Abstract
Risks of radiation-induced second primary cancer following prostate radiotherapy using 3D-conformal radiotherapy (3D-CRT), intensity-modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), flattening filter free (FFF) and stereotactic ablative radiotherapy (SABR) were evaluated. Prostate plans were created using 10 MV 3D-CRT (78 Gy in 39 fractions) and 6 MV 5-field IMRT (78 Gy in 39 fractions), VMAT (78 Gy in 39 fractions, with standard flattened and energy-matched FFF beams) and SABR (42.7 Gy in 7 fractions with standard flattened and energy-matched FFF beams). Dose-volume histograms from pelvic planning CT scans of three prostate patients, each planned using all 6 techniques, were used to calculate organ equivalent doses (OED) and excess absolute risks (EAR) of second rectal and bladder cancers, and pelvic bone and soft tissue sarcomas, using mechanistic, bell-shaped and plateau models. For organs distant to the treatment field, chamber measurements recorded in an anthropomorphic phantom were used to calculate OEDs and EARs using a linear model. Ratios of OED give relative radiation-induced second cancer risks.SABR resulted in lower second cancer risks at all sites relative to 3D-CRT. FFF resulted in lower second cancer risks in out-of-field tissues relative to equivalent flattened techniques, with increasing impact in organs at greater distances from the field. For example, FFF reduced second cancer risk by up to 20% in the stomach and up to 56% in the brain, relative to the equivalent flattened technique. Relative to 10 MV 3D-CRT, 6 MV IMRT or VMAT with flattening filter increased second cancer risks in several out-of-field organs, by up to 26% and 55%, respectively. For all techniques, EARs were consistently low. The observed large relative differences between techniques, in absolute terms, were very low, highlighting the importance of considering absolute risks alongside the corresponding relative risks, since when absolute risks are very low, large relative risks become less meaningful.A calculated relative radiation-induced second cancer risk benefit from SABR and FFF techniques was theoretically predicted, although absolute radiation-induced second cancer risks were low for all techniques, and absolute differences between techniques were small.
Highlights
The development of a radiation-induced second primary cancer is an unwanted consequence of radiotherapy treatment
Owing to the relative newness of intensity-modulated radiotherapy (IMRT) compared to the latency of second primary cancers, the clinical evidence regarding the impact of modern radiotherapy techniques on radiation-induced second cancer risk is too immature to determine if these concerns are warranted (Huang et al 2011, Zelefsky et al 2012a, 2012b)
The number of monitor units (MU) required for all fractions in the delivered plans are shown in table 3
Summary
The development of a radiation-induced second primary cancer is an unwanted consequence of radiotherapy treatment. Owing to the relative newness of IMRT compared to the latency of second primary cancers, the clinical evidence regarding the impact of modern radiotherapy techniques on radiation-induced second cancer risk is too immature to determine if these concerns are warranted (Huang et al 2011, Zelefsky et al 2012a, 2012b). While radiation-induced second cancer risk from IMRT has been compared to that from 3D-conformal radiotherapy (3D-CRT) in prostate planning studies (Followill et al 1997, Kry et al 2005a, 2005b, Stathakis et al 2007, Ruben et al 2008, Bednarz et al 2010), far fewer comparisons with other techniques such as volumetric modulated arc therapy (VMAT) (Rechner et al 2012), stereotactic ablative radiotherapy (SABR) (Dasu et al 2011) and flattening filter free (FFF) techniques (Kry et al 2010, Halg et al 2012) have been performed. Fractionated schedules using 3D-CRT, IMRT and VMAT with standard (flattened) and FFF beams were evaluated, together with SABR using VMAT with standard and FFF beams
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