2351P - Whole genome sequencing of AYA patients

Background

Cancer in adolescents and young adults (AYAs, aged 18-39 years at first cancer diagnosis) is nowadays considered as a separate entity with specific care needs. However, once the diagnosis has been established, AYA patients are mostly treated as having cancer at an older age. Breakthroughs in treatment options are scarce and AYA patients are underrepresented in clinical trials. To improve healthcare outcomes, there is a large unmet need for obtaining more knowledge and better (genomic) understanding of cancers at AYA age.

Methods

As an independent not-for-profit cancer diagnostics organization and data provider, Hartwig Medical Foundation performs clinical-grade whole genome sequencing (WGS) for cancer patients using a single small fresh-frozen biopsy and a matching blood sample. In addition to comprehensive diagnostic reporting of oncology-related genomics aberrations (including mutations, copy-number alterations, fusions and mutational signatures like MSI, TMB, HRD) all WGS data is (following patient consent) stored in the Hartwig Database. This data (>5500 patients) is available to the academic community to facilitate research and improve future cancer patient care.

Results

The Hartwig Database currently includes WGS and associated clinical data for 192 metastatic AYA cancer patients. Although a fair number in total, the numbers per tumor indication are quite small with n > 30 for only three indications (breast n=49, bone/soft tissue n=33 and GI-tract n=34). Also, the distribution does not follow the AYA cancer type prevalence as registered in the Dutch national cancer registry, with e.g. GI-tract (18% vs 9%) and bone/soft tissue (17% vs 2%) overrepresented and male/female reproductive organs underrepresented (8 vs 18%). Preliminary analysis of the frequency of driver alterations of some of the well-known oncogenes (e.g. PIK3CA, BRAF, KRAS, ERBB2) do not reveal differences between AYA and non-AYA cancers although the low number of AYA samples hamper conclusiveness.

Conclusions

To better facilitate research for AYA patients and to offer all possible treatment options (e.g. clinical trials), more patients will need to be analyzed by WGS. For this purpose, a dedicated project has been initiated that includes tumor-normal WGS of 1000 AYA patients in the next 3 years.

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.