Researchers from The Princess Margaret Cancer Centre with funding from the Sarcoma Foundation of Canada presented new research at the 2023 American Society of Clinical Oncology Annual Meeting demonstrating the presence of cancer-causing mutations in a majority of soft tissue sarcoma patients and the prognostic value of measuring their circulating tumor DNA (ctDNA) as part of an overall treatment strategy.
About ctDNA
Cancer is caused by genetic mutations, and these mutations can be detected by measuring ctDNA, in the blood. Detection of ctDNA allows for personalized cancer surveillance based on an individual’s unique set of cancer mutations. Circulating tumor DNA is 150–200-base-pair fragments of DNA, which originate from cancer cells and are present in the bloodstream or other body fluids. ctDNA is different than cell-free DNA (cfDNA) which is ALL the DNA in the bloodstream including germline DNA and tumor DNA. ctDNA is the portion of cfDNA that is derived specifically from the cancer.
Across all stages of surgically removed cancer, detection of ctDNA following surgery is a strong predictor of cancer recurrence. For example, measurement of ctDNA is performed routinely in early-stage colon cancer and can help clinicians decide when to intensify therapy in certain situations, and conversely, the absence of ctDNA can provide an opportunity to minimize surveillance or avoid adjuvant treatment.
Surgery and (neo) adjuvant radiotherapy are the mainstay curative treatments for localized soft tissue sarcoma (STS). Despite treatment, up to 50% of STS patients experience metastatic relapse. Routine use of adjuvant systemic therapy remains controversial because it’s unclear which STS patients benefit from treatment. The presence of ctDNA in the blood following treatment of STS is a potential biomarker for detecting residual cancer and may help identify patients who are likely to benefit from additional adjuvant therapy following surgery.
About Signatera
Signatera is a custom-built ctDNA test for treatment monitoring and molecular residual disease assessment in patients diagnosed with cancer. The Signatera test is personalized and tumor-informed, providing each individual with a customized blood test tailored to fit the unique signature of clonal mutations found in that individual’s tumor. Signatera is intended to detect and quantify cancer left in the body, at levels down to a single tumor molecule in a tube of blood.
Researchers conducted a clinical trial evaluating longitudinal assessment of tumor informed ctDNA every 3 months from diagnosis and post-surgery treatment surveillance in 20 patients with localized soft tissue sarcomas.
- ctDNA was detected in 80% of patients at diagnosis.
- 73% of patients who were ctDNA-positive converted to negative following treatment with neoadjuvant radiation.
- 93% of patients who were ctDNA positive converted to ctDNA negative.
- Patients who became ctDNA positive at any point during post-treatment surveillance had ~18 times higher risk of disease relapse.
The authors concluded that a personalized, tumor-informed ctDNA assays can detect residual cancer after definitive local therapy and/or prior to radiologic recurrence in patients with localized high-risk STS. Serial ctDNA monitoring provides prognostic value and may further identify patients that will benefit from adjuvant treatment.
References
- https://www.nature.com/articles/s41591-022-02115-4
- Molecular residual disease detection using bespoke circulating tumor DNA assays in localized soft tissue sarcoma. Abdulazeez Salawu, Elizabeth Demicco, Peter Chung Jordan Feeney, Erik Spickard, Richa Rathore, Jasmine Lee, Phillip Wong, Eoghan Malone, Charles Catton, Limore Arones, Madeline Phillips, Peter Ferguson, Jay Wunder, Antony Tin, Himanshu Sethi, Minetta C. Liu, David Shultz, and Albiruni R Abdul Razak. ASCO 2023 oral presentation.
