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EP236/#459  Developing a whole exome sequencing-based homologous recombination deficiency test of epithelial ovarian cancer
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  1. Po-Han Lin1,
  2. Kuan-Ting Kuo2,
  3. Wuh-Liang Hwu3,
  4. Hsien-Neng Huang4,
  5. Tzu-Ying Lin5,
  6. Chieh Min Chen5,
  7. Ying-Cheng Chiang6 and
  8. Wen-Fang Cheng6
  1. 1National Taiwan University Hospital, Department of Medical Genetics, Taipei, Taiwan
  2. 2National Taiwan University Hospital, Department of Pathology, College of Medicine, Taipei, Taiwan
  3. 3National Taiwan University Hospital, Department of Pediatrics, Taipei, Taiwan
  4. 4National Taiwan University Hospital Hsin-Chu Branch, Department of Pathology, Hsinchu, Taiwan
  5. 5Takeda Pharmaceuticals Taiwan, Ltd, Medical Affairs, Taipei, Taiwan
  6. 6National Taiwan University Hospital, Department of Obstetrics and Gynecology, College of Medicine, Taipei, Taiwan

Abstract

Introduction Some studies revealed a very good correlation in HRD detection between Myriad testing and WGS/WES method for breast cancer. However, the clinical value of WES based HRD analysis was less validated in EOC.

Methods We developed a HRD test by WES-based tissue samples (N=44) of EOC patients. Samples were concordantly examined by Myriad myChoice. The correlation of HRD and clinical outcomes among the three tests were analyzed

Results High correlation of HRD score was observed between Myriad and our WES-based scarHRD test (coefficient 0.82, p<0.001) in the linear regression model. In compared to positive HRD status of Myriad test, the sensitivity,specificity, PPV and NPV was 93.5%, 76.9%, 90.6% and 83.3% respectively in our WES-based scarHRD test. The percentages of EOC patients with positive HRD statusof our test/Myriad test were higher in advanced FIGO stage (Early vs Advanced: 0% vs 76.2%; p = 0.018)/(Early vs Advanced: 0% vs 73.8% , p =0.025), and sensitive platinum-response (Sensitive vs Resistant: 84.6% vs 55.6%, p = 0.033)/(Sensitive vs Resistant: 84.6% vs 50%, p = 0.013). In multivariate Cox regression model, optimal debulking surgery (H.R; 0.39, p=0.017) and positive HRD status of our test (H.R; 0.42, p=0.026) were independent factors for lower risk of diseaserecurrence. Only optimal debulking surgery (H.R; 0.41, p=0.023) but not positive HRD status of Myriad test (H.R; 0.99, p=0.083) was independent factor for lower risk ofdisease recurrence.

Conclusion/Implications This test had favorable sensitivity, specificity and PPV/NPV and will provide a new feasible option to determine the HRD status of EOC patients

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