Bernier J, Thames H D, Smith C D, Horiot J C
Department of Radiation Oncology, Ospedale San Giovanni, Bellinzona, Switzerland.
Radiother Oncol. 1998 May;47(2):137-43. doi: 10.1016/s0167-8140(97)00221-1.
Relationships between normal tissue reactions and tumor response to radiotherapy have generally been investigated in retrospective studies, with the attendant difficulties such as different times of treatment and lack of standard scales for scoring of normal tissue reactions. This study analyses the correlation between normal tissue reactions and tumor response in a randomized trial of hyperfractionation versus conventional radiotherapy.
EORTC trial 22791, which accrued 325 T2-3, N0-1 and M0 oropharynx squamous cell carcinomas, compared conventional radiotherapy (70 Gy in 7 weeks) to a hyperfractionated regime (two daily irradiations of 1.15 Gy up to 80.5 Gy in 7 weeks). Acute and late toxicities were assessed according to the RTOG/EORTC scales. The variables were tumor regression at treatment completion, tumor control for unlimited follow-up, severity of acute mucosal reactions (grade of the peak reaction, time to onset of grade 2 mucositis, or duration of acute reactions of grade 3) and severity of late effects in normal tissues (late ulceration, cervical edema secondary to lymphatic drainage damage, late muscular fibrosis, or late mucosal necrosis as consequential damage). Kendall's rank correlation was used to assess the levels of significance of the correlation. The 95% confidence interval (95% CI) was calculated for each correlation tau-b coefficient.
Irradiation doses and overall treatment times were consistent between the treatment arms. The time to onset of patchy mucosal reactions was inversely correlated to tumor regression at treatment completion in the hyperfractionated arm (arm 2) but not in the conventional fractionation arm (arm 1). The other significant correlations were restricted to the following pairs of end-points and patient subgroups: acute mucositis of grade 3 versus tumor regression at the end of treatment in arm 2 for T2 tumors, late ulceration versus tumor control in arm 2 and acute mucosal reactions versus late effects in normal tissues in arm 2 for T3 tumors. By and large, the 95% CIs for Kendall's tau-b included zero and did not include 0.5, an indication that the comparison had sufficient power to detect a difference, if indeed one existed.
These results do not represent clinical evidence strong enough to demonstrate that individual differences in sensitivity influence the response of tumors to radiation.
正常组织反应与肿瘤放疗反应之间的关系通常是在回顾性研究中进行调查的，存在诸如治疗时间不同以及缺乏正常组织反应评分标准尺度等伴随困难。本研究在超分割放疗与传统放疗的随机试验中分析了正常组织反应与肿瘤反应之间的相关性。
欧洲癌症研究与治疗组织（EORTC）试验22791纳入了325例T2 - 3、N0 - 1和M0的口咽鳞状细胞癌患者，将传统放疗（7周内给予70 Gy）与超分割方案（7周内每天两次照射，每次1.15 Gy，总计80.5 Gy）进行比较。根据美国放射肿瘤学协作组（RTOG）/欧洲癌症研究与治疗组织（EORTC）标准评估急性和晚期毒性。变量包括治疗结束时的肿瘤退缩情况、无限期随访的肿瘤控制情况、急性黏膜反应的严重程度（峰值反应分级、2级黏膜炎的发生时间或3级急性反应的持续时间）以及正常组织晚期效应的严重程度（晚期溃疡、继发于淋巴引流损伤的颈部水肿、晚期肌肉纤维化或作为继发损伤的晚期黏膜坏死）。采用肯德尔等级相关性来评估相关性的显著水平。为每个相关性tau - b系数计算95%置信区间（95% CI）。
各治疗组之间的照射剂量和总治疗时间一致。在超分割组（第2组）中，斑片状黏膜反应的发生时间与治疗结束时的肿瘤退缩呈负相关，但在传统分割组（第1组）中并非如此。其他显著相关性仅限于以下终点和患者亚组对：第2组中T2肿瘤在治疗结束时3级急性黏膜炎与肿瘤退缩、第2组中晚期溃疡与肿瘤控制以及第2组中T3肿瘤的急性黏膜反应与正常组织晚期效应。总体而言，肯德尔tau - b的95% CI包含零且不包含0.5，这表明该比较有足够的检验效能来检测差异（如果确实存在差异的话）。
这些结果并不代表有足够强的临床证据来证明敏感性的个体差异会影响肿瘤对放疗的反应。
