Bone-sparing chemoradiotherapy for anal cancer - Results of a phase II trial by the Danish Anal Cancer Group - The DACG II (NCT05385250).

Abstract

Radiotherapy-induced bone damage and pelvic insufficiency fractures (PIFs) are known complications from pelvic radiotherapy. In anal cancer (AC), PIFs have been reported in up to 50% of patients with associated pain. This multicenter phase II trial aimed to reduce PIF rates from 50% to < 35% using bone-specific MRIs and associated symptoms in AC. Patients with localized AC eligible for curatively intended chemoradiotherapy (CRT) were prospectively included. Detailed bone substructure delineation was performed using a standardized atlas. For each patient, a standard plan and an optimized bone-sparing plan were compared. The optimal plan was selected for treatment. Toxicity data were collected at baseline, during CRT, and at 1-year follow-up. The primary endpoint was the 1-year PIF rate evaluated on bone-specific MRI. Power calculations estimated a sample size of N = 85 to detect a reduction from 50% to 35%. We enrolled 100 patients from three centers. Most were female, had T2 and p16-positive tumors. 97% completed the prescribed radiotherapy (54 Gy-64 Gy), and 97% received concomitant chemotherapy. At the 1-year endpoint, bone-specific MRIs were available for 79 patients. Bone-sparing plans consistently reduce bone dose without increasing exposure to other organs of interest (OOIs), while preserving target coverage. The one-year PIF rate was 27.8%. Bone-related symptoms were reported by 34% of all patients, 18% potentially related to CRT. Among patients with PIFs, 55% reported bone pain. This is the first study to demonstrate that bone-sparing radiotherapy reduced PIF rates compared to historical data without compromising target coverage or increasing OOI toxicity.