ctDNA Could Predict Relapse in Ovarian Cancer Earlier

Pathologists at the Mayo Clinic have validated a technique in a small number of patients with ovarian cancer to show that liquid biopsies have the potential to predict relapse much before the tumor reappears.

The technique of monitoring the circulation of DNA fragments released from tumor cells has been shown advantageous in a number of different tumor types, including breast, prostate, melanoma, and colorectal cancers. The fact that patients with advanced disease have higher levels of circulating tumor DNA (ctDNA) compared with patients with early stage disease can be a significant advantage for earlier diagnosis over traditional biopsy methods.

“With liquid biopsies, we don’t have to wait for tumor growth to get a DNA sample,” according to George Vasmatzis, PhD, senior author on the study. “This important discovery makes it possible for us detect recurrence of the disease earlier than other diagnostic methods,” which he believes could ensure a better treatment plan.

For this proof-of-concept study, researchers drew blood samples from 10 patients with advanced stage ovarian cancer, before and after surgery. Using mate-pair sequencing—a next generation sequencing (NGS) technique—they identified somatic structural genomic alterations in primary tumors and in the blood samples. This NGS technique is a precision approach that allows a more individualized approach to treatment by mapping aberrant DNA junctions in the samples.

For 8 of the patients, rearrangements in the cfDNA from pre-surgical plasma matched the primary tumor; further, 3 patients continued to show presence of ctDNA in their postsurgery samples, consistent with recurrence, as documented at the time of blood draw. For the 5 patients whose blood samples did not show the presence of ctDNA, they had been confirmed as being in remission at the time of blood draw. This confirmed a concordance between detection of ctDNA and clinical presentation at the time of blood draw, the authors write.

The authors list the following limitations of their study:

• Need for fresh frozen tumor or biopsy tissue
• Laborious, as each case would need an individual panel for detection of rearrangements
• Method cannot be used to screen for ovarian cancer.

Reference

Harris FR, Kovtun IV, Smadbeck J, et al. Quantification of somatic chromosomal rearrangements in circulating cell-free DNA from ovarian cancers [published online July 20, 2016]. Sci Rep. doi:10.1038/srep29831.