A reduced schedule for hypofractionated radiotherapy with concurrent chemotherapy led to numerically similar survival outcomes and a more favorable safety profile compared with a standard course of conventional fractionated radiotherapy for patients with limited-stage small cell lung cancer (LS-SCLC), according to findings from a phase III randomized trial presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer (WCLC; Abstract PL03.07).
“Our findings suggest that hypofractionated radiotherapy can provide a shorter, more convenient treatment course with fewer side effects while maintaining comparable survival outcomes to conventional radiotherapy,” said Nan Bi, MD, Professor and Director of Thoracic Division Department of Radiation Oncology, The National Cancer Center of China/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing. “This approach could be an important option for patients, especially in settings where reducing treatment time and toxicity is a priority.”
Background and Study Methods
No randomized trials have ever been done before to directly compare hypofractionated radiotherapy with conventional radiotherapy for concurrent treatment with chemotherapy for patients with LS-SCLC.
The researchers conducted a multicenter, open-label, randomized phase III trial across 16 hospitals in China to determine if a 3-week schedule of hypofractionated radiotherapy is as effective and safe as a 6-week schedule of conventional radiotherapy in patients with LS-SCLC. A total of 530 patients were enrolled in the study and randomly assigned to receive either hypofractionated radiotherapy at 45 Gy in 15 daily fractions over 3 weeks or conventional therapy of 60 Gy in 30 daily fractions over 6 weeks, given no later than the third cycle of chemotherapy. Radiotherapy was intensity modulated in both groups.
The researchers had planned to conduct overall survival analyses after at least 324 deaths had occurred, but a change in the treatment landscape led them to conducting the final analysis before the data had reached full maturity.
Key Study Findings
Patients were followed for a median of 43.4 months, at which point the median overall survival was 40.2 months in the hypofractionated arm compared with 47.9 months in the conventional radiotherapy arm (hazard ratio [HR] = 1.04; 95% confidence interval [CI] = 0.81–1.33).
The estimated overall survival rate at 1 year was 86.6%, 68.9% at 2 years, 53.5% at 3 years, and 42.4% at 5 years in the hypofractionated radiotherapy arm compared with rates of 87.2%, 68.0%, 55.5%, and 43.9%, respectively, in the conventional radiotherapy arm.
The median progression-free survival was also similar between the two arms at 16.5 months with hypofractionated radiotherapy and 18.0 months with conventional radiotherapy (HR = 1.06; 95% CI = 0.86–1.32; P = .75).
Rates of acute treatment-related adverse events of grade 3 or higher were significantly lower in the hypofractionated radiotherapy arm than in the conventional radiotherapy arm (48.7% vs 67.7%; P < .001), primarily due to fewer hematologic adverse events. Fewer patients in the hypofractionated arm experienced grade 2 or higher lymphopenia during concurrent chemotherapy than in the conventional radiotherapy arm (60.5% vs 88.8%; P < .001) and at 1 month (34.3% vs 48.7%; P = .001) and 6 months after radiotherapy (14.4% vs 28.7%; P = .013). In terms of late adverse events, no significant differences were observed between the two arms.
The study authors believe that the findings warrant the clinical adoption of hypofractionated radiotherapy, and that hypofractionated radiotherapy in combination with immunotherapy should be studied further given its potential immune-sparing benefits.
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