2

With recent increased interest in altered fractionation schedules for radiation therapy, accelerated hyperfractionation appears to be a logical choice for SCLC due to the high sensitivity of cancer cells, the normal-tissuesparing effect of twice-daily fractionation (with a greater than six-hour interval between fractions), and the ability to defeat rapid proliferation of tumor cells. Several phase II studies of radiation given in multiple daily fractions, either concurrently with cisplatin and etoposide or in an interdigitated sequence, have been followed by a large intergroup randomized trial. 22,23 In this study, 417 patients were treated with concurrent TI starting with the first cycle of etoposide and cisplatin (PE) chemotherapy and randomized between a standard schedule (1.8 Gy in 25 daily fractions over five weeks to a total dose of 45 Gy) or a hyperfractionated schedule (45 Gy in 1.5 Gy fractions twice daily over three weeks). With mature follow-up, the five-year survival rate was significantly improved in the twice-daily arm (26 vs 19%). However, the hyperfractionated arm had higher rates of acute toxicity, as would be expected. 23 An additional trial studying this issue was a North Central Cancer Treatment Group (NCCTG) study, which compared concurrent cisplatin/etoposide (two cycles) and either twice-daily, split-course TI to 48 Gy in 5.5 weeks or once-daily TI to 50.4 Gy in daily fractions of 1.8 Gy, both given after three cycles of cisplatin/ etoposide. They found no difference in three-year overall survival and locoregional control between the splitcourse/twice-daily fractionation and daily fractionation treatment schemas. 24 Schild et al reported the median and five-year survival rates to be 20.4 months and 22% for twice-daily versus 20.5 months and 21% for oncedaily thoracic radiation, respectively ( p = 0.7). 25 In analyzing these studies side-by-side, it appears that one possible explanation is that the split-course regimen is an inferior regimen due to an extension of overall treatment time allowing for tumor cell regeneration.