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.
August 2023 Update: Levine Cancer Institute researchers completed testing and data analysis of the main sequencing technique (looking for structural changes in the chromosomes). It appears to work great! They were able to detect evidence of sarcoma in the blood in 90% of the samples where they expected to see those structural changes!!
With these results, the researchers submitted an abstract to the annual Musculoskeletal Tumor Society meeting this October in Banff, Alberta, and it was accepted for a podium presentation! Dr. Colin Anderson of Levine Cancer Institute will be traveling there to present at the conference.
There is another sequencing technique that looks for evidence of translocations in the blood that they are still troubleshooting.
September 2023 Update: LCI is in the early stages of designing a prospective clinical trial to evaluate sarcoma liquid biopsies in their patients. This potential trial would need to be approved by the IRB (Institutional Review Board) before moving ahead.
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.
August 2023 Update: Levine Cancer Institute researchers have completed a majority of the sequencing work with only a few remaining sequencing techniques to finalize. Their bioinformatics team has been diligently working on analyzing the data, which is a tremendous undertaking. They have encouraging preliminary results that show that there are differences between patients who’s tumors stay localized versus those that eventually metastasize.
November 2023 Update: Dr. Jagosky was awarded a poster presentation of this work to the Connective Tissue Oncology Society meeting in November in Dublin, Ireland, the largest gathering of sarcoma experts in the world! Further study stemming from the sucess of this project is slated for 2024.
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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