Hypofractionated vs. Twice Daily Radiotherapy for Limited Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis

Abstract

<h3>Purpose/Objective(s)</h3> Concurrent twice-daily 45Gy radiotherapy (concurrent-BID) remains the standard treatment for limited stage small-cell lung cancer (LS-SCLC). However, this regime is inconvenient and not universally adopted across different institutions, therefore hypofractionated schedule is more and more investigated. The aim of this study was to compare concurrent -BID with sequential hypofractionated radiotherapy (sequential-Hypo) in LD-SCLC by propensity score-matched analysis. We hypothesize that sequential-Hypo could be used as an alternative without increased toxicities. <h3>Materials/Methods</h3> A retrospective analysis was conducted in 108 LS-SCLC patients treated between January 2015 and July 2019 in our institution. All patients received BID (45Gy/30F, n = 79, twice daily) or sequential-Hypo (54Gy/18F, n = 18; 45Gy/15F, n = 6; 60Gy/20F, n = 5, once daily) radiotherapy. After matching by propensity score, the survival, failure patterns and toxicities were compared. <h3>Results</h3> After propensity score matching, the confounders of patient characteristics between BID group (n = 24) and sequential-Hypo group (n = 24) were well balanced (age, <i>P</i> = 0.718; T staging, <i>P</i> = 0.149; N staging, <i>P</i> = 0.712; PCI, <i>P</i> = 0.755; performance status, <i>P</i> = 0.578). Before PSM, multivariate analysis showed that patients treated with sequential-Hypo had significantly better OS and DMFS (<i>P</i> = 0.009, HR = 0.353; <i>P</i> = 0.020, HR = 0.315, respectively). Total radiotherapy time≥24 days and stage III (<i>P</i> = 0.004, HR = 2.452; <i>P</i> = 0.055, HR = 2.310, respectively) were poor prognostic indicators for OS. Patients with T3 and T4 were more likely to recur than others (HR = 3.269, <i>P</i> = 0.040). N 2-3 and PS = 1 (<i>P</i> = 0.006, HR = 7.342; <i>P</i> = 0.023, HR = 10.384, respectively) were poor prognostic indicators for DMFS. After PSM by multivariable analyses, age≥65 years and total radiotherapy time≥24 days were associated with poorer OS (<i>P</i> = 0.004, HR = 4.222; <i>P</i> = 0.046, HR = 2.671, respectively). Although there was no significant difference, the patients in sequential-Hypo group had a trend to have a better OS. Before PSM, distant metastasis was the dominant failure pattern and was significantly less in sequential-Hypo group (17.7% vs 40.5%, <i>P</i> < 0.05). No significant difference was observed between BID group and Hypo group before and after PSM. <h3>Conclusion</h3> Sequential-Hypo schedule was associated with comparable survival and toxicity outcomes and may be considered as an alternative to concurrent-BID. Prospective trials are needed to confirm this result.