Combined Immunotherapy and Stereotactic Radiotherapy Improves Neurologic Outcomes in Patients with Non-small-cell Lung Cancer Brain Metastases.

The purpose of this study was to compare the outcomes of patients with non-small cell lung cancer (NSCLC) brain metastases treated with stereotactic radiotherapy (SRT) alone versus SRT and immune checkpoint inhibitors (ICIs). Patients treated for their first diagnosis of intracranial metastases with SRT or SRT plus ICI were retrospectively identified. Overall survival (OS), local control (LC), distant brain failure (DBF), neurologic death, and rates of radiation necrosis were calculated. Univariate (UVA) and multivariable (MVA) analyses with competing risk analysis were performed. Seventy-seven patients with 132 lesions were analyzed, including 44 patients with 68 lesions in the SRT group and 33 patients with 64 lesions in the SRT plus ICI group. There were no differences in baseline factors between groups. Use of ICI predicted for decreased DBF (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.24-0.84; P = .01), decreased rates of neurologic death (HR, 0.29; 95% CI, 0.10-0.85; P = .02), and better OS (HR, 0.46; 95% CI, 0.23-0.91; P = .03). Two-year LC was 97% for the SRT + ICI group, and 86% for the SRT-alone group (P = .046). Actuarial 2-year DBF was 39% for the SRT + ICI group and 66% for the SRT alone group (P = .016). On MVA, ICI use persisted in predicting lower incidence of neurologic death (HR, 0.25; 95% CI, 0.09-0.72; P = .01) and DBF (HR, 0.47; 95% CI, 0.25-0.85; P = .01) when adjusted for competing risk of death. In this cohort of patients with NSCLC brain metastases, ICI use combined with SRT predicted for improved LC and OS and decreased DBF and risk of neurologic death.

Enright TL ，Witt JS ，Burr AR ，Yadav P ，Leal T ，Baschnagel AM ... -  《-》

Concurrent Immune Checkpoint Inhibitors and Stereotactic Radiosurgery for Brain Metastases in Non-Small Cell Lung Cancer, Melanoma, and Renal Cell Carcinoma.

To characterize the effect of concurrent stereotactic radiosurgery-stereotactic radiation therapy (SRS-SRT) and immune checkpoint inhibitors on patient outcomes and safety in patients with brain metastases (BMs). We retrospectively identified metastatic non-small cell lung cancer, melanoma, and renal cell carcinoma patients who had BMs treated with SRS-SRT from 2010 to 2016 without prior whole-brain radiation therapy. We included SRS-SRT patients who were treated with anti-cytotoxic T-lymphocyte-associated protein 4 (ipilimumab) and anti-programmed cell death protein 1 receptor (nivolumab, pembrolizumab). Patients who were given immune checkpoint inhibitors on active or unreported clinical trials were excluded, and concurrent immune checkpoint inhibition (ICI) was defined as ICI given within 2 weeks of SRS-SRT. Patients were managed with SRS-SRT, SRS-SRT with nonconcurrent ICI, or SRS-SRT with concurrent ICI. Progression-free survival and overall survival (OS) were estimated using Kaplan-Meier survival curves, and Cox proportional hazards models were used for multivariate analysis. Logistic regression was used to identify predictors of acute neurologic toxicity, immune-related adverse events, and new BMs. A total of 260 patients were treated with SRS-SRT to 623 BMs. Of these patients, 181 were treated with SRS-SRT alone, whereas 79 received SRS-SRT and ICI, 35% of whom were treated with concurrent SRS-SRT and ICI. Concurrent ICI was not associated with increased rates of immune-related adverse events or acute neurologic toxicity and predicted for a decreased likelihood of the development of ≥3 new BMs after SRS-SRT (P=.045; odds ratio, 0.337). Median OS for patients treated with SRS-SRT, SRS-SRT with nonconcurrent ICI, and SRS-SRT with concurrent ICI was 12.9 months, 14.5 months, and 24.7 months, respectively. SRS-SRT with concurrent ICI was associated with improved OS compared with SRS-SRT alone (P=.002; hazard ratio [HR], 2.69) and compared with nonconcurrent SRS-SRT and ICI (P=.006; HR, 2.40) on multivariate analysis. The OS benefit of concurrent SRS-SRT and ICI was significant in comparison with patients treated with SRS-SRT before ICI (P=.002; HR, 3.82) or after ICI (P=.021; HR, 2.64). Delivering SRS-SRT with concurrent ICI may be associated with a decreased incidence of new BMs and favorable survival outcomes without increased rates of adverse events.

Chen L ，Douglass J ，Kleinberg L ，Ye X ，Marciscano AE ，Forde PM ，Brahmer J ，Lipson E ，Sharfman W ，Hammers H ，Naidoo J ，Bettegowda C ，Lim M ，Redmond KJ ... -  《-》

Immune checkpoint inhibition in patients treated with stereotactic radiation for brain metastases.

Kowalski ES ，Remick JS ，Sun K ，Alexander GS ，Khairnar R ，Morse E ，Cherng HR ，Berg LJ ，Poirier Y ，Lamichhane N ，Becker S ，Chen S ，Molitoris JK ，Kwok Y ，Regine WF ，Mishra MV ... -  《Radiation Oncology》

Local tumor response and survival outcomes after combined stereotactic radiosurgery and immunotherapy in non-small cell lung cancer with brain metastases.

Singh C ，Qian JM ，Yu JB ，Chiang VL ... -  《-》

Comparative effectiveness of multi-fraction stereotactic radiosurgery for surgically resected or intact large brain metastases from non-small-cell lung cancer (NSCLC).

to investigate clinical outcomes in patients with large brain metastases from non-small-cell lung cancer (NSCLC) who received surgical resection and postoperative stereotactic radiosurgery or SRS alone. Two hundred and twenty-two patients with 241 large brain metastases (2-4 cm in size) who received surgery and multi-fraction SRS (mfSRS) to the resection cavity or mfSRS alone were analyzed. For all lesions the delivered dose was 3 x 9 Gy over three consecutive days. Primary endpoint of the study was local control (LC). Secondary endpoints included early improvement of neurological deficits, changes in performance status, treatment-related toxicity, radiation-induced brain necrosis (RN), distant brain failure (DBF), and overall survival (OS). Kaplan-Meier analysis and cumulative incidence function were used for comparing the probability of failure. At a median follow-up of 13 months, median OS times and 1-year survival rates were comparable: 13.5 months and 59% for patients receiving surgery and postoperative mfSRS to the resection cavity and 15.2 months and 68% for those treated with mfSRS alone (p = 0.2). Median DBF did not differ significantly between groups (surgery and mfSRS,12 months; mfSRS,14 months). Eighteen patients receiving surgery and mfSRS and 17 patients treated with mfSRS alone recurred locally (p = 0.2); respective 6-month and 12-month LC rates were 87% and 83% and 96% and 91% (p = 0.15). The 1-year cumulative incidence rates of RN were 15% and 7% after postoperative mfSRS and mfSRS alone (p = 0.03), respectively. In conclusion, mfSRS is an effective treatment for patients with large brain metastases from NSCLC resulting in equivalent LC and lower RN and risk of leptomeningeal spread compared to surgery and mf-SRS to the resection cavity. Surgery is an effective treatment option for patients with large symptomatic brain metastases who require rapid relief of neurological symptoms caused by tumor mass effect.

Minniti G ，Scaringi C ，Lanzetta G ，Anzellini D ，Bianciardi F ，Tolu B ，Morace R ，Romano A ，Osti M ，Gentile P ，Paolini S ... -  《-》