Analysis of non-genetic risk factors for adverse skin reactions to radiotherapy among 284 breast cancer patients.
OBJECTIVE
We analyzed non-genetic risk factors for adverse skin reactions to irradiation at 4 collaborating Japanese institutions, to design future investigation into genetic risk factors for adverse skin reactions to irradiation in a multicenter setting.


METHODS
From April 2001, 284 breast cancer patients, who underwent radiotherapy with breast-conserving surgery, were enrolled from 4 collaborating institutions in Japan. We graded skin reactions according to international scoring systems. Clinical factors were tested against adverse effects.


RESULTS
Grade 1+ skin reactions were observed in 261 (92%) of the patients in less than 3 months, 118 (42%) at 3 months, and 29 (10%) at 6 months in the late phase. Univariate analysis of treatment risk factors (such as the use of a multi-leaf colimeter, wedge-filter, or immobilization device) for skin reactions revealed a significant association (p< 0.0001). After a variable selection procedure with logistic regression, the institution, operative procedure, and magnitude of photon energy remained significantly associated with acute skin reactions. Only the institution was an explanatory variable for skin reactions at 3 and 6 months in the final logistic model.


CONCLUSIONS
After stratification, substantial remaining variations in the occurrence of skin reactions of a given level suggested that individual genetic factors contribute markedly to individual radiosensitivity. Analysis of genetic factors associated with adverse effects would be possible by stratifying patients according to institution. Selection of eligible institutions, where appropriate treatment modalities could be performed, would also be possible when planning such a study.
Iwakawa
Mayumi
M
RadGenomics Project, Frontier Research Center, National Institute of Radiological Sciences, Japan. mayumii@nirs.go.jp.
Noda
Shuhei
S
RadGenomics Project, Frontier Research Center, National Institute of Radiological Sciences, Japan.
Yamada
Shigeru
S
Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Japan.
Yamamoto
Naohito
N
Chiba Cancer Center, Japan.
Miyazawa
Yukimasa
Y
Chiba University Hospital, Japan.
Yamazaki
Hideya
H
Toyonaka Municipal Hospital, Japan.
Kawakami
Yoshihiro
Y
Kawakami Breast Thyroid Clinic, Japan.
Matsui
Yoshifumi
Y
RadGenomics Project, Frontier Research Center, National Institute of Radiological Sciences, Japan.|Shimizu Kosei General Hospital, Japan.
Tsujii
Hirohiko
H
Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Japan.
Mizoe
Junetsu
J
Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Japan.
Oda
Eisei
E
Foundation of Biomedical Research and Innovation, Japan.|Medical Toukei Corporation, Japan.
Fukunaga
Yukihiro
Y
Foundation of Biomedical Research and Innovation, Japan.|Dainippon Sumitomo Pharma Co., Ltd, Japan.
Imai
Takashi
T
RadGenomics Project, Frontier Research Center, National Institute of Radiological Sciences, Japan.
D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D008875:Middle Aged; D011855:Radiodermatitis / Q000209:etiology*; D012307:Risk Factors; D012867:Skin / Q000528:radiation effects*