Chemotherapy-induced neutropenia (CIN) is a dose-limiting factor for cytotoxic chemotherapy, but recently, it was suggested that CIN contributes to prolonged survival. In this study, we examined the association between severe CIN and survival, and determined whether CIN affected survival in patients with extensive-stage small cell lung cancer (ED-SCLC).The medical records from 214 patients with ED-SCLC treated with etoposide or irinotecan in combination with cisplatin (EP/IP) between 2012 and 2016 were collected and retrospectively analyzed. Landmark analysis was performed at the end of cycle 4 and the relationship between severe CIN and survival was determined by a log-rank test. In addition, a multivariate analysis using COX proportional hazard model was performed to identify independent predictive factors. The Landmark analysis included 102 patients in the IP-group and 47 patients in the EPgroup. No signi cant difference was found between grade 0-3 and grade 4 neutropenia and overall survival (OS) in the EP-group. (P = 0.57). Contrariwise, for the IP patients, the median OS was 444 days for grade 0-3 and 633 days for grade 4 neutropenia, which was signi cantly longer for patients who developed grade 4 neutropenia (P = 0.03). Multivariate analysis adjusted for potential factors revealed that the development of grade 4 CIN was identi ed as a signi cant predictor of longer OS (hazard ratio[HR], 0.46; 95% con dence interval (CI), 0.26-0.81, P = 0.008). The results indicated that the development of severe CIN with IP therapy is associated with prolonged OS. Patients and treatmentsPatients who received standard doses of IP or EP as initial therapy for advanced and previously untreated SCLC were selected from the electronic medical record system of each participating institution. A total of 214 patients were selected and divided into two groups: those who received IP (n = 138) and those who received EP (n = 76). Clinical data and assessment of CINClinical data including patient characteristics and prognostic factors were collected from each hospital's electronic medical records. Hematologic toxicity was assessed based on the Common Terminology Criteria for Adverse Events, version 5.0 (CTCAE v5.0). CIN grade was determined based on the lowest neutrophil count for each patient recorded during rst-line treatment. The endpoint of the study was severe CIN survival. This was de ned as the time from the start date of cisplatin-based chemotherapy to the date of death or the last day of the follow-up period. Statistical analysisNeutropenia occurring during the treatment period was graded (grade 0-4) according to CTCAE v5.0.Survival curves for overall survival (OS) were generated for each grade of neutropenia using the Kaplan-Meier method and compared using the log-rank test. To analyze the effect of severe CIN development on

Chemotherapy-induced neutropenia (CIN) is a dose-limiting factor for cytotoxic chemotherapy, but recently, it was suggested that CIN contributes to prolonged survival. In this study, we examined the association between severe CIN and survival, and determined whether CIN affected survival in patients with extensive-stage small cell lung cancer (ED-SCLC).The medical records from 214 patients with ED-SCLC treated with etoposide or irinotecan in combination with cisplatin (EP/IP) between 2012 and 2016 were collected and retrospectively analyzed. Landmark analysis was performed at the end of cycle 4 and the relationship between severe CIN and survival was determined by a log-rank test. In addition, a multivariate analysis using COX proportional hazard model was performed to identify independent predictive factors. The Landmark analysis included 102 patients in the IP-group and 47 patients in the EP-group. No significant difference was found between grade 0–3 and grade 4 neutropenia and overall survival (OS) in the EP-group. (P = 0.57). Contrariwise, for the IP patients, the median OS was 444 days for grade 0–3 and 633 days for grade 4 neutropenia, which was significantly longer for patients who developed grade 4 neutropenia (P = 0.03). Multivariate analysis adjusted for potential factors revealed that the development of grade 4 CIN was identified as a significant predictor of longer OS (hazard ratio [HR], 0.46; 95% confidence interval (CI), 0.26–0.81, P = 0.008). The results indicated that the development of severe CIN with IP therapy is associated with prolonged OS.