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Abstract
Purpose: Emerging data suggest that higher radiation doses in post-mastectomy radiotherapy may be associated with an increased risk of reconstruction complications. This study aimed to validate previous findings regarding the impact of radiation dose on complications among women with breast cancer using a multi-center dataset.

Methods: Fifteen institutions participated, and women with breast cancer who received radiotherapy after either autologous or prosthetic breast reconstruction were included. The primary endpoint was major post-radiation therapy complications requiring re-operation for explantation, flap failure, or bleeding control.

Results: In total, 314 patients were included. Radiotherapy was performed using both conventional fractionation and hypofractionation in various schedules. The range of the radiation therapy dose in Equivalent Dose in 2 Gy fractions (EQD2; α/β = 3.5) varied from 43.4 to 71.0 Gy (median dose: 48.6 Gy). Boost radiation therapy was administered to 49 patients. Major post-radiation therapy complications were observed in 24 (7.6%) patients. In multivariate analysis, an increasing EQD2 per Gy (odds ratio [OR]: 1.58, 95% confidence interval [CI]: 1.26-1.98; p < 0.001), current smoking status (OR: 25.48, 95% CI: 1.56-415.65; p = 0.023), and prosthetic breast reconstruction (OR: 9.28, 95% CI: 1.84-46.70; p = 0.007) were independently associated with an increased risk of major complications.

Conclusion: A dose-response relationship between radiation dose and the risk of complications was validated in this multi-center dataset. In this context, we hypothesize that the use of hypofractionated radiotherapy (40 Gy in 15 fractions) may improve breast reconstruction outcomes. Our multi-center prospective observational study (NCT03523078) is underway to further validate this hypothesis.

Affiliations

Seung Yeun Chung  1 , Jee Suk Chang  2 , Kyung Hwan Shin  3 , Jin Ho Kim  4 , Won Park  5 , Haeyoung Kim  5 , Kyubo Kim  6 , Ik Jae Lee  7 , Won Sup Yoon  8 , Jihye Cha  9 , Kyu-Chan Lee  10 , Jin Hee Kim  11 , Jin Hwa Choi  12 , Sung-Ja Ahn  13 , Boram Ha  14 , Sun Young Lee  15 , Dong Soo Lee  16 , Jeongshim Lee  17 , Sei One Shin  18 , Sea-Won Lee  19 , Jinhyun Choi  20 , Mi Young Kim  21 , Yeon Joo Kim  22 , Jung Ho Im  23 , Chang-Ok Suh  23 , Yong Bae Kim  24
1 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea; Department of Radiation Oncology, Ajou University School of Medicine, Suwon, Republic of Korea.
2 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea.
3 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea. Electronic address: radiat@snu.ac.kr.
4 Department of Radiation Oncology, Seoul National University College of Medicine, Seoul, Republic of Korea.
5 Department of Radiation Oncology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
6 Department of Radiation Oncology, Ewha Womans University College of Medicine, Seoul, Republic of Korea.
7 Department of Radiation Oncology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea.
8 Department of Radiation Oncology, Korea University Ansan Hospital, Korea University Medical College, Seoul, Republic of Korea.
9 Department of Radiation Oncology, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Republic of Korea.
10 Department of Radiation Oncology, Gachon University Gil Medical Center, Incheon, Republic of Korea.
11 Department of Radiation Oncology, Keimyung University Dongsan Medical Center, Keimyung University School of Medicine, Daegu, Republic of Korea.
12 Department of Radiation Oncology, Chung-Ang University Hospital, Seoul, Republic of Korea.
13 Department of Radiation Oncology, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Hwasun, Republic of Korea.
14 Department of Radiation Oncology, Hallym University Dongtan Sacred Heart Hospital, Hwasung, Republic of Korea.
15 Department of Radiation Oncology, Chonbuk National University Hospital, Jeonju, Republic of Korea.
16 Department of Radiation Oncology, Uijeongbu St. Mary's Hospital, The Catholic University of Korea, Uijeongbu, Republic of Korea.
17 Department of Radiation Oncology, Inha University Hospital, Inha University of Medicine, Incheon, Republic of Korea.
18 Department of Radiation Oncology, Andong Medical Group Andong Hospital, Andong, Republic of Korea.
19 Department of Radiation Oncology, Eunpyeong St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
20 Department of Radiation Oncology, Jeju National University Hospital, Jeju, Republic of Korea.
21 Department of Radiation Oncology, Kyungpook National University Chilgok Hospital, Daegu, Republic of Korea.
22 Department of Radiation Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
23 Department of Radiation Oncology, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea.
24 Department of Radiation Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Republic of Korea. Electronic address: ybkim3@yuhs.ac.