A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 5-year results of local control and cosmetic outcome

Radiat Oncol. 2015 Jul 25:10:150. doi: 10.1186/s13014-015-0469-6.

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.

Materials and 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.

Conclusion: 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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

  • Aged
  • Aged, 80 and over
  • Breast Neoplasms / radiotherapy*
  • Breast Neoplasms / surgery
  • Cicatrix, Hypertrophic / epidemiology
  • Cicatrix, Hypertrophic / etiology
  • Combined Modality Therapy
  • Disease-Free Survival
  • Electrons / therapeutic use*
  • Esthetics
  • Female
  • Fibrosis
  • Follow-Up Studies
  • Humans
  • Intraoperative Care / methods
  • Japan / epidemiology
  • Mastectomy, Segmental / adverse effects
  • Mastectomy, Segmental / methods*
  • Middle Aged
  • Prospective Studies
  • Radiotherapy Dosage
  • Radiotherapy, Adjuvant / adverse effects
  • Radiotherapy, Adjuvant / methods*
  • Radiotherapy, High-Energy / methods*
  • Treatment Outcome