Interruptions of modest dose once-daily (QD) thoracic radiotherapy (TRT) do not correlate with outcome in limited small cell lung cancer (L-SCLC): Analysis of CALGB 9235

Background: TRT dose intensity (dose/time) may be an important variable in the treatment of L-SCLC. A prospective trial demonstrated improved survival (OS) for patients receiving accelerated TRT, and retrospective data suggests TRT interruptions (TRT-1) negatively impact local tumor control (LC) and OS. We examined the impact of toxicity mandated TRT-I in a phase III CALGB trial. Materials and Methods: CALGB 9235 was conducted to determine whether the addition of tamoxifen to etoposide, cisplatin and TRT improved OS for patients with L-SCLC.A total of 307 eligible patients were accrued between 8/93 and 1/99. TRT, 50 Gy/2 Gy QD/5 weeks, was initiated with cycle 4 (of 5) chemotherapy. This analysis includes 267 patients who proceeded to TRT. Criteria mandating TRT-1 were hématologie toxicity (HT; granulocytes < 1000/mm' or platelets < 75,000/mm3) or esophageal toxicity (ET; dysphagia necessitating intravenous hydration). Results: TRT-I occurred in 115 patients (43%), most frequently during the 4th week of TRT, and did not differ between treatment arms. The reasons stated for TRT-I were HT (57%), ET (4%), HT + ET (5%), or other (34%). Elderly patients (age 70 years) did not experience increased TRT-I. Gender and race did not predict for TRT-1, ET, or HT. There was a trend towards increased grade 4 HT (P = .10), but not TRT-I or ET, with increasing radiation treatment volume. OS and LC did not correlate with the incidence.duration or timing of TRT-1. Three-year OS was 31%, 29%,and 35% for TRT-1 of 0-3 days, 4-10 days, and 10 + days, respectively. Conclusion: Dose intensity may not be critical for patients receiving modest dose QD TRT concurrent with chemotherapy. The implications for more intensive or high dose TRT regimens are not clear, and evaluation of other data sets is warranted.

Duke Scholars

Author James Emmett Herndon II Biostatistics & Bioinformatics, Division of Biostatistics