Geara F B, Peters L J, Ang K K, Garden A S, Tucker S L, Levy L B, Brown B W
Department of Clinical Radiotherapy, The University of Texas, M.D. Anderson Cancer Center, Houston, TX, 77030, USA.
Int J Radiat Oncol Biol Phys. 1996 Jun 1;35(3):455-62. doi: 10.1016/s0360-3016(96)80006-x.
This study was conducted to test for the relationship between tumor and normal tissue radiosensitivity, by comparing local tumor control to the severity of acute and late normal tissue reactions in head and neck cancer patients treated by definitive radiotherapy.
Two hundred eighty-six patients with head and neck cancer who were treated at the University of Texas M. D. Anderson Cancer Center between 1983 and 1993 were selected for the study. Of these, 124 (43%) were treated by a concomitant boost regimen and 162 (57%) by hyperfractionation. All patients had at least 1 year of follow-up. The tumor stage distribution according to the 1992 American Joint Committee on Cancer (AJCC) staging system was as follows: T1, 3%; T2, 53%; T3, 40%; T4, 4%. The average doses delivered were 71.2 Gy and 76.2 Gy for the concomitant boost and hyperfractionation regimens, respectively, with no significant variation between patients. Acute and late reactions were recorded using the Radiation Therapy Oncology Group (RTOG)/European Organization for Research on Treatment of Cancer (EORTC) grading system (0 to 4). The median follow-up period was 38 months (range: 12-107 months). The time to local tumor recurrence was analyzed in relation to the severity of acute and late reactions expressed as the maximum recorded grades, and to the time intensity of acute mucositis, expressed as the area under the curve of mucositis grade vs. time. Univariate and multivariate analyses also included T stage, N stage, and site of origin as other prognostic variables, and were carried out using a proportional hazards model.
Fifty-four patients (19%) suffered local failure. T stage was found to significantly influence local control (p = 0.009). There was a nonsignificant trend for higher failure rates in patients with maximum Grade 1 or 2 vs. those with Grade 3 or 4 acute mucositis (28 and 18%, respectively; p = 0.17). No correlation was found between the severity of late reactions and local tumor control after radiotherapy. Analysis by time intensity of mucositis revealed a wide variation between individuals with a nonsignificant trend for higher local failure rates in patients with low mucositis time intensity scores.
These clinical results suggest a possible relationship between normal tissue and tumor radiosensitivity. However, additional studies with a larger numbers of patients, and using refined normal tissue endpoints that incorporate a time function are needed to fully elucidate this question.
本研究旨在通过比较接受根治性放疗的头颈癌患者的局部肿瘤控制情况与急性和晚期正常组织反应的严重程度，来检测肿瘤组织与正常组织放射敏感性之间的关系。
选取1983年至1993年间在德克萨斯大学MD安德森癌症中心接受治疗的286名头颈癌患者进行研究。其中，124例（43%）采用同步加量放疗方案，162例（57%）采用超分割放疗方案。所有患者均至少随访1年。根据1992年美国癌症联合委员会（AJCC）分期系统，肿瘤分期分布如下：T1期，3%；T2期，53%；T3期，40%；T4期，4%。同步加量放疗方案和超分割放疗方案的平均剂量分别为71.2 Gy和76.2 Gy，患者之间无显著差异。使用放射治疗肿瘤学组（RTOG）/欧洲癌症研究与治疗组织（EORTC）分级系统（0至4级）记录急性和晚期反应。中位随访期为38个月（范围：12 - 107个月）。分析局部肿瘤复发时间与以最高记录分级表示的急性和晚期反应严重程度，以及以口腔黏膜炎分级与时间曲线下面积表示的急性口腔黏膜炎时间强度之间的关系。单因素和多因素分析还将T分期、N分期和原发部位作为其他预后变量，使用比例风险模型进行分析。
54例患者（19%）出现局部复发。发现T分期对局部控制有显著影响（p = 0.009）。与3级或4级急性口腔黏膜炎患者相比，1级或2级急性口腔黏膜炎患者的失败率有升高趋势，但无统计学意义（分别为28%和18%；p = 0.17）。放疗后晚期反应严重程度与局部肿瘤控制之间未发现相关性。通过口腔黏膜炎时间强度分析发现，个体间差异较大，口腔黏膜炎时间强度评分低的患者局部失败率有升高趋势，但无统计学意义。
这些临床结果提示正常组织与肿瘤放射敏感性之间可能存在关系。然而，需要进行更多患者参与的研究，并使用纳入时间函数的更精确的正常组织终点指标，以充分阐明这个问题。
