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Background Image-guided adaptive proton therapy (IGAPT) can potentially be applied to take into account interfraction motion while limiting organ at risk (OAR) dose in cervical cancer radiation therapy (RT). In this study, the potential dosimetric advantages of IGAPT compared with photon-based image-guided adaptive RT (IGART) were investigated. Material and methods For 13 cervical cancer patients, full and empty bladder planning computed tomography (CT) images and weekly CTs were acquired. Based on both primary clinical target volumes (pCTVs) [i.e. gross tumor volume (GTV), cervix, corpus-uterus and upper part of the vagina] on planning CTs, the pretreatment observed full range primary internal target volume (pITV) was interpolated to derive pITV subranges. Given corresponding ITVs (i.e. pITVs including lymph nodes), patient-specific photon and proton plan libraries were generated. Using all weekly CTs, IGART and IGAPT treatments were simulated by selecting library plans and recalculating the dose. For each recalculated IGART and IGAPT fraction, CTV (i.e. pCTV including lymph nodes) coverage was assessed and differences in fractionated substitutes of dose-volume histogram (DVH) parameters (V15Gy, V30Gy, V45Gy, Dmean, D2cc) for bladder, bowel and rectum were tested for significance (Wilcoxon signed-rank test). Also, differences in toxicity-related DVH parameters (rectum V30Gy, bowel V45Gy) were approximated based on accumulated dose distributions. Results In 92% (96%) of all recalculated IGAPT (IGART) fractions adequate CTV coverage (V95% >98%) was obtained. All dose parameters for bladder, bowel and rectum, except the fractionated substitute for rectum V45Gy, were improved using IGAPT. Also, IGAPT reduced the mean dose to bowel, bladder and rectum significantly (p < 0.01). In addition, an average decrease of rectum V30Gy and bowel V45Gy indicated reductions in toxicity probabilities when using IGAPT. Conclusion This study demonstrates the feasibility of IGAPT in cervical cancer using a plan-library based plan-of-the-day approach. Compared to photon-based IGART, IGAPT maintains target coverage while significant dose reductions for the bladder, bowel and rectum can be achieved.

Background: To safely optimize target volumes using magnetic resonance imaging (MRI) for uterine cervical cancer radiation therapy, MRI findings need to be validated. The aim of this study was to correlate pre-operatively acquired MRI and surgical specimen imaging for uterine cervical cancer patients using deformable image registration and quantify gross tumor volume (GTV) delineation discrepancies., Material and Methods: For 16 retrospectively selected early-stage uterine cervical cancer patients, the cervix-uterus structure, uterine cavity and the GTV were delineated on 2D pathology photos after macroscopic intersection and corresponding pre-operatively acquired T2-weighted 2D sagittal MR images. Segmentations of pathology photos and MR images were simultaneously registered using a three-step multi-image registration strategy. The registration outcome was evaluated by the Dice similarity coefficient (DSC) and the surface distance error (SDE). In addition, GTV expansions within the cervix-uterus structure needed to obtain 95% GTV coverage were determined., Results: After three-step multi-image registration, the median DSC and median SDE were 0.98 and 0.4 mm (cervix-uterus) and 0.90 and 0.4 mm (uterine cavity), respectively. The average SDE around the GTV was 0.7 mm (range, 0.1 mm - 2.6 mm). An underestimation of MRI-based GTV delineations was found when no margin was applied, indicated by a mean GTV coverage of 61%. To obtain 95% GTV coverage for 90% of the patients, a minimum 12.0 mm margin around MRI-based GTVs was needed., Conclusion: The presented three-step multi-image registration strategy was suitable and accurate to correlate MRI and pathology data for uterine cervical cancer patients. To cover the pathology-based GTV, a margin of at least 12.0 mm around GTV delineations on T2-weighted MRI is needed.