Gaspar L E, Qian C, Kocha W I, Coia L R, Herskovic A, Graham M
Department of Radiation Oncology, Wayne State University, Detroit, MI 48201, USA.
Int J Radiat Oncol Biol Phys. 1997 Feb 1;37(3):593-9. doi: 10.1016/s0360-3016(96)00591-3.
A multi-institutional, prospective study was designed to determine the feasibility and tolerance of external beam irradiation plus concurrent chemotherapy and esophageal brachytherapy (EB) in a potentially curable group of patients with adenocarcinoma or squamous cell carcinoma of the esophagus.
Planned treatment was 50 Gy external beam radiation (25 fractions/5 weeks) followed 2 weeks later by EB [either high dose rate (HDR) 5 Gy, weeks 8, 9, and 10, for a total of 15 Gy, or low dose rate (LDR) 20 Gy, week 8]. The protocol was later revised to delete the LDR alternative, owing to poor accrual, and to decrease the HDR dose to 10 Gy (i.e. 5 Gy, weeks 8 and 9). Chemotherapy was given weeks 1, 5, 8, and 11 with cisplatin 75 mg/m2 and 5-fluorouracil 1000 mg2/m per 24 h, 96-h infusion. The study closed in January 1995 after 56 patients had been entered on the HDR arm. Six patients were declared ineligible owing to tumor extension to the gastroesophageal junction (three patients) or involved celiac lymph nodes (three patients). Of the 50 eligible patients, the planned EB dose was 15 and 10 Gy in 40 and 10 patients, respectively. Forty-six (92%) of the eligible patients had squamous histology, and three (6%) adenocarcinoma.
Life-threatening toxicity or treatment-related death occurred in 13 (26%) and 4 (8%) of the 50 eligible patients, respectively. Treatment-related esophageal fistulas occurred in three patients (12% overall, 14% of patients starting EB) at 0.5-6.2 months from the first day of brachytherapy, leading to death in three. The fourth death was secondary to renal toxicity and infection attributed to chemotherapy. No correlation was found between the development of fistula and location of primary tumor, brachytherapy active length or applicator diameter. So far, 5 of the 6 treatment-related fistulas have occurred following 15 Gy EB. The other fistula occurred after only 5 Gy of a planned 15 Gy was delivered.
Thirty-five patients (70%) were able to complete external beam, EB, and at least two courses of chemotherapy. Estimated survival rate at 12 months is 48%, with an estimated 11-month median survival rate. Survival following external beam radiation plus concurrent chemotherapy and EB does not appear to be significantly different from survival seen following external beam radiation and chemotherapy only. The development of six fistulas in the 35 patients completing EB is of concern. Based on the high incidence of fistulas, we urge extreme caution in employing EB as a boost following concurrent external beam radiation and chemotherapy.
开展一项多机构前瞻性研究，以确定体外照射联合同步化疗及食管近距离放疗（EB）在一组可能治愈的食管腺癌或鳞状细胞癌患者中的可行性和耐受性。
计划的治疗方案为体外照射50 Gy（25次分割/5周），2周后进行EB治疗[高剂量率（HDR）5 Gy，第8、9和10周，共15 Gy；或低剂量率（LDR）20 Gy，第8周]。由于入组情况不佳，该方案后来进行了修订，删除了LDR方案，并将HDR剂量降至10 Gy（即第8和9周各5 Gy）。化疗在第1、5、8和11周进行，顺铂剂量为75 mg/m²，5-氟尿嘧啶剂量为1000 mg²/m，每24小时持续静脉输注96小时。在56例患者进入HDR组后，该研究于1995年1月结束。6例患者因肿瘤侵犯至胃食管交界（3例）或累及腹腔淋巴结（3例）而被判定不符合入组标准。在50例符合条件的患者中，计划接受EB剂量为15 Gy的有40例，10 Gy的有10例。符合条件的患者中46例（92%）为鳞状组织学类型，3例（6%）为腺癌。
50例符合条件的患者中，分别有13例（26%）发生危及生命的毒性反应或与治疗相关的死亡，4例（8%）出现与治疗相关的死亡。3例患者（总体12%，开始接受EB治疗患者的14%）在近距离放疗第一天后的0.5至6.2个月发生与治疗相关的食管瘘，导致3例患者死亡。第四例死亡继发于化疗引起的肾毒性和感染。未发现瘘的发生与原发肿瘤位置、近距离放疗活性长度或施源器直径之间存在相关性。到目前为止，6例与治疗相关的瘘中有5例发生在接受15 Gy EB治疗后。另一例瘘发生在计划的15 Gy中仅给予5 Gy之后。
35例患者（70%）能够完成体外照射、EB及至少两个疗程的化疗。估计12个月生存率为48%，中位生存期估计为11个月。体外照射联合同步化疗及EB后的生存率与仅接受体外照射和化疗后的生存率似乎无显著差异。在完成EB治疗的35例患者中出现6例瘘令人担忧。基于瘘的高发生率，我们强烈建议在同步体外照射和化疗后使用EB作为强化治疗时要极度谨慎。
