Early biomarkers related to secondary primary cancer risk in radiotherapy treated prostate cancer patients: IMRT versus IMAT

Purpose: To investigate whether rotational techniques (Volumetric Modulated Arc Therapy - VMAT) are associated with a higher risk for secondary primary malignancies compared to step-and-shoot Intensity Modulated Radiation Therapy (ss-IMRT). To this end, radiation therapy (RT) induced DNA double-strand-breaks and the resulting chromosomal damage were assessed in peripheral blood T-lymphocytes of prostate cancer (PCa) patients applying gamma H2AX foci and G(0) micronucleus (MN) assays. Methods and materials: The study comprised 33 PCa patients. A blood sample was taken before start of therapy and after the 1st and 3rd RT fraction to determine respectively the RT-induced gamma H2AX foci and MN. The equivalent total body dose (D-ETB) was calculated based on treatment planning data. Results: A linear dose response was obtained for gamma H2AX foci yields versus D-ETB while MN showed a linear-quadratic dose response. Patients treated with large volume (LV) VMAT show a significantly higher level of induced gamma H2AX foci and MN compared to IMRT and small volume (SV) VMAT (p < 0.01). Assuming a linear-quadratic relationship, a satisfactory correlation was found between both endpoints (R-2 0.86). Conclusions: Biomarker responses were governed by dose and irradiated volume of normal tissues. No significant differences between IMRT and rotational therapy inherent to the technique itself were observed. (c) 2013 The Authors. Elsevier Ireland Ltd. All rights reserved.