Feasibility and clinical utility of cancer whole-genome sequencing in adult solid tumors.

person Minsuk Kwon Ajou University, Suwon-Si, South Korea info_outline Minsuk Kwon, Ryul Kim, Baek-Lok Oh, Seokhwi Kim, Jin Roh, Hoon Hur, Woo Sik Yu, Chang Woo Kim, Jeong Seok Lee, Young Seok Ju

Authors person Minsuk Kwon Ajou University, Suwon-Si, South Korea info_outline Minsuk Kwon, Ryul Kim, Baek-Lok Oh, Seokhwi Kim, Jin Roh, Hoon Hur, Woo Sik Yu, Chang Woo Kim, Jeong Seok Lee, Young Seok Ju Organizations Ajou University, Suwon-Si, South Korea, Genome Insight Inc., San Diego, CA, Department of Pathology, Ajou University School of Medicine, Suwon, South Korea, Ajou University School of Medicine, Suwon, South Korea, Department of Thoracic and Cardiovascular Surgery, Ajou University College of Medicine, Suwon, South Korea, Department of Surgery, Ajou University School of Medicine, Suwon, South Korea Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Genome Insight Technology, Inc. Background: As sequencing costs decrease, whole-genome sequencing (WGS) is expected to be utilized in actual cancer patient care. However, there is insufficient evidence that WGS can be applied to the real-world cancer patient care, and how it can help in the diagnosis and treatment process. Methods: This prospective cohort study was designed to evaluate the feasibility and clinical utility of WGS in adult solid cancer care at a tertiary hospital. All solid cancer patients who were scheduled to undergo biopsy or surgery for diagnosis or treatment were eligible for the study. Either fresh or formalin-fixed paraffin-embedded tissue with match peripheral blood were obtained. Tumors were sequenced to depth of 40x, and WGS data were curated by Genome Insight Inc. The WGS reports were provided to clinician through a web-based, user-browsable reporting system in real time. Results: 97 patients were enrolled between Sep 2022 and Jan 2023. Besides 10 QC failed cases, 87 patients were provided WGS reports. Median turn-around-time was 14 day (range 12-23). The clinical utility of WGS was evaluated in 77 cancer patients, excluding 10 cases with estimated cancer cell fraction less than 15%. 31 patients (40.3%) had more than one actionable alteration targeted by on-label drugs. 49 patients (63.6%) also had more than one actionable alteration targeted by either on-label or off-label drugs. In selected cases (N = 6), WGS could suggest the diagnosis for cancer of unknown origin or the revision of pathologic diagnosis that was regarded as a double primary cancer into a metastasis of a single cancer. By providing information of total mutation counts, whole-genome-wide mutational signature analysis, copy number variation with high accuracy, germline alterations, detection of homologous recombination deficiency, and presence of loss-of-heterozygosity, WGS could further refine the actionable mutations in 39% cases, and estimate the etiology of cancer (genomic or environmental) or to determine hereditary or sporadic cancer in 60% cases. In 90% cases, WGS demonstrated clinical utility with supporting diagnosis, informing carcinogenesis, or annotating actionable alterations. Conclusions: WGS was applicable in real-world cancer care. WGS demonstrated clinical utility in the diagnosis and treatment of adult cancer patients. Clinical trial information: KCT0008118. N Actionable alteration for on-label Actionable alteration for on-label or off-label Colorectal cancer 21 10 (47.6%) 13 (57.1%) Non-small cell lung cancer 15 9 (60.0%) 12 (80.0%) Stomach cancer 15 4 (26.7%) 9 (60.0%) Urothelial carcinoma 7 3 (42.9%) 6 (85.7%) Breast cancer 5 3 (60.0%) 0 (0.0%) Pancreatic cancer 4 0 (0.0%) 1 (25.0%) Head and neck cancer 3 1 (33.3%) 2 (66.7%) Other* 7 1 (14.3%) 3 (42.9%) Sum 77 31 (40.3%) 49 (63.6%) * 1 gastrointestinal stromal tumor; 1 anal cancer; 1 renal cell carcinoma; 1 small cell lung cancer; 1 endometrial cancer; 1 soft tissue sarcoma; 1 neuroendocrine tumor.

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