Incidence of pneumonitis among limited-stage small cell lung cancer patients exposed to concurrent chemoradiation: A systematic literature review and meta-analysis.
Authors: Ke (Kirsten) Zu, Yuting Kuang, Arianna Nevo, Maria Catherine Pietanza, Mike Liu, Anne Deitz, Jennifer Uyei, Darpan Darpan
Journal: Journal of Clinical Oncology (2021)

e20592 Background: Concurrent chemoradiation (cCRT) has been the standard first line treatment for patients with limited-stage small cell lung cancer (LS-SCLC) for decades. Despite continued progress in refining chemotherapy and radiation modalities, the prognosis for LS-SCLC remains unsatisfactory with cCRT alone. Recent clinical trials have sought to further improve survival by combining cCRT and other newly developed therapeutic agents in treating LS-SCLC. Severe (grade 3 or higher) pneumonitis is one of the major toxicities related to cCRT. The objective of this study was to establish a benchmark rate of pneumonitis in LS-SCLC patients receiving first line cCRT. Methods: A systematic literature review and meta-analysis was performed in accordance with Cochrane, PRISMA, and Food and Drug Administration guidelines to summarize and quantify the incidence of grade 3−5 and fatal pneumonitis (including radiation pneumonitis) in patients with LS-SCLC exposed to cCRT alone. MEDLINE, Embase, and the Cochrane Central Register were searched from 2014 to July 16, 2020 to identify relevant randomized controlled trials (RCTs) and non-RCT studies (observational studies or non-randomized trials). The study quality of included RCTs and non-RCT studies was evaluated using the Revised Cochrane Risk of Bias Tool for Randomized Trials (RoB2) and the Newcastle-Ottawa scale, respectively. The incidence of pneumonitis across studies was pooled using a frequentist method with correction for zero events, using the metafor package in R 3.6.1. Results: Thirteen studies (4 RCTs, 9 non-RCTs) were included in the review. Patient populations were comparable across studies and the median follow-up ranged from 20−59 months. All patients received etoposide with either cisplatin or carboplatin, and radiation doses, given once or twice daily, ranging from 40−72 Gy. While all RCTs were open-label studies that could have some deviations from the intended interventions, this did not impact the reported incidence of pneumonitis. All non-RCTs were of high quality. Ten studies were included in the meta-analysis (3 RCTs, 7 non-RCTs; 1,539 patients). The pooled incidence of grade 3−5 pneumonitis was 3.28% [95% confidence interval (CI): 1.52−5.04%] in RCTs from random-effects model, and 6.34% [95% CI: 3.64−9.04%] in non-RCTs from fixed-effects model. The pooled incidence risk of grade 5 (fatal) pneumonitis was 0.29% [95% CI: 0.00−0.62%] in RCTs and 0.88% [95% CI: 0.02−1.74%] in non-RCTs, both from fixed-effects model. Conclusions: In LS-SCLC patients exposed to cCRT, the incidence of grade 3−5 pneumonitis and fatal pneumonitis ranges from 3.28−6.34% and 0.29−0.88%, respectively. These results can be used to understand the safety of other therapeutic agents with regard to pneumonitis when used in combination with cCRT to treat patients with LS-SCLC.