Internal dose escalation is associated with increased local control for non-small cell lung cancer (NSCLC) brain metastases treated with stereotactic radiosurgery (SRS)

Objective: To identify potentially actionable dosimetric predictors of local control (LC) for non-small cell lung cancer (NSCLC) brain metastases treated with single-fraction stereotactic radiosurgery (SRS). Methods and materials: Patients with NSCLC brain metastases treated with single-fraction SRS were identified. Eligible patients had at least 1 follow-up magnetic resonance imaging scan and were without prior metastasectomy or SRS to the same lesion. LC and overall survival (OS) were estimated using the Kaplan-Meier method. The Cox proportional hazards model was used for univariate (UVA) and multivariate analysis (MVA). Receiver operating characteristic (ROC) analysis was used to identify optimal cut points for dose-volume histogram metrics relative to LC. Results: A total of 612 NSCLC brain metastasis were identified in 299 patients with single-fraction SRS between 1999 and 2014. Median follow-up was 10 months. Median OS from time of SRS was 11 months. Overall LC was 75% and 66% at 1 and 2 years, respectively. On UVA, increasing dose by any measure was associated with improved LC. On MVA, volume receiving at least 32 Gy (V32; hazard ratio [HR], 0.069; P < .000), along with higher prescription isodose (HR, 0.953; P = .031) and lower volume (HR, 1.359; P < .000), were independent predictors of improved LC. ROC analysis demonstrated a V32 of 24% to be most predictive for LC. For the entire cohort, 1-year LC for V32 ≥24% was 89% versus 67% for V32 <24% (P = .000). Stratifying by volume, lesions ≤2 cm (n = 323) had a 1-year LC of 95% versus 82% (P = .005) for V32 above and below 24%, respectively. For lesions 2.1 to 3 cm (n = 211), 1-year LC was 79% versus 59% (P = .003) for V32 above and below 24%, respectively. Total tumor volume alone was predictive for OS. Conclusions: Volume, prescription isodose line, and V32 are independent predictors of LC. V32 represents an actionable SRS treatment planning parameter for NSCLC brain metastases

Distant intracranial failure in melanoma brain metastases treated with stereotactic radiosurgery in the era of immunotherapy and targeted agents

Purpose: Stereotactic radiosurgery (SRS) in combination with immunotherapy (IMT) or targeted therapy is increasingly being used in the setting of melanoma brain metastases (MBMs). The synergistic properties of combination therapy are not well understood. We compared the distant intracranial failure rates of intact MBMs treated with SRS, SRS + IMT, and SRS + targeted therapy. Methods and materials: Combination therapy was defined as delivery of SRS within 3 months of IMT (anti-CTLA-4 /anti-PD-1 therapy) or targeted therapy (BRAF/MEK inhibitors). The primary endpoint was distant intracranial failure after SRS, which was defined as any new MBM identified on brain magnetic resonance imaging. Outcomes were evaluated using the Kaplan Meier method and Cox proportional hazards. Results: A total of 72 patients with melanoma with 233 MBMs were treated between April 2006 and April 2016. The number of MBMs within each treatment group was as follows: SRS: 121; SRS + IMT: 48; and SRS + targeted therapy: 64. The median follow-up was 8.9 months. One-year distant intracranial control rates for SRS, SRS + IMT, and SRS + targeted therapy were 11.5%, 60%, and 10%, respectively (P < .001). On multivariate analysis, after adjusting for steroid use and number of MBMs, SRS + IMT remained associated with a significant reduction in distant intracranial failure compared with SRS (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.29-0.80; P = .003) and compared with SRS + targeted therapy (HR, 0.41; 95% CI, 0.25-0.68; P = .001).One-year local control for SRS, SRS + IMT, and SRS + targeted therapy was 66%, 85%, and 72%, respectively (P = .044). On multivariate analysis, after adjusting for dose, SRS + IMT remained associated with a significant reduction in local failure compared with SRS alone (HR, 0.37; 95% CI, 0.14-0.95; P = .04). Conclusions: SRS with immunotherapy is associated with decreased distant and local intracranial failure compared with SRS alone. Prospective studies are warranted to validate this result