The combination of an anti-VEGF agent with an immune checkpoint inhibitor has shown efficacy in various cancer types, potentially through increasing immune infiltrate by normalizing vasculature and decreasing T-cell suppression. REGOBONE and SARC024 trials showed an improvement in progression-free survival (PFS) with regorafenib compared to placebo. In SARC038, the hypothesis is that by adding nivolumab, a PD-1 inhibitor, to regorafenib may further improve PFS compared to regorafenib alone.
The SARC038 clinical trial is slated to open at Levine Children’s Hospital and Levine Cancer Institute in Charlotte, NC once the initial cohort data is analyzed by the lead researchers and the next phase of the trial is approved for enrollment. (10/2022 update)SARC038 Clinical Trial Details
This prospective, observational study of patients with intermediate- and high-grade bone and soft tissue sarcomas will evaluate the use of a sarcoma-specific liquid biopsy circulating tumor DNA technique capable of identifying molecular patterns in sarcoma patients’ blood samples and correlating them with treatment response and disease progression. Blood specimens will be collected at various time points during a patient’s disease from diagnosis to up to two years post-treatment. Plasma samples will be sequenced to identify structural variants and targeted translocations that are specific to sarcoma. The molecular patterns identified by liquid biopsy will be compared to standard surveillance methods utilized to detect treatment response and distant metastasis. The results of this study will provide valuable information that will allow for more effective patient management and a greater understanding of the underlying mechanisms driving sarcomas.
Preliminary data showed evidence of circulating tumor DNA of several sarcoma subtypes in the blood. Researchers are excited! (10/2022 update)
Sarcomas are a rare and aggressive group of cancers that arise from connective tissues such as muscle, fat, nerve, tendon, bone, and cartilage. Despite their rarity, over 100 different subtypes have been described. Synovial sarcoma is one subtype of sarcoma that often occurs in the soft tissues of the lower extremities of young adults. Synovial sarcoma is characterized by a specific translocation, which is an inappropriate joining, of the X chromosome with chromosome 18. Research has shown that this translocation affects the system that controls the physical packaging and orientation of the chromosomes within the nucleus – also known as the epigenome. These ‘epigenetic’ changes flip the on/off state of countless genes, resulting in the cell becoming the synovial sarcoma cancer. While this basic mechanism has been understood, there is very little research into how those changes impact the prognosis or treatability of each different case of synovial sarcoma. At our institution, we have over 70 synovial sarcoma specimens that have been carefully preserved over the last few decades. The purpose for this study is to perform comprehensive sequencing of these specimens and compare to patient outcomes to characterize how these changes affect prognosis and help to uncover avenues for new future treatments.
This genetic sequencing study of synovial sarcomas is currently the largest in the world and publication is forthcoming. No bigger study has been published yet. (10/2022 update)
As part of the LCI-SAR-STS-PEM-001 study, Levine will evaluate the correlation between immunotherapy markers (PD-L1 expression levels) and the clinical effectiveness of pembrolizumab, investigate other biomarkers that may correlate with tumor responses, and evaluate differences in tumor tissue characteristics in biopsies taken during or post-treatment with pembrolizumab versus baseline. (Study fully enrolled). This study was chosen by the Scientific Program Committee of the American Society of Clinical Oncology (ASCO) for a prestigious poster discussion at the May 2020 ASCO Annual Meeting due to the significance of the study’s results.
Michael B Livingston , Megan H Jagosky , Myra M Robinson , William A Ahrens , Jennifer H Benbow , Carol J Farhangfar , David M Foureau , Deirdre M Maxwell , Emily A Baldrige , Xhevahire Begic , James T Symanowski , Nury M Steuerwald , Colin J Anderson , Joshua C Patt , Jeffrey S Kneisl , & Edward S Kim (2021). Phase II study of pembrolizumab in combination with doxorubicin in metastatic and unresectable soft tissue sarcoma. Clinical Cancer Research, 2021 Dec 1;27(23):6424-6431. doi: 10.1158/1078-0432.CCR-21-2001. Epub 2021 Sep 2.
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One of the largest retrospective studies evaluating genetic abnormalities for patients with dedifferentiated liposarcoma (DDLPS) versus how this patient corresponded with survival and risk of metastases. There were notable gene mutations and amplifications commonly found, some of which had interesting prognostic implications.
Jagosky MH, Anderson CJ, Symanowski JT, et al. Genomic alterations and clinical outcomes in patients with dedifferentiated liposarcoma. Cancer Med. 2022;00:1-10. doi:10.1002/cam4.5502
Kneisl, J. S., Ferguson, C., Robinson, M., Crimaldi, A., Ahrens, W., Symanowski, J., . . . Kim, E. S. (2017). The effect of radiation therapy in the treatment of adult soft tissue sarcomas of the extremities: A long-term community-based cancer center experience. Cancer Medicine,6(3), 516-525. doi:10.1002/cam4.972Read the Publication
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