Aristizabal S A, Oleson J R
Cancer Res. 1984 Oct;44(10 Suppl):4757s-4760s.
Low-dose-rate continuous irradiation in conjunction with localized current fields has been investigated in Phase I human trials at several institutions since 1977. To date, nearly 100 patients with a variety of malignant lesions (carcinomas, melanomas, sarcomas, lymphomas) in different anatomical locations (skin, head and neck, breast, pelvis, extremities) have been entered into experimental protocols. Different radiation and thermal dose levels have been evaluated. Significant progress in equipment and techniques has been accomplished. A wide range of complete response rates (38 to 83%) and complication rates (7 to 25%) has been reported. Analysis of results showed a good correlation of complete response rates with the radiation dose level and minimum temperature. The most successful regimens included either an "optimal radiation dose" (greater than 6000 rads) or an "effective time-averaged minimum temperature" (44 degrees). Important considerations in the design of clinical trials for Phases II and III are: (a) in regimens with curative aim, a hyperthermic effect may not be achieved in all regional sites of disease, especially in those areas harboring subclinical disease. Radiation dose-fractionation schedules of proven adjuvant efficacy thus must be used; (b) whether the total radiation dose to the site of bulky disease when combined with hyperthermia can be reduced without loss of therapeutic efficacy relative to conventional radiation doses is critically dependent upon minimum temperatures and uniformity of temperature within the tumor; (c) optimized combined therapy is likely to reflect a high level of quality assurance in administering both the interstitial irradiation and the interstitial hyperthermia; (d) the present criteria for evaluation of tumor response (no response, partial response, and complete response) are clinically meaningless. The criterion, "local control" or "failure," should be adopted in future trials in Phases II and III with the curative aim to allow comparison of results with historical or concurrent controls treated with radiation alone.
自1977年以来，几家机构已在I期人体试验中对低剂量率连续照射与局部电流场相结合的方法进行了研究。迄今为止，已有近100名患有不同解剖部位（皮肤、头颈部、乳房、骨盆、四肢）各种恶性病变（癌、黑色素瘤、肉瘤、淋巴瘤）的患者进入实验方案。已评估了不同的辐射和热剂量水平。在设备和技术方面取得了重大进展。报告的完全缓解率（38%至83%）和并发症发生率（7%至25%）范围很广。结果分析表明，完全缓解率与辐射剂量水平和最低温度有良好的相关性。最成功的方案包括“最佳辐射剂量”（大于6000拉德）或“有效时间平均最低温度”（44摄氏度）。II期和III期临床试验设计中的重要考虑因素包括：（a）在以治愈为目的的方案中，可能并非在疾病的所有区域部位都能实现热疗效果，尤其是在那些存在亚临床疾病的区域。因此必须使用已证实具有辅助疗效的辐射剂量分割方案；（b）与传统辐射剂量相比，当与热疗联合使用时，对大块疾病部位的总辐射剂量是否可以降低而不损失治疗效果，关键取决于肿瘤内的最低温度和温度均匀性；（c）优化的联合治疗可能反映出在进行间质照射和间质热疗时的高水平质量保证；（d）目前评估肿瘤反应的标准（无反应、部分反应和完全反应）在临床上没有意义。在II期和III期以治愈为目的的未来试验中应采用“局部控制”或“失败”的标准，以便将结果与单独接受放疗的历史或同期对照进行比较。
