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Toxicity reduction required for MRI-guided radiotherapy to be cost-effective in the treatment of localized prostate cancer.

ABSTRACT: OBJECTIVE:To determine the toxicity reduction required to justify the added costs of MRI-guided radiotherapy (MR-IGRT) over CT-based image guided radiotherapy (CT-IGRT) for the treatment of localized prostate cancer. METHODS:The costs of delivering prostate cancer radiotherapy with MR-IGRT and CT-IGRT in conventional 39 fractions and stereotactic body radiotherapy (SBRT) 5 fractions schedules were determined using literature values and cost accounting from two institutions. Gastrointestinal and genitourinary toxicity rates associated with CT-IGRT were summarized from 20 studies. Toxicity-related costs and utilities were obtained from literature values and cost databases. Markov modeling was used to determine the savings per patient for every 1% relative reduction in acute and chronic toxicities by MR-IGRT over 15 years. The costs and quality adjusted life years (QALYs) saved with toxicity reduction were juxtaposed with the cost increase of MR-IGRT to determine toxicity reduction thresholds for cost-effectiveness. One way sensitivity analyses were performed. Standard $100,000 and $50,000 per QALY ratios were used. RESULTS:The added cost of MR-IGRT was $1,459 per course of SBRT and $10,129 per course of conventionally fractionated radiotherapy. Relative toxicity reductions of 7 and 14% are required for SBRT to be cost-effective using $100,000 and $50,000 per QALY, respectively. Conventional radiotherapy requires relative toxicity reductions of 50 and 94% to be cost-effective. CONCLUSION:From a healthcare perspective, MR-IGRT can reasonably be expected to be cost-effective. Hypofractionated schedules, such a five fraction SBRT, are most likely to be cost-effective as they require only slight reductions in toxicity (7-14%). ADVANCES IN KNOWLEDGE:This is the first detailed economic assessment of MR-IGRT, and it suggests that MR-IGRT can be cost-effective for prostate cancer treatment through toxicity reduction alone.

SUBMITTER: Schumacher LD

PROVIDER: S-EPMC7548359 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:We report the results of a retrospective analysis of localized prostate cancer (LPCa) treated with transperineal ultrasound image-guided radiotherapy (TPUS-IGRT). A total of 124 patients (median age: 74 y, 46-84 y) with LPCa who underwent TPUS-IGRT (Clarity Autoscan system; CAS, Elekta; Stockholm, Sweden) between April 2016 and October 2021 for curative/after hormone induction were enrolled. The number of patients by risk (National Comprehensive Cancer Network 2019) was 7, 25, 42, and 50 for low (LR), good intermediate (good IR), poor intermediate (poor IR), and high (HR)/very high (VHR), respectively. Ninety-five patients were given neoadjuvant hormonal therapy. The planning target volume margin setting was 3 mm for rectal in most cases, 5-7 mm for superior/inferior, and 5 mm for anterior/right/left. The principle prescribed dose is 74 Gy (LR), 76 Gy (good IR), and 76-78 Gy (poor IR or above). CAS was equipped with a real-time prostate intrafraction monitoring (RTPIFM) system. When a displacement of 2-3 mm or more was detected, irradiation was paused, and the patients were placed on standby for prostate reinstatement/recorrection. Of the 3135 fractions in 85 patients for whom RTPIFM was performed, 1008 fractions (32.1%) were recorrected at least once after starting irradiation. A total of 123 patients completed the radiotherapy course. The 5-year overall survival rate was 95.9%. The 5-year biological prostate-specific antigen relapse-free survival rate (bPFS) was 100% for LR, 92.9% for intermediate IR, and 93.2% for HR/VHR (Phoenix method). The 5-year late toxicity rate of Grade 2+ was 7.4% for genitourinary (GU) and 6.5% for gastrointestinal (GI) organs. Comparing the ≤ 76 Gy group to the 78 Gy group for both GU and GI organs, the incidence was higher in the 78 Gy group for both groups. These results suggest that TPUS-IGRT is well tolerated, as the bPFS and incidence of late toxicity are almost comparable to those reported by other sources of image-guided radiotherapy.

Project description:BackgroundNormofractionated radiation regimes for definitive prostate cancer treatment usually extend over 7-8 weeks. Recently, moderate hypofractionation with doses per fraction between 2.2 and 4 Gy has been shown to be safe and feasible with oncologic non-inferiority compared to normofractionation. Radiobiologic considerations lead to the assumption that prostate cancer might benefit in particular from hypofractionation in terms of tumor control and toxicity. First data related to ultrahypofractionation demonstrate that the overall treatment time can be reduced to 5-7 fractions with single doses > 6 Gy safely, even with simultaneous focal boosting of macroscopic tumor(s). With MR-guided linear accelerators (MR-linacs) entering clinical routine, invasive fiducial implantations become unnecessary. The aim of the multicentric SMILE study is to evaluate the use of MRI-guided stereotactic radiotherapy for localized prostate cancer in 5 fractions regarding safety and feasibility.MethodsThe study is designed as a prospective, one-armed, two-stage, multi-center phase-II-trial with 68 patients planned. Low- and intermediate-risk localized prostate cancer patients will be eligible for the study as well as early high-risk patients (cT3a and/or Gleason Score ≤ 8 and/or PSA ≤ 20 ng/ml) according to d'Amico. All patients will receive definitive MRI-guided stereotactic radiation therapy with a total dose of 37.5 Gy in 5 fractions (single dose 7.5 Gy) on alternating days. A focal simultaneous integrated boost to MRI-defined tumor(s) up to 40 Gy can optionally be applied. The primary composite endpoint includes the assessment of urogenital or gastrointestinal toxicity ≥ grade 2 or treatment-related discontinuation of therapy. The use of MRI-guided radiotherapy enables online plan adaptation and intrafractional gating to ensure optimal target volume coverage and protection of organs at risk.DiscussionWith moderate hypofractionation being the standard in definitive radiation therapy for localized prostate cancer at many institutions, ultrahypofractionation could be the next step towards reducing treatment time without compromising oncologic outcomes and toxicities. MRI-guided radiotherapy could qualify as an advantageous tool as no invasive procedures have to precede in therapeutic workflows. Furthermore, MRI guidance combined with gating and plan adaptation might be essential in order to increase treatment effectivity and reduce toxicity at the same time.

Project description:Registration and fusion of magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS) of the prostate can provide guidance for prostate brachytherapy. However, accurate registration remains a challenging task due to the lack of ground truth regarding voxel-level spatial correspondence, limited field of view, low contrast-to-noise ratio, and signal-to-noise ratio in TRUS. In this study, we proposed a fully automated deep learning approach based on a weakly supervised method to address these issues. We employed deep learning techniques to combine image segmentation and registration, including affine and nonrigid registration, to perform an automated deformable MRI-TRUS registration. To start with, we trained two separate fully convolutional neural networks (CNNs) to perform a pixel-wise prediction for MRI and TRUS prostate segmentation. Then, to provide the initialization of the registration, a 2D CNN was used to register MRI-TRUS prostate images using an affine registration. After that, a 3D UNET-like network was applied for nonrigid registration. For both the affine and nonrigid registration, pairs of MRI-TRUS labels were concatenated and fed into the neural networks for training. Due to the unavailability of ground-truth voxel-level correspondences and the lack of accurate intensity-based image similarity measures, we propose to use prostate label-derived volume overlaps and surface agreements as an optimization objective function for weakly supervised network training. Specifically, we proposed a hybrid loss function that integrated a Dice loss, a surface-based loss, and a bending energy regularization loss for the nonrigid registration. The Dice and surface-based losses were used to encourage the alignment of the prostate label between the MRI and the TRUS. The bending energy regularization loss was used to achieve a smooth deformation field. Thirty-six sets of patient data were used to test our registration method. The image registration results showed that the deformed MR image aligned well with the TRUS image, as judged by corresponding cysts and calcifications in the prostate. The quantitative results showed that our method produced a mean target registration error (TRE) of 2.53 ± 1.39 mm and a mean Dice loss of 0.91 ± 0.02. The mean surface distance (MSD) and Hausdorff distance (HD) between the registered MR prostate shape and TRUS prostate shape were 0.88 and 4.41 mm, respectively. This work presents a deep learning-based, weakly supervised network for accurate MRI-TRUS image registration. Our proposed method has achieved promising registration performance in terms of Dice loss, TRE, MSD, and HD.

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Toxicity reduction required for MRI-guided radiotherapy to be cost-effective in the treatment of localized prostate cancer.

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