Peters L J, Goepfert H, Ang K K, Byers R M, Maor M H, Guillamondegui O, Morrison W H, Weber R S, Garden A S, Frankenthaler R A
Dept. of Radiotherapy, University of Texas M. D. Anderson Cancer Center, Houston 77003.
Int J Radiat Oncol Biol Phys. 1993 Apr 30;26(1):3-11. doi: 10.1016/0360-3016(93)90167-t.
This study was designed to determine in a prospective randomized trial the optimal dose of conventionally fractionated postoperative radiotherapy for advanced head and neck cancer in relation to clinical and pathologic risk factors.
Between January 1983 and March 1991, 302 patients were enrolled on the study. This analysis is based on the first 240 patients entered through September 1989, of whom 221 (92%) had AJC Stage III or IV cancers of the oral cavity, oropharynx, hypopharynx, or larynx. The patients were stratified by postulated risk factors and randomized to one of three dose levels ranging between 52.2 Gy and 68.4 Gy, all given in daily doses of 1.8 Gy. Patients receiving > 57.6 Gy had a field reduction at this dose level such that boosts were only given to sites of increased risk.
The overall crude and actuarial 2-year local-regional recurrence rates were 25.4% and 26%, respectively. Patients who received a dose of < or = 54 Gy had a significantly higher primary failure rate than those receiving > or = 57.6 Gy (p = 0.02). No significant dose response could be demonstrated above 57.6 Gy except for patients with extracapsular nodal disease in the neck in whom the recurrence rate was significantly higher at 57.6 Gy than at > or = 63 Gy. Analysis of prognostic factors predictive of local-regional recurrence showed that the only variable of independent significance was extracapsular nodal disease. However, clusters of two or more of the following risk factors were associated with a progressively increased risk of recurrence: oral cavity primary, mucosal margins close or positive, nerve invasion, > or = 2 positive lymph nodes, largest node > 3 cm, treatment delay greater than 6 weeks, and Zubrod performance status > or = 2. Moderate to severe complications of combined treatment occurred in 7.1% of patients; these were more frequent in patients who received > or = 63 Gy.
With daily fractions of 1.7 Gy, a minimum tumor dose of 57.6 Gy to the whole operative bed should be delivered with a boost of 63 Gy being given to sites of increased risk, especially regions of the neck where extracapsular nodal disease is present. Treatment should be started as soon as possible after surgery. Dose escalation above 63 Gy at 1.8 Gy per day does not appear to improve the therapeutic ratio.
本研究旨在通过一项前瞻性随机试验，确定与临床和病理风险因素相关的晚期头颈癌术后常规分割放疗的最佳剂量。
1983年1月至1991年3月期间，302例患者纳入本研究。本分析基于截至1989年9月入组的前240例患者，其中221例（92%）患有口腔、口咽、下咽或喉的美国癌症联合委员会（AJC）III期或IV期癌症。患者按假定风险因素分层，并随机分为三个剂量水平之一，剂量范围在52.2 Gy至68.4 Gy之间，均采用每日1.8 Gy的剂量给予。接受>57.6 Gy的患者在该剂量水平时缩野，仅对高风险部位进行加量照射。
总的粗略和精算2年局部区域复发率分别为25.4%和26%。接受剂量≤54 Gy的患者原发灶失败率显著高于接受剂量≥57.6 Gy的患者（p = 0.02）。除颈部有包膜外淋巴结转移的患者外，在57.6 Gy以上未显示出明显的剂量反应，此类患者在57.6 Gy时的复发率显著高于≥63 Gy时。对预测局部区域复发的预后因素分析表明，唯一具有独立意义的变量是包膜外淋巴结转移。然而，以下两个或更多风险因素聚集与复发风险逐渐增加相关：口腔原发、黏膜切缘接近或阳性、神经侵犯、≥2个阳性淋巴结、最大淋巴结>3 cm、治疗延迟超过6周以及Zubrod体能状态≥2。联合治疗的中度至重度并发症发生在7.1%的患者中；在接受≥63 Gy的患者中更常见。
采用每日1.7 Gy的分割剂量时，应对整个手术床给予至少57.6 Gy的肿瘤剂量，并对高风险部位，特别是存在包膜外淋巴结转移的颈部区域给予63 Gy的加量照射。手术后应尽快开始治疗。每日1.8 Gy剂量下高于
