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A substantial proportion of patients with unresectable stage III non-small-cell lung cancer (NSCLC) cannot either tolerate or access concurrent chemoradiotherapy, so sequential chemoradiotherapy is commonly used. We assessed the efficacy and safety of sugemalimab, an anti-PD-L1 antibody, in patients with stage III NSCLC whose disease had not progressed after concurrent or sequential chemoradiotherapy.GEMSTONE-301 is a randomised, double-blind, placebo-controlled, phase 3 trial in patients with locally advanced, unresectable, stage III NSCLC, done at 50 hospitals or academic research centres in China. Eligible patients were aged 18 years or older with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 who had not progressed after concurrent or sequential chemoradiotherapy. We randomly assigned patients (2:1, using an interactive voice-web response system) to receive sugemalimab 1200 mg or matching placebo, intravenously every 3 weeks for up to 24 months. Stratification factors were ECOG performance status, previous chemoradiotherapy, and total radiotherapy dose. The investigators, trial coordination staff, patients, and study sponsor were masked to treatment allocation. The primary endpoint was progression-free survival as assessed by blinded independent central review (BICR) in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of assigned study treatment. The study has completed enrolment and the results of a preplanned analysis of the primary endpoint are reported here. The trial is registered with ClinicalTrials.gov, NCT03728556.Between Aug 30, 2018 and Dec 30, 2020, we screened 564 patients of whom 381 were eligible. Study treatment was received by all patients randomly assigned to sugemalimab (n=255) and to placebo (n=126). At data cutoff (March 8, 2021), median follow-up was 14·3 months (IQR 6·4-19·4) for patients in the sugemalimab group and 13·7 months (7·1-18·4) for patients in the placebo group. Progression-free survival assessed by BICR was significantly longer with sugemalimab than with placebo (median 9·0 months [95% CI 8·1-14·1] vs 5·8 months [95% CI 4·2-6·6]; stratified hazard ratio 0·64 [95% CI 0·48-0·85], p=0·0026). Grade 3 or 4 treatment-related adverse events occurred in 22 (9%) of 255 patients in the sugemalimab group versus seven (6%) of 126 patients in the placebo group, the most common being pneumonitis or immune-mediated pneumonitis (seven [3%] of 255 patients in the sugemalimab group vs one [1%] of 126 in the placebo group). Treatment-related serious adverse events occurred in 38 (15%) patients in the sugemalimab group and 12 (10%) in the placebo group. Treatment-related deaths were reported in four (2%) of 255 patients (pneumonia in two patients, pneumonia with immune-mediated pneumonitis in one patient, and acute hepatic failure in one patient) in the sugemalimab group and none in the placebo group.Sugemalimab after definitive concurrent or sequential chemoradiotherapy could be an effective consolidation therapy for patients with stage III NSCLC whose disease has not progressed after sequential or concurrent chemoradiotherapy. Longer follow-up is needed to confirm this conclusion.CStone Pharmaceuticals and the National Key Research and Development Program of China.For the Chinese translation of the abstract see Supplementary Materials section.

Purpose Stereotactic ablative body radiotherapy (SABR) represents an exciting, tolerable, and highly effective form of radiotherapy. Ongoing investigations into the interactions between radiotherapy and the immune system have uncovered new mechanisms that can be exploited to improve efficacy. We determined whether baseline or posttreatment immune parameters could predict disease control and toxicity in stage I non–small-cell lung cancer (NSCLC) patients treated with SABR. Patients and Methods Peripheral blood samples were collected from 62 patients 24 hours before treatment and within 4 weeks after treatment for lymphocyte subset count analysis. All peripheral blood samples were analyzed by flow cytometry. Associated parameters were evaluated to determine their association with progression-free survival (PFS) and symptomatic radiation pneumonitis (grade 2 or higher). The survival rates were estimated with Kaplan-Meier and multivariable analyses using binary logistic regression analysis or a Cox proportional hazards model. Results At a median follow-up time of 36.0 months, the PFS rates for years 1, 2, and 3 were 91.0%, 82.5%, and 48.9%, respectively. The multivariable logistic regression analysis showed that only proportion of lung receiving 20 Gy of radiotherapy (odds ratio = 1.41; 95% confidence interval, 1.05-1.87; P = .023) and mean lung dose (odds ratio = 2.02; 95% confidence interval, 1.16-3.53; P = .016) were associated with symptomatic radiation pneumonitis (grade 2 or higher). Moreover, the immune parameters had no predictive value. In the multivariable Cox regression analysis, an elevated posttreatment cytotoxic CD8+ T-cell level was an independent prognostic factor for longer PFS in stage I NSCLC (hazard ratio, 1.16; 95% confidence interval, 1.01-1.28; P = .01). Conclusion A higher posttreatment cytotoxic CD8+ T-cell level was predictive of better PFS in stage I NSCLC patients receiving SABR. Thus, enhancing tumor antigen-specific cellular immunity by combining radiotherapy and immunotherapy might be a crucial strategy for improving survival in these patients.

Purpose In patients with esophageal cancer (EC), intensity modulated radiation therapy (IMRT) improves dose sparing to the heart and lung, with some evidence showing clinical benefit. Herein, we report our cumulative clinical experience with the use of IMRT for EC. Methods and materials This is a retrospective analysis of 587 patients with nonmetastatic EC who were treated consecutively with IMRT from January 2004 to June 30, 2013. All patients with stage I-IVA (American Joint Committee on Cancer 2002) received concurrent chemoradiation therapy either preoperatively or definitively. The Kaplan-Meier method was used to compute overall survival (OS) and locoregional recurrence-free survival and disease-free survival. The Common Terminology Criteria for Adverse Events, Version 4.0 were used to grade acute and subacute complications. Results The median radiation dose was 50.4 Gy in 28 daily fractions. As of July 2015, the median follow-up was 31.4 months (range, 2.9-130.7 months) for all patients and 61.8 months (range, 7.7-130.7 months) for survivors. The median OS was 38.9 months, and the 1-, 3-, and 5-year OS rates were 86.7%, 51.8%, and 41.2%, respectively. The 1-, 3-, and 5-year locoregional recurrence-free survival rates were 77.6%, 68.2%, and 66.1%, respectively, and the 1-, 3-, and 5-year disease-free survival rates were 58.6%, 43.7%, and 41.4%, respectively. Outcomes for both trimodality and bimodality treated patients were better than the outcomes reported in the literature. Eight patients (1.4%) experienced grade ≥3 pneumonitis, and 74 patients (13%) developed grade ≥3 esophagitis. For patients who underwent surgery, the most common postoperative complications were pneumonia (9.6%), anastomotic leakage (11.1%), and atrial fibrillation (12.5%). Conclusions This is the largest, single institutional study to date on the long-term outcomes of treatment with IMRT for EC. For photon-based radiation therapy, IMRT yields excellent outcomes and should be considered for the treatment of EC.