Walter, Kevin A.

OBJECTIVE The aim of this study was to evaluate mortality and progression outcomes in patients undergoing stereotactic radiosurgery (SRS) for breast cancer brain metastases and to identify associated risk factors using a national quality registry. METHODS The NeuroPoint Alliance (NPA) SRS Registry was employed for this study, which conducted prospective enrollment of patients undergoing SRS at 16 participating centers from 2017 to 2024. Outcomes of interest included the post-SRS EQ-5D score change, overall survival, local progression, out-of-field progression, and overall intracranial progression. For all time-to-event analyses, Kaplan-Meier curves and multivariable Cox regressions with hazard ratios were used. RESULTS A total of 138 patients (127 female, mean age 59.8 years) were identified; 46.4% had a single lesion, 42.0% had 2–4 lesions, and 11.6% had ≥ 5 lesions, while 87.0% had a Karnofsky Performance Status (KPS) score between 80 and 100. The median overall survival was 17.9 months, and independent predictors of all-cause mortality included a KPS score ≤ 90 (HR 6.73) and diabetes mellitus (HR 3.35). The median time to local progression was 19.8 months. More than 5 lesions at baseline (HR 9.03) and a marginal dose ≤ 17.6 Gy (HR 8.00) were predictive of local recurrence. The median was not reached for out-of-field progression, and predictors included ≥ 2 lesions at the time of SRS (HR 3.20) and a marginal dose ≤ 17.6 Gy (HR 4.61). At the final follow-up assessment, 17.1% of patients experienced no change according to the EQ-5D, while 34.3% had improvement, 11.4% had mixed results, and 37.1% had worsened health. In the multivariable linear regression model, pre-SRS resection (r = 1.92) and baseline EQ-5D score (r = 1.29) were statistically significant predictors of quality of life at the final follow-up assessment. CONCLUSIONS Using real-world data from the NPA SRS Registry, this study demonstrated comparable outcomes in patients who underwent SRS for breast cancer brain metastases compared with those of previous literature. The number of lesions at the time of SRS and the marginal dose were independent risk factors for local recurrence, out-of-field progression, and overall intracranial progression. Pre-SRS resection and baseline EQ-5D score were independent predictors of quality of life following SRS.

OBJECTIVE The literature on non–small cell lung cancer (NSCLC) brain metastases (BMs) managed using stereotactic radiosurgery (SRS) relies mainly on single-institution studies or randomized controlled trials (RCTs). There is a literature gap on clinical and radiological outcomes of SRS for NSCLC metastases in real-world practice. The objective of this study was to benchmark mortality and progression outcomes in patients undergoing SRS for NSCLC BMs and identify risk factors for these outcomes using a national quality registry. METHODS The SRS Registry of the NeuroPoint Alliance was used for this study. This registry included patients from 16 enrolling sites who underwent SRS from 2017 to 2022. Data are prospectively collected without a prespecified research purpose. The main outcomes of this analysis were overall survival (OS), out-of-field recurrence, local progression, and intracranial progression. All time-to-event investigations included Kaplan-Meier analyses and multivariable Cox regressions. RESULTS Two hundred sixty-four patients were identified, with a mean age of 66.7 years and a female proportion of 48.5%. Most patients (84.5%) had a Karnofsky Performance Status (KPS) score of 80–100, and the mean baseline EQ-5D score was 0.539 quality-adjusted life years. A single lesion was present in 53.4% of the patients, and 29.1% of patients had 3 or more lesions. The median OS was 28.1 months, and independent predictors of mortality included no control of primary tumor (hazard ratio [HR] 2.1), KPS of 80 (HR 2.4) or lower (HR 2.4), coronary artery disease (HR 2.8), and 5 or more lesions present at the time of SRS treatment (HR 2.3). The median out-of-field progression-free survival (PFS) was 24.8 months, and the median local PFS was unreached. Intralesional hemorrhage was an independent risk factor of local progression, with an HR of 6.0. The median intracranial PFS was 14.0 months and was predicted by the number of lesions at the time of SRS (3–4 lesions, HR 2.2; 5–14 lesions, HR 2.5). CONCLUSIONS In this real-world prospective study, the authors used a national quality registry and found favorable OS in patients with NSCLC BMs undergoing SRS compared with results from previously published RCTs. The intracranial PFS was mainly driven by the emergence of new lesions rather than local progression. A greater number of lesions at baseline was associated with out-of-field progression, while intralesional hemorrhage at baseline was associated with local progression.

Abstract BACKGROUND Standard of care (SOC) and patient survival in glioblastoma have changed little in the past 17 years. We evaluated in a phase 3 trial whether adding an autologous tumor lysate-loaded dendritic cell vaccine (murcidencel) to SOC extends survival. Patients and METHODS Newly diagnosed glioblastoma patients were randomized 2:1 to either murcidencel or placebo. Under a crossover design, all patients could receive murcidencel following tumor recurrence. All parties remained blinded regarding treatments before recurrence. Patients thus received murcidencel at new diagnosis (nGBM) or at recurrence (rGBM) following crossover from placebo. The primary and secondary endpoints compare overall survival (OS) with contemporaneous, matched external controls. Four sets of analyses were conducted to ensure rigorous matching of the controls, reduce biases, and confirm the robustness of the results. RESULTS 331 patients were enrolled. With the crossover, 89% received murcidencel. Median OS (mOS) for nGBM patients (n = 232) was 19.3 months from randomization (22.4 months from surgery) with murcidencel vs. 16.5 months from randomization in the controls (HR = 0.80, p = 0.002). Survival at 48 months from randomization was 15.7% vs. 9.9%, and at 60 months was 13% vs. 5.7%. For rGBM (n = 64), mOS was 13.2 months from relapse vs. 7.8 months in the controls (HR = 0.58, p < 0.001). Survival at 24 months post-recurrence was 20.7% vs. 9.6%, and at 30 months post-recurrence was 11.1% vs 5.1%. In nGBM patients with methylated MGMT (n = 90), mOS was 30.2 months from randomization (33 months from surgery) with murcidencel vs. 21.3 months from randomization in the controls (HR = 0.74, p = 0.027). The treatment was well tolerated, with only 5 serious adverse events deemed at least possibly related to the vaccine. CONCLUSION Clinically meaningful and statistically significant survival extension was seen in both nGBM and rGBM patients treated with murcidencel and SOC compared with contemporaneous, matched external controls who received SOC alone.