Prospective clinical trial of 12-fraction carbon-ion radiotherapy for primary renal cell carcinoma

// Goro Kasuya 1 , Hiroshi Tsuji 1 , Takuma Nomiya 2 , Hirokazu Makishima 1 , Yasuo Haruyama 3 , Gen Kobashi 3 , Kazuhiko Hayashi 4 , Daniel K. Ebner 1, 5 , Tokuhiko Omatsu 1 , Riwa Kishimoto 1 , Shigeo Yasuda 6 , Tatsuo Igarashi 7, 8 , Mototsugu Oya 9 , Koichiro Akakura 10 , Hiroyoshi Suzuki 11 , Tomohiko Ichikawa 12 , Jun Shimazaki 12 , Tadashi Kamada 1 and the Working Group for Genitourinary Tumors 1 Hospital of the National Institute of Radiological Sciences, National Institutes for Quantum and Radiological Science and Technology, Chiba, Japan 2 Department of Radiology, Joban Hospital, Iwaki, Japan 3 Department of Public Health, Dokkyo Medical University, Tochigi, Japan 4 Osaka Heavy Ion Therapy Center, Osaka, Japan 5 Harvard TH Chan School of Public Health, Boston, MA, USA 6 Department of Radiation Oncology, Chiba Rosai Hospital, Chiba, Japan 7 Department of Urology, Seirei Sakura Citizen Hospital, Chiba, Japan 8 Center for Frontier Medical Engineering, Chiba University, Chiba, Japan 9 Department of Urology, Keio University School of Medicine, Tokyo, Japan 10 Department of Urology, Japan Community Health Care Organization Tokyo, Shinjuku Medical Center, Tokyo, Japan 11 Department of Urology, Toho University Sakura Medical Center, Chiba, Japan 12 Department of Urology, Graduate School of Medicine, Chiba University, Chiba, Japan Correspondence to: Goro Kasuya, email: kasuya.goro@qst.go.jp Keywords: carbon-ion radiotherapy; renal cell carcinoma; prospective study; radiation therapy; renal function Received: November 07, 2018      Accepted: December 20, 2018      Published: January 01, 2019 ABSTRACT The aims of this study were to clarify the safety and efficacy of 12-fraction carbon-ion radiotherapy (CIRT) for primary renal cell carcinoma (RCC) and to confirm the recommended dose in a prospective clinical trial. This clinical trial was planned as a non-randomized, open-label, single-center phase I/II study of CIRT monotherapy. The incidence of acute adverse events was the primary endpoint. Dose-limiting toxicities (DLTs) were defined as grade ≥3 skin, gastrointestinal tract, or urologic adverse events. Based on the eligibility criteria, 8 patients with primary RCC, including 3 medically inoperable patients and 5 patients with tumors >4 cm, were enrolled. Of the 8 patients, 5 were treated with 66 Gy (relative biological effectiveness [RBE]), and subsequently, the dose was escalated to 72 Gy (RBE) for the remaining 3 patients. The median follow-up time was 43.1 months. No DLTs were observed at any dose level though the end of follow-up. Although 1 patient died of pneumonia 3 months after CIRT, which was determined to be unrelated to CIRT, no grade 3 or higher adverse events were observed, and both local control and cancer-specific survival rates were 100%. In conclusion, the safety and efficacy of CIRT hypofractionation using 12-fractions for the treatment of eligible RCC patients, including those with inoperable or tumor size >4 cm, were confirmed in this prospective trial, and a recommended dose of 72 Gy (RBE) was established.