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ICREATE: imaging features of primary and metastatic alveolar soft part sarcoma from the EORTC CREATE study.

ABSTRACT: BACKGROUND:Alveolar Soft Part Sarcoma (ASPS) is a rare, slow-growing, but highly vascular soft tissue sarcoma, characterised by a high rate of metastases at presentation. Although imaging features of the primary are well described, less detail is available on the imaging pattern of metastatic ASPS. The EORTC 90101 (CREATE) study assessed the efficacy of Crizotinib in patients with metastatic ASPS and presents a unique opportunity to describe the imaging phenotype of primary and metastatic ASPS, based on prospectively collected imaging. METHODS:A retrospective review of the staging CT scans of 32 patients with ASPS from the CREATE study was undertaken and the imaging features of primary and metastatic disease were assessed. RESULTS:Imaging of the primary tumour was available in 7/32 cases (28%). All primary tumours demonstrated marked vascularity with prominent feeding vessels (7/7, 100%). The most frequent sites of metastases included lung (30/32, 94%), nodal (7/32, 22%), bone (5/32, 16%) and muscle/subcutaneous (5/32, 16%). Features of hypervascularity were identified at all sites, more appreciable in the lungs, with feeding vessels frequently demonstrated in pulmonary metastases (21/32, 66%). CONCLUSION:Analysis of imaging from the CREATE cohort of patients with metastatic ASPS demonstrates that metastases from ASPS are predominantly hypervascular and demonstrate feeding vessels comparable to primary ASPS, suggesting potential sensitivity of this rare sarcoma for antivascular/antiangiogenic treatment approaches.

SUBMITTER: Mcaddy NC

PROVIDER: S-EPMC7597361 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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iCREATE: imaging features of primary and metastatic alveolar soft part sarcoma from the EORTC CREATE study.

Mcaddy Naami Charlotte NC Saffar Hind H Litière Saskia S Jespers Pieter P Schöffski Patrick P Messiou Christina C

Cancer imaging : the official publication of the International Cancer Imaging Society 20201030 1

<h4>Background</h4>Alveolar Soft Part Sarcoma (ASPS) is a rare, slow-growing, but highly vascular soft tissue sarcoma, characterised by a high rate of metastases at presentation. Although imaging features of the primary are well described, less detail is available on the imaging pattern of metastatic ASPS. The EORTC 90101 (CREATE) study assessed the efficacy of Crizotinib in patients with metastatic ASPS and presents a unique opportunity to describe the imaging phenotype of primary and metastati ...[more]

PMID: 33121537

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Project description:BACKGROUND:Alveolar soft part sarcoma (ASPS) is an exceedingly rare and orphan disease, without active drugs approved in the front line. Pazopanib and trabectedin are licensed for sarcoma treatment from second-line, but very little and contradictory data are available on their activity in ASPS. Lacking ongoing and/or planned clinical trials, we conducted a multi-institutional study involving the reference sites for sarcoma in Europe, U.S., and Japan, within the World Sarcoma Network, to investigate the efficacy of pazopanib and trabectedin. MATERIALS AND METHODS:From May 2007, 14 of the 27 centers that were asked to retrospectively review their databases had identified 44 advanced ASPS patients treated with pazopanib and/or trabectedin. Response was evaluated by Response Evaluation Criteria in Solid Tumors 1.1. Progression-free survival (PFS) and overall survival (OS) were computed by Kaplan-Meier method. RESULTS:Among 30 patients who received pazopanib, 18 were pretreated (13 with other antiangiogenics). Response was evaluable in 29/30 patients. Best responses were 1 complete response, 7 partial response (PR), 17 stable disease (SD), and 4 progressions. At a 19-month median follow-up, median PFS was 13.6 months (range: 1.6-32.2+), with 59% of patients progression-free at 1 year. Median OS was not reached.Among 23 patients treated with trabectedin, all were pretreated and evaluable for response. Best responses were 1 PR, 13 SD, and 9 progressions. At a 27-month median follow-up, median PFS was 3.7 months (range: 0.7-109), with 13% of patients progression-free at 1 year. Median OS was 9.1 months. CONCLUSION:The value of pazopanib in advanced ASPS is confirmed, with durable responses, whereas the value of trabectedin appears limited. These results are relevant to defining the best approach to advanced ASPS. IMPLICATIONS FOR PRACTICE:This retrospective study, conducted among the world reference centers for treatment of sarcoma, confirms the value of pazopanib in patients with advanced alveolar soft part sarcoma (ASPS), with dimensional and durable responses, whereas trabectedin shows a limited activity. Alveolar soft part sarcoma is resistant to conventional cytotoxic chemotherapy. Pazopanib and trabectedin are licensed for treatment of sarcoma from second line; in the lack of prospective clinical trials, these results are relevant to defining ASPS best management and strongly support initiatives aimed at obtaining the approval of pazopanib in the front line of the disease.

Project description:BackgroundAlveolar soft part sarcoma (ASPS) is an extremely rare metastatic soft tissue tumor with a poor prognosis for which no effective systemic therapies have yet been established. Therefore, the development of novel effective treatment approaches is required. Tyrosine kinases (TKs) are being increasingly used as therapeutic targets in a variety of cancers. The purpose of this study was to identify novel therapeutic target TKs and to clarify the efficacy of TK inhibitors (TKIs) in the treatment of ASPS.Experimental designTo identify novel therapeutic target TKs in ASPS, we evaluated the antitumor effects and kinase activity of three TKIs (pazopanib, dasatinib, and cabozantinib) against ASPS cells using an in vitro assay. Based on these results, we then investigated the phosphorylation activities of the identified targets using western blotting, in addition to examining antitumor activity through in vivo assays of several TKIs to determine both the efficacy of these substances and accurate targets.ResultsIn cell proliferation and invasion assays using pazopanib, cabozantinib, and dasatinib, all three TKIs inhibited the cell growth in ASPS cells. Statistical analyses of the cell proliferation and invasion assays revealed that dasatinib had a significant inhibitory effect in cell proliferation assays, and cabozantinib exhibited marked inhibitory effects on cellular functions in both assays. Through western blotting, we also confirmed that cabozantinib inhibited c-MET phosphorylation and dasatinib inhibited SRC phosphorylation in dose-dependent fashion. Mice that received cabozantinib and dasatinib had significantly smaller tumor volumes than control animals, demonstrating the in vivo antitumor activity of, these substances.ConclusionsOur findings suggest that cabozantinib and dasatinib may be more effective than pazopanib against ASPS cells. These in vitro and in vivo data suggest that c-MET may be a potential therapeutic target in ASPS, and cabozantinib may be a particularly useful therapeutic option for patients with ASPS, including those with pazopanib-resistant ASPS.

Dataset Information

ICREATE: imaging features of primary and metastatic alveolar soft part sarcoma from the EORTC CREATE study.

Publications

iCREATE: imaging features of primary and metastatic alveolar soft part sarcoma from the EORTC CREATE study.

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