The overall survival of patients with stage III non-small cell lung cancer (NSCLC) was not improved by high-dose radiotherapy, which was compared with standard-dose radiotherapy. Both treatment arms had concurrent chemotherapy. The trial was presented June 4 at the 2013 annual conference of the American Society of Clinical Oncology in Chicago, Illinois.

NSCLC accounts for 75%-80% of all patients in the US with lung cancer, and 30%-40% of them are considered locally advanced (stage IIIA or IIIB). The standard of care for locally advanced NSCLC is radiotherapy plus chemotherapy, but research has focused more on chemotherapy drugs than on revisiting the 60-Gy radiotherapy dose that was established 30 years ago.

Unfortunately, local tumor progression rates are near 85%. These rates led to the development of this trial by the Radiation Therapy Oncology Group. This trial sought to identify the optimal radiotherapy dose to treat patients with locally advanced NSCLC, and it also tested the hypothesis that adding cetuximab to chemoradiation would lead to improved survival.

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The trial randomized 464 patients with pathologically diagnosed unresectable stage IIIA or IIIB NSCLC to the standard dose of 60 Gy or a high dose of 74 Gy. The patients all received concurrent chemotherapy that consisted of paclitaxel and carboplatin, as well as additional cycles of consolidation chemotherapy that followed the combined chemotherapy and radiotherapy.

The median survival times were 28.7 months for the standard dose of radiotherapy and 19.5 months for the high dose of radiotherapy. The 18-month overall survival rates were 66.9% for the standard dose and 53.9% for the high dose. The median follow-up time was 17.2 months. At 18 months, the local failure rates also favored the standard dose over the high dose arm.

“In the setting of concurrent chemotherapy with daily radiation therapy for stage III lung cancer, these results definitively confirm that 60 Gray is superior to 74 Gray, with a clear detriment associated with the higher radiation dose,” concluded the principal investigator, Jeffrey D. Bradley, MD, of Washington University School of Medicine in St. Louis, Missouri. 

This trial, which has confirmed the efficacy of the lower radiotherapy dose, helps to inform new research that addresses how to improve radiotherapy in the setting of concurrent chemotherapy. Bradley explained that efforts will now focus on evaluating the use of adaptive radiotherapy, which involves changing the radiation treatment plan delivered to a patient during a course of radiotherapy.