatic, skull-based meningiomas is not well defined. The aim of this study is to compare the imaging and clinical outcomes of patients with asymptomatic, skull-based meningiomas managed either with upfront stereotactic radiosurgery (SRS) or active surveillance. This retrospective, multicenter study involved patients with asymptomatic, skull-based meningiomas. The study end-points included local tumor control and the development of new neurological deficits attributable to the tumor. Factors associated with tumor progression and neurological morbidity were also analyzed. The combined unmatched cohort included 417 patients. Following propensity score matching for age, tumor volume, and follow-up 110 patients remained in each cohort. Tumor control was achieved in 98.2% and 61.8% of the SRS and active surveillance cohorts, respectively. SRS was associated with superior local tumor control (p < 0.001, HR = 0.01, 95% CI = 0.002-0.13) compared to active surveillance. Three patients (2.7%) in the SRS cohort and six (5.5%) in the active surveillance cohort exhibited neurological deterioration. One (0.9%) patient in the SRS-treated and 11 (10%) patients in the active surveillance cohort required surgical management of their meningioma during follow-up. SRS is associated with superior local control of asymptomatic, skull-based meningiomas as compared to active surveillance and does so with low morbidity rates. SRS should be offered as an alternative to active surveillance as the initial management of asymptomatic skull base meningiomas. Active surveillance policies do not currently specify the optimal time to intervention when meningioma growth is noted. Our results indicate that if active surveillance is the initial management of choice, SRS should be recommended when radiologic tumor progression is noted and prior to clinical progression.

Outcomes of Immune-Checkpoint Inhibitors (ICIs) and Stereotactic Radiosurgery (SRS) in Non-Small Cell Lung Cancer Brain Metastases (NSCLCBM) Patients

<h3>Purpose/Objective(s)</h3> Non-small cell lung cancer (NSCLC) is the leading cause of brain metastases. Systemic therapies and radiation therapy are both potential treatment options for NSCLCBM patients. ICIs have been designated as a promising alternative in patients without targetable molecular alterations, while SRS has also grown into favor, as it is non-invasive and irradiates only the lesion. In our retrospective study, we evaluated overall survival (OS) and progression-free survival (PFS) between NSCLCBM patients who received ICIs, SRS, and a combination of both treatments. We hypothesize that the combination of ICIs and SRS will be associated with improved OS and PFS when compared to either treatment alone. <h3>Materials/Methods</h3> We investigated all NSCLCBM patients diagnosed between 2010 and 2019. Molecular marker status, types of therapies used, and dates of progression were collected. OS was defined as the start date of either type of therapy to the date of last follow-up or death. Most NSCLCBM patients who received SRS or ICIs therapies also received standard chemotherapy. The Cox proportional model was used to estimate OS and PFS. <h3>Results</h3> A total of 2989 NSCLCBM patients were analyzed. 286 patients received only ICIs, 916 received only SRS, and 469 were treated with both SRS and ICIs. The median OS (mOS) in patients treated with ICI was 17.2 months, while the mOS in patients treated with SRS or both ICI and SRS were 23.2 months (hazard ratio (HR) = 0.79 (95% confidence interval (CI) = 0.68, 0.92), <i>P</i>-value (<i>P</i>) < 0.002) and 48.2 months (HR = 0.45) (95% CI = 0.38, 0.54), <i>P</i> < 0.001), respectively. The median PFS (mPFS) in patients treated with ICIs, SRS, and both SRS and ICIs was 9.92 months, 23.25 months (HR = 0.56 (95% CI = 0.48, 0.64), <i>P</i> < 0.001), and 29.33 months (HR = 0.45 (95% CI = 0.39, 0.53), <i>P</i> < 0.001), respectively. <h3>Conclusion</h3> ICIs and SRS are both common therapies in the field of NSCLCBM. Our retrospective study data showed improved mOS and mPFS in patients who received SRS or the combination of SRS and ICIs when compared to those who received ICIs. Though there was longer mOS and mPFS in the combination group compared to the SRS group, the statistical significance has yet to be analyzed. However, our data is encouraging that there may be a synergistic survival benefit in the combination of SRS and ICIs cohort, which could be especially beneficial in patients with strong PDL1 expression.

VEGF Inhibition Reduces Intracranial Edema Following SRS of Brain Metastases From Renal Cell Carcinoma

Optimal control of brain metastases (BM) from renal cell carcinoma (RCC) with stereotactic radiosurgery (SRS) is critical as tyrosine kinase inhibitors (TKI) and immunotherapy has significantly prolonged overall survival (OS), emphasizing the importance of minimizing potential morbidity from treatment-associated edema. Clinically, we have observed that RCC BM-associated edema seems to be less prominent when VEGF-targeted agents (VEGFi) such as axitinib are administered contemporaneously with SRS. We therefore investigated the role of VEGFi in intracranial edema reduction in pts treated with SRS.We conducted a single institution retrospective analysis of all clear cell or unknown RCC pts with BM treated with SRS from 2013 onwards. We excluded non-clear cell RCC, lack of post-SRS imaging, and failure to complete SRS. The SRS plus VEGFi cohort was defined as VEGFi within 6 months of SRS. Volumetric data was obtained from SRS plans, edema was contoured on MR Brain T2 Flair, and paired t-test was performed. Multivariate analysis for OS performed with the Cox proportional hazards model.We identified 38 pts who received 78 courses of SRS + VEGFi and 18 pts who received 29 courses of SRS alone. For the SRS + VEGFi and SRS groups, median OS was 4.1y and 6.0y, median SRS dose was 21 Gy and 27 Gy with comparable pre-SRS steroid use of 52% and 57% (HR 0.51, P = 0.200) and baseline neurologic symptoms 50% and 74% (HR 0.943, P = 0.904), respectively. Among the SRS + VEGFi group, the mean intact tumor volume decreased from pre-SRS 1.89cc to 0.42cc at 6m post-SRS, compared to a decrease from 1.82cc to 1.28cc in the SRS group. Edema volume decreased from 17.65cc to 3.28cc in the SRS + VEGFi group with an increase from pre-SRS 5.78cc to 6.39cc at 6mo post-SRS in the SRS alone group (95% CI -3.67, 1.15, P = 0.154).Despite similar pre-SRS steroid use and increased edema volume, VEGFi appeared to improve post-SRS edema with a notable reduction of neurological symptoms. Our data suggest VEGFi may offer symptomatic benefit for significant peritumoral edema even without overt disease progression, and that re-challenge or continuation of VEGFi with SRS should be considered in such patients.

Brain Metastases in Metastatic Cutaneous Melanoma: Patterns of Care and Clinical Outcomes in the Era of Immunotherapy and Targeted Therapy

Immune checkpoint inhibitors (CPIs) and BRAF inhibitors (BIs) are standard treatments for metastatic melanoma and have intracranial activity against melanoma brain metastases (MBMs). However, optimal use of CPI/BI with radiation therapy (RT) is not well established. This study evaluates the current practice pattern of how these systemic therapies are chosen and combined with either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS) for MBMs. The study also examines if upfront SRS+CPI results in superior intracranial control (IC) than upfront SRS without CPI or upfront CPI/BI followed by salvage RT.Patients with MBMs who received their first course of intracranial RT with between 1/2014 and 12/2019 at a tertiary cancer center were retrospectively reviewed. Patients with leptomeningeal disease and MBMs from non-cutaneous melanoma were excluded. Prior exposure before MBM diagnosis and concomitant use of CPIs/BIs within 3 months of RT were evaluated. Binary logistic regression was performed to determine predictors of SRS or CPI use. Cox regression analysis was used to assess the association with IC, which was calculated from the time of MBM diagnosis to the first intracranial progression after upfront MBM treatment.A total of 123 patients with MBMs with a median age of 61 (IQR: 51-69) were identified, and 55% were BRAF-mutant. There were 75 patients (61%) with 1-4 MBMs, 31 patients (25%) with 5-10 MBMs, and 17 (14%) patients with > 10 MBMs. Before MBM diagnosis, 30% had prior CPI and 18% had prior BI. For the upfront MBM treatment, 64% received SRS (66% with CPI and 23% with BI), 27% received WBRT (42% with CPI and 30% with BI), 9% received upfront CPI/BI. The baseline characteristics were balanced between the patients who received upfront SRS and upfront CPI/BI except patients who received upfront CPI/BI were more likely to have a BRAF mutation (82% vs. 49%, P = 0.04). The median follow-up was 8.7 mo (IQR: 2.8-22) for all patients and 32 mo (IQR: 18-45) for living patients. For patients who received upfront CPI/BI, 73% underwent salvage SRS and 27% with salvage WBRT at a median of 5.7 mos [IQR: 3.0-7.7] after MBM diagnosis. Fewer number of MBMs, higher KPS, and craniotomy were significant predictors of SRS use on multivariable logistic regression. For the upfront SRS cohort, treatment after 2016, BRAF-wild type status, and prior CPI exposure were associated with higher likelihood of concomitant CPI use with SRS. After adjusting for the number of MBMs, upfront SRS+CPI was associated with higher IC than upfront SRS without CPI (HR: 0.43, 95% CI: 0.22-0.84, P = 0.02). Upfront SRS+ CPI also trended towards a higher IC than upfront CPI/BI with salvage RT (HR: 0.54, 95% CI: 0.27-1.1, P = 0.07) after adjusting for the number of MBMs.Upfront SRS with concomitant CPI was the most frequently used approach to treat newly diagnosed favorable MBMs and may yield superior IC than upfront SRS without CPI or upfront CPI/BI.R. Chin: None. K. Chen: None. C.D. Abraham: None. C.G. Robinson: Research Grant; Varian. Consultant; Varian, AstraZeneca, EMD Serono. Advisory Board; Radialogica. Stock Options; Radialogica. S.M. Perkins: I serve on the Medical Advisory Committee for Mevion Medical Systems and receive compensation for this role.; Mevion Medical Systems. T.M. Johanns: None. L.F. Hernandez-Aya: None. J.W. Keller: None. J. Dowling: None. K. Rich: None. M. Chicoine: None. A.H. Kim: None. G.P. Dunn: None. G. Ansstas: None. J. Huang: None.

Outcomes following stereotactic radiosurgery or whole brain radiation therapy by molecular subtype of metastatic breast cancer.

BackgroundThis study quantified clinical outcomes by molecular subtype of metastatic breast cancer (BC) following whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Doing so is important for patient counseling and to assess the potential benefit of combining targeted therapy and brain radiotherapy for certain molecular subtypes in ongoing trials.Materials and methodsThe National Cancer Database was queried for BC (invasive ductal carcinoma) cases receiving brain radiotherapy (divided into WBRT and SRS ). Statistics included multivariable logistic regression to determine factors associated with SRS delivery, Kaplan-Meier analysis to evaluate overall survival (OS), and Cox proportional hazards modeling.ResultsOf 1,112 patients, 186 (16.7%) received SRS and 926 (83.3%) underwent WBRT. Altogether, 410 (36.9%), 195 (17.5%), 162 (14.6%), and 345 (31.0%) were ER+/HER2−, ER+/HER2+, ER−/HER2+, and ER−/HER2−, respectively. In the respective molecular subtypes, the proportion of subjects who underwent SRS was 13.4%, 19.4%, 24.1%, and 15.7%. Respective OS for WBRT patients were 12.9, 22.8, 10.6, and 5.8 months; corresponding figures for the SRS cohort were 28.3, 40.7, 15.0, and 12.9 months (p < 0.05 for both). When comparing OS between treatment different histologic subtypes, patients with ER−/HER2+ and ER−/HER2− disease had worse OS than patients with ER+/HER2− disease, for both patients treated with SRS and for patients treated with WBRT.ConclusionsMolecular subtype may be a useful prognostic marker to quantify survival following SRS/WBRT for metastatic BC. Patients with HER 2-enriched and triple-negative disease had the poorest survival following brain irradiation, lending credence to ongoing studies testing the addition of targeted therapies for these subtypes.

RADT-07. STEREOTACTIC RADIOSURGERY OF PATIENTS WITH BRAIN METASTASES AND POOR PROGNOSIS

Abstract PURPOSE/OBJECTIVE(S) Stereotactic radiosurgery (SRS) in patients with risk factors other than the number of intracranial metastases remains controversial. Here we define factors related to early death after SRS alone and compared SRS alone with WBRT in high-risk patients. The aim of our study was to verify if optimal brain treatment may extend survival in patients with poor prognosis and select optimal candidates. MATERIALS AND METHODS In this prospectively collected data, 180 patients with brain metastases and adverse prognostic factors not previously treated with WBRT were analyzed. SRS patients were divided into training (n=82) and validation (n=48) cohorts and compared to retrospective data of WBRT patients (n=50). Overall survival (OS) and probability of 3-month survival in relation to risk factors were defined by univariable and multivariable analyses. RESULTS In multivariable analysis, GPA (OR 0.44, 95%CI 0.21-0.95; p=0.001), extensive extracranial disease (OR 0.13, 95%CI 0.02-0.66; p=0.013), and serious neurological deficits (OR 0.13, 95%CI 0.04-0.45; p=0.001) were associated with early death. If one factor was favorable, 73% (training) and 92% (validation) of patients survived 3 months. Patients with coexisting GPA&amp;lt; 2, serious neurological deficits, and extracranial extensive disease had the highest risk of death within 3 months (AUC 0.822 training; 0.932 validation). Median survival of the WBRT and SRS cohorts was 86 days (interquartile range (IQR): 38-172 days) and 201 days (IQR: 86-not reached), respectively (p&amp;lt; 0.0001). OS in very high-risk patients (GPA&amp;lt; 2) was significantly longer in the SRS vs. WBRT group (123 vs. 58 days; p=0.008). CONCLUSIONS Extracranial oligometastatic disease, intact neurological status, or GPA ≥2 should be present to justify SRS in patients with 1-10 brain metastases. SRS alone is a viable treatment option in comparison to WBRT and most importantly survival benefits may be expected even for high-risk patients (GPA&amp;lt; 2).