Radiation Biology

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SU_41_2410 - Prediction of Radiation-induced Breast Fibrosis by the Radiation-induced Lymphocyte Apoptosis Assay: Relation to the Surgical Area

Sunday, October 21
1:15 PM - 2:45 PM
Location: Innovation Hub, Exhibit Hall 3

Prediction of Radiation-induced Breast Fibrosis by the Radiation-induced Lymphocyte Apoptosis Assay: Relation to the Surgical Area
M. R. Veldwijk1, P. Seibold2, I. Helmbold2, E. Sperk1, F. A. Giordano1, S. Behrens2, F. Wenz1, J. Chang-Claude2, and C. Herskind1; 1Department of Radiation Oncology, Universitaetsmedizin Mannheim, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany, 2German Cancer Research Center (DKFZ), Heidelberg, Germany

Purpose/Objective(s): Late normal-tissue reactions limit the dose of radiotherapy (RT) given to cancer patients and affect the quality of life of many patients. Thus identification of radiosensitive or -resistant patients would enable improved personalized treatment, e.g. by modifying the dose, fractionation scheme, or offering an alternative treatment. Radiation-induced lymphocyte apoptosis (RILA) after in vitro irradiation of T cells is a promising predictive test. The development of subcutaneous fibrosis after adjuvant RT following breast-conserving surgery is however also influenced by wound healing and scar formation. Aim of the study was to determine, whether the correlation between RILA and fibrosis is differential according to location of the fibrosis (within or outside the surgical area).

Materials/Methods: A total of 252 patients from the German ISE cohort (BCS and adjuvant RT without chemotherapy) with at least 10 years follow-up (median: 11.6 years) were included in the analysis. Peripheral blood was obtained and CD4+ T cell RILA was analyzed by flow cytometry. RT-induced moderate to severe fibrosis (grade 2-3 vs 0-1) was scored according to the LENT-SOMA scheme. In addition, the location of the fibrosis was determined, discriminating between fibrosis within only (Fibin) and outside of the surgical area (Fibout). Multivariate logistic regression model included following clinical parameter: Age at surgery, BMI, hypertension, smoking status, EQD2 and hormonal treatment. Multivariate predictive modelling was performed by bootstrapping using c statistics to evaluate discrimination of risk.

Results: Ten years after RT, 30.6% of the patients had developed subcutaneous fibrosis (grade ≥2), of which 21.4% Fibin and 9.1% Fibout, respectively. A significant correlation with low CD4+ RILA was observed for Fibout (p=0.004) but not for Fibin (p=0.17; both univariate). In addition, predictive ROC analysis yielded an area under the curve which was clearly higher for Fibout (0.69) than for Fibin (0.56). In multivariate regression analysis, lowest tertile of CD4+ RILA versus higher tertiles was associated with a higher odds ratio for Fibout (OR 4.33, 95% CI 1.60-11.7) than for Fibin (OR 3.01, 95% CI 1.50-6.34), although there was no significant heterogeneity (p=0.5). Nevertheless, predictive modelling showed that inclusion of CD4+ RILA into the model yielded a larger increase in c statistics for Fibout (from 0.605 to 0.694) than for Fibin (from 0.621 to 0.661).

Conclusion: CD4+ RILA is a stronger predictor for fibrosis outside rather than within the surgical area, suggesting that RILA is a predictor for development of specifically radiation-induced fibrosis.

Author Disclosure: M.R. Veldwijk: None. P. Seibold: None. I. Helmbold: None. E. Sperk: Travel Expenses; Zeiss. F. Wenz: Research Grant; Elekta AB, Carl Zeiss Meditec AG, IBA. Honoraria; Carl Zeiss Medtec AG. Travel Expenses; Carl Zeiss Meditec AG, Elekta AB. J. Chang-Claude: None.

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