The Parametric Response Map Is An Imaging Biomarker For Early Cancer Treatment Outcome


Here we describe the parametric response map (PRM), a voxel-wise approach for image analysis and quantification of hemodynamic alterations during treatment for 44 patients with high-grade glioma. Relative cerebral blood volume (rCBV) and flow (rCBF) maps were acquired before treatment and after 1 and 3 weeks of therapy. We compared the standard approach using region-of-interest analysis for change in rCBV or rCBF to the change in perfusion parameters on the basis of PRM (PRMrCBV and PRMrCBF) for their accuracy in predicting overall survival. Neither the percentage change of rCBV or rCBF predicted survival, whereas the regional response evaluations made on the basis of PRM were highly predictive of survival. Even when accounting for baseline rCBV, which is prognostic, PRMrCBV proved more predictive of overall survival.

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Topological Parametric Response Mapping for Use in Radiation Treatment Planning of Non-Small Cell Lung Cancer Patients


Non-small cell lung cancer (NSCLC) patients are at an increased risk for pulmonary comorbidities, which are known to effect radiation treatment (RT) outcomes. And yet, RT plans are currently developed without considering underlying functionality of the lung. A promising new CT-based analytic technique called topological parametric response mapping (tPRM) offers the ability to quantify pulmonary dysfunction. By analyzing the voxelwise change in Hounsfield Units (HU) between inhale and exhale breathing phases, topological contours of diseased tissue can be mapped and are potentially useful for patient-specific radiation treatment plans.


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Prospective Analysis of Parametric Response Map–Derived MRI Biomarkers: Identification of Early and Distinct Glioma Response Patterns Not Predicted by Standard Radiographic Assessment


Imaging biomarkers capable of providing early cancer treatment response assessment would allow the opportunity to individualize patient care. For this purpose, images can be obtained which detect treatment-associated alterations in tissue properties including cellular viability, vascular function and volume, and biochemical and molecular responses. In this study, multiparametric quantification of perfusion- and diffusion-weighted MRI brain tumor maps was accomplished using a novel voxel-by-voxel analysis approach known as the parametric response map (PRM). The PRM composite imaging biomarker was found to provide early identification of patients resistant to standard chemoradiation. Validation of the PRM imaging biomarker would allow for routine clinical application as an early identifier of patients who may benefit from alternative treatment strategies.

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DCE and DW-MRI Monitoring of Vascular Disruption following VEGF-Trap Treatment of a Rat Glioma Model


Vascular-targeted therapies have shown promise as adjuvant cancer treatment. As these agents undergo clinical evaluation, sensitive imaging biomarkers are need to assess drug target interaction and treatment response. In this study, dynamic contrast enhanced MRI (DCE-MRI) and diffusion-weighted MRI (DW-MRI) were evaluated for detecting response of intracerebral 9L gliosarcomas to the antivascular agent VEGF-Trap, a fusion protein designed to bind all forms of Vascular Endothelial Growth Factor-A (VEGF-A) and Placental Growth Factor (PGF). Rats with 9L tumors were treated twice weekly for two weeks with vehicle or VEGF-Trap. DCE- and DW-MRI were performed one day prior to treatment initiation and one day following each administered dose. Kinetic parameters (Ktrans: volume transfer constant, kep: efflux rate constant from extravascular/extracellular space to plasma, and vp: blood plasma volume fraction) and the apparent diffusion coefficient (ADC) over the tumor volumes were compared between groups. A significant decrease in kinetic parameters was observed 24 hours following the first dose of VEGF-Trapin treated versus control animals (p<0.05) and was accompanied by a decline in ADC values. In addition to the significant hemodynamic effect, VEGF-Trap treated animals exhibited significantly longer tumor doubling times (p<0.05) compared to the controls. Histological findings were found to support imaging response metrics. In conclusion, kinetic MRI parameters and change in ADC have been found to serve as sensitive and early biomarkers of VEGF-Trapanti-vascular targeted therapy.

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