Tumor-informed circulating tumor DNA detection for personalized monitoring of treatment response in epithelial ovarian cancer

Abstract

Background

Circulating tumor DNA (ctDNA) has emerged as a valuable biomarker in liquid biopsies for monitoring treatment responses in cancer patients. However, detecting ctDNA in epithelial ovarian cancer (EOC) is challenging due to its high heterogeneity and the absence of hotspot driver mutations. Therefore, a personalized approach to ctDNA analysis is essential, tailored to the specific tumor mutations of each EOC patient. In this study, we aimed to evaluate a droplet digital PCR (ddPCR) method targeting various genetic alterations in ctDNA identified through a targeted next-generation sequencing (NGS) panel in EOC tumors.

Methods

EOC tumor tissues were sequenced using a targeted NGS panel to identify oncogenic mutations. ddPCR assays were subsequently designed and optimized to detect these tumor-specific mutations in ctDNA. ctDNA levels were monitored and compared with CA-125 for EOC.

Results

Fourteen pathogenic mutations, including TP53, PIK3CA, PTEN, KRAS, and RB1, were identified in 13 patients with EOC and selected as targets for ctDNA detection. The performance of ddPCR assays was validated for 10 mutations, and mutated ctDNA was successfully detected for 8 mutations in 7 patients. In most cases, ctDNA levels showed trends consistent with CA-125 levels, reflecting the treatment response. However, in one case, PTEN (E91∗) mutated ctDNA was detected during recurrence, while CA-125 levels remained within the normal range.

Conclusion

This study demonstrates the clinical utility of ddPCR for monitoring treatment responses in EOC by targeting patient-specific mutations. Integrating ddPCR with NGS-based mutation identification offers an effective approach for assessing therapeutic outcomes in EOC patients.