Data Favor Twice-Daily vs Once-Daily Chemoradiotherapy in LS-SCLC

In a conversation with CancerNetwork^® during the 2025 American Society of Radiation Oncology (ASTRO) Annual Meeting, Bin Gui, MD, spoke about the rationale of a study comparing twice-daily chemoradiotherapy (CRT) with once-daily treatment among patients with limited-stage small cell lung cancer (LS-SCLC). Gui and colleague presented findings from this research in a poster session at the meeting.¹

According to Gui, resident physician in the Department of Radiation Medicine at Northwell Health Cancer Institute, prior research demonstrated superior outcomes with twice-daily CRT compared with once-daily therapy, although he noted the limited clinical adoption of the twice-daily schedule based on concerns regarding esophagitis and other logistical challenges. Moreover, he highlighted how findings from the phase 3 ADRIATIC trial (NCT03703297) exhibited the benefit of supplementing CRT with consolidation immunotherapy, inspiring the need to further research how immunotherapy can be combined with radiation in this patient population.²

Findings from the poster presented at ASTRO 2025 showed that twice-daily CRT prolonged 2-year overall survival (OS) by 13% (RR, 1.13; 95% CI, 1.06-1.21) and produced similar progression-free survival (PFS; RR, 1.08; 95% CI, 0.90-1.30) vs once-daily CRT. Data supported the conclusion that the addition of immunotherapy appeared to favor twice-daily CRT vs once-daily CRT based on improved survival and fewer hematologic toxicities.

Transcript:

The assessment of twice-daily vs. once-daily thoracic radiotherapy for LS-SCLC stemmed from a need to determine the optimal radiotherapy regimen as the standard of care with concurrent chemoradiotherapy [CCRT] continues to evolve. Earlier studies suggested twice-daily accelerated radiotherapy improved outcomes. However, its clinical adoption has been limited, particularly in North America, due to concerns about esophagitis and logistical challenges. More recently, the ADRIATIC trial [NCT03703297] demonstrated a significant benefit from adding consolidation immunotherapy following CCRT, creating the need to understand how best to integrate this strategy with the CCRT regimen, including the choice of radiotherapy fractionation schedule.

The addition of immunotherapy appears to favor twice-daily over once-daily CCRT for LS-SCLC, with improved survival and reduced lymphocyte depletion.

References

1. Gui B, Akerman M, Sekari J, Plann-Curley B, Parashar B. 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. Presented at the 2025 American Society of Radiation Oncology (ASTRO) Annual Meeting; September 27 – October 1, 2025; San Francisco, CA.
2. Cheng Y, Spigel DR, Cho BC, et al. Durvalumab after chemoradiotherapy in limited-stage small-cell lung cancer. N Engl J Med. 2024;391(14):1313-1327. doi:10.1056/NEJMoa2404873