A landmark multi-center phase III trial has demonstrated that hypofractionated radiotherapy combined with concurrent chemotherapy delivers comparable survival outcomes to conventional radiotherapy while significantly reducing treatment time and toxicity for patients with limited-stage small cell lung cancer (LS-SCLC). The results were presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Conference on Lung Cancer.
Trial Design and Patient Population
The study, conducted across 16 hospitals in China, randomized 530 patients to receive either hypofractionated radiotherapy (HypoRT) delivering 45 Gy in 15 daily fractions over three weeks, or conventional fractionated radiotherapy (ConvRT) delivering 60 Gy in 30 daily fractions over six weeks. Both treatment arms included concurrent cisplatin/carboplatin-etoposide chemotherapy.
Hypofractionated radiotherapy deviates from traditional approaches by delivering higher doses of radiation per session over fewer treatments, thereby shortening the overall course of radiation therapy while potentially minimizing cumulative toxicities associated with prolonged treatment.
Survival Outcomes Show Non-Inferiority
After a median follow-up of 43.4 months, the trial demonstrated non-inferior survival outcomes between the two approaches. Median overall survival was 40.2 months in the HypoRT arm compared to 47.9 months in the ConvRT arm, with a hazard ratio of 1.04 (95% CI, 0.81–1.33), indicating no statistically significant difference. Progression-free survival was similarly comparable between the groups.
Significant Reduction in Treatment Toxicity
The condensed HypoRT regimen provided substantial advantages in treatment tolerability. Patients receiving hypofractionated radiotherapy experienced significantly lower rates of severe treatment-related adverse events, including reduced hematologic toxicity, lymphopenia, and radiation pneumonitis. Acute grade ≥3 adverse events occurred in 48.7% of HypoRT patients compared to 67.7% in the ConvRT group.
"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. This approach could be an important option for patients, especially in settings where reducing treatment time and toxicity is a priority," said Dr. Nan Bi from The National Cancer Center of China/Cancer Hospital, Chinese Academy of Medical Sciences, Beijing.
Clinical Implications and Future Directions
Small cell lung cancer accounts for approximately 10-15% of all lung cancer diagnoses and is characterized by rapid growth, early metastasis, and generally poor prognosis. Limited-stage disease, where malignancy is confined to one hemithorax and regional lymph nodes, represents the window where curative intent treatment remains feasible.
The biological rationale underlying hypofractionation's comparable efficacy may relate to radiobiological principles involving tumor cell kill dynamics and normal tissue repair mechanisms. The delivery of higher doses per fraction is theorized to achieve greater tumor cytotoxicity, potentially offsetting the shorter overall treatment time.
Researchers highlighted the potential immunomodulatory effects of hypofractionated radiation, noting that unlike conventional fractionation, HypoRT may more effectively spare immune cell populations, particularly lymphocytes, from radiation-induced depletion. This finding suggests promising avenues for combining HypoRT with emerging immunotherapeutic agents in future clinical trials.
The validation of HypoRT could enhance clinical practice by reducing radiotherapy wait times, optimizing resource allocation, and expanding treatment accessibility globally while aligning with patient-centered care principles.
