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

Radiation Oncology, Jul 2015

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.

A PDF file should load here. If you do not see its contents the file may be temporarily unavailable at the journal website or you do not have a PDF plug-in installed and enabled in your browser.

Alternatively, you can download the file locally and open with any standalone PDF reader:

http://www.ro-journal.com/content/pdf/s13014-015-0469-6.pdf

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

Kawamura et al. Radiation Oncology A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 5-year results of local control and cosmetic outcome Mariko Kawamura 0 Yoshiyuki Itoh 0 Masataka Sawaki 2 Toyone Kikumori 1 Nobuyuki Tsunoda 1 Takeshi Kamomae 0 Seiji Kubota 0 Tohru Okada 0 Rie Nakahara 0 Junji Ito 0 Hironori Hayashi 1 Shinji Naganawa 0 0 Department of Radiology, Nagoya University Graduate School of Medicine , 65 Tsurumai-cho, Shouwa-ku, Nagoya, Aichi 466-8550 , Japan 1 Department of Breast and Endocrine Surgery, Nagoya University Graduate School of Medicine , Nagoya, Aichi , Japan 2 Department of Breast Oncology, Aichi Cancer Center Hospital , Nagoya, Aichi , Japan 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. Breast cancer; APBI; IORT; Asia; Cosmesis; Recurrences - Introduction The standard treatment for early breast cancer is breastconserving therapy (BCT) with whole-breast external irradiation therapy (WBI) [1]. Local recurrences after BCT with or without WBI arise most often in the same quadrant as the primary cancer [2], which has led to multiple trials on accelerated partial breast irradiation (APBI), many with promising results [3]. Despite the positive results from clinical trials around the world, the Japanese Breast Cancer Society has stated in their guidelines regarding the APBI technique that there is “not enough evidence to perform in clinical use”. In addition, they state, "to start APBI, we need to solve the technical problems arises from breast and body size difference from Western women" [4] because the same target dose would result in a higher skin, heart, and lung dose for patients with smaller breasts, making it difficult to increase the fractional dose. Intraoperative radiotherapy (IORT) is a form of APBI. The biggest advantage of IORT is its short course of treatment and the fact that adjuvant radiotherapy is performed during surgery, eliminating the need for multiple visits to the hospital for adjuvant radiotherapy. IORT also offers the advantages of excellent delineation of the tumor bed under visual control and a high rate of sparing of the normal tissue, especially the skin [5, 6]. There are multiple IORT techniques currently reported. One technique uses electron-beam accelerators that can be employed in the operating room. This technique was used in the Phase III electron intraoperative radiation (ELIOT) trial by the European Institute of Oncology group [6, 7]. With this method, unnecessary radiation to the heart and lungs can be avoided by placing a shield between the mammary gland and the pectoralis muscle [6]. Another device used for IORT consists of a miniature electron beam-driven X-ray source that provides a point source of low-energy X rays, with a maximum dose of 50 kV. The radiation source is surrounded by a conical sheath with a sphere at the tip of various sizes, and can be inserted into the surgical cavity tumor excision. A (...truncated)


This is a preview of a remote PDF: http://www.ro-journal.com/content/pdf/s13014-015-0469-6.pdf

Mariko Kawamura, Yoshiyuki Itoh, Masataka Sawaki, Toyone Kikumori, Nobuyuki Tsunoda, Takeshi Kamomae, Seiji Kubota, Tohru Okada, Rie Nakahara, Junji Ito, Hironori Hayashi, Shinji Naganawa. A phase I/II trial of intraoperative breast radiotherapy in an Asian population: 5-year results of local control and cosmetic outcome, Radiation Oncology, 2015, pp. 150, 10, DOI: 10.1186/s13014-015-0469-6