Abstract 726P
Background
Adrenocortical carcinoma (ACC) is a rare aggressive endocrine cancer with heterogeneous behaviour. Disease surveillance relies on frequent imaging, which comes with significant radiation exposure. We investigated the role of circulating cell-free DNA (ccfDNA)-related biomarkers (BM) for prognostication and monitoring of ACC.
Methods
We studied 33 patients with primary ACC and 23 healthy subjects (HS) as controls. ccfDNA was extracted by commercial kits from pre-surgical and serial EDTA plasma samples and quantified by fluorimeter (BM1). All ccfDNA samples passed the quality check showing a desired fragment length of 150-200 bp. Primary tumour DNA was isolated from paraffin-embedded tissue for 25/33 patients. Next-generation sequencing was performed using a customised panel of 30 ACC-specific genes (Cell3TM Target Nonacus). Leucocyte DNA was sequenced to discriminate germline from somatic variants (BM2). BM1 and BM2 were merged into a combined ccfDNA-BM score to be correlated with clinical outcome.
Results
ccfDNA concentrations were higher in ACC than HS (median 0.40 vs 0.05 ng/μl, P<0.001) and correlated with tumour stage and ki67 index (R=0.48 and 0.55, respectively). 94% of ACC were positive for BM1 (cut off 0.146 ng/μl, median HS+2SD) and 45.5% for BM2 (at least one somatic mutation in ccfDNA, variant allele frequency 1.0-30.5%). Mutational status at ccfDNA matched with tumour DNA in 60% of cases (additional variants in 16% and missed variants in 12%). ccfDNA-BM score (0-1=negative, 2-3=positive) was strongly associated with progression-free and overall survival (P=0.0004, HR=8.68, 95%CI=2.88-26.5, and P=0.003, HR=3.35, 95%CI=1.34-8.37, respectively). Among 13 patients followed up for at least 3 months (range 1-6), 10 tumour-free at last imaging and 1/3 with early relapse had negative ccfDNA-BM score (100% vs 33%). In two recurrent cases, somatic mutations in ACC-specific genes remained detectable during monitoring.
Conclusions
ccfDNA-related BMs are frequently detected in patients with ACC, representing a promising non-invasive tool to predict early disease recurrence and complement imaging for monitoring. Our findings will be validated in a larger cohort of ACCs with long-term follow up.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Deutsche Krebshilfe Stifftung (Project Grant 70113526), patient association AMEND (Research Fund).
Disclosure
C.L. Ronchi: Financial Interests, Personal, Research Grant: HRA Pharma. A. Prete: Financial Interests, Personal, Research Grant: NIHR. All other authors have declared no conflicts of interest.
Resources from the same session
750P - PFS2 and adjustment of overall survival (OS) for subsequent anticancer therapy in patients (pts) with primary advanced or recurrent endometrial cancer (pA/rEC) treated with dostarlimab plus chemotherapy or chemotherapy alone in the ENGOT-EN3-NSGO/GOG-3031/RUBY trial
Presenter: Brian Slomovitz
Session: Poster session 11
751P - Patients with endometrial cancer: Expectations and understanding of genetic counseling and hereditary carcinomas - First results of an international NOGGO/GCIG/ENGOT survey (EXPRESSION XI/IMPROVE)
Presenter: Jalid Sehouli
Session: Poster session 11
752P - Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic squamous cell cervix carcinoma: Subgroup analysis of the PEVOsq basket trial
Presenter: Olivia Le Saux
Session: Poster session 11
753P - IN10018 in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (PROC): A single-arm, phase Ib clinical trial
Presenter: Lingying Wu
Session: Poster session 11
754P - Ubamatamab (MUC16xCD3 bispecific antibody) with cemiplimab (anti-PD-1 antibody) in recurrent ovarian cancer: Phase I dose-escalation study
Presenter: Roisin O'Cearbhaill
Session: Poster session 11
755P - Retifanlimab in patients with recurrent microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) endometrial cancer: Final results from the POD1UM-101 study (Cohort H)
Presenter: Dominique Berton-Rigaud
Session: Poster session 11
756P - First-in-human phase I study of a novel claudin 6 (CLDN6) targeted antibody drug conjugate (ADC) TORL-1-23
Presenter: Gottfried Konecny
Session: Poster session 11
757P - The efficacy and safety of recombinant human adenovirus type 5 (H101) intra-tumor therapy in patients with recurrent or metastatic cervical cancer: A prospective, open-label, single-arm study
Presenter: Qiying Zhang
Session: Poster session 11
758P - Phase II trial evaluating the efficacy of pembrolizumab combined with vorinostat in patients with recurrent and/or metastatic vulvar and vaginal squamous cell carcinoma: Subgroup analysis of the PEVOsq basket trial
Presenter: Mathilde Saint-Ghislain
Session: Poster session 11