Once-Daily RT Fails to Improve Over Standard in Limited-Stage SCLC

A once-daily radiotherapy (RT) regimen given concurrently with chemotherapy showed no difference in survival outcomes compared with the standard twice-daily regimen in a randomized trial of patients with limited-stage small-cell lung cancer (LS-SCLC).

Previous research found that twice-daily RT was superior to once-daily RT in this malignancy, but treatment techniques have evolved since that work was done several decades ago. “It is unclear whether twice-daily RT resulted in better outcomes because of the increase in the biologically effective dose of radiation or because of shorter overall treatment time, which is important in this rapidly proliferating disease,” wrote study authors led by Corinne Faivre-Finn, PhD, of the University of Manchester in the United Kingdom.

Because some experts have suggested that local control could be improved by a higher dose of once-daily concurrent chemoradiotherapy, researchers conducted the new CONVERT trial to test the hypothesis. It included 547 patients (4 lost to follow-up) with LS-SCLC randomized to receive either 45 Gy in 30 twice-daily fractions of 1.5 Gy over 19 days (273 patients), or 66 Gy in 33 once-daily fractions of 2 Gy over 45 days (270 patients); RT was started on day 22 after initiation of cisplatin/etoposide chemotherapy. Results of the study were published in Lancet Oncology.

The median overall survival (OS) was 30 months in the twice-daily group and 25 months in the once-daily group, with a hazard ratio (HR) for death of 1.18 (95% CI, 0.95–1.45; P = .14). At 2 years, the OS rate was 56% with twice-daily RT and 51% in the once-daily group; at 5 years, these rates were 34% and 31%, respectively.

A total of 181 twice-daily patients and 189 once-daily patients had disease progression at the time of the analysis (66% vs 70%; P = .26). The median progression-free survival was 15.4 months with twice-daily RT and 14.3 months with once-daily RT, for an HR of 1.12 (95% CI, 0.92–1.38; P = .26).

Neutropenia was the most commonly seen grade 3/4 adverse event, affecting 74% of the twice-daily patients and 65% of the once-daily patients. The authors wrote that most adverse events occurred at similar frequencies between the groups, with the exception of grade 4 neutropenia: this occurred in 49% of the twice-daily RT group, and in 38% of the once-daily group (P = .05). Acute RT toxicity was similar, with grade 3/4 esophagitis occurring in 18% and 19% of the twice- and once-daily groups, respectively.

“Since the trial was designed to show superiority of once-daily RT and not powered to show equivalence, twice-daily RT should continue to be considered standard of care,” the authors concluded. “Furthermore, twice-daily RT concurrently with chemotherapy is well tolerated, with better compliance and shorter treatment time than once-daily treatment.”