A Comparison of Hypofractionated and Twice-Daily Thoracic Irradiation in Limited-Stage Small-Cell Lung Cancer: An Overlap-Weighted Analysis

Abstract

Despite evidence for the superiority of twice-daily (BID) radiotherapy schedules, their utilization in practice remains logistically challenging. Hypofractionation (HFRT) is a commonly implemented alternative. We aim to compare the outcomes and toxicities in limited-stage small-cell lung cancer (LS-SCLC) patients treated with hypofractionated versus BID schedules. A bi-institutional retrospective cohort review was conducted of LS-SCLC patients treated with BID (45 Gy/30 fractions) or HFRT (40 Gy/15 fractions) schedules from 2007 to 2019. Overlap weighting using propensity scores was performed to balance observed covariates between the two radiotherapy schedule groups. Effect estimates of radiotherapy schedule on overall survival (OS), locoregional recurrence (LRR) risk, thoracic response, any ≥grade 3 (including lung, and esophageal) toxicity were determined using multivariable regression modelling. A total of 173 patients were included in the overlap-weighted analysis, with 110 patients having received BID treatment, and 63 treated by HFRT. The median follow-up was 20.4 months. Multivariable regression modelling did not reveal any significant differences in OS (hazard ratio [HR] 1.67, p = 0.38), LRR risk (HR 1.48, p = 0.38), thoracic response (odds ratio [OR] 0.23, p = 0.21), any ≥grade 3+ toxicity (OR 1.67, p = 0.33), ≥grade 3 pneumonitis (OR 1.14, p = 0.84), or ≥grade 3 esophagitis (OR 1.41, p = 0.62). HFRT, in comparison to BID radiotherapy schedules, does not appear to result in significantly different survival, locoregional control, or toxicity outcomes.

Patient-reported health-related quality of life from a randomized phase II trial comparing standard-dose with high-dose twice daily thoracic radiotherapy in limited stage small-cell lung cancer

“…It has been stated that BID TRT is inconvenient for the patients and that it might impact their quality of life [33]. Our study was not designed to clarify whether twice daily TRT impacts quality of life more than once daily TRT, but the transient and modest change in role-and social functioning and fatigue indicates that the impact on quality of life of twice daily TRT was minimal.…”

Sequential Hypofractionated versus Concurrent Twice-Daily Radiotherapy for Limited-Stage Small-Cell Lung Cancer: A Propensity Score-Matched Analysis

“…A recent phase II randomized study compared concurrent hypofractionated radiotherapy (65 Gy in 26 fractions) with concurrent twice-daily therapy in LS-SCLC, the hypofractionated radiotherapy obtained improved PFS and similar toxicities [ 13 ]. In another overlap-weighted analysis, there was no significant difference in the overall survival, local control, and toxicity for LS-SCLC patients in the hypo group versus the twice-daily group [ 14 ]. However, the efficacy of “sequential” hypoTRT in the treatment of LS-SCLC remains unclear, and we believed that patients might experience relatively better tolerance.…”

“…A recent phase II randomized study indicated that concurrent hypofractionated radiotherapy (65 Gy in 26 fractions) improved PFS and had similar toxicities compared with a concurrent twice-daily regimen in LS-SCLC [ 13 ]. In another overlap-weighted analysis, there was no significant difference in overall survival, local control, and toxicity for LS-SCLC patients treated with hypofractionated radiotherapy versus the twice-daily group [ 14 ]. However, few studies have investigated the efficacy and toxicities of sequential chemotherapy and hypofractionated radiotherapy compared to the concurrent twice-daily schedule.…”

Limited-Stage Small-Cell Lung Cancer: Current Progress and the Next Frontier

“…This heterogeneity of regimens and the prevalence of 40-45 Gy in 15 once-daily fractions is likely informed by historical precedent as evidenced by a Canadian randomized controlled trial reported in 1993 [10]. Interestingly, a retrospective study in 2021 comparing 40 Gy in 15 fractions once daily versus 45 Gy in 30 fractions BID showed no difference in OS, locoregional recurrence, or ≥grade 3 toxicities in LS-SCLC following propensity score adjustment [15].…”