One‐year follow‐up after fractionated ultra‐high‐dose‐rate FLASH radiotherapy in patient with extramammary Paget disease of the scrotum

Abstract Objective Ultrahigh‐dose‐rate radiotherapy (FLASH‐RT) has been shown to reduce radiation‐induced normal tissue injury in preclinical studies. Here, we describe the first patient worldwide to receive fractionated FLASH‐RT. Methods An elderly male patient was diagnosed with extramammary Paget disease of the scrotum along with multiple lymph node and bone metastases. After 6 cycles of chemotherapy, the disease progressed in the scrotum. The scrotal lesions were evaluated for FLASH‐RT. 9 MeV electron FLASH‐RT was performed at a dose rate of 120 Gy/s. The field size was 5 cm × 5 cm, and the prescribed dose was 40 Gy in five fractions. Dosimetric verification was performed daily. Treatment response was evaluated at 3‐month post FLASH‐RT, and normal tissue toxicity was assessed from the beginning of FLASH‐RT to 12‐month post‐irradiation. Results A 1‐year follow‐up was achieved for scrotal lesions treated with electron FLASH‐RT in patients with extramammary Paget disease. Electron FLASH‐RT was safe, and treatment‐related adverse events were mild. Transient skin toxicity occurred 2–5 weeks post FLASH‐RT, and exudation and burning pain were significantly alleviated. A complete response was achieved 2–3 months post FLASH‐RT, and the tumor lesions were covered by the normal epithelium of the scrotum. At the end of the one‐year follow‐up, the tumor lesions continued to respond, and one‐year survival was achieved without additional injury to the irradiated areas after FLASH‐RT. Conclusion Fractionated electron FLASH‐RT is feasible and safe for the treatment of extramammary Paget disease of the scrotum. Our findings support further exploration of electron FLASH‐RT in patients with skin tumors.