Personal characteristics, therapy modalities and individual DNA repair capacity as predictive factors of acute skin toxicity in an unselected cohort of breast cancer patients receiving radiotherapy.
OBJECTIVE
Intrinsic and extrinsic factors can affect the occurrence of side effects of radiotherapy. The influence of therapy modalities, personal characteristics and individual DNA repair capacity on the risk of acute skin toxicity was thus evaluated.


METHODS
In a prospective study of 478 female breast cancer patients receiving adjuvant radiotherapy of the breast after breast-conserving surgery, acute skin toxicity was documented systematically using a modified version of the common toxicity criteria. Prognostic personal and treatment characteristics were identified for the entire cohort. Individual DNA repair capacity was determined in a subgroup of 113 patients with alkaline comet assay using phytohemagglutinin stimulated lymphocytes. Using proportional hazards analysis to account for cumulative biologically effective radiation dose, the hazard for the development of acute skin reactions (moist desquamation) associated with DNA repair capacity was modeled.


RESULTS
Of the 478 participants, 84 presented with acute reactions by the end of treatment. Higher body mass index was significantly associated with an increased risk for acute reactions (hazard ratio=1.09 per 1 kg/m(2)), adjusted for treating hospital and photon beam quality. The comet assay parameters examined, including background DNA damage in non-irradiated cells, DNA damage induced by 5 Gy, and DNA repair capacity, were not significantly associated with risk of acute skin toxicity.


CONCLUSIONS
Higher BMI is predictive of acute skin toxicity, however, individual repair parameters as determined by the alkaline comet assay are not informative enough. More comprehensive analyses including late effects of radiotherapy and repair kinetics optimized for different radiation-induced DNA lesions are warranted.
Twardella
Dorothee
D
German Cancer Research Center, Division of Clinical Epidemiology, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
Popanda
Odilia
O
Helmbold
Irmgard
I
Ebbeler
Reinhard
R
Benner
Axel
A
von Fournier
Dietrich
D
Haase
Wulf
W
Sautter-Bihl
Marie Luise
ML
Wenz
Frederik
F
Schmezer
Peter
P
Chang-Claude
Jenny
J
D001943:Breast Neoplasms / Q000235:genetics / Q000532:radiotherapy* / Q000601:surgery; D020552:Comet Assay; D004260:DNA Repair; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D011379:Prognosis; D011446:Prospective Studies; D011836:Radiation Tolerance / Q000235:genetics; D011878:Radiotherapy / Q000009:adverse effects; D012307:Risk Factors; D012871:Skin Diseases / Q000209:etiology; D016019:Survival Analysis