Abstract 132P
Background
Following the 100,000 genomes project, across England, all patients diagnosed with sarcoma are entitled to WGS, funded by NHSE (2018). There are ongoing challenges of optimising uptake of testing and utilising results to enhance patient care including access to personalised therapies and clinical trials. The clinical utility of WGS for paediatric, teenage and young adult (TYA) and adult sarcoma patients requires further elucidation.
Methods
Retrospective analysis of local electronic healthcare record system clinical data for all new/relapsed sarcoma diagnoses in paediatric, TYA and adult patients consented for WGS from May 2021 - September 2022 within the London Sarcoma Service (LSS). - timing from consent/sample collection to acquisition of results - genetic findings - genomic tumour advisory board (GTAB) outcomes.
Results
WGS was completed for 25 paed/TYA and 5 adult patients. 24 patients were informed of results (22 paed/TYA, 2 adult), at a median time of 13 weeks (range 6 – 67) from consent. The most common histological subtypes were osteosarcoma (OS) (n=18) and Ewing sarcoma (n= 5). WGS identified two patients with germline variants – MLH1 and TP53 (both OS). Both were referred to clinical genetics services and Lynch syndrome and Li-Fraumeni syndrome were confirmed. The patient with Lynch syndrome subsequently received compassionate access immunotherapy, based on this result. Overall, 47% of patients had at least one AMP tier IA variant. The most frequent somatic variants were TP53, RB1, gain of 8q, gain of MYC, gain of 17p and CDKN2A. In one paediatric OS patient a novel fusion gene (PSMC1::NFATC2) was identified.
Conclusions
WGS has shown clinical utility in identifying pathogenic germline variants and novel somatic genetic alterations. Although almost 50% of patients had a clinically relevant somatic variant, these remain non-actionable for sarcoma patients and therefore no patients were referred to clinical trials based on these results. Long intervals from sampling to issuing of results remain a challenge. In October 2022, local pathway protocol formalised that all WGS results are discussed at the LSS GTAB. Work is ongoing to establish a WGS sarcoma database to facilitate improved access to clinical trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.