Clinical and Pathologic Features Associated with Low Circulating Tumor DNA Fraction in Endometrial and Ovarian Cancers

Currently, there are few effective methods to monitor patients with gynecologic malignancies, including ovarian and endometrial cancers. The ‘tumor fraction’ of circulating tumor DNA may offer a minimally-invasive method to evaluate tumor aggressiveness via simple blood draw. To date, there is limited data on utility of ctDNA TFx interrogation in gynecologic malignancies, although there is evidence that TFx may be low or undetectable in malignancies primarily confined to the peritoneal cavity. The objective was a descriptive assessment of ctDNA TFx in a cohort of patients with ovarian and endometrial cancer. The association of TFx to continuous and categorical baseline clinicopathologic factors and progression-free survival was assessed. In a large cohort comprised of 210 plasma samples from 78 patients with biopsy-proven ovarian and endometrial cancer, plasma samples collected between 4/2018 and 4/2020 were subjected to shallow whole genome sequencing with determination of TFx. Overall, we demonstrate that TFx was low for most samples with mean TFx for ovarian cancer 5.5% and endometrial cancer 2.4%, yet can be quantified above lower limit of detection in many patients particularly when evaluating serial samples. There was no significant association between TFx level and clinical (primary vs recurrent, best response) or pathologic (e.g. histology, grade) features. Our data demonstrates low TFx levels in ovarian and endometrial cancers likely reflect that tumor types are ‘low ctDNA shed’, suggesting that higher sensitivity assessments may be required for clinical utility.