Preoperative radiochemotherapy in locally advanced or recurrent rectal cancer: regional radiofrequency hyperthermia correlates with clinical parameters

Abstract

Purpose: 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. Methods and Materials: 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°C), and equivalent minutes (equ min) (with respect to 43°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. Results: 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°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°C) had a tendency for better overall survival. We found even higher temperatures in patients with recurrences (T 90 = 40.7°C versus T 90 = 40.2°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. Conclusion: 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°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 sessions as more or less effective. However, cautious interpretation of these relationships is essential, since we have found that subgroups (e.g., RRC) achieve higher temperatures due to reasons regarding the tumor biology or disturbed microcirculation nevertheless indicating an unfavorable prognosis.