Abstract 1204P
Background
Comprehensive molecular profiling is essential for personalised cancer care. In the United Kingdom, Genomics England partners with the National Health Service to provide whole-genome sequencing (WGS). The 100,000 Genomes Project established infrastructures to incorporate WGS into clinical practice. However, the real-world utility of whole genome sequencing in adult cancer patients is poorly described.
Methods
The 100,000 Genome Project is a national prospective cohort study, which sought to sequence 100,000 whole genomes from patients with cancers or rare diseases. This is a retrospective evaluation of data collated during the 100,000 Genome Project for patients with cancers recruited by the West Midlands Genomic Medicine Centre. Actionable genes are defined by the GenomOncology Knowledge Management System as genes with reported therapeutic, prognostic or clinical trial associations. The presented work evaluates the clinical utility of WGS by assessing the variants identified, GTAB recommendations, and whether recommendations altered clinical practice.
Results
4851 participants were included. A third of patients had no sample or sample failed quality control (1451/4851; 29.9%). 37.4% of patients (1816/4851) were clinically excluded (including due to death or poor fitness) before Genomics Tumour Advisory Board (GTAB) discussion. For those with successful sequencing (24.4%; 1183/4851), 7 in 10 (846/1183; 71.5%) had reported potentially actionable variants, of whom 428/846 (50.6%) had recommendations made. One in 12 participants (8.6%; 416/4851) had GTAB recommendations, the majority being additional treatments or clinical trials (60.6%; 252/416). Clinical exclusion rates and the availability of GTAB recommendations varied between cancer types (p<0.0001). At the last follow up, only a small proportion of patients had therapeutic recommendations followed, representing 5.2% of all recommendations (13/252).
Conclusions
The 100,000 Genomes Project has established essential infrastructure and regional experience to deliver WGS. The majority had potentially actionable variants. Ensuring GTAB recommendations are followed will maximize benefits for patients.
Clinical trial identification
The current work is a retrospective analysis of patients enrolled in the 100,000 genome project in the West Midlands. All data analysed was routinely collected. The 100,000 genome project was approved by the HRA Committee East of England Cambridge South (REC Ref 14/EE/1112).
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. Middleton: Financial Interests, Personal, Advisory Board: BMS, Roche, Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: BMS, Roche, Boehringer Ingelheim, AstraZeneca, Servier, Takeda; Financial Interests, Institutional, Research Grant, Funding for organoids: AstraZeneca; Financial Interests, Institutional, Research Grant, Clinical Trial Funding: BMS, MSD. A.D. Beggs: Financial Interests, Personal and Institutional, Speaker, Consultant, Advisor, Laboratory support and consultancy fees: Illumina Inc, Oxford Nanopre. All other authors have declared no conflicts of interest.
Resources from the same session
1199P - Developing and systematically validating homologous recombination repair gene detection method based on next-generation sequencing
Presenter: Yi Sun
Session: Poster session 10
1200P - Investigation of multiphoton microscopy as an innovative tool for intraoperative section-free histologic investigations in just a few minutes
Presenter: Martí Homs Soler
Session: Poster session 10
1201P - Novel deep learning model and validation of whole slide images in lung cancer diagnosis
Presenter: Alhassan Ahmed
Session: Poster session 10
Resources:
Abstract
1202P - A deep learning approach using routine pathology images to guide precision medicine in metastatic CRC
Presenter: Chaitanya Parmar
Session: Poster session 10
1203P - Analytical evaluation of whole genome sequencing for acute myeloid leukemia
Presenter: Guidantonio Malagoli Tagliazucchi
Session: Poster session 10
1205P - A retrospective machine learning-based analysis of nationwide cancer CGP data across cancer types to identify features associated with recommendation of mutation-based therapy
Presenter: Hiroaki Ikushima
Session: Poster session 10
1478P - Dual single-nucleotide polymorphism biomarker combination to select opioid for cancer pain management
Presenter: Yoshihiko Fujita
Session: Poster session 10
1479P - Use of rescue opioids and pain control after ketamine initiation in refractory cancer pain: A multicentric observational study
Presenter: Pablo Gallardo Melo
Session: Poster session 10
1480P - Long term therapy with denosumab and zoledronic acid: A comparative real-world retrospective observational study on skeletal-related events and pain in patients with metastatic breast cancer
Presenter: Giacomo Massa
Session: Poster session 10
1481P - A case-control study of drug-eluting microspheres and blank microspheres in bronchial artery embolization for hemoptysis in non-small cell lung cancer
Presenter: Tongguo Si
Session: Poster session 10