Garden A S, Morrison W H, Ang K K, Peters L J
Department of Radiotherapy, Box 97, U.T.M.D. Anderson Cancer, Houston, TX 77030.
Int J Radiat Oncol Biol Phys. 1995 Feb 1;31(3):493-502. doi: 10.1016/0360-3016(94)00334-H.
In 1984 we began treating patients with squamous cell carcinomas of the larynx and hypopharynx with hyperfractionated radiotherapy. Patients received 76.8 Gy in 1.2 Gy fractions twice daily, with a 4 h interfraction interval. In 1988, this schedule was modified in patients treated with shrinking field techniques. The dose per fraction was slightly reduced (while not changing the total dose), and the interfraction interval was increased to 6 h. The goal was to decrease toxicity while maintaining satisfactory local-regional control. This retrospective study analyzes the results of this schedule modification.
Two hundred thirty-six patients were included in the analysis. Distribution of patients by primary site and T stage was as follows: supraglottic larynx, 120 patients; hypopharynx, 70; true vocal cord, 24; and oropharynx, 22; T1, 5 patients; T2, 118; T3, 93; T4, 19; and Tx, 1. Ninety-nine patients presented with cervical nodal disease. Seventy-eight patients (group A), including 16 treated with induction chemotherapy, were treated throughout with 1.2 Gy fractions twice daily and a 4-h interfraction interval. Subsequently, 158 patients (group B), 57 of whom received chemotherapy, received 1.1 Gy fractions to 55 Gy, and then 1.2 Gy fractions to their boost volumes to 76.6 Gy. The interfraction interval was 6 h. Median follow-up was 91 and 35 months for group A and B, respectively.
Two-year actuarial survival, local control, and ultimate local rates were 70%, 75%, and 85%, respectively. Differences between survival rates for group A and group B were not statistically significant, with 2-year rates of 66% and 72%, respectively. Overall local control rates at 2 years were 77% and 74%, respectively, for groups A and B (p = 0.22). However, there was a trend toward inferior results in group B patients with T3 disease (67% at 2 years compared to 76% in group A, p = 0.13). Confluent mucositis and persistent mucositis developed in 52% and 14% of group A patients, but only 37% and 4% of group B patients (p = 0.02 and p < 0.01, respectively). There was a near significant trend toward fewer late complications in group B who developed an 8% complication rate at 3 years compared to 15% of group A patients (p = 0.07).
The net effect of reducing the dose per fraction to 1.1 Gy twice daily for fields covering gross disease and subclinical sites, and increasing the interfraction interval to 6 h was to reduce the incidence of both acute and late complications. Excellent overall local control rates (85%) for T2 lesions were achieved with both hyperfractionation regimens and we, therefore, continue to treat patients with T2 tumors with the modified schedule. The overall results in selected patients with T3 lesions was also satisfactory (69%), but as there was a trend towards poorer local control in patients treated with 1.1 Gy fractions, we recommend using 1.2 Gy for the entire treatment of these patients, while maintaining the 6 h interfraction interval to reduce the risk of late complications.
1984年我们开始采用超分割放疗治疗喉和下咽鳞状细胞癌患者。患者每天分两次接受1.2 Gy的分次照射，总剂量为76.8 Gy，两次照射间隔4小时。1988年，对于采用缩野技术治疗的患者，该方案进行了修改。每次照射剂量略有降低（同时不改变总剂量），照射间隔延长至6小时。目的是在维持满意的局部区域控制的同时降低毒性。这项回顾性研究分析了该方案修改的结果。
236例患者纳入分析。按原发部位和T分期的患者分布如下：声门上喉，120例；下咽，70例；真声带，24例；口咽，22例；T1，5例；T2，118例；T3，93例；T4，19例；Tx，1例。99例患者有颈部淋巴结转移。78例患者（A组），包括16例接受诱导化疗的患者，每天分两次接受1.2 Gy的分次照射，照射间隔4小时。随后，158例患者（B组），其中57例接受了化疗，先接受1.1 Gy的分次照射至55 Gy，然后对加量区接受1.2 Gy的分次照射至76.6 Gy。照射间隔为6小时。A组和B组的中位随访时间分别为91个月和35个月。
两年精算生存率、局部控制率和最终局部控制率分别为70%、75%和85%。A组和B组生存率差异无统计学意义，两年生存率分别为66%和72%。A组和B组两年的总体局部控制率分别为77%和74%（p = 0.22）。然而，B组T3期疾病患者的结果有较差的趋势（两年时为67%，而A组为76%，p = 0.13）。A组52%和14%的患者发生了融合性黏膜炎和持续性黏膜炎，但B组仅为37%和4%（分别为p = 0.02和p < 0.01）。B组晚期并发症有减少的趋势，接近显著差异，3年时并发症发生率为8%，而A组患者为15%（p = 0.07）。
对于覆盖大体病变和亚临床部位的野，将每次照射剂量减至1.1 Gy，每天两次，并将照射间隔延长至6小时的总体效果是降低了急性和晚期并发症的发生率。两种超分割方案对T2病变均取得了优异的总体局部控制率（85%），因此，我们继续采用修改后的方案治疗T2肿瘤患者。选定的T3病变患者的总体结果也令人满意（69%），但由于采用1.1 Gy分次照射的患者局部控制有较差的趋势，我们建议对这些患者全程采用1.2 Gy照射，同时维持6小时的照射间隔以降低晚期并发症风险。
