Pathologic tumor and normal mucosa responses after hyperfractionated versus hypofractionated preoperative radiotherapy for rectal cancer.

Abstract

556 Background: The aim of the study is to assess radiation-induced tumor and normal mucosa responses in patients who underwent preoperative radiotherapy according to two different fractionation protocols. This research constitutes one of the secondary endpoints of a prospective randomized trial. Methods: Pathological samples after preoperative radiotherapy and surgery were obtained from 106 patients: 50 were treated with hypofractionation 39 Gy in 3.0 Gy per fraction (HYPO) and 56 with accelerated hyperfractionation 42 Gy given in two daily fractions of 1.5 Gy with a minimal interfraction interval of 6 hours (HART). This sample represents approximately 30% of an overall trial size. Over 50 pathological features were assessed for each sample including tumor/nodal response, normal mucosa and cellular matrix response, ulceration and morphology of tumor cells. The observed grades of responses in HYPO vs. HART were compared using U Mann-Whitney test. Results: The primary tumor downstaging was observed in 41% vs. 35% of the patients treated with HYPO and HART respectively, the difference was not significant (p=0.5). By contrast, a trend towards improved nodal response among the patients treated with HYPO was recorded, with 94% achieving complete or major nodal response, compared to 73% in HART (p=0.03). Mucosal atrophy and edema were significantly higher in HYPO (p=0.003 and p=0.02, respectively). A trend for increased mucosal inflammation was also recorded in HYPO (p=0.06). Tumor/nodal responses were not significantly influenced by time-interval radiotherapy-surgery (below or above the median of 11 days), however, more cellular injury to normal mucosa (atrophy, ulceration) was observed at short RT-surgery intervals (p=0.01). Conclusions: Radiation-induced tumor and normal mucosa responses differ significantly according to fractionation schedule, with more mucosa injury observed in HYPO. Pathological responses of mucosa are also influenced by time-interval radiotherapy-surgery.