Rau B, Wust P, Tilly W, Gellermann J, Harder C, Riess H, Budach V, Felix R, Schlag P M
Campus Berlin-Buch, Robert-Roessle Hospital, Department of Surgery and Surgical Oncology, Charité Medical School of the Humboldt University of Berlin, Berlin, Germany.
Int J Radiat Oncol Biol Phys. 2000 Sep 1;48(2):381-91. doi: 10.1016/s0360-3016(00)00650-7.
Preoperative radiochemotherapy (RCT) is a widely used means of treatment for patients suffering from primary, locally advanced, or recurrent rectal cancer. We evaluated the efficacy of treatment due to additional application of regional hyperthermia (HRCT) to this conventional therapy regime in a Phase II study, employing the annular phased-array system BSD-2000 (SIGMA-60 applicator). The clinical results of the trial were encouraging. We investigated the relationship between a variety of thermal and clinical parameters in order to assess the adequacy of thermometry, the effectiveness of hyperthermia therapy, and its potential contribution to clinical endpoints.
A preoperative combination of radiotherapy (1.8 Gy for 5 days a week, total dose 45 Gy applied over 5 weeks) and chemotherapy (low-dose 5-fluorouracil [5-FU] plus leucovorin in the first and fourth week) was administered to 37 patients with primary rectal cancer (PRC) and 18 patients with recurrent rectal cancer (RRC). Regional hyperthermia (RHT) was applied once a week prior to the daily irradiation fraction of 1.8 Gy. Temperatures were registered along rectal catheters using Bowman thermistors. Measurement points related to the tumor were specified after estimating the section of the catheter in near contact with the tumor. Three patients with local recurrence after abdominoperineal resection, had their catheters positioned transgluteally under CT guidance, where the section of the catheter related to the tumor was estimated from the CT scans. Index temperatures (especially T(max), T(90)) averaged over time, cumulative minutes (cum min) (here for T(90) > reference temperature 40.5 degrees C), and equivalent minutes (equ min) (with respect to 43 degrees C) were derived from repetitive temperature-position scans (5- to 10-min intervals) utilizing software specially developed for this purpose on a PC platform. Using the statistical software package SPSS a careful analysis was performed, not only of the variance of thermal parameters with respect to clinical criteria such as toxicity, response, and survival but also its dependency on tumor characteristics.
The rate of resectability (89%) and response (59%) were high for the PRC group, and a clear positive correlation existed between index temperatures (T(90)) and thermal doses (cum min T(90) >/= 40.5 degrees C). Even though the overall 5-year survival was encouraging (60%) and significantly associated with response, there was no statistically significant relationship between temperature parameters and long-term survival for this limited number of patients. However, nonresectable tumors with higher thermal parameters (especially cum min T(90) >/= 40.5 degrees C) had a tendency for better overall survival. We found even higher temperatures in patients with recurrences (T(90) = 40.7 degrees C versus T(90) = 40.2 degrees C). However, these conditions for easier heating did not involve a favorable clinical outcome, since surgical resectability (22%) and response rate (28%) for the RRC group were low. We did not notice any other dependency of thermal parameters to a specific tumor or patient characteristics. Finally, neither acute toxicity (hot spots) induced by hyperthermia or RCT nor perioperative morbidity were correlated with temperature-derived parameters. Only a higher probability for the occurrence of hot spots was found during treatment with elevated power levels.
In this study with two subgroups, i.e., patients with PRC (n = 37) and RRC (n = 18), there exists a positive interrelationship between thermal parameters (such as T(90), cum min T(90) >/= 40,5 degrees C) and clinical parameters concerning effectiveness. Additional hyperthermia treatment does not seem to enhance toxicity or subacute morbidity. Procedures to measure temperatures and to derive thermal parameters, as well as the hyperthermia technique itself appear adequate enough to classify heat treatments in
术前放化疗（RCT）是治疗原发性、局部晚期或复发性直肠癌患者的一种广泛应用的方法。在一项II期研究中，我们评估了在这种传统治疗方案中额外应用区域热疗（HRCT）的治疗效果，该研究采用环形相控阵系统BSD - 2000（SIGMA - 60施源器）。试验的临床结果令人鼓舞。我们研究了各种热参数和临床参数之间的关系，以评估温度测量的充分性、热疗的有效性及其对临床终点的潜在贡献。
对37例原发性直肠癌（PRC）患者和18例复发性直肠癌（RRC）患者进行术前放疗（每周5天，每天1.8 Gy，5周内总剂量45 Gy）和化疗（第1周和第4周低剂量5 - 氟尿嘧啶[5 - FU]加亚叶酸钙）联合治疗。在每天1.8 Gy照射部分之前每周进行一次区域热疗（RHT）。使用鲍曼热敏电阻沿直肠导管记录温度。在估计导管与肿瘤近接触部分后，确定与肿瘤相关的测量点。3例腹会阴切除术后局部复发的患者，在CT引导下经臀定位导管，根据CT扫描估计导管与肿瘤相关的部分。通过在PC平台上为此专门开发的软件，从重复的温度 - 位置扫描（间隔5至10分钟）中得出随时间平均的指标温度（特别是T(max)、T(90)）、累积分钟数（cum min）（此处针对T(90)>参考温度40.5摄氏度）和等效分钟数（equ min）（相对于43摄氏度）。使用统计软件包SPSS进行了仔细分析，不仅分析了热参数相对于毒性、反应和生存等临床标准的方差，还分析了其对肿瘤特征的依赖性。
PRC组的可切除率（89%）和缓解率（59%）较高，指标温度（T(90)）与热剂量（cum min T(90)≥40.5摄氏度）之间存在明显的正相关。尽管总体5年生存率令人鼓舞（60%）且与缓解显著相关，但对于这有限数量的患者，温度参数与长期生存之间没有统计学上的显著关系。然而，热参数较高（特别是cum min T(90)≥40.5摄氏度）的不可切除肿瘤总体生存有更好的趋势。我们发现复发患者的温度更高（T(90)=40.7摄氏度对比T(90)=40.2摄氏度）。然而，这些更容易加热的情况并未带来良好的临床结果，因为RRC组的手术可切除率（22%）和缓解率（28%）较低。我们没有注意到热参数对特定肿瘤或患者特征的任何其他依赖性。最后，热疗或RCT引起的急性毒性（热点）以及围手术期发病率均与温度衍生参数无关。仅发现在高功率水平治疗期间热点出现的可能性更高。
在这项有两个亚组（即PRC患者[n = 37]和RRC患者[n = 18]）的研究中，热参数（如T(90)、cum min T(90)≥40.5摄氏度）与有效性相关的临床参数之间存在正相关关系。额外的热疗似乎不会增加毒性或亚急性发病率。测量温度和得出热参数的程序以及热疗技术本身似乎足以对热疗进行分类。
