title: Phase I/II study of intraoperative radiotherapy for early breast cancer in Japan.
abstract: 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.
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya University School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan. m-sawaki@med.nagoya-u.ac.jp
authors.forename: Masataka
authors.initials: M
authors.lastname: Sawaki
authors.forename: Shigenori
authors.initials: S
authors.lastname: Sato
authors.forename: Sumiyo
authors.initials: S
authors.lastname: Noda
authors.forename: Ai
authors.initials: A
authors.lastname: Idota
authors.forename: Hiroki
authors.initials: H
authors.lastname: Uchida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tsunoda
authors.forename: Toyone
authors.initials: T
authors.lastname: Kikumori
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Aoyama
authors.forename: Shunichi
authors.initials: S
authors.lastname: Ishihara
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Itoh
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Imai
mesh_terms: D000368:Aged; D044466:Asian People; D001943:Breast Neoplasms / Q000473:pathology / Q000532:radiotherapy* / Q000601:surgery*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005355:Fibrosis / Q000209:etiology; D005500:Follow-Up Studies; D006406:Hematoma / Q000209:etiology; D006801:Humans; D007432:Intraoperative Period; D008875:Middle Aged; D009336:Necrosis / Q000209:etiology; D011878:Radiotherapy / Q000009:adverse effects*; D016896:Treatment Outcome