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
648P - Medium to long-term effects of the COVID-19 pandemic on colorectal cancer diagnosis and management in Italy: Preliminary findings from an updated analysis of the real-world multicenter COVID-DELAY study
Presenter: Alessandro Parisi
Session: Poster session 11
649P - The genomic landscape of appendiceal adenocarcinoma (AA) revealed by 855 whole exome sequences (WES)
Presenter: Michael White
Session: Poster session 11
650P - Genomic profiling of small bowel adenocarcinoma: A pooled analysis
Presenter: Thomas Aparicio
Session: Poster session 11
651P - DCF versus doublet chemotherapy as first-line treatment of advanced squamous anal cell carcinoma: A multicenter propensity score matching study
Presenter: Christophe Borg
Session: Poster session 11
727P - Clinical outcome of anlotinib (A) and tislelizumab (T) in metastatic adrenocortical carcinoma(mACC): A one-arm single-center experience
Presenter: HAO LI
Session: Poster session 11
728P - Brain metastases in advanced thyroid carcinoma: Clinical and molecular characteristics and outcomes
Presenter: Thais Megid
Session: Poster session 11
729P - Prognostic significance of nodal micrometastases in patients with non-functioning pancreatic neuroendocrine tumors (NF-PanNETs): A survival analysis from a prospective observational study
Presenter: Valentina Andreasi
Session: Poster session 11
730P - The outcome of combine radioligand and CAPTEM therapy in patients with advanced, unresectable, progressive GEP-NET
Presenter: Jaroslaw Cwikla
Session: Poster session 11
748P - Outcomes for patients (pts) with advanced endometrial cancer (aEC) who completed pembrolizumab (pembro) and continued lenvatinib (LEN) in the phase III Study 309/KEYNOTE-775
Presenter: Emeline Colombo
Session: Poster session 11