Lung Stereotactic Body Radiation Therapy and Concurrent Immunotherapy: A Multicenter Safety and Toxicity Analysis.

PURPOSE: Radical treatment of metastases with stereotactic body radiation therapy (SBRT) is commonly implemented in patients receiving concurrent immune checkpoint inhibition (ICI), despite limited safety and toxicity data. The purpose of this study was to evaluate the safety and tolerability of lung SBRT with concurrent ICI. METHODS AND MATERIALS: Records from a single academic institution were reviewed to identify patients treated with lung SBRT and concurrent (within 30 days) ICI; a contemporaneous cohort receiving lung SBRT alone was included for reference. Treatment-related adverse effects occurring within 30 days (acute) and 180 days (subacute) of SBRT were evaluated. RESULTS: Our study included 117 patients; 54 received SBRT with concurrent ICI (56 courses, 69 target lesions), and 63 received SBRT alone (68 courses, 79 lesions). Median follow-up was 9.2 months in the SBRT + ICI cohort. Among the patients, 67.9% received ICI monotherapy, 17.9% ICI/chemotherapy, and 14.3% ICI/ICI combinations; 25% received ICI between SBRT fractions, and 42.9% received ICI both before and after SBRT. The risk of grade 3 pneumonitis was higher in the SBRT + ICI versus SBRT alone cohort (10.7% vs 0%, P < .01) and any-grade pneumonitis was similar (33.9% vs 27.9%, SBRT + ICI vs SBRT, P = .47). The risk of any-grade pneumonitis appeared elevated with ICI/ICI combinations (62.5% vs 29.2%). Receipt of ICI, planning treatment volume, and lobes involved in SBRT were linked to high-grade pneumonitis. Subacute grade 3+ adverse effects occurred in 26.8% of SBRT + ICI and 2.9% of SBRT-alone patients. CONCLUSIONS: Overall, concurrent lung SBRT + ICI is safe. Given the clinically meaningful risk of pneumonitis, closer monitoring should be considered for SBRT + ICI patients, especially those receiving radiation therapy with ICI/ICI combinations.

Dosimetric Factors Related to Radiation Necrosis After 5-Fraction Radiosurgery for Patients With Resected Brain Metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is increasingly used in the management of patients with resected brain metastases (rBMs). A significant complication of this therapy can be radiation necrosis (RN). Despite radiation therapy dose de-escalation and the delivery of several rather than a single dose fraction, rates of RN after SRS for rBMs remain high. We evaluated the dosimetric parameters associated with radiographic RN for rBMs. METHODS AND MATERIALS: From 2008 to 2016, 55 rBMs at a single institution that were treated postoperatively with 5-fraction linear accelerator-based SRS (25-35 Gy) with minimum 3 months follow-up were evaluated. For each lesion, variables recorded included radiation therapy dose to normal brain, location and magnitude of hotspots, clinical target volume (CTV), and margin size. Hotspot location was stratified as within the tumor bed alone (CTV) or within the planning target volume (PTV) expansion margin volume (PTV minus CTV). Cumulative incidence with competing risks was used to estimate rates of RN and local recurrence. Optimal cut-points predicting for RN for hotspot magnitude based on location were identified via maximization of the log-rank test statistic. RESULTS: Median age for all patients was 58.5 years. For all targets, the median CTV was 17.53 cm3, the median expansion margin to PTV was 2 mm, and the median max hotspot was 111%. At 1 year, cumulative incidence of radiographic RN was 18.2%. Univariate analysis showed that max hotspots with a hazard ratio of 3.28 (P = .045), hotspots within the PTV expansion margin with relative magnitudes of 105%, 110%, and 111%, and an absolute dose of 33.5 Gy predicted for RN (P = .029, P = .04, P = .038, and P = .0488, respectively), but hotspots within the CTV did not. CONCLUSIONS: To our knowledge, this is the first study that investigated dosimetric factors that predict for RN after 5-fraction hypofractionated SRS for rBM. Hotspot location and magnitude appear important for predicting RN risk, thus these parameters should be carefully considered during treatment planning.