2372 - Should We Return to Old School in a New Era? A Meta-Analysis of Twice Daily vs. Once Daily Concurrent Chemoradiotherapy for Limited-Stage Small Cell Lung Cancer

Purpose/Objective(s): Concurrent chemoradiation is the standard treatment for limited-stage small cell lung cancer (LS-SCLC), but the optimal thoracic radiation schedule remains debated. Consolidation immune checkpoint inhibitor (ICI) immunotherapy (IO) is now standard of care after chemoradiation (CRT) in LS-SCLC. This meta-analysis of prospective trials compared twice-daily (BID) versus once-daily (QD) CRT for LS-SCLC, including an evaluation of the impact of adding IO.

Materials/Methods: We searched PubMed, Ovid MEDLINE, Google Scholar, and ClinicalTrials.gov from January 1, 1999, to February 10, 2025, to identify relevant clinical trials. Two investigators (BG and JS) independently screened trials comparing BID and QD thoracic radiotherapy, considering primary or secondary outcome analyses. Data were also extracted from ASTRO and ESMO conference proceedings. Eligible trials were selected according to PRISMA guidelines. Meta-analysis was performed to compare 2-year overall survival (OS) and progression-free survival (PFS) using risk ratios (RRs). Toxicities were compared using odds ratios (ORs). All results are reported with 95% confidence intervals (CIs).

Results: Eight trials comprising 2827 patients were included from 637 screened studies. BID CRT significantly improved 2-year OS compared with QD CRT by 13% (RR=1.13; 95% CI, 1.06-1.21; I²=35% [moderately low heterogeneity]). Two-year PFS was similar between BID and QD CRT (RR=1.08; 95% CI, 0.90-1.30; I²=59% [relatively high heterogeneity]). In three trials incorporating IO, 2-year OS was 25% higher with BID CRT than with QD CRT (RR=1.25; 95% CI, 1.13-1.39; I²=0%). Across all trials, there were no differences in Grade 3 or higher esophagitis or pneumonitis. In the two trials without ICIs that reported lymphocyte counts, BID CRT was associated with significantly less leukocyte depletion (OR=0.70; 95% CI, 0.52-0.94; I²=0%) and lymphocyte depletion (OR=0.39; 95% CI, 0.19-0.78; I²=67%).

Conclusion: The addition of ICIs appears to favor BID over QD CRT for LS-SCLC, with improved survival and reduced hematologic adverse events. The lower lymphocyte depletion observed with BID CRT warrants further investigation to optimize the synergistic effect of RT and IO. Head-to-head randomized trials comparing BID and QD CRT with consolidation ICI are needed to validate these findings.