Data from Association of CD4<sup>+</sup> Radiation-Induced Lymphocyte Apoptosis with Fibrosis and Telangiectasia after Radiotherapy in 272 Breast Cancer Patients with >10-Year Follow-up

Abstract

<div>AbstractPurpose:<p>Radiation-induced lymphocyte apoptosis (RILA) has been suggested as a predictive assay for adverse late reactions after radiotherapy. Thus, low RILA values of T-lymphocyte subpopulations have been associated with increased risk for various endpoints at 2 to 3 years of follow-up. The purpose was to test if such associations persist for specific endpoints (subcutaneous fibrosis, telangiectasia) in breast cancer patients with at least 10 years of follow-up.</p><p><b>Experimental Design:</b> Two hundred and seventy-two female patients who had received breast-conserving therapy within the German ISE study were included (median follow-up: 11.6 years). Radiotherapy-induced side effects were scored according to the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic (LENT-SOMA) classification system. RILA in the CD4<sup>+</sup>, CD8<sup>+</sup>, and natural killer (NK) subpopulations from peripheral blood was analyzed by flow cytometry. Multivariate predictive modeling was performed including relevant clinical risk factors.</p>Results:<p>Low CD4<sup>+</sup> RILA was associated with increased risk for both fibrosis (<i>P</i> = 0.011) and telangiectasia (<i>P</i> < 0.001). For fibrosis, the association was stronger outside the surgical area (Fib<sub>out</sub>; <i>P</i> = 0.004) than within (Fib<sub>in</sub>; <i>P</i> = 0.17). Predictive multivariate modeling including clinical risk factors yielded OR of 3.48 (95% confidence interval, 1.84–6.58) for any fibrosis and 8.60 (2.71–27.3) for telangiectasia. Addition of CD4<sup>+</sup> RILA to the clinical variables improved discrimination (c statistics) from 0.62 to 0.68 for any fibrosis, 0.62 to 0.66 for Fib<sub>in</sub>, 0.61 to 0.69 for Fib<sub>out</sub>, and from 0.65 to 0.76 for telangiectasia. CD8<sup>+</sup> and NK RILA were not significantly associated with radiotherapy-related late reactions.</p>Conclusions:<p>The results provide first evidence that low CD4<sup>+</sup> RILA is associated with increased subcutaneous fibrosis and telangiectasia even after 10 years. This supports the potential usefulness for predicting individual clinical risk.</p></div>