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Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases.

ABSTRACT: Purpose: Tumor vessels influence the growth and response of tumors to therapy. Imaging vascular changes in vivo using dynamic contrast-enhanced MRI (DCE-MRI) has shown potential to guide clinical decision making for treatment. However, quantitative MR imaging biomarkers of vascular function have not been widely adopted, partly because their relationship to structural changes in vessels remains unclear. We aimed to elucidate the relationships between vessel function and morphology in vivo Experimental Design: Untreated preclinical tumors with different levels of vascularization were imaged sequentially using DCE-MRI and CT. Relationships between functional parameters from MR (iAUC, K trans, and BATfrac) and structural parameters from CT (vessel volume, radius, and tortuosity) were assessed using linear models. Tumors treated with anti-VEGFR2 antibody were then imaged to determine whether antiangiogenic therapy altered these relationships. Finally, functional-structural relationships were measured in 10 patients with liver metastases from colorectal cancer.Results: Functional parameters iAUC and K trans primarily reflected vessel volume in untreated preclinical tumors. The relationships varied spatially and with tumor vascularity, and were altered by antiangiogenic treatment. In human liver metastases, all three structural parameters were linearly correlated with iAUC and K trans For iAUC, structural parameters also modified each other's effect.Conclusions: Our findings suggest that MR imaging biomarkers of vascular function are linked to structural changes in tumor vessels and that antiangiogenic therapy can affect this link. Our work also demonstrates the feasibility of three-dimensional functional-structural validation of MR biomarkers in vivo to improve their biological interpretation and clinical utility. Clin Cancer Res; 24(19); 4694-704. ©2018 AACR.

SUBMITTER: Kannan P

PROVIDER: S-EPMC6171743 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases.

Kannan Pavitra P Kretzschmar Warren W WW Winter Helen H Warren Daniel D Bates Russell R Allen Philip D PD Syed Nigar N Irving Benjamin B Papiez Bartlomiej W BW Kaeppler Jakob J Markelc Bosjtan B Kinchesh Paul P Gilchrist Stuart S Smart Sean S Schnabel Julia A JA Maughan Tim T Harris Adrian L AL Muschel Ruth J RJ Partridge Mike M Sharma Ricky A RA Kersemans Veerle V

Clinical cancer research : an official journal of the American Association for Cancer Research 20180629 19

<b>Purpose:</b> Tumor vessels influence the growth and response of tumors to therapy. Imaging vascular changes <i>in vivo</i> using dynamic contrast-enhanced MRI (DCE-MRI) has shown potential to guide clinical decision making for treatment. However, quantitative MR imaging biomarkers of vascular function have not been widely adopted, partly because their relationship to structural changes in vessels remains unclear. We aimed to elucidate the relationships between vessel function and morphology < ...[more]

PMID: 29959141

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Project description:Purpose/objectiveStereotactic body radiation therapy (SBRT) has emerged as a valid treatment alternative for non-resectable liver metastases or hepatocellular carcinomas (HCC). Magnetic resonance (MR) guided SBRT has a high potential of further improving treatment quality, allowing for higher, tumoricidal irradiation doses whilst simultaneously sparing organs at risk. However, data on treatment outcome and patient acceptance is still limited.Material/methodsWe performed a subgroup analysis of an ongoing prospective observational study comprising patients with liver metastases or HCC. Patients were treated with ablative MR-guided SBRT at the MRIdian Linac in the Department of Radiation Oncology at Heidelberg University Hospital between January 2019 and February 2020. Local control (LC) and overall survival (OS) analysis was performed using the Kaplan-Meier method. An in-house designed patient-reported outcome questionnaire was used to measure patients' experience with the MR-Linac treatment. Toxicity was evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0).ResultsTwenty patients (with n = 18 metastases; n = 2 HCC) received MR-guided SBRT for in total 26 malignant liver lesions. Median biologically effective dose (BED at α/β = 10) was 105.0 Gy (range: 67.2-112.5 Gy) and median planning target volume was 57.20 ml (range: 17.4-445.0 ml). Median treatment time was 39.0 min (range: 26.0-67.0 min). At 1-year, LC was 88.1% and OS was 84.0%. Grade I° gastrointestinal toxicity °occurred in 30.0% and grade II° in 5.0% of the patients with no grade III° or higher toxicity. Overall treatment experience was rated positively, with items scoring MR-Linac staff's performance and items concerning the breath hold process being among the top positively rated elements. Worst scored items were treatment duration, positioning and low temperature.ConclusionMR-guided SBRT of liver tumors is a well-tolerated and well-accepted treatment modality. Initial results are promising with excellent local control and only mildest toxicity. However, prospective studies are warranted to truly assess the potential of MR-guided liver SBRT and to identify which patients profit most from this new versatile technology.

Dataset Information

Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases.

Publications

Functional Parameters Derived from Magnetic Resonance Imaging Reflect Vascular Morphology in Preclinical Tumors and in Human Liver Metastases.

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