Might Circulating Tumor DNA Guide Clinical Decisions in Aggressive Ovarian Cancer?
Posted: Wednesday, June 5, 2019
Based on study findings, circulating tumor DNA (ctDNA) may not only be useful to guide clinical decisions in ovarian cancer, but it also help to identify patients who are not responding well to the first cycles of chemotherapy for high-grade serous ovarian cancer. Jaana Oikkonen, PhD, of the University of Helsinki, Finland, and colleagues published a comprehensive ctDNA workflow in the Journal of Clinical Oncology Precision Oncology.
“Response to therapy can be inferred using two or three consecutive ctDNA samples during therapy. Rapid discovery of resistant cell population expansion provides an early opportunity to interfere with the development of recurrence,” proposed the authors.
The research team collected a cohort of 78 ctDNA samples with more than 500 cancer-related genes from 12 different patients with high-grade serous ovarian cancer before, during, and after treatment. Patients were treated with either primary debulking surgery followed by platinum-taxane chemotherapy or with neoadjuvant chemotherapy. Actionable genomic alterations were ranked according to the European Society for Medical Oncology scale for clinical actionability of molecular targets.
The study showed that the team’s ctDNA panel can reliably capture mutations and copy number alterations. In addition, there seems to be good concordance of mutations and copy number alterations between ctDNA and tumor samples.
As for the clinical implications of these findings, the ctDNA mutation profiles were found to reflect the long-term response to treatment and may be used to monitor therapeutic response. Additionally, several targetable pathways were revealed in 7 of the 12 patients (58%); the actionable mutations included mTOR-activating mutations, hormone receptor deficiency, cyclin-dependent kinase alterations, and ERBB2 amplifications. In fact, the treatment of one chemoresistant patient was changed on the basis of detection of ERBB2 amplification in the ctDNA, leading to significant tumor shrinkage and normalization of the CA-125 tumor marker.
Disclosure: The study authors’ disclosure information may be found at ascopubs.org.