Study Shows Value of Circulating Tumor DNA for Guiding Treatment in Most Common Ovarian Cancer Type

A minimally invasive method of capturing snapshots of genomic alterations in cancer can give clinicians a way to select drug combinations to treat a common type of ovarian cancer, a new study has found.

Results appearing in JCO Precision Oncology show that circulating tumor DNA (ctDNA), which has been used for detection and monitoring of genomic alterations in cancer, can be used to make treatment decisions and may be especially helpful if cancer relapsed after initial treatment with chemotherapy.

Researchers from the University of Helsinki and the University of Turku in Finland created a clinical ctDNA workflow to detect clinically actionable changes in more than 500 cancer-related genes. They used 78 ctDNA samples from 12 patients with ovarian cancer, gathering samples before, during, and after treatment and then analyzing them with bioinformatics, as well as an in-house translational oncology database, to detect actionable alterations.

The team found DNA alterations linked to existing drugs in 58% of the patients, and one is already being treated successfully based on the results.

“Analyzing circulating tumor DNA enables us to detect genomic alterations also in late stage cancers in which taking biopsies from the tumor is difficult or even impossible,” Sampsa Hautaniemi, DTech, director of the Systems Oncology Research Program at the University of Helsinki, said in a statement. “In current research, we demonstrated that circulating tumor DNA can be used to monitor the patient response to treatment, and find drug combinations to target the Achilles’ heels of the tumor’s genomic profile.”

Using ctDNA for treatment decisions has been controversial, the authors write, because doing so “requires multidisciplinary expertise in medical genetics, bioinformatics, and clinical oncology.” Earlier studies zeroed in on a single gene or a handful, which is at odds with the results that ctDNA provides.

In contrast, a longitudinal ctDNA analysis—a panel of 500 cancer-related genes—could offer an alternative for patients who are treated for high-grade serous ovarian cancer (HGSOC), a common an aggressive form of epithelial cancer with a 5-year survival rate of 43%. Patients are typically treated with surgery and then platinum-based chemotherapy, but nearly all patients relapse. “There is an urgent need to find effective therapy targets for HGSOC in general and for relapsed, chemotherapy-resistant disease in particular,” the authors write.

The authors say the results show that ctDNA works in concept in guiding clinical decisions and can be used for patients who respond poorly after the first cycles of chemotherapy. “We provide what we believe to be the first comprehensive, open source ctDNA workflow for detecting clinically actionable alterations in solid cancers,” they conclude.

Reference

Oikkonen J, Zhang K, Salminen L, et al. Prospective longitudinal ctDNA workflow reveals clinically actionable alterations in ovarian cancer [published online May 3, 2019]. JCO Prec Oncol. doi: 10.1200/PO.18.00343.