Establishing a Pipeline for Personalized Therapy in Ovarian Cancer

Abstract

Background: Despite important progress, ovarian cancer remains a major cause of morbidity and mortality worldwide. As we become better at understanding and targeting the molecular mechanisms that drive cancer growth in an individual patient, more sensitive diagnostic tools will be key to translating research into a meaningful benefit for patients.

Methods: Blood and ascites were drawn from HGSOC patients in the Department of Gynecology at the University Medical Centre Hamburg-Eppendorf between July 2020 and April 2022. Liquid biopsy analysis was performed using CellSearch®, Parsortix®, Next Generation Sequencing and a novel slanted microfluidic device to enumerate patient-derived CTCs for cell culture.

Results: The concentration of cfDNA in the ascites of patients with primary and recurrent disease was found to be significantly higher than in their plasma. In patients with primary disease, the concentration of cfDNA in postoperative plasma was significantly higher than preoperatively. At least one CTC could be found in 48% of preoperative samples, 35% of postoperative samples, 24% of samples at first follow-up, and 15% of samples at second follow-up. We found a statistically significant decrease in the number of CTCs recovered at second follow up compared to pre-operatively (p<0.018) The median CTC count was 0 for each group. No statistically significant difference regarding the presence of residual tumor, presence of metastasis, recurrence or progression, and death could be found between patients with no CTCs at baseline and patients with one or more CTCs at baseline, patients where CTCs were not observable throughout the duration of the study, or for patients whose CTC count either increased or decreased following cytoreductive surgery. In two of five experiments where CTC cell culturing was attempted, there was expansion of a distinct group of large cells which were maintained for a maximum of 139 days. Sequencing of these cells showed genomic alterations consistent with those found in HGSOC.

Conclusion: This study demonstrates a role for liquid biopsy and its derived applications in detecting, monitoring and molecularly characterizing high-grade serous ovarian cancer. We envisage that CTC and cfDNA analysis may be used to aid clinicians in detecting recurrence and choosing the optimal therapy in the future. CTC cell culture may have applications in cases where the cancer has relapsed and is not sensitive to platinum chemotherapy.