Evaluation of Magnetic Resonance Imaging in Prostate Radiotherapy for Improved Treatment Outcomes

Abstract

External beam radiation therapy is among the most common modalities of curative treatment for prostate cancer and has evolved substantially with the inclusion of multimodality imaging in treatment planning. It has been documented that treatment planning with a magnetic resonance image (MRI) delineated prostate registered to computed tomography (CT) may reduce bladder and rectal toxicity due to a reduction in overall prostate volume as seen on MRI compared to CT. However, due to the smaller target volume when delineating prostate on MRI, margins may be too tight as compared to CT delineation, potentially reducing tumor control probability. In this dissertation research we hypothesized that a unique MRI-based target expansion method based on exclusions of organs-at-risk may provide adequate margins to maintain tumor control probability yet limit normal tissue toxicity as compared to CT-based delineation. We developed and clinically implemented an MRI-based expansion method, which excluded organs-at-risk when performing a 5 mm isotropic (except 4 mm posterior) expansion from gross tumor volume to clinical target volume (CTV), followed by an isotropic 5 mm expansion to generate the planning target volume (PTV). To test our hypothesis, ten retrospective patients' treatment plans using MRI-based method were first compared to treatment plans using CT-delineated prostate with CTV-to-PTV expansion of isotropic 8 mm, except for a 5 mm posterior expansion. Patients were treated to 79.2 Gy in 44 fractions uniformly via intensity modulated radiotherapy. Radiobiological model-based calculations were then performed to determine tumor control probability and normal tissue complication probability for both methods. In addition, daily image guidance was analyzed for prostate shifts via fiducial tracking to ensure full target coverage during treatment. Under IRB approved protocol, we retrospectively evaluated 51 patients treated with the MRI-based method for acute bladder and rectal toxicity with CTC-AE version 4.0 used for scoring, including analysis of prostate-specific antigen (PSA). Treatment planning comparison showed that our MRI-based method PTV volume was similar within 3.79% of conventional CT-based PTV volume. Bladder QUANTEC constraints were on average less for the MRI-based method as compared to the conventional CT-based method and observed as statistically significant with 2.64% reduction in volume receiving 65 Gy. Rectal constraints appeared to follow the same trend. Radiobiological calculated tumor control probability of the MRI-based method was found comparable to CT-based methods. Statistically significant decrease in bladder normal tissue complication probability was observed in the MRI- based method. Analysis of shift data showed prostate anatomy was within proposed PTV margins. Outcomes data collected showed 65% and 100% of patients studied experienced Grade 0/1 bladder and rectal acute toxicity respectively. Grade 2 bladder toxicity was indicated in the remaining 35% of patients studied with no Grade 3 toxicity reported. All patients experienced decreasing PSA post-radiotherapy. Hence, the results appear to align with our hypothesis, as toxicity was reduced while maintaining tumor control probability with favorable outcomes.