Phase I/II study of intraoperative radiotherapy for early breast cancer in Japan.

Background: Intraoperative radiotherapy (IORT) is under evaluation in breast-conserving surgery. We have begun our study with the first step being a phase I-II study. This study was designed to identify the recommended dose and to test the feasibility of and tolerance to IORT in Japanese patients (UMIN000000918).

Methods: A phase I study was designed using a scheme of dose escalation from 19 to 20 to 21 Gy. We designed the phase II study to use the recommended dose. The primary endpoint was early toxicity. Secondary endpoints were efficacy for a long period and late toxicity. Inclusion criteria included the following: (1) T < 2.5 cm, (2) age >50 years, (3) surgical margin >1 cm, (4) intraoperative pathologically free margins, and (5) sentinel node negative. Partial resection was performed with at least a 1 cm margin around the tumor. Radiation was delivered directly to the mammary gland with the use of a Mobetron(®). The toxicity was evaluated with the Common Terminology Criteria for Adverse Events (CTCAE) v3.0.

Results: Nine patients were enrolled for the phase I study. All patients tolerated and we therefore recommend 21 Gy. The following 23 patients were enrolled in a phase II study and received 21 Gy. After a median follow-up of 26.0 months, their toxicities within 3 months included deep connective tissue fibrosis (G1 23/26, G2 2/26), hematoma (G1 9/26), infection in the musculoskeletal soft tissue (G1 4/26), and soft tissue necrosis (G2 3/26). There have been no local recurrences.

Conclusions: The first group of Japanese female patients treated with IORT showed very good tolerability in the phase I/II study.