Abstract 589P
Background
Analysis of circulating tumor DNA (ctDNA) has the potential to reflect the molecular features of a tumor without the need for surgical biopsies. We aimed to investigate the association of ctDNA with stage, histological type and oncological outcome in endometrial cancer (EC) patients.
Methods
Blood plasma samples were collected pre-operatively from 83 patients diagnosed with EC and treated at the Bern University Hospital, Switzerland (n= 36), Oslo University Hospital (n= 34) and Haukeland University Hospital (n= 13), Norway. cfDNA was isolated using the QIAvac system and concentration was measured with the Qubit fluorometer. Selected mutations were detected using the Oncomine™ Pan-Cancer cell free assay.
Results
Baseline clinicopathological data are provided in the table. Mean follow-up was 30 months. Mean concentration of cfDNA was 11.4 ng/ml. 24 (29%) patients were considered ctDNA positive due to mutations in one or more genes, including: TP53, ESR1, CTNNB1, PTEN, PIK3CA, MTOR, KRAS, GNAS, NRAS, FGFR2, SMAD4 and CCND3. Four patients were excluded from further analysis due to suspected MET or ALK germline mutation with mutated allelic frequencies of 50%. The association of ctDNA positivity with clinicopathological characteristics is shown in the table. Patients with positive ctDNA presented with a significantly shorter recurrence-free (P= .009) and disease-specific (P= .006) survival compared to ctDNA negative patients. In multivariable Cox regression analysis including lymphovascular space invasion, histological type, ESGO prognostic risk group and stage, ctDNA positivity remained an independent predictor of recurrence (HR 3.4, 95% CI 1.0 – 11.9). Table: 589P
Baseline clinicopathological data (* four patients excluded due to suspected germline mutation)
| Clinicopathological characteristics | Total n= 83 | ctDNA positive n= 24* | ctDNA negative n= 55 | P-value |
| Mean age, years ± SD | 68 ± 10 | 70 ± 11 | 68 ± 9 | .538 |
| Mean BMI, kg/m 2 ± SD | 29 ± 6 | 27 ± 6 | 29 ± 7 | .301 |
| FIGO stage, n (%) - I - II - III - IV | 66 (80) 2 (2) 13 (16) 2 (2) | 17 (71) 1 (4) 6 (25) 0 (0) | 45 (82) 1 (2) 7 (13) 2 (4) | .388 |
| Histological type, n (%) - endometroid, grade 1 and 2 - endometroid, grade 3 - serous - other | 33 (40) 23 (28) 20 (24) 7 (8) | 5 (21) 10 (42) 4 (17) 5 (21) | 27 (49) 11 (20) 15 (27) 2 (4) | .005 |
| Lymphovascular space invasion, n (%) - positive - negative - missing | 31 (37)42 (51)10 (12) | 14 (58)7 (29)3 (13) | 17 (31)33 (60)5 (9) | .012 |
Conclusions
In this series of ctDNA from EC patients, 29% of the patients were considered ctDNA positive. ctDNA positivity was prognostic for risk of recurrence and warrant longitudinal analysis in EC.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Swiss National Foundation, Wildhainweg 3, Postfach, CH-3001 Bern, Switzerland Foundation for clinical and experimental tumor research, Bern, Switzerland The SAKK / Dr. Paul Janssen Fellowship 2021 Rakel og Otto Kristian Bruun's Legat, Norway.
Disclosure
F. Siegenthaler: Financial Interests, Personal and Institutional, Funding: SAKK, SNF; Financial Interests, Institutional, Funding: Foundation for clinical and experimental tumor research; Other, Personal, Member: ESGO, SAKK. K. Lindemann: Financial Interests, Personal, Advisory Board: MSD, Eisai; Financial Interests, Personal, Invited Speaker: GSK; Financial Interests, Personal, Funding: GSK; Financial Interests, Institutional, Funding: GSK, AstraZeneca, MSD, Roche, Nykode; Financial Interests, Institutional, Advisory Role: AstraZeneca; Non-Financial Interests, Personal and Institutional, Leadership Role: NSGO; Other, Personal and Institutional, Member: ESGO, NSGO, ASMO. All other authors have declared no conflicts of interest.