PC02.04 BID Radiation - PRO

Abstract

The optimal thoracic radiotherapy dose for treating limited stage small cell lung cancer remains to be defined. Given the radiosensitivity of small cell lung cancer cell lines in preclinical studies in the 1980's it was postulated that twice daily radiotherapy would result in improved efficacy. Subsequent clinical experience included the landmark Intergroup 0096 trial, which demonstrated improved overall survival for patients assigned to twice daily radiotherapy (45 Gy) compared with once daily radiotherapy to the same total dose. Despite being one of the few randomized trials showing that changing the radiotherapy regimen impacts overall survival, the twice-daily regimen was slow to be adopted in clinical practice and many NCI cooperative group studies continued to use once-daily radiotherapy. Reluctance to routinely use the twice-daily regimen likely relate to concerns with acute toxicity, logistic issues, and use of a modest radiotherapy dose of only 45 Gy on the standard arm. In addition, a contemporaneous study from NCCTG did not show an advantage to twice-daily radiotherapy, although a planned treatment break was included such that radiotherapy was not accelerated. Alternate strategies to improve the efficacy of thoracic radiotherapy have included the development of high dose once-daily regimens with a 70 Gy regimen utilized in several phase II trials from the Cancer and Leukemia Group B. These trials are somewhat difficult to interpret, as radiotherapy was not initiated until the 3rd cycle of chemotherapy and novel induction chemotherapy regimens were included. The RTOG has also studied a concomitant boost regimen, though overall survival was lower than expected in the phase II experience. Results from the CONVERT trial, comparing 45 Gy twice-daily and 66 Gy once-daily radiotherapy, were recently published. The trial was powered to show superiority of high dose daily radiotherapy and failed to do so, and thus the authors concluded that 45 Gy twice-daily remain the standard of care. The CALGB 30610 trial, which uses 70 Gy in the once-daily arm, is near completion and will provide further data regarding the therapeutic ratio of these regimens. For the time being it should be kept in mind that the long held assumption that increasing radiotherapy dose with conventional fractionation will result in improved outcomes may not be justified – particularly in the setting of concurrent chemotherapy. For example, increasing the radiotherapy dose from 50.4 Gy to 64.8 Gy, with cisplatin and 5-FU, did not improve outcomes for patients with esophageal cancer on the phase 3 Intergroup 0123 trial. Perhaps even more suprising are the results of RTOG 0617, where even in the era of advanced radiotherapy treatment planning raising the radiotherapy dose resulted in worse outcomes. accelerated, thoracic radiotherapy, twice daily