Targeted Radiosensitizers for MR-Guided Radiation Therapy of Prostate Cancer.
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ABSTRACT:
SUBMITTER: Luo D
PROVIDER: S-EPMC9109254 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Targeted Radiosensitizers for MR-Guided Radiation Therapy of Prostate Cancer.
Luo Dong D Johnson Andrew A Wang Xinning X Li Hao H Erokwu Bernadette O BO Springer Sarah S Lou Jason J Ramamurthy Gopalakrishnan G Flask Chris A CA Burda Clemens C Meade Thomas J TJ Basilion James P JP
Nano letters 20200831 10
Adjuvant radiotherapy is frequently prescribed to treat cancer. To minimize radiation-related damage to healthy tissue, it requires high precision in tumor localization and radiation dose delivery. This can be achieved by MR guidance and targeted amplification of radiation dose selectively to tumors by using radiosensitizers. Here, we demonstrate prostate cancer-targeted gold nanoparticles (AuNPs) for MR-guided radiotherapy to improve the targeting precision and efficacy. By conjugating Gd(III) ...[more]
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Project description:BackgroundDose escalation radiotherapy enables increased control of prostate cancer (PCa) but requires segmentation of dominant index lesions (DIL). This motivates the development of automated methods for fast, accurate, and consistent segmentation of PCa DIL.PurposeTo construct and validate a model for deep-learning-based automatic segmentation of PCa DIL defined by Gleason score (GS) ≥3+4 from MR images applied to MR-guided radiation therapy. Validate generalizability of constructed models across scanner and acquisition differences.MethodsFive deep-learning networks were evaluated on apparent diffusion coefficient (ADC) MRI from 500 lesions in 365 patients arising from internal training Dataset 1 (156 lesions in 125 patients, 1.5Tesla GE MR with endorectal coil), testing using Dataset 1 (35 lesions in 26 patients), external ProstateX Dataset 2 (299 lesions in 204 patients, 3Tesla Siemens MR), and internal inter-rater Dataset 3 (10 lesions in 10 patients, 3Tesla Philips MR). The five networks include: multiple resolution residually connected network (MRRN) and MRRN regularized in training with deep supervision implemented into the last convolutional block (MRRN-DS), Unet, Unet++, ResUnet, and fast panoptic segmentation (FPSnet) as well as fast panoptic segmentation with smoothed labels (FPSnet-SL). Models were evaluated by volumetric DIL segmentation accuracy using Dice similarity coefficient (DSC) and the balanced F1 measure of detection accuracy, as a function of lesion aggressiveness and size (Dataset 1 and 2), and accuracy with respect to two-raters (on Dataset 3). Upon acceptance for publication segmentation models will be made available in an open-source GitHub repository.ResultsIn general, MRRN-DS more accurately segmented tumors than other methods on the testing datasets. MRRN-DS significantly outperformed ResUnet in Dataset2 (DSC of 0.54 vs. 0.44, p < 0.001) and the Unet++ in Dataset3 (DSC of 0.45 vs. p = 0.04). FPSnet-SL was similarly accurate as MRRN-DS in Dataset2 (p = 0.30), but MRRN-DS significantly outperformed FPSnet and FPSnet-SL in both Dataset1 (0.60 vs. 0.51 [p = 0.01] and 0.54 [p = 0.049] respectively) and Dataset3 (0.45 vs. 0.06 [p = 0.002] and 0.24 [p = 0.004] respectively). Finally, MRRN-DS produced slightly higher agreement with experienced radiologist than two radiologists in Dataset 3 (DSC of 0.45 vs. 0.41).ConclusionsMRRN-DS was generalizable to different MR testing datasets acquired using different scanners. It produced slightly higher agreement with an experienced radiologist than that between two radiologists. Finally, MRRN-DS more accurately segmented aggressive lesions, which are generally candidates for radiative dose ablation.
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Project description:PurposeThe total time of radiation treatment delivery for pancreatic cancer patients with daily online adaptive radiation therapy (ART) on an MR-Linac can range from 50 to 90 min. During this period, the target and normal tissues undergo changes due to respiration and physiologic organ motion. We evaluated the dosimetric impact of the intrafraction physiological organ changes.MethodsTen locally advanced pancreatic cancer patients were treated with 50 Gy in five fractions with intensity-modulated respiratory-gated radiation therapy on a 0.35-T MR-Linac. Patients received both pre- and post-treatment volumetric MRIs for each fraction. Gastrointestinal organs at risk (GI-OARs) were delineated on the pre-treatment MRI during the online ART process and retrospectively on the post-treatment MRI. The treated dose distribution for each adaptive plan was assessed on the post-treatment anatomy. Prescribed dose volume histogram metrics for the scheduled plan on the pre-treatment anatomy, the adapted plan on the pre-treatment anatomy, and the adapted plan on post-treatment anatomy were compared to the OAR-defined criteria for adaptation: the volume of the GI-OAR receiving greater than 33 Gy (V33Gy) should be ≤1 cubic centimeter.ResultsAcross the 50 adapted plans for the 10 patients studied, 70% were adapted to meet the duodenum constraint, 74% for the stomach, 12% for the colon, and 48% for the small bowel. Owing to intrafraction organ motion, at the time of post-treatment imaging, the adaptive criteria were exceeded for the duodenum in 62% of fractions, the stomach in 36%, the colon in 10%, and the small bowel in 48%. Compared to the scheduled plan, the post-treatment plans showed a decrease in the V33Gy, demonstrating the benefit of plan adaptation for 66% of the fractions for the duodenum, 95% for the stomach, 100% for the colon, and 79% for the small bowel.ConclusionPost-treatment images demonstrated that over the course of the adaptive plan generation and delivery, the GI-OARs moved from their isotoxic low-dose region and nearer to the dose-escalated high-dose region, exceeding dose-volume constraints. Intrafraction motion can have a significant dosimetric impact; therefore, measures to mitigate this motion are needed. Despite consistent intrafraction motion, plan adaptation still provides a dosimetric benefit.
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Project description: Not available
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Project description:High intensity focused ultrasound (HIFU) systems have been approved for therapeutic ultrasound delivery to cause tissue ablation or induced hyperthermia. Microbubble agents have also been used in combination with sonication exposures. These require temperature feedback and monitoring to prevent unstable cavitation and prevent excess tissue heating. Previous work has utilized lower power and pressure to oscillate microbubbles and transfer energy to endothelial cells in the absence of thermally induced damage that can radiosensitize tumors. This work investigated whether reduced acoustic power and pressure on a commercial available MR-integrated HIFU system could result in enhanced radiation-induced tumor response after exposure to ultrasound-stimulated microbubbles (USMB) therapy. A commercially available MR-integrated HIFU system was used with a hyperthermia system calibration provided by the manufacturer. The ultrasound transducer was calibrated to reach a peak negative pressure of − 750 kPa. Thirty male New Zealand white rabbits bearing human derived PC3 tumors were grouped to receive no treatment, 14 min of USMB, 8 Gy of radiation in a separate irradiation cabinet, or combined treatments. In vivo temperature changes were collected using MR thermometry at the tumor center and far-field muscle region. Tissues specimens were collected 24 h post radiation therapy. Tumor cell death was measured and compared to untreated controls through hematoxylin and eosin staining and immunohistochemical analysis. The desired peak negative pressure of − 750 kPa used for previous USMB occurred at approximately an input power of 5 W. Temperature changes were limited to under 4 °C in ten of twelve rabbits monitored. The median temperature in the far-field muscle region of the leg was 2.50 °C for groups receiving USMB alone or in combination with radiation. Finally, statistically significant tumor cell death was demonstrated using immunohistochemical analysis in the combined therapy group compared to untreated controls. A commercial MR-guided therapy HIFU system was able to effectively treat PC3 tumors in a rabbit model using USMB therapy in combination with radiation exposures. Future work could find the use of reduced power and pressure levels in a commercial MR-guided therapy system to mechanically stimulate microbubbles and damage endothelial cells without requiring high thermal doses to elicit an antitumor response.
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