Jeremic Branislav, Milicic Biljana, Dagovic Aleksandar, Aleksandrovic Jasna, Milisavljevic Slobodan
Department of Oncology, University Hospital, Kragujevac, Yugoslavia.
Am J Clin Oncol. 2004 Dec;27(6):616-25. doi: 10.1097/01.coc.0000138964.98445.c4.
We investigated the influence of interfraction interval (IFI) on treatment outcome in patients with stage III non-small-cell lung cancer (NSCLC) treated with hyperfractionated radiation therapy (Hfx RT) with or without concurrent chemotherapy (CHT). During 3 randomized phase III and 1 phase II study, a total of 536 patients were treated with Hfx RT alone or with concurrent carboplatin/etoposide. Two hundred eighty-five patients were treated with IFI of 4.5-5.0 hours, while 251 patients were treated with IFI of 5.5-6.0 hours. "Shorter" (4.5-5.0 hours) IFI led to better overall survival (OS) (P = 0.0000) and local recurrence-free survival (LRFS) (P = 0.0000). Multivariate analyses showed IFI to be an independent prognosticator of both OS and LRFS. These results were confirmed when we separated all patients (n = 536) into those treated with Hfx RT only (n = 127) and those treated with concurrent RT/CHT (n = 409). Various RT-related high-grade acute toxicity was not different between the 2 IFI, but patients treated with shorter IFI had a significantly higher incidence of hematological toxicity (P = 0.002). None of the late high-grade toxicities were different between the 2 interfraction intervals. Using regression analysis, it was shown that IFI was not a significant predictor of any of acute or late high-grade (> or =3) toxicity. IFI is an important prognosticator of OS and LRFS in patients with stage III NSCLC treated with Hfx RT with or without concurrent carboplatin/etoposide. IFI led to higher incidence only of hematological toxicity, but was not predictive of any acute or late high-grade (> or =3) toxicity. A carefully designed randomized trial seems necessary to give better insight into the issue of optimal IFI in this disease.
我们研究了分次照射间隔时间（IFI）对接受超分割放射治疗（Hfx RT）联合或不联合同步化疗（CHT）的Ⅲ期非小细胞肺癌（NSCLC）患者治疗结果的影响。在3项随机Ⅲ期研究和1项Ⅱ期研究中，共有536例患者接受单纯Hfx RT或联合卡铂/依托泊苷同步化疗。285例患者的IFI为4.5 - 5.0小时，而251例患者的IFI为5.5 - 6.0小时。“较短”（4.5 - 5.0小时）的IFI导致更好的总生存期（OS）（P = 0.0000）和局部无复发生存期（LRFS）（P = 0.0000）。多因素分析显示IFI是OS和LRFS的独立预后因素。当我们将所有患者（n = 536）分为仅接受Hfx RT治疗的患者（n = 127）和接受同步RT/CHT治疗的患者（n = 409）时，这些结果得到了证实。两种IFI之间各种与放疗相关的高级别急性毒性无差异，但接受较短IFI治疗的患者血液学毒性发生率显著更高（P = 0.002）。两种分次照射间隔之间的晚期高级别毒性均无差异。通过回归分析表明，IFI不是任何急性或晚期高级别（≥3级）毒性的显著预测因素。对于接受Hfx RT联合或不联合卡铂/依托泊苷同步化疗的Ⅲ期NSCLC患者，IFI是OS和LRFS的重要预后因素。IFI仅导致血液学毒性发生率更高，但不能预测任何急性或晚期高级别（≥3级）毒性。似乎有必要进行一项精心设计的随机试验，以便更好地了解该疾病中最佳IFI的问题。
