Higher-Dose Radiotherapy Improved Survival, Maintained Level of Toxicity for Limited-Stage SCLC

Data from The Lancet Oncology found that higher-dose radiotherapy of 60 Gy for patients with small cell lung cancer resulted in survival benefit while maintaining the toxicity profile compared with a radiotherapy at a dose of 45 Gy.

Patients with limited-stage small cell lung cancer (LS-SCLC) experienced a substantial survival benefit without increased toxicity with a radiotherapy dose of 60 Gy compared with a lower dose of 45 Gy, according to data from a phase 2 trial (NCT02041845) published in The Lancet Oncology.

These results suggest that twice-daily thoracic radiotherapy at this dose level may represent an alternative treatment option to existing radiotherapy schedules.

“Hyperfractionated, accelerated, twice-daily thoracic radiotherapy of 60 Gy was feasible in most patients,” wrote the investigators, who were led by Bjørn Henning Grønberg, MD. “The higher dose of thoracic radiotherapy resulted in a significant improvement in both 2-year and median overall survival compared with the standard 45 Gy schedule, without adding toxicity.”

The research team enrolled 176 patients between July 8, 2014, and June 6, 2018, with a total of 89 randomly assigned to the 60-Gy dose and 81 assigned to the 45-Gy dose. The median follow-up was 49 months (interquartile range, 38-56).

At a 2-year analysis of overall survival, 66 patients (74.2%) were alive in the 60-Gy group (95% CI, 63.8%-82.9%) versus only 39 (48.1%) in the 45-Gy group (95% CI, 36.9%-59.5%; odds ratio [OR], 3.09; 95% CI, 1.62-5.89; P = .0005).

Although the higher dose improved survival, it did not result in increased toxicity. Common grade 3/4 adverse events included neutropenia (81% in the 60-Gy group vs 81% in the 45-Gy group), neutropenic infections (27% vs 39%), thrombocytopenia (24% vs 25%), anemia (16% vs 20%), and esophagitis (21% vs 18%).

When examining serious adverse events, 38 patients in the 60-Gy group experienced a total of 55 events, while 44 patients experienced 56 serious adverse events in the 45-Gy group. There was a total of 6 treatment-related deaths, with 3 deaths in each group.

“Twice-daily radiotherapy schedules are not widely adopted, probably due to logistical challenges and concerns about toxicity,” wrote the investigators. “Our study shows that these concerns are no longer justified. None of the patients discontinued due to inconvenience.”

The phase 2 trial was conducted across 22 public hospitals in Norway, Denmark, and Sweden. The patient cohort was aged 18 or older, with confirmed LS-SCLC, an ECOG performance status between 0 and 2, and measurable disease.

The research team explained that the main limiting factor of the research was the sample size. More, there was no central quality assurance for radiotherapy, with results reflecting that of clinical practice at various sites.

“To our knowledge, this is the first randomised trial comparing high-dose, hyperfractionated, accelerated, twice-daily thoracic radiotherapy with the established 45 Gy schedule,” wrote the investigators. “Our results show that administering 60 Gy is feasible, does not cause more toxic effects, and suggest that the higher dose provides a large survival benefit.”


Gronberg BH, Killingberg KT, Flotten O, et al. High-dose versus standard-dose twice-daily thoracic radiotherapy for patients with limited stage small-cell lung cancer: an open-label, randomised, phase 2 trial. Lancet Oncol. 2021;22(3):321-331. doi:10.1016/S1470-2045(20)30742-7

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