Using ctDNA for Detecting Residual Disease and Predicting Recurrence in Ovarian Cancer
Advanced-stage serous ovarian cancer is responsible for 80% of all ovarian cancer deaths and is associated with a 15% five-year survival rate. The majority of women with high-grade serous ovarian cancer will have a recurrence and ultimately die of their disease. Recurrence arises because of the growth and dissemination of cancer cells that remain after initial surgery and chemotherapy. The report of residual cancer is based on visual inspection, and thus, may not be an accurate reflection of true residual disease. Given the limitations associated with surgical reporting of residual disease, along with the prognostic role of no visible residual disease, we explore the utility of circulating cell-free tumour DNA (ctDNA) to quantify residual disease, and secondarily, to predict recurrence and ultimately long-term outcome among women with serous ovarian cancer.
This is a collaborative study with Dr. Joanne Kotsopoulos at Women’s College Research Institute and Dr. Taymaa May and Dr. Alicia Tone from Princess Margaret Hospital. Our objectives are to evaluate whether: 1) variants of the primary tumor are present in plasma DNA (ctDNA) prior to debulking surgery; 2) ctDNA is detected in patients with residual disease after debulking surgery 3) ctDNA is detected in patients with no residual disease after debulking surgery as an indicator of microscopic residual disease; 4) the presence of ctDNA after surgery is associated with cancer recurrence and survival and 5) detecting ctDNA in serial plasma samples can diagnose recurrence at early stages.
Improvements in the quantification of disease after cytoreduction will provide important information for clinical decision making. Findings from this study will have the potential to modify the existing treatment regimens of ovarian cancer which have essentially remained unchanged for over two decades. In the future, the ability to integrate a non-invasive circulating biomarker to improve the detection of recurrence would allow for timely interventions and ultimately, improved outcomes in these patients with a highly fatal disease.