Advances in radiotherapy and its impact on second primary cancer risk: A multi-center cohort study in prostate cancer patients

Background: Modelling studies suggest that advanced intensity-modulated radiotherapy may increase second primary cancer (SPC) risks, due to increased radiation exposure of tissues located outside the treatment fields. In the current study we investigated the association between SPC risks and character-istics of applied external beam radiotherapy (EBRT) protocols for localized prostate cancer (PCa).Methods: We collected EBRT protocol characteristics (2000-2016) from five Dutch RT institutes for the 3D-CRT and advanced EBRT era (N = 7908). From the Netherlands Cancer Registry we obtained patient/-tumour characteristics, SPC data, and survival information. Standardized incidence ratios (SIR) were cal-culated for pelvis and non-pelvis SPC. Nationwide SIRs were calculated as a reference, using calendar period as a proxy to label 3D-CRT/advanced EBRT. Results: From 2000-2006, 3D-CRT with 68-78 Gy in 2 Gy fractions, delivered with 10-23 MV and weekly portal imaging was the most dominant protocol. By the year 2010 all institutes routinely used advanced EBRT (IMRT, VMAT, tomotherapy), mainly delivering 78 Gy in 2 Gy fractions, using various kV/MV imag-ing protocols. Sixteen percent (N = 1268) developed >= 1 SPC. SIRs for pelvis and non-pelvis SPC (all insti-tutes, advanced EBRT vs 3D-CRT) were 1.17 (1.00-1.36) vs 1.39 (1.21-1.59), and 1.01 (0.89-1.07) vs 1.03 (0.94-1.13), respectively. Nationwide non-pelvis SIR was 1.07 (1.01-1.13) vs 1.02 (0.98-1.07). Other RT protocol characteristics did not correlate with SPC endpoints.Conclusion: None of the studied RT characteristics of advanced EBRT was associated with increased out-of-field SPC risks. With constantly evolving EBRT protocols, evaluation of associated SPC risks remains important.(c) 2023 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 183 (2023) 1-8 This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).