The results of the largest trial in limited stage small cell lung cancer ever performed could have major implications for treating the illness, with the researchers finding similar outcomes and long-term survival in patients treated with twice-a-day versus once-a-day radiotherapy.
The clinical trial was led by US radiation oncologist Dr Jeffrey Bogart and Upstate Medical University, and published in the Journal of Clinical Oncology.
Previously, the twice-a-day regime was recommended as standard, based on prior trials, but many patients were not able to receive twice-a-day radiation in part due to the challenge of coming in for appointments two times each day.
The trial included more than 700 patients throughout the United States from 2008 to 2019. About 30 000 people are diagnosed with small-cell lung cancer each year. That type of cancer, which is treated with chemotherapy and radiation, accounts for about 15% to 20% of all lung cancer patients.
Earlier trials showed that radiation twice a day for three weeks was a more effective treatment than the same dose of radiation once a day for five weeks, Bogart said. However, despite undergoing radiation for a shorter period – three weeks compared with five – receiving two doses of radiation in one day is difficult for many patients, he said.
Twice daily radiation must be administered at least six hours apart, which means the patient has to be at the hospital twice in one day. That’s a tiring regimen and can be difficult for those who don’t live nearby.
And even though that was the recommended regimen, only 15% of patients nationwide opted for twice-daily radiation treatments.
This latest trial showed that a higher dose of radiation given once daily over seven weeks showed no statistical difference in survival rates than the twice-a-day regimen. He said the technology today is much more advanced than it was 30 years ago, including very focused treatment with image guidance that can produce targeted radiation, resulting in fewer side-effects.
The study results now allow for two equal options for patients.
“It allows patients a real choice, understanding there may be some differences in side effects, or their ability to complete the longer therapy, but now they know both regimens can be associated with good outcomes,” he said. “We still offer the twice-a-day for small cell but are more comfortable with the high dose once a day because of the results from this trial.”
Bogart said the next step in assessing the benefit of this treatment protocol is to look at subpopulations, for example, based on gender or age.
“The goal over time is to get away from the one-size-fits-all approach to now offer better, more personalised therapy.”
The clinical trial was conducted with patients from across the US, including at Upstate, and was overseen by the Alliance for Clinical Trials in Oncology, for which Bogart chairs the Radiation Oncology Committee. Bogart said that another Upstate Cancer Centre radiation oncologist, Dr Michael Mix, is in discussion to lead a new national initiative to study twice daily radiotherapy at a dose of 60 Gy in small cell lung cancer at another dose, and that trial should start later this year.
Study details
High-Dose Once-Daily Thoracic Radiotherapy in Limited-Stage Small-Cell Lung Cancer: CALGB 30610 (Alliance)/RTOG 0538
Jeffrey Bogart, Xiaofei Wang, Gregory Masters, Junheng Gao, Ritsuko Komaki, Laurie Gaspar.
Published in American Society of Clinical Oncology on 9 January 2023
Purpose
Although level 1 evidence supports 45-Gy twice-daily radiotherapy as standard for limited-stage small-cell lung cancer, most patients receive higher-dose once-daily regimens in clinical practice. Whether increasing radiotherapy dose improves outcomes remains to be prospectively demonstrated.
Methods
This phase III trial, CALGB 30610/RTOG 0538, was conducted in two stages. In the first stage, patients with limited-stage disease were randomly assigned to receive 45-Gy twice-daily, 70-Gy once-daily, or 61.2-Gy concomitant-boost radiotherapy, starting with either the first or second (of four total) chemotherapy cycles. In the second stage, allocation to the 61.2-Gy arm was discontinued following planned interim toxicity analysis, and the study continued with two remaining arms. The primary end point was overall survival (OS) in the intention-to-treat population.
Results
Trial accrual opened on March 15, 2008, and closed on December 1, 2019. All patients randomly assigned to 45-Gy twice-daily (n = 313) or 70-Gy once-daily radiotherapy (n = 325) are included in this analysis. After a median follow-up of 4.7 years, OS was not improved on the once-daily arm (hazard ratio for death, 0.94; 95% CI, 0.76 to 1.17; P = .594). Median survival is 28.5 months for twice-daily treatment, and 30.1 months for once-daily treatment, with 5-year OS of 29% and 32%, respectively. Treatment was tolerable, and the frequency of severe adverse events, including oesophageal and pulmonary toxicity, was similar on both arms.
Conclusion
Although 45-Gy twice-daily radiotherapy remains the standard of care, this study provides the most robust information available to help guide the choice of thoracic radiotherapy regimen for patients with limited-stage small-cell lung cancer.
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