Dataset Information

Tumor Response to Stroma-Modifying Therapy: Magnetic Resonance Imaging Findings in Early-Phase Clinical Trials of Pegvorhyaluronidase alpha (PEGPH20).

ABSTRACT: Pre-clinical and clinical studies have shown that PEGPH20 depletes intratumoral hyaluronic acid (HA), which is linked to high interstitial fluid pressures and poor distribution of chemotherapies. 29 patients with metastatic advanced solid tumors received quantitative magnetic resonance imaging (qMRI) in 3 prospective clinical trials of PEGPH20, HALO-109-101 (NCT00834704), HALO-109-102 (NCT01170897), and HALO-109-201 (NCT01453153). Apparent Diffusion Coefficient of water (ADC), T1, k^trans, v_p, v_e, and iAUC maps were computed from qMRI acquired at baseline and ≥ 1 time point post-PEGPH20. Tumor ADC and T1 decreased, while iAUC, k^trans, v_p, and v_e increased, on day 1 post-PEGPH20 relative to baseline values. This is consistent with HA depletion leading to a decrease in tumor water content and an increase in perfusion, permeability, extracellular matrix space, and vascularity. Baseline parameter values that were predictive of pharmacodynamic responses were: ADC > 1.46×10^-3 mm²/s (Balanced Accuracy (BA) = 72%, p < 0.01), T1 > 0.54s (BA = 82%, p < 0.01), iAUC < 9.2 mM-s (BA = 76%, p < 0.05), k^trans<0.07min^-1 (BA = 72%, p = 0.2), v_e<0.17 (BA = 68%, p < 0.01), and v_p<0.02 (BA = 60%, p < 0.01). Further, v_e<0.39 at baseline was moderately predictive of response in any parameter (BA = 65.6%, p < 0.01 averaged across patients). These qMRI biomarkers are potentially useful for guiding patient pre-selection and post-treatment follow-up in future clinical studies of PEGPH20 and other tumor stroma-modifying anti-cancer therapies.

SUBMITTER: Arias-Lorza AM

PROVIDER: S-EPMC10503830 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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Tumor Response to Stroma-Modifying Therapy: Magnetic Resonance Imaging Findings in Early-Phase Clinical Trials of Pegvorhyaluronidase alpha (PEGPH20).

Arias-Lorza Andrés M AM Costello James R JR Hingorani Sunil R SR Von Hoff Daniel D DD Korn Ronald L RL Raghunand Natarajan N

Research square 20230905

Pre-clinical and clinical studies have shown that PEGPH20 depletes intratumoral hyaluronic acid (HA), which is linked to high interstitial fluid pressures and poor distribution of chemotherapies. 29 patients with metastatic advanced solid tumors received quantitative magnetic resonance imaging (qMRI) in 3 prospective clinical trials of PEGPH20, HALO-109-101 (NCT00834704), HALO-109-102 (NCT01170897), and HALO-109-201 (NCT01453153). Apparent Diffusion Coefficient of water (ADC), T1, <i>k</i><sup>< ...[more]

PMID: 37720027

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Project description:The aim of this study was to analyze the computed tomography (CT) and magnetic resonance imaging (MRI) findings of dermatofibrosarcoma protuberans (DFSP), with a view to improving the diagnosis of this kind of tumor. A total of 27 cases of histopathologically confirmed DFSP were analyzed retrospectively. Of these, 18 patients underwent a CT scan and 9 patients underwent an MRI. All patients underwent unenhanced and contrast-enhanced examinations; 1 patient underwent multiphrase CT enhancement examination. Imaging characteristics, including location, shape, size, number, edge, and attenuation or intensity of each lesion, both unenhanced and contrast enhanced, were analyzed. Of the 27 cases, 24 were solitary, 2 had 2 nodules, and 1 had multiple confluent tumors. The lesion with multiple confluent tumors was ill defined and irregular; the other lesions were oval or round, well-defined nodules or masses. The unenhanced CT images showed 19 homogenous isodense lesions. There was no calcification in any of the patients. The contrast-enhanced CT images showed intermediate and marked nonhomogeneous enhancement in 13 lesions, intermediate homogeneous enhancement in 4 lesions, and a mild heterogeneous enhancement in 2 lesions. MR T1-weighted images revealed 1 ill-defined and 9 well-defined homogeneous isointense lesions. T2-weighted images showed homogeneous hyperintensity to the muscles in 6 lesions, 3 mild hyperintense lesions with hypointense lesions, and 1 mixed, mild hyperintense and isointense lesion. Contrast-enhanced T1-weighted images demonstrated intermediate and marked nonhomogeneous enhancement in 9 lesions and intermediate homogeneous enhancement in 1 lesion. DFSP is characterized by a subcutaneous well-defined soft tissue nodule or mass on plain CT/MR scans, and shows intermediate-to-marked enhancement on contrast-enhanced CT/MR scans. The imaging findings for DFSP are nonspecific, but may help to define the diagnosis in an appropriate clinical setting.

Project description:BackgroundThe anterior chest wall (ACW) involvement is characteristic of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome, yet little research has focused on its magnetic resonance imaging (MRI) findings.PurposeTo characterize the MRI features of the ACW in patients with SAPHO syndrome.MethodsSeventy-one patients with SAPHO syndrome and ACW involvement evidenced by bone scintigraphy were recruited in this cross-sectional study. The ACW region was scanned using sagittal, axial, and oblique coronal Dixon T2-weighted sequences and axial Dixon T1-weighted sequences. The characteristics of both active inflammatory and chronic structural lesions were evaluated.ResultsThe ACW lesions exhibited an asymmetrical distribution and a predilection for the sternocostoclavicular region (93.0%). Notably, 91.5% of the patients had lesions in the area of the anterior first ribs. Bone marrow edema (BME) was observed in 63 (88.7%) patients, which mainly affected the sternocostal joints (87.3%) and the manubrium sterni (84.5%). All of the BMEs were distributed under the articular surface or the bone cortex, consistent with the distribution of the ligaments and joint capsules. Synovitis was detected in 64 (90.1%) patients, with a predilection for the sternoclavicular joints (76.1%). A soft tissue mass or infiltration was found in all the patients who had bone marrow edema. Thirteen (18.3%) patients showed venous stenosis. Structural changes included bone bridge formation (80.3%), hyperostosis (43.7%), and fat infiltration (39.4%). Four common patterns of involvement were observed: the first rib area, the sternoclavicular area, the sternal angle area, and the areas of the second to sixth sternocostal joints.ConclusionThe ACW lesions of SAPHO syndrome demonstrated a triad of enthesitis, synovitis, and osteitis, suggesting complex interactions among the ligaments, synovium, and bones in the region. The inflammatory changes in the first rib area were highlighted in SAPHO syndrome.

Dataset Information

Tumor Response to Stroma-Modifying Therapy: Magnetic Resonance Imaging Findings in Early-Phase Clinical Trials of Pegvorhyaluronidase alpha (PEGPH20).

Publications

Tumor Response to Stroma-Modifying Therapy: Magnetic Resonance Imaging Findings in Early-Phase Clinical Trials of Pegvorhyaluronidase alpha (PEGPH20).

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