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 γH2AX foci and G0 micronucleus (MN) assays.

Methods and materials: The study comprised 33PCa patients. A blood sample was taken before start of therapy and after the 1st and 3rd RT fraction to determine respectively the RT-induced γH2AX 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 γH2AX 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 γH2AX 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.