The completed pilot study, “Prospective Observational Trial Utilizing Liquid Biopsy Techniques for Treatment Response and Disease Surveillance in Resectable Non-Metastatic Intermediate- and High-grade Sarcoma Patients” demonstrated promising efficacy of an untargeted circulating tumor (ctDNA) liquid biopsy in sarcoma patients utilizing ultra-low passage whole genome sequencing (ULP-WGS). Liquid biopsy is an approach for evaluating treatment response, monitoring for cancer relapse, and assessing mechanisms of cancer resistance in real time. The study tested 13 sarcoma plasma samples with 9 paired tissue samples, 2 carcinoma plasma samples, and 3 normal controls. Evidence of ctDNA was found in 9 of 13 sarcoma plasma samples, and the pattern of ctDNA structural alterations matched between the tissue and blood in all paired sarcoma samples.
Researchers are now evaluating the ability of ULP-WGS to detect ctDNA in over 200 adult and pediatric patients with new or existing diagnosis of bone or soft tissue sarcoma. They plan to obtain quantitative levels of ctDNA at various time points in their treatment course, including pre-treatment, at disease evaluations during treatment, post-treatment, at remission/complete response, during surveillance, and at recurrence/progression. The development of a sarcoma-specific liquid biopsy could greatly help clinicians with diagnosis, prognostication, treatment response, minimal recurrent disease, and recurrence.
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.
Levine Cancer Institute researchers were awarded a podium presentation of this study at the Musculoskeletal Tumor Society annual meeting in October 2023.
Prospective clinical trial to commence 2024/2025.
From the Abstract published June 21, 2024, “Can a Liquid Biopsy Detect Circulating Tumor DNA With Low-passage Whole-genome Sequencing in Patients With a Sarcoma? A Pilot Evaluation – PubMed (nih.gov),” available on PubMed:
Background: A liquid biopsy is a test that evaluates the status of a disease by analyzing a sample of bodily fluid, most commonly blood. In recent years, there has been progress in the development and clinical application of liquid biopsy methods to identify blood-based, tumor-specific biomarkers for many cancer types. However, the implementation of these technologies to aid in the treatment of patients who have a sarcoma remains behind other fields of cancer medicine. For this study, we chose to evaluate a sarcoma liquid biopsy based on circulating tumor DNA (ctDNA).
Conclusion: In this small pilot study, we were able to detect sarcoma ctDNA with an LP-WGS liquid biopsy searching for CNAs in the plasma of most patients who had a sarcoma representing a variety of histologic subtypes.
Synovial sarcoma is an aggressive subtype of soft tissue sarcoma that can occur at any age but has a predilection for the third decade of life. Treatment for synovial sarcoma includes surgical resection as well as adjuvant chemotherapy or radiation therapy. Unfortunately, metastases develop in approximately 50% of patients, often occurring 5 years or later from original diagnosis. Patients who present with metastatic disease have dismal outcomes with a five-year survival of around 20%.
In the completed study “Identification of Novel Prognostic and Therapeutic Biomarkers of Synovial Sarcoma through Comprehensive Molecular Analysis” researchers performed comprehensive molecular sequencing on 51 tissue samples obtained from 38 patients previously diagnosed with synovial sarcoma. Preliminary results from the RNA sequencing portion of this study were presented at the Connective Tissue Oncology Society annual meeting in November 2023. This next study will analyze integrated bioinformatics of these samples with the objective of characterizing how the epigenetic changes in synovial sarcoma drive oncogenesis through downstream effects. Through this analysis, researchers will be able to evaluate what molecular aberrations portend a better or worse prognosis. The data from this study will help guide pre-clinical and clinical trials in synovial sarcoma.
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.
The purpose for this study is to perform comprehensive sequencing of 51 tissue specimens and compare to patient outcomes to characterize how these changes affect prognosis and help to uncover avenues for new future treatments.
November 2023: Levine Cancer Institute was awarded a poster presentation of this study at the Connective Tissue Oncology Society annual meeting, the largest gathering of sarcoma experts in the world.
Bioinformatics analysis of these tissue samples will commence in 2024/2025, which will be critical to characterizing how the epigenetic changes in synovial sarcoma drive normal cells to become cancerous.
As part of the LCI-SAR-STS-PEM-001 study, Levine Cancer Institute researchers 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. 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.
Study Publication:
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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/cam4.972
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Physician researchers at Levine Cancer Institute discuss how the research partnership with our foundation to conduct trials and studies elevates hope, increases awareness, and creates community.
Dr. Edward Kim, former Chair of Solid Tumor Oncology and Investigative Therapeutics, Atrium Health’s Levine Cancer Institute, discusses results of the Institute’s first pilot study in soft tissue sarcomas; its poster discussion honor at ASCO 2020, and its ability to conduct significant investigator-initiated research through its partnership with the Paula Takacs Foundation for Sarcoma Research.
“WHEN I THINK OF LCI, THE WORD HOPE COMES TO MIND. THE EFFORTS BY THE PAULA TAKACS FOUNDATION TO HELP CURE CANCER ARE SO GENEROUS AND SO NECESSARY.”
–Hank Povinelli, Levine Cancer Institute Patient
