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PurposeDysphagia is a common toxicity after head and neck (HN) radiotherapy that negatively affects quality of life. We explored the relationship between radiotherapy dose to normal HN structures and dysphagia one year after treatment using image-based datamining (IBDM), a voxel-based analysis technique.Materials and MethodsWe used data from 104 oropharyngeal cancer patients treated with definitive (Chemo)RT. Swallow function was assessed pre-treatment and 1 year after treatment using three validated measures: M.D. Anderson Dysphagia Inventory (MDADI), performance status scale for normalcy of diet (PSS-HN), and water swallowing test (WST).For IBDM, we spatially normalised all patients’ planning dose matrices to three reference anatomies. Regions where the dose was associated with dysphagia measures at 1 year were found by performing voxel-wise statistics and permutation testing.Clinical factors, treatment variables and pre-treatment measures were used in multivariable analysis to predict each dysphagia measure at 1 year. Clinical baseline models were found using backward stepwise selection. Improvement in model discrimination after adding the mean dose to the identified region was quantified using Akaike information criterion. We also compared the prediction performance of the identified region to a well-established association: mean doses to the pharyngeal constrictor muscles.ResultsIBDM revealed highly significant associations between dose to distinct regions and the three outcomes. These regions overlapped around the inferior section of the brainstem. All clinical models were significantly improved by including mean dose to the overlap region (p≤0.006). Including pharyngeal dosimetry only significantly improved WST (p=0.04), but not PSS-HN nor MDADI (p≥0.06).ConclusionsIn this hypothesis-generating study, we found that mean dose to the inferior section of the brainstem is strongly associated with dysphagia 1 year after treatment. The identified region includes the swallowing centres in the medulla oblongata, providing a possible mechanistic explanation. Further work including validation in an independent cohort is required.

Tumor and target volume manual delineation remains a challenging task in head and neck cancer radiation therapy. The purpose of this study was to conduct a multi-institutional evaluation of manual delineations of gross tumor volume (GTV), high-risk clinical target volume (CTV), parotids, and submandibular glands on treatment simulation magnetic resonance scans of patients with oropharyngeal cancer.We retrospectively collected pretreatment T1-weighted, T1-weighted with gadolinium contrast, and T2-weighted magnetic resonance imaging scans for 4 patients with oropharyngeal cancer under an institution review board-approved protocol. We provided the scans to 26 radiation oncologists from 7 international cancer centers that participated in this delineation study. We also provide the patients' clinical history and physical examination findings, along with a medical photographic image and radiologic results. We used both the Simultaneous Truth and Performance Level Estimation algorithm and pair-wise comparisons of the contours, using overlap/distance metrics. Lastly, to assess experience and CTV delineation institutional practices, we had participants complete a brief questionnaire.Large variability was measured between observers' delineations for GTVs and CTVs. The mean Dice similarity coefficient values across all physicians' delineations for GTVp, GTVn, CTVp, and CTVn were 0.77, 0.67, 0.77, and 0.69, respectively, for Simultaneous Truth and Performance Level Estimation algorithm comparison, and 0.67, 0.60, 0.67, and 0.58, respectively, for pair-wise analysis. Normal tissue contours were defined more consistently when considering overlap/distance metrics. The median radiation oncology clinical experience was 7 years. The median experience delineating on magnetic resonance imaging was 3.5 years. The GTV-to-CTV margin used was 10 mm for 6 of 7 participant institutions. One institution used 8 mm, and 3 participants (from 3 different institutions) used a margin of 5 mm.The data from this study suggests that appropriate guidelines, contouring quality assurance sessions, and training are still needed for the adoption of magnetic resonance-based treatment planning for head and neck cancers. Such efforts should play a critical role in reducing delineation variation and ensure standardization of target design across clinical practices.

Purpose: To assess (1) the potential benefit that MRI may bring to prostate radiotherapy planning and delivery; (2) a method of improving registration of MRI and CT imaging to aid the RT planning workflow; (3) the role of in-bore MRI guided biopsy in informing management; (4) dosimetric outcome and toxicity of an integrated High Dose Rate (HDR-B) or Volumetric Modulated Arc Therapy (VMAT-IB) boost to the area of dominant disease within the prostate; (5) whether a predictive response can be identified measuring changes in Diffusion Weighted Imaging (DWI) and Dynamic Contrast Enhancement (DCE) during prostate RT after neo-adjuvant HT (NA-HT); (6) the necessity of hormone therapy (HT) with dose escalated radiotherapy (DE-RT) for intermediate risk prostate cancer.Methods: (1) Perform a systematic review of literature pertaining to MRI and image guided radiotherapy; (2) compare registration accuracy, based on displacement of fiducial markers or degree of overlap of segmented prostate measured by Dice Similarity Coefficient (DSC), of MRI and CT for 14 patients after conventional operator driven visual matching and then an additional registration step using interstitial points identified on high quality volumetric CT (HQVCT); (3) assess the predictive power of in-bore MRI guided biopsy of areas with suspicious appearance on multi-parametric MRI by comparing biopsy accuracy to histological findings and repeat biopsy results for 42 PIRADS 4-5 lesions in 31 men; (4) analyse patients treated in a prospective study receiving standard radiotherapy to the prostate plus a HDR-B (20 patients) or VMAT-IB (26) to a total dose of 250 Gy BED to assess acute and late toxicity and dosimetric variation between the two methods; (5) prospectively recruit 15 patient who have received NA-HT and perform DWI and DCE before, during and after completion of radiotherapy to look for significant changes in values in normal and malignant tissue which may predict for ultimate outcome; (6) Assess clinical outcome for patients receiving 75.6 – 78 Gy +/- bicalutamide.Results: (1) The review has quantified uncertainties in treatment delivery and the degree that the addition of MRI may mitigate this; (2) point based registration of CT and MRI imaging after visual registration achieved a significant reduction in fiducial marker displacement and a significant increase in DSC; (3) seven lesions targeted by in-bore MR guided biopsy had non-significant or negative results, most with biopsy needle deflected to the target periphery with four confirmed false negative on repeat biopsy; (4) with a median follow up of 12 months acute and late toxicity was similar after either treatment with HDR-B delivering a significantly higher dose to a proportion of the gross tumour volume (GTV) but with significantly lower minimum dose to the planned target volume (PTV); (5) tumour DWI values during RT after NA-HT were not found to significantly alter, DCE was found to vary significantly during treatment and initial changes correlated with changes in DWI; (6) the addition of bicalutamide did not significantly improve biochemical control or overall survival.Conclusions: (1) Routine use of MRI will to improve radiotherapy planning and delivery; (2) repeat point based registration using interstitial points has the potential to improve visual CT and MRI registration; (3) an in-bore MRI guided biopsy has little value in informing a decision to offer focal therapy to an MRI identified PIRADS 4-5 lesion due to its high false negative rate; (4) with limited follow up HDR-B and VMAT-IB appear safe methods of focal dose escalation although with significant dosimetric variations;(5) early changes in DWI and DCE during RT after NA-HT appear to correlate, longer follow up will assess their prognostic value; (6) A benefit of HT combined with DE-RT was not shown in this study.

PURPOSE: To improve the accuracy and precision of tracer kinetic model parameter estimates for use in dynamic contrast enhanced (DCE) MRI studies of solid tumors.THEORY: Quantitative DCE-MRI requires an estimate of precontrast T1 , which is obtained prior to fitting a tracer kinetic model. As T1 mapping and tracer kinetic signal models are both a function of precontrast T1 it was hypothesized that its joint estimation would improve the accuracy and precision of both precontrast T1 and tracer kinetic model parameters.METHODS: Accuracy and/or precision of two-compartment exchange model (2CXM) parameters were evaluated for standard and joint fitting methods in well-controlled synthetic data and for 36 bladder cancer patients. Methods were compared under a number of experimental conditions.RESULTS: In synthetic data, joint estimation led to statistically significant improvements in the accuracy of estimated parameters in 30 of 42 conditions (improvements between 1.8% and 49%). Reduced accuracy was observed in 7 of the remaining 12 conditions. Significant improvements in precision were observed in 35 of 42 conditions (between 4.7% and 50%). In clinical data, significant improvements in precision were observed in 18 of 21 conditions (between 4.6% and 38%).CONCLUSION: Accuracy and precision of DCE-MRI parameter estimates are improved when signal models are fit jointly rather than sequentially. Magn Reson Med 76:1270-1281, 2016. © 2015 Wiley Periodicals, Inc.