Clinical Outcomes of Extensive Stage Small Cell Lung Cancer Patients Treated With Thoracic Radiotherapy at Different Timing and Fractionation

Abstract

Objective: The purpose of this study was to assess whether combined thoracic radiotherapy (TRT) on the basis of chemotherapy (ChT) showed promising anti-tumor activity in extensive-stage small cell lung cancer (ES-SCLC), then to explore practice patterns for radiation time and dose/ fractionation and to identify prognostic factors for patients who would benefit from ChT/TRT.Methods: A total of 492 ES-SCLC patients were included from January 2010 to March 2019, of which 244 patients experienced ChT/TRT. Propensity score matching (PSM) was performed to minimize bias between the ChT/TRT and ChT-alone groups. Patients in ChT/TRT group were categorized into four groups based on the number of induction chemotherapy cycles. For effective dose fractionation calculation, we introduced the time-adjusted biological effective dose(tBED). Categorical variables were analyzed with Chi-square tests and Fisher’s exact tests. Survival rates were computed by the Kaplan-Meier method. Multivariate prognostic analysis was performed with Cox proportional hazard models. Results: Patients who received ChT/TRT were associated with improved OS (18.2 vs 10.8 months), PFS (9.0 vs 6.0 months) and LRFS (12.0 vs 6.0 months) before matching, with similar results after matching. In the ChT/TRT group, the median LRFS times for groups based on radiation time were 12.7, 12.0, 12.7, and 9.0 months, respectively. Earlier TRT had a tendency to prolong PFS (median 10.6 vs 9.8 vs 9.1 vs 7.7 months, respectively, p = 0.1095), as was not seen in OS (median 17.6 vs 19.5 vs 17.2 vs 19.1 months, respectively, p = 0.7224). To note, patients within 6 cycles had better LRFS (p = 0.0006). For radiation dose, patients in high-dose group (tBED>50Gy) had worse OS (median 25.9 vs 22.9, p = 0.0484) and PFS (median 12.1 vs 11.2, p=0.0042) in patients with complete response and partial response (CR and PR) to systemic therapy, but the above-mentioned results were not drawn when the population was confined to those receiving standard fractionation with CR and PR. Conclusion: ChT/TRT could improve survival for ES-SCLC patients. We cautiously recommend that TRT should be performed within 6 cycles and receiving hyperfractionated 45Gy in 30 fractions may be a feasible treatment scheme for ES-SCLC patients.