Preoperative Hypoxyradiotherapy of Colorectal Carcinoma

Abstract

The article focuses on the radioprotective effect of acute hypoxia on healthy tissues during preoperative accelerated hypoxyradiotherapy of colorectal carcinoma performed as locoregional irradiation including the common iliac lymph nodes. Analysis of early and late side effects and complications. In this prospective study, early and late complications were assessed in 50 patients as a function of hypoxyradiotherapeutic dose increase. The preliminary treatment results of this radiotherapeutic modification were evaluated after a median follow-up of 48 months using Kaplen-Meier analysis. Between April 1991 and February 1997, 50 patients (36 men and 14 women) with colorectal carcinoma were treated preoperatively with locoregional accelerated hypofractionated hypoxyradiotherapy. The extent of disease was classified according to Dukes' criteria (A: four patients, B. 28 patients, C: 18 patients). We used a 20-MeV linear accelerator with two parallel opposed fields. Hypoxyradiotherapy was performed extending from the perineum to the L4 region. Acute hypoxia was induced during irradiation by ventilation of a hypoxic gas mixture containing 7.8-8.0% oxygen. Total doses of 24 Gy/8 days, 28 Gy/9 days, and 32 Gy/10 days were applied in five, 20, and 25 patients, respectively. Low anterior resection or abdominoperineal amputation of the rectum was performed the day after completion of preoperative hypoxyradiotherapy. The early reactions after irradiation were evaluated according to the Common Toxicity Criteria of the National Cancer Institute (CTC-NCI). Early postirradiation proctitis was documented in three and early radiation-induced cystitis in two patients only. Neither early nor late radiation-associated complications were observed in any of the three hypoxyradiotherapy schedules during the follow-up period of 6-105 months. Based on Kaplan-Meier analysis (median 48 months), a 5-year overall survival rate of 61.5% and a local relapse-free survival rate of 84.2% can be expected. Treatment failures were predominantly systemic. We believe it can be concluded that acute hypoxia has a radioprotective effect on normal tissues during accelerated hypoxyradiotherapy of colorectal carcinoma. Hypoxyradiotherapy permits safe administration of doses higher than those tolerated by normoxic, noncanceorus tissue, resulting in the amplification of the biological effect of radiation on tumor tissue and contributing to an improved outcome after combined radiosurgical treatment of colorectal carcinoma.