Abstract 1249P
Background
Whole genome sequencing (WGS) has matured and proven feasible and valid for routine clinical cancer care. Here, we report on the value of WGS in a real-world setting as part of standard clinical practice at the Netherlands Cancer Institute.
Methods
WGS (tumour-normal pairs at 90x-30x depth) was used for diagnostic testing in patients with metastatic cancer, rare primary tumours and cancer of unknown primary (CUP). All WGS requests initiated by medical specialists (Jan 2021-Nov 2022) were evaluated for test success rate and clinical decision consequences, as defined by detection of actionable biomarkers, relevance for CUP tissue-of-origin diagnosis, and identification of pathogenic germline alterations.
Results
A total of 888 matching tumour tissue and blood samples were received from 810 unique patients. 823/888 WGS tests were successful, leading to a clinical feasibility of 93%. The major cause of failure (47/65) was insufficient tumour cellularity (<20%). Based on preliminary analysis results (412/823 samples from 408 patients) we found clinical decision consequences of WGS-based diagnostics in 77% of patients (complete cohort data will be presented at ESMO). This is based on: (1) 73% of analysed patients (298/408) having, after assessment by a molecular tumour board, ≥1 potentially actionable biomarker for standard (24%) or experimental (63%) treatment options, (2) added value when integrated with the routine diagnostic work-up for CUP patients for identifying a primary tumour type in 66% (62/94) of patients, and (3) pathogenic germline variants in 7% (28/388) of patients (for patients that have given consent for germline analysis; ∼50% were not previously identified). For 320 patients, follow-up data (median 10 months) was available, which revealed that in 25% a WGS-informed targeted treatment was started.
Conclusions
WGS in routine clinical practice has a clinical feasibility of 93%. When successful, clinically relevant information is retrieved for 77% of patients. Short-term follow-up revealed that in 25% of patients, WGS information was used to inform treatment decision. This percentage may increase with longer follow-up and exhaustion of standard treatment lines.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
K. Monkhorst: Financial Interests, Institutional, Advisory Board: AbbVie, AstraZeneca, BMS, Bayer, Boehringer Ingelheim, Lilly, MSD, Merck, Pfizer, Roche; Financial Interests, Institutional, Coordinating PI: AstraZeneca; Non-Financial Interests, Institutional, Product Samples: Roche SS. All other authors have declared no conflicts of interest.
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