title: A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 5-year results of local control and cosmetic outcome.
abstract: BACKGROUND
  To date, there are no reports of intraoperative radiotherapy (IORT) use with long-term follow up as a method of accelerated partial breast irradiation (APBI) in Asian countries. We initiated a prospective phase I/II clinical trial of IORT in Japan in 2007, and herein, we report the 5-year follow-up results.
  
  
  METHODS
  The following inclusion criteria were used for enrollment in the trial: (1) tumor size < 2.5 cm, (2) desire for breast-conserving surgery, (3) age >50 years, and (4) negative margins after resection. In February 2009, the eligibility criteria were changed to include only patients with sentinel lymph node-negative disease. In phase I, the radiotherapy dose was escalated from 19 Gy/fr to 21 Gy/fr, incremented by 1 Gy per step, with 3 patients in each step. Doses were escalated after all patients in the preceding cohort had completed treatment and exhibited only grade 1 or 2 toxicities at a given dose level. The recommended phase II dose was set at 21 Gy at 90 % isodose. The primary endpoint was early toxicity. Secondary endpoints were long-term efficacy and late toxicity. In addition, Hypertrophic scarring was evaluated retrospectively as a cosmetic outcome by a radiation oncologist.
  
  
  RESULTS
  Between December 2007 and March 2010, 32 women with breast cancer were enrolled in the trial. The median age was 65 years (51-80 years), and the median follow-up time was 6 years. No recurrence or metastasis was observed in any patient. Grade 2 fibrosis was detected in 3 patients as an acute adverse event and in 2 patients as a late adverse event. Ten patients developed a hypertrophic scar 1 year after the IORT; the number of patients decreased to 7 in the 3 years of follow-up.
  
  
  CONCLUSIONS
  The first group of female Asian patients tolerated the treatment with IORT in this Phase I/II study and remained recurrence-free for more than 5 years after treatment. However, 24 % of the patients developed hypertrophic scarring, an event that is being further examined in our ongoing multi-center Phase II trial of IORT for early breast cancer.
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi, 466-8550, Japan. mkawamura@med.nagoya-u.ac.jp.
authors.forename: Mariko
authors.initials: M
authors.lastname: Kawamura
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi, 466-8550, Japan. itoh@med.nagoya-u.ac.jp.
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Itoh
authors.affiliation: Department of Breast Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, Japan. m-sawaki@aichi-cc.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Sawaki
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. kikumori@med.nagoya-u.ac.jp.
authors.forename: Toyone
authors.initials: T
authors.lastname: Kikumori
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. nobtsun@med.nagoya-u.ac.jp.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Tsunoda
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi, 466-8550, Japan. kamomae@med.nagoya-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Kamomae
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi, 466-8550, Japan. sjkubota@med.nagoya-u.ac.jp.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kubota
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi, 466-8550, Japan. tohruokada@med.nagoya-u.ac.jp.
authors.forename: Tohru
authors.initials: T
authors.lastname: Okada
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi, 466-8550, Japan. rie-naka@med.nagoya-u.ac.jp.
authors.forename: Rie
authors.initials: R
authors.lastname: Nakahara
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi, 466-8550, Japan. jito0513@gmail.com.
authors.forename: Junji
authors.initials: J
authors.lastname: Ito
authors.affiliation: Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine, Nagoya, Aichi, Japan. hhayashi@med.nagoya-u.ac.jp.
authors.forename: Hironori
authors.initials: H
authors.lastname: Hayashi
authors.affiliation: Department of Radiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi, 466-8550, Japan. naganawa@med.nagoya-u.ac.jp.
authors.forename: Shinji
authors.initials: S
authors.lastname: Naganawa
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D017439:Cicatrix, Hypertrophic / Q000453:epidemiology / Q000209:etiology; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D004583:Electrons / Q000627:therapeutic use*; D004954:Esthetics; D005260:Female; D005355:Fibrosis; D005500:Follow-Up Studies; D006801:Humans; D007430:Intraoperative Care / Q000379:methods; D007564:Japan / Q000453:epidemiology; D015412:Mastectomy, Segmental / Q000009:adverse effects / Q000379:methods*; D008875:Middle Aged; D011446:Prospective Studies; D011879:Radiotherapy Dosage; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects / Q000379:methods*; D011882:Radiotherapy, High-Energy / Q000379:methods*; D016896:Treatment Outcome