Risk evaluation of secondary malignancies after radiotherapy of breast cancer in light of the continuous development of planning techniques

Secondary cancer risk is a significant concern for women treated with breast radiation therapy due to improved long-term survival rates. We evaluated the potential of new advanced automated planning algorithms together with hybrid techniques to minimize the excess absolute risk (EAR) for secondary cancer in various organs after radiation treatment for early staged breast cancer. Using CT data set of 25 patients, we generated 4 different radiation treatment plans of different complexity, including 3-dimensional conformal radiotherapy (3D-CRT), field-in-field (FinF), hybrid-IMRT (HMRT) and automated hybrid-VMAT (HVMAT) techniques. The organ-equivalent dose (OED) was calculated from differential dose-volume histograms on the basis of the “linear-exponential,” “plateau,” and “full mechanistic” dose-response models and was used to evaluate the EAR for secondary cancer in the contralateral breast (CB), contralateral lung (CL), and ipsilateral lung (IL). Statistical comparisons of data were performed by a Kruskal-Wallis analysis of variance. The planning objectives were fulfilled with all the planning techniques for both target coverage and organs-at-risk sparing. The differences in EAR for CB, CL and IL secondary tumor induction were not significant among the 4 techniques. For the CB and CL, the mean absolute difference did not reach 1 case of 10000 patient-years. For the IL, the mean absolute difference was up to 5 cases of 10,000 patient-years. In conclusion, the automated HVMAT technique allows an EAR reduction at the level of well-consolidated tangential 3D-CRT or FinF techniques, keeping all the HVMAT dosimetric improvements unchanged. On the basis of this analysis, the adoption of the HVMAT technique poses no increase in EAR and could be considered safe also for younger patients.