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 ... -  《-》

Adverse Radiation Effect and Disease Control in Patients Undergoing Stereotactic Radiosurgery and Immune Checkpoint Inhibitor Therapy for Brain Metastases.

Immune checkpoint inhibitors (ICIs) and stereotactic radiosurgery (SRS) are increasingly used together to manage brain metastases (BMs). We assessed adverse radiation effect, disease control, and overall survival in patients with BMs who received SRS with anticytotoxic T-lymphocyte-associated protein 4 and/or anti- programmed cell death protein receptor/ligand therapies. We retrospectively reviewed the records of patients with intact or resected BMs treated with SRS and ICIs within 5 months of SRS between 2010 and 2018. Patients were defined as receiving concurrent SRS and ICI if a dose of ICI was given within 4 weeks of SRS. Local failure, distant intracranial failure, extracranial failure, and adverse radiation effect were assessed using cumulative incidence rates and competing risk regressions with death as a competing risk. Overall survival was assessed using the Kaplan-Meier method and Cox proportional hazards models. A total of 97 patients with 580 BMs were included in our analysis. Competing risk analyses showed that concurrent SRS-ICI therapy is associated with higher rates of adverse radiation effect (6.4% vs. 2.0% at 1 year; multivariable hazard ratio [HR], 4.47; 95% confidence interval [CI], 1.57-12.73; P = 0.005), lower rates of extracranial failure (69.7% vs. 80.8% at 1 year; multivariable HR, 0.60; 95% CI, 0.42-0.87; P = 0.007), and better overall survival (48.6% vs. 25.4% at 1 year; multivariable HR, 0.57; 95% CI, 0.33-0.99; P = 0.044) compared with nonconcurrent therapy. SRS-ICI timing was not associated with local failure or distant intracranial failure. Concurrent SRS-ICI therapy has a tolerable adverse event profile and may improve extracranial disease control and overall survival, supporting concurrent use in the management of BMs.

Koenig JL ，Shi S ，Sborov K ，Gensheimer MF ，Li G ，Nagpal S ，Chang SD ，Gibbs IC ，Soltys SG ，Pollom EL ... -  《-》

The combination of stereotactic radiosurgery with immune checkpoint inhibition or targeted therapy in melanoma patients with brain metastases: a retrospective study.

Martins F ，Schiappacasse L ，Levivier M ，Tuleasca C ，Cuendet MA ，Aedo-Lopez V ，Gautron Moura B ，Homicsko K ，Bettini A ，Berthod G ，Gérard CL ，Wicky A ，Bourhis J ，Michielin O ... -  《-》

Stereotactic radiosurgery combined with nivolumab or Ipilimumab for patients with melanoma brain metastases: evaluation of brain control and toxicity.

Minniti G ，Anzellini D ，Reverberi C ，Cappellini GCA ，Marchetti L ，Bianciardi F ，Bozzao A ，Osti M ，Gentile PC ，Esposito V ... -  《Journal for ImmunoTherapy of Cancer》

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》