Multicenter phase 2 trial of bone-sparing chemoradiotherapy for anal cancer

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. The multicenter phase 2 DACG II trial in Denmark aimed to reduce PIF rates in AC to less than 35% using bone-specific MRI. Patients with localized AC eligible for curative-intent chemoradiotherapy (CRT) were included. For each patient, an optimized bone-sparing plan was compared to a standard plan. Toxicity data were collected at baseline, during CRT, and at 1-year follow-up. The primary endpoint was the one-year PIF rate on bone-specific MRI. Among 100 enrolled patients, 97% completed the prescribed radiotherapy (54-64 Gy) and 97% received concomitant chemotherapy. At one year, bone-specific MRIs were available for 79 patients. Bone-sparing plans consistently reduced bone dose without increasing exposure to other organs of interest (OOI), while preserving target coverage. The one-year PIF rate was 27.8%. Bone-related symptoms were reported by 34% of patients; 18% potentially related to CRT. Among patients with PIFs, 55% reported bone pain. The authors conclude that 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.