112P - Reporting of molecular test results from cell-free DNA analyses: Expert consensus recommendations from the 2023 European Liquid Biopsy Society ctDNA workshop

Background

Molecular profiling of circulating tumor DNA (ctDNA) may guide treatment-decisions in patients with cancer, particularly if tumor material is limited or of insufficient quality. However, high variability of ctDNA levels adds complexity to the interpretation of test results. Moreover, although the use of larger gene panels maximizes detection of actionable targets, variant calling and interpretation is even more challenging and there is a high need for recommendations to report ctDNA results.

Methods

In a 2-day workshop, held in October 2023 in Barcelona (Spain), the European Liquid Biopsy Society (ELBS) brought together key stakeholders to develop expert opinion consensus recommendations on how to accurately report molecular ctDNA test results to treating physicians. Forty-four experts from various disciplines including molecular diagnostics laboratories, regulatory healthcare authorities and oncologists from thirteen European countries participated. Following group discussions, cases were deliberated upon in plenary sessions involving all workshop attendees.

Results

After the workshop, 77 statements were formulated in a digital questionnaire covering various topics such as disclosure of clinical information, technical test specifications, management of variants with low allelic frequency, variants derived from clonal hematopoiesis, as well as reporting of copy number alterations, fusions, negative test results and unexpected findings. All 44 participants completed the questionnaire and in a preliminary analysis, consensus agreement (≥80% agreement) was reached for 52 out of 77 statements.

Conclusions

For clinical decision making, reports from molecular profiling of cfDNA need to be accurate and unequivocal. At ESMO 2024, we will present our recommendations developed in an ELBS ctDNA workshop.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

European Liquid Biopsy Society (ELBS) - ctDNA working group (E. Schuuring, E. Heitzer, P. Giacomini, C. Koch).

Funding

EU project CAN.HEAL.

Disclosure

R.D.A. Toledo: Financial Interests, Institutional, Research Grant, Research Funding: Novartis, AstraZeneca, BeiGene Pharmaceuticals. S. Deans: Financial Interests, Personal, Invited Speaker: AstraZeneca, MSD; Financial Interests, Institutional, Other, Educational Grant for external quality assessment: Meninari, Lilly, Qiagen. E. Schuuring: Financial Interests, Institutional, Advisory Board: MSD/Merck, AtraZeneca, Astellas Pharma, Roche, Illumina, Agena Biosciences, Lilly, Jansen Cilag, CC Diagnostics, Amgen, GSK, Novartis, Bayer; Financial Interests, Institutional, Invited Speaker: Biocartis, Illumina, Agena Biosciences, BioRAD, Lilly, SeraCare/LGT, Jansen Cilag, Roche; Financial Interests, Institutional, Research Grant, ZonMw: Predictive Analysis for Therapy: Path to Optimizing Access to Personalised Cancer Therapy in the Netherlands; from Tissue to Therapy: Abbott, CC Diagnostics; Financial Interests, Institutional, Research Grant, ctKRAS testing using BioRad ddPCR in cfDNA from plasma as a predictive biomarkers for tumor response to Nivolumab in KRAS-mutated non-small cell lung cancer: BioRad; Financial Interests, Institutional, Research Grant, EU-IHI-Horizon: GUIDE.MRD - GUIding multi-moDal thErapies against MRD by liquid biopsies – steering committee/WP-leader: BMS; Financial Interests, Institutional, Funding, Roche/Ventana: Validation and implementation of pan-TRK immuno staining and RNA-based NTRK-fusion detection in a diagnostic setting: Roche; Financial Interests, Institutional, Research Grant, B-IO - Unraveling tumor response and resistance to combined chemotherapy and PD-L1 inhibition with minimal invasive techniques in patients with advanced NSCLC with targetable disease: Roche; Financial Interests, Institutional, Research Grant, ALPINE-study - Identification of resistant mechanisms in progressing lung cancer patients with an initial tumor response or with stable disease on immunotherapy using comprehensive ultrasensitive NGS biomarker analysis: Roche; Financial Interests, Institutional, Research Grant, CLINBASE - validation and implementation of Agena UltraSEEK using plasma cfDNA samples from NSCLC patients: Agena Biosciences; Financial Interests, Institutional, Research Grant, Alpe d’HuZes/KWF/Agena Biosciences: GALLOP-11 study - treatment of gastrointestinal stromal tumors based on serial mutation analysis of circulating tumor DNA – WP-leader: Agena Biosiences; Financial Interests, Institutional, Research Grant, De validatie van Illumina’s TSO500 NGS panel voor DNA-analyse van HRD-genen in het kader van diagnostiek van prostaatkanker - (mede) projectleider: AstraZeneca; Financial Interests, Institutional, Research Grant, Evaluation of CIN2+ specific methylation markers as triage testing optimizing referral to gynecologist for colposcopy after primary hrHPV-positive test in the new Dutch population-based screening program - (mede) projectleider: CC Diagnostics; Financial Interests, Institutional, Research Grant, Imalife/Siemens: NEO-PUSH study - cfDNA from whole blood to detect lung cancer in high risk group of Imalife patients undergoing ULD-CT screening - (mede) projectleider: Siemens; Financial Interests, Institutional, Research Grant, Implementatie Invitae-ArcherDX fusiegendetectie tbv NTRK diagnostiek - (mede) projectleider: Archer/Bayer/Invitae:; Financial Interests, Institutional, Research Grant, HPV genotype distribution in cervical scrapings of low/high-grade intraepithelial lesions and cervical cancer in the Netherlands - an observational study”: MSD/Merck; Financial Interests, Institutional, Research Grant, Innovative diagnostics to improve screening for gynecological cancer: SNN/EFRO; Non-Financial Interests, Advisory Role: ZINL (Health Care Agency); Other, Dutch Advisory committee for assessment of molecular diagnostics (cieBOD): Dutch Society of Pathology; Other, National guideline advisory committee member (for NSCLC): Dutch Society of Thorical Cancer. All other authors have declared no conflicts of interest.