Shibamoto Y, Jeremic B, Acimovic L, Milicic B, Nikolic N
Department of Oncology, Institute for Frontier Medical Sciences, Kyoto University, Japan.
Int J Radiat Oncol Biol Phys. 2001 Jun 1;50(2):295-300. doi: 10.1016/s0360-3016(01)01440-7.
To investigate the influence of the interfraction interval (IFI) on treatment outcome and toxicity in hyperfractionated (HF) radiotherapy (RT) for Stage III non-small-cell lung cancer.
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 carboplatin and etoposide (CE) given on RT days (163 patients) or (2) 30 mg of CE 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.
No difference was observed in treatment outcome due to the chemotherapy protocol, and the 2 groups were combined. Patients treated with the shorter IFI had a better local control rate (38% at 5 years) and survival rate (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 < or =5% in the previous 6 months, or Stage IIIA disease had been more often treated with the shorter IFI, and these characteristics were associated with better treatment outcome. In multivariate analysis, only gender, KPS, and weight change proved to be significant prognostic factors influencing both local control and survival, and the effect of IFI was not significant. The incidence of Grade 4 acute esophagitis tended to be higher in the shorter interval group (p = 0.072), but there were no differences in the incidence of late or other acute RT-related toxicities between the 2 groups.
The possible influence of the IFI on local control and survival could not be verified using multivariate analysis. To better understand the influence of the IFI, randomized studies with more patients and wider ranges of intervals (e.g., 5 h vs. 8 h) seem to be necessary.
探讨分割间期（IFI）对Ⅲ期非小细胞肺癌超分割放疗（HF-RT）治疗效果和毒性的影响。
分析了我们3项前瞻性研究中301例接受每日两次1.2 Gy、总剂量69.6 Gy及同步化疗的患者数据。化疗方案为：（1）放疗日给予卡铂和依托泊苷各50 mg（163例患者）；或（2）放疗日给予30 mg卡铂和依托泊苷，放疗期间周六和周日给予100 mg卡铂和依托泊苷（138例患者）。为每位患者非随机分配4.5 - 5小时或5.5 - 6小时的IFI，并在整个治疗过程中保持该间期。
化疗方案对治疗效果无差异，两组合并分析。接受较短IFI治疗的患者局部控制率（5年时为38%）和生存率（5年时为30%）优于接受较长间期治疗的患者（分别为23%和14%；p < 0.001）。然而，女性患者、卡氏评分（KPS）高、前6个月体重减轻≤5%或ⅢA期疾病患者更常接受较短IFI治疗，而这些特征与较好的治疗效果相关。多因素分析显示，仅性别、KPS和体重变化是影响局部控制和生存的显著预后因素，IFI的影响不显著。较短间期组4级急性食管炎发生率有升高趋势（p = 0.072），但两组晚期或其他急性放疗相关毒性发生率无差异。
多因素分析无法证实IFI对局部控制和生存的可能影响。为更好地理解IFI的影响，似乎有必要进行更多患者、更宽间期范围（如5小时与8小时）的随机研究。
