We investigated the influence of PD-1 expression on the systemic antitumor response (abscopal effect) induced by stereotactic ablative radiotherapy (SABR) in preclinical melanoma and renal cell carcinoma models. We compared the SABRinduced antitumor response in PD-1-expressing wild-type (WT) and PD-1-deficient knockout (KO) mice and found that PD-1 expression compromises the survival of tumor-bearing mice treated with SABR. None of the PD-1 WT mice survived beyond 25 days, whereas 20% of the PD-1 KO mice survived beyond 40 days. Similarly, PD-1-blocking antibody in WT mice was able to recapitulate SABR-induced antitumor responses observed in PD-1 KO mice and led to increased survival. The combination of SABR plus PD-1 blockade induced near complete regression of the irradiated primary tumor (synergistic effect), as opposed to SABR alone or SABR plus control antibody. The combination of SABR plus PD-1 blockade therapy elicited a 66% reduction in size of nonirradiated, secondary tumors outside the SABR radiation field (abscopal effect). The observed abscopal effect was tumor specific and was not dependent on tumor histology or host genetic background. The CD11a high CD8 þ T-cell phenotype identifies a tumor-reactive population, which was associated in frequency and function with a SABR-induced antitumor immune response in PD-1 KO mice. We conclude that SABR induces an abscopal tumorspecific immune response in both the irradiated and nonirradiated tumors, which is potentiated by PD-1 blockade. The combination of SABR and PD-1 blockade has the potential to translate into a potent immunotherapy strategy in the management of patients with metastatic cancer.

Purpose To compare 2 stereotactic body radiotherapy (SBRT) schedules for medically inoperable early-stage lung cancer to determine which produces the lowest rate of grade ≥ 3 protocol-specified adverse events (psAEs) at 1 year. Methods Patients with biopsy-proven peripheral (greater than 2 cm from the central bronchial tree) T1/T2, N0 (clinically node negative by positron emission tomography), M0 tumors were eligible. Patients were randomized to receive either 34 Gy in one fraction (Arm 1) or 48 Gy in 4 consecutive daily fractions (Arm 2). Rigorous central accreditation and quality assurance confirmed treatment per protocol guidelines. This study was designed to detect a psAEs rate > 17% at a 10% significance level (1-sided) and 90% power. Secondary endpoints included rates of primary tumor control (PC), overall survival (OS) and disease-free survival (DFS) at 1 year. Designating the better of the two regimens was based on pre-specified rules of psAEs and PC for each Arm. Results Ninety four patients were accrued between September 2009 and March 2011. Median follow up time was 30.2 months. Of 84 analyzable patients, 39 were in Arm 1 and 45 in Arm 2. Patient and tumor characteristics were balanced between Arms. Four (10.3%) patients on Arm 1 (95% confidence interval (CI): 2.9%-24.2%) and six (13.3%) patients on Arm 2 (95% CI: 5.1%-26.8%) experienced psAEs. The 2-year OS rate was 61.3% (95% CI: 44.2%-74.6%) for Arm 1 patients and 77.7% (95% CI: 62.5%-87.3%) for Arm 2. The 2-year DFS was 56.4% (95% 39.6%-70.2%) for Arm 1 and 71.1% (95% CI: 55.5%-82.1%) for Arm 2. The 1-year PC rate was 97.0% (95% CI: 84.2%-99.9%) for Arm 1 and 92.7% (80.1%-98.5%) for Arm 2. Conclusions 34 Gy in 1 fraction met pre-specified criteria and of the two schedules, warrants further clinical research.

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Purpose/Objective(s): To present long-term results of RTOG 0915/NCCTG N0927, a randomized lung stereotactic body radiotherapy (SBRT) trial of 34 Gy in 1 fraction versus 48 Gy in 4 fractions. Materials/Methods: This was a phase II multicenter study of medically inoperable non-small cell lung cancer patients with biopsy-proven peripheral T1 or T2 N0M0 tumors, with 1-year toxicity rates as primary endpoint and selected failure and survival outcomes as secondary endpoints. The study opened in September 2009 and closed in March 2011. Final data were analyzed through May 17, 2018. Results: Eighty four of 94 patients accrued were eligible for analysis: 39 in arm 1 and 45 in arm 2. Median follow-up time was 4.0 years for all patients, and 6.0 years for those alive at analysis. Rates of grade 3 and higher toxicity were 2.6% in arm 1 and 11.1% in arm 2. Median survival times (in years) for 34 Gy and 48 Gy were 4.1 vs. 4.6, respectively. Five-year outcomes as % (95% CI) for 34 Gy and 48 Gy were: primary tumor failure rate of 10.6 (3.3, 23.1) vs. 6.8 (1.7, 16.9); overall survival of 29.6 (16.2, 44.4) vs. 41.1 (26.6, 55.1); and progression-free survival of 19.1 (8.5, 33.0) vs. 33.3 (20.2, 47.0); respectively. Distant failure as the sole failure or a component of first failure occurred in 6 patients (37.5%) in the 34 Gy arm and in 7 (41.2%) in the 48 Gy arm. Conclusions: No excess in late-appearing toxicity was seen in either arm. Primary tumor control rates at 5 years were similar by arm. Median survival times of 4 years for each arm suggest similar efficacy pending any larger studies appropriately powered to detect survival differences.

Purpose/objective(s): To report outcomes and toxicity for patients with oligometastatic (≤5 lesions) prostate cancer (PCa) treated with stereotactic body radiation therapy (SBRT). Materials/methods: Seventeen men with 21 PCa lesions were treated with SBRT between February 2009 and November 2011. All patients had a detectable prostate-specific antigen (PSA) at the time of SBRT, and 11 patients (65%) had hormone-refractory (HR) disease. Treatment sites included bone (n = 19), lymph nodes (n = 1), and liver (n = 1). For patients with bone lesions, the median dose was 20 Gy (range, 8–24 Gy) in a single fraction (range, 1–3). All but two patients received some form of anti-androgen therapy after completing SBRT. Results: Local control (LC) was 100%, and the PSA nadir was undetectable in nine patients (53%). The first post-SBRT PSA was lower than pre-treatment levels in 15 patients (88%), and continued to decline or remain undetectable in 12 patients (71%) at a median follow-up of 6 months (range, 2–24 months). Median PSA measurements before SBRT and at last follow-up were 2.1 ng/dl (range, 0.13–36.4) and 0.17 ng/dl (range, <0.1–140), respectively. Six (55%) of the 11 patients with HR PCa achieved either undetectable or declining PSA at a median follow-up of 4.8 months (range, 2.2–6.0 months). Reported toxicities included one case each of grade 2 dyspnea and back pain, there were no cases of grade ≥3 toxicity following treatment. Conclusion: We report excellent LC with SBRT in oligometastatic PCa. More importantly, over half the patients achieved an undetectable PSA after SBRT. Further follow-up is necessary to assess the long-term impact of SBRT on LC, toxicity, PSA response, and clinical outcomes.