腔内加温合并放疗局部进展期宫颈癌的远期疗效分析

Long-term outcomes of intracavitary hyperthermia in combination with radiotherapy for locally advanced uterine cervical cancer

目的前瞻性非随机对照比较腔内加温合并放疗与单纯放疗的远期疗效及并发症。方法对中晚期宫颈癌310例进行分析，腔内加温合并放疗181例（热放疗组）；体外照射合并传统腔内放疗129例（放疗组）。体外放疗采用^60Coγ线或6～8MVX线常规分割放疗。加温组给盆腔前后对穿野中平面40Gy后，缩野从体两侧水平加量至60～65Gy；腔内加温采用915MHz微波热疗机，附有阴道施源器，肿瘤表面温度46～47℃，2次／周，40min／次，共加温10～12次。放疗组给予盆腔前后对穿照射，中平面40Gy。1989年前腔内放疗用后装上镭（官腔50mg，阴道30mg，24h／次，1次／周，共3次，总量7200mg·h）与外照射交替进行，1989年后腔内照射采用^192 Ir源，5—6Gy／次，2次／周，给予A点总屠30—36Gy。结果Ⅱ期病例热放疗组、放疗组5年生存率分别为67．4％、52．1％（X^2=7．55，P=0．006），10年生存率分别为46．5％、42．6％（X^2=3．90，P=0．058）；Ⅲ期病例5年生存率分别为60．0％、32．3％（X^2=7．06，P=0．007），10年生存率分别为43．7%、20．6％（X^2=17．28，P=0．000）。Cox回归分析显示肿瘤分期（P=0．023）、是否接受热疗（P=0．019）是影响生存的因素。晚期轻中度放射性直肠炎和膀胱炎热放疗组、放疗组分别为32例（17．7％）、42例（33．t％）（X^2=9．18，P=0．002），直肠阴道瘘分别为1例（0．6％）、5例（3．9％）（X^2=4．38，P=0．036）。结论腔内加温合并外照射治疗中晚期宫颈癌远期疗效明显优于单纯放疗，晚期副反应也明显低且无严重副反应发生，值得进一步随机临床研究。

Objective To evaluate the long-term clinical efficacy and toxicities of combined intracavitary hyperthermia and radiotherapy for locally advanced uterine cervical cancer. Methods 310 patients with locally advanced uterine cervical cancer were assigned into intracavitary hyperthermia ＋ radiotherapy group （TRT, 181 patients） and external-beam radiotherapy ＋ traditional intracavitary radiation group （RT, 129 patients）. The external-beam radiotherapy were given with ^60Co γ-ray or 6-8 MV X-ray in traditional fractionation. In TRT group,radiotherapy was 40 Gy using the anterior-posterior pelvic fields and additional 20-25 Gy using the lateral fields. Hyperthermia was delivered by the 915 MHz microwave hyperthermia device within 15-60 min after external radiotherapy for 10-12 times （40 rain each time, 1-2 times per week）. The temperature of tumor surface was 46-47 ℃. In the RT group, the external-beam radiotherapy of 40 Gy was delivered using the anterior-posterior pelvic fields. The intracavity radiotherapy of radium was delivered before 1989 ,with 50 mg radium in the vagina and 30 mg in uterine cavity for 24 hours ,weekly for 3 times to a total dose of 7200 mg· h. After 1989 ,intracavity radiotherapy of ^192Ir was delivered to a total dose of 30-36 Gy to point A in 5-6 Gy fractions,2 fractions per week. Results The 5-year survival of patients in TRT group and RT group was 67.4% versus 52.1% for stage Ⅱ disease （ X^2 = 7.55, P = 0. 006 ） , and 60.0% versus32.3% for stage Ⅲ （ X2 = 7.06 , P = 0. 007 ） . The 10 - year survival was46.5% versus42.6% forstage H （ X^2 = 3.90,P = 0.058） , and 43.7% versus 20.6% for stage HI （ X^2 = 17.28,P = 0.000）. Cox regression analysis showed that the tumor stage（P = 0. 023 ） and intracavitary hyperthermia （P = 0. 019 ） were prognostic factors. According to the RTOG criteria, the rate of mild to moderate late side effects of rectum and bladder in TRT and RT group was 17.7% and 33.1% , respectively （X^2 = 9.18,P = 0. 002）. Rectovagi nal fistula was developed in 5 patients（3.9% ） in RT group and 1 patient （0.6%） in TRT group（ X^2 = 4.38,P = 0. 036）. Conclusions The long-term survival of patients with stage m uterine eervieal cancer is better of TRT group than RT group. The TRT is well tolerated and the late toxicity rate is obviously low. It is necessary to carry out large randomized clinical trials to confirm these outcomes.