Influence of interfraction interval on the efficacy and toxicity of hyperfractionated radiotherapy in combination with concurrent daily chemotherapy in stage III non-small-cell lung cancer

Purpose: To investigate the influence of the interfraction interval (IFI) o n treatment outcome and toxicity in hyperfractionated (HF) radiotherapy (RT ) for Stage III non-small-cell lung cancer. Methods and Materials: Data for 301 patients treated with 1.2 Gy b.i.d. to a total of 69.6 Gy and concurrent chemotherapy in our 3 prospective studies were analyzed. The chemotherapy regimen was either (1) 50 mg each of carbo platin and etoposide (CE) given on RT days (163 patients) or (2) 30 mg of C E on RT days and 100 mg of CE on Saturdays and Sundays during the RT course (138 patients). An IFI of 4.5-5 h or 5.5-6 h had been nonrandomly assigned for each patient, and this interval was kept throughout the treatment. Results: No difference was observed in treatment outcome due to the chemoth erapy protocol, and the 2 groups were combined. Patients treated with the s horter IFI had a better local control rate (38% at 5 years) and survival ra te (30% at 5 years) than those treated with the longer interval (23% and 14 %, respectively; p < 0.001). However, female patients and those with a high Karnofsky performance status score (KPS), weight loss of <less than or equ al to>5% in the previous 6 months, or Stage ILIA disease had been more ofte n treated with the shorter LFI, and these characteristics were associated w ith better treatment outcome. In multivariate analysis, only gender, KPS, a nd weight change proved to be significant prognostic factors influencing bo th local control and survival, and the effect of IFI was not significant. T he incidence of Grade 4 acute esophagitis tended to be higher in the shorte r interval group (p, = 0.072), but there were no differences in the inciden ce of late or other acute PT-related toxicities between the 2 groups. Conclusions: The possible influence of the IFI on local control and surviva l could not be verified using multivariate analysis. To better understand t he influence of the IFI, randomized studies with more patients and wider ra nges of intervals (e.g., 5 h vs. 8 h) seem to be necessary. (C) 2001 Elsevi er Science Inc.