Qin Xi

Economic evaluation of extended panel analysis in cancer patients with historical NHS diagnostic germline genetic testing – A modeling study based on real-world data

The South West Thames Centre for Genomics implemented a wider diagnostic Next Generation Sequencing (NGS) gene panel for eligible cancer patients undergoing diagnostic testing whilst restricting data analysis and reporting for BRCA1/BRCA2/PALB2/CHEK2 1100delC only as per contemporaneous guidelines. This study investigated the cost-utility of reanalyzing existing diagnostic grade extended panel data for truncating germline pathogenic variants (GPVs) in known moderate risk cancer susceptibility genes (CSGs) and performing follow-up genetic testing for first-degree relatives if patients have an identified CSG allele. Reanalysis of existing NGS data was undertaken in 889 samples from cancer patients contemporaneously eligible through the NHS England National Genomic Test Directory (NGTD) codes R207 (ovarian) or R208 (breast) who had tested negative for BRCA1/BRCA2/PALB2 and CHEK2 1100delC founder variant. We modeled the cost and health outcomes for comparisons between: 1. Extending reanalysis to ATM truncating GPVs (partial extended testing) versus historical genetic testing, and 2. Extending analysis to ATM truncating GPV/BRIP1 truncating GPV/CHEK2 truncating GPV excluding CHEK2 1100delC/RAD51C truncating GPV/RAD51D truncating GPV (full extended testing) versus historical genetic testing. For partial extended testing, the ICER compared with historical genetic testing was UK£49,671/QALY. For full extended testing, the ICER compared with historical genetic testing of historical genetic testing was UK£5716/QALY. The full extended testing remained cost-effective with a 30% increase in genetic testing cost. Where existing NGS data for cancer susceptibility genes is stored to diagnostic standard in UK laboratories, this study suggests it is cost-effective to analyze, report and clinically manage patients and relatives by extended analysis to an 8-gene panel compared to the historical genetic testing.

Economic evaluation of personalised versus conventional risk assessment for women who have undergone testing for hereditary breast and ovarian cancer genes: a modelling study

Background The management of women with germline pathogenic variants (GPVs) in breast (BC) and ovarian cancer (OC) susceptibility genes is focused on surveillance and risk-reducing surgery/medication. Most women are assigned an average range of risk and treated accordingly, but it is possible to personalise this. Here, we explore the economic impact of risk personalisation. Method We compared two strategies for risk stratification for female participants: conventional risk assessment (CRA), which only involves information from genetic testing and personalised risk assessment (PRA), using genetic and non-genetic risk modifiers. Three different versions of PRA were compared, which were combinations of polygenic risk score and questionnaire-based factors. A patient-level Markov model was designed to estimate the overall National Health Service cost and quality-adjusted life years (QALYs) after risk assessment. Results were given for 20 different groups of women based on their GPV status and family history. Results Across the 20 scenarios, the results showed that PRA was cost-effective compared with CRA using a £20 000 per QALY threshold in women with a GPV in PALB2 who have OC or BC+OC family history, and women with a GPV in ATM, CHEK2, RAD51C or RAD51D. For women with a GPV in BRCA1 or BRCA2, women with no pathogenic variant and women with a GPV in PALB2 who have unknown family history or BC family history, CRA was more cost-effective. PRA was cost-effective compared with CRA in specific situations predominantly associated with moderate-risk BC GPVs (RAD51C/RAD51D/CHEK2/ATM), while CRA was cost-effective compared with PRA predominantly with high-risk BC GPVs (BRCA1/BRCA2/PALB2). Conclusion PRA was cost-effective in specific situations compared with CRA in the UK for assessment of women with or without GPVs in BC and OC susceptibility genes.