Insterstitial hyperthermia and high dose rate brachytherapy in the treatment of anal cancer: A phase I/II study

Abstract

Purpose : The rate of local failure is sufficiently high following sphincter conserving surgery and radiation therapy for advanced anal cancers to warrant investigation of improved local treatment techniques. This Phase I/II study was undertaken to investigate the site-specific toxicities and response of Stage II and III anal cancers to interstitial thermoradiotherapy using a hot water interstitial system. Methods and Materials : Between September 1988 and March 1991, 14 patients with primary carcinomas of the anal canal, UICC Stage T 2–3, N 0–1, Mo, were treated with split-course external beam irradiation to the pelvis (30 Gy + 20 Gy) and 1 or 2 interstitial Iridium-192 high dose rate (Ir-192 HDR) implants (6–8 Gy each) immediately followed by interstitial hyperthermia (HT). Patients with tumor diameters > 3 cm were scheduled to receive chemotherapy consisting of 2 courses of 5-fluorouracil and mitomycin C given concomitantly with external beam radiation. Interstitial hyperthermia was induced by circulating warm water through the needles that were implanted to hold the Ir-192 source. The treatment goal was to achieve and maintain a temperature of 42.5°C over a time period of 40 min. A 3-point thermocouple probe inserted into one or two additional needles was used for thermometry. The temperatures were recorded by manual mapping along these needles at steps of 0.5 or 1 cm. Results : A total of 20 Ir-192 HDR-HT implants were performed in 14 patients. All but two patients completed the external beam irradiation; five patients received concomitant chemotherapy. Analysis of thermal parameters showed that minimum intratumoral temperatures (T min) of 42°C, 42.5°C, 43°C, and 44°C were achieved in 64%, 37.5%,14%, and 7% of patients, respectively. Intratumoral mean T min, mean average, and mean maximum temperatures for these patients were 41.7°C, 42.4°C, and 43.4°C, respectively. Brachytherapy and HT were well tolerated. Clinical complete responses (cCR) were obtained in 11/14 (78.5%) patients, complete histopathological responses (pCR) in 10/14 (71%). Only one patient with pCR recurred and succumbed to her disease. Patients with persistent disease (1 minimal and 3 partial responders, including 1 cCR) underwent abdominal-perineal resection but subsequently died from local-regional recurrence. One patient with pCR died from unrelated causes. Median survival for all patients from onset of radiation to death or last follow-up is 26 months. Eight patients are alive disease-free after a follow-up ranging from 16–44 months (median: 30, mean: 30 months). Treatment complications were limited to two patients who developed persistent ulcers. Sphincter function was maintained in 50% of patients. Conclusion : This study demonstrates that interstitial warm water hyperthermia in combination with brachytherapy for anal carcinomas is feasible and did not add to complications when compared to studies employing external beam irradiation and brachytherapy alone. The thermal parameters obtained by the warm water system compare favorably to those reported by others using radiofrequency and microwave systems.