{"id":1633,"date":"2021-03-23T08:35:46","date_gmt":"2021-03-23T08:35:46","guid":{"rendered":"https:\/\/aceoncology.org\/?p=1633"},"modified":"2021-04-15T18:11:25","modified_gmt":"2021-04-15T18:11:25","slug":"the-clinical-utility-of-genomic-testing-in-advanced-solid-tumors","status":"publish","type":"post","link":"https:\/\/aceoncology.org\/zh-hans\/the-clinical-utility-of-genomic-testing-in-advanced-solid-tumors\/","title":{"rendered":"The Clinical Utility of Genomic Testing in Advanced Solid Tumors"},"content":{"rendered":"\n<p>Developments in next-generation sequencing (NGS) and other molecular profiling technologies are facilitating precision medicine for patients with advanced cancer, leading to improved clinical outcomes.&nbsp;However, although comprehensive genomic profiling may detect a wide range of clinically actionable alterations, the clinical utility of such testing is not clear-cut.&nbsp;&nbsp;<\/p>\n\n\n\n<p>To determine which patients derive the most clinical benefit from&nbsp;NGS-directed therapy, researchers at the University of Michigan, Ann Arbor, Michigan, US, analyzed the clinical outcomes of patients with advanced solid tumors who had&nbsp;NGS&nbsp;performed on metastatic tissue in a&nbsp;<a href=\"https:\/\/jamanetwork.com\/journals\/jamaoncology\/fullarticle\/2776760\" target=\"_blank\" rel=\"noreferrer noopener\">prospective clinical cohort&nbsp;study<\/a>, the Michigan Oncology Sequencing Program (Mi-ONCOSEQ). Patients underwent fresh tumor biopsy and blood sample collection for genomic profiling of paired tumor and normal DNA (whole-exome or targeted-exome capture with analysis of 1700 genes), as well as tumor RNA sequencing. Somatic and germline genomic alterations were then annotated and classified according to clinical actionability, and a report was shared with treating oncologists. Information on subsequent treatments and clinical responses were extracted from patients\u2019 medical records.&nbsp;&nbsp;<\/p>\n\n\n\n<p>Among 1138 patients who underwent biopsy of metastasis, 1015 (89.2%) had successful&nbsp;NGS&nbsp;testing and 817 (80.5%) harbored at least one potentially actionable genomic alteration. Of these patients, 132 (16.2%) had sequencing-directed therapy (SDT): 74 patients during a clinical trial; 43 with off-label therapy; and 15 with on-label therapy.&nbsp;SDT&nbsp;resulted in clinical benefit, defined as receiving&nbsp;SDT&nbsp;for&nbsp;at least&nbsp;6 months, in 49 patients (37.1%); the most common cancer types to experience clinical benefit were sarcoma (8.7%), prostate adenocarcinoma (6.5%), and carcinoma of unknown primary origin (CUP; 12.7%). Responses lasting&nbsp;\u226512 months (exceptional responses) were seen in 26 patients (19.7%). Genomic profiling identified pathogenic germline variants (PGV), which confer increased cancer risk, in 160 patients (15.8% of cohort), with potential therapeutic implications for 49&nbsp;PGVs&nbsp;(4.8% of cohort).&nbsp;Notably, most&nbsp;PGVs&nbsp;were unknown before study enrolment. For patients with CUP (n=55),&nbsp;NGS&nbsp;sequencing identified the primary site in 28 patients (50.9%). Thirteen patients (23.6%) received&nbsp;SDT, and clinical benefit was seen in seven cases (53.8%), with five patients experiencing exceptional responses.&nbsp;<\/p>\n\n\n\n<p>The investigators conclude that given the high incidence of&nbsp;PGVs&nbsp;identified by genomic profiling, the data support directed germline testing for inherited cancer predisposition as standard of care for all patients with advanced solid tumors. In addition, the significant clinical benefit of&nbsp;SDT&nbsp;in patients with CUP and other rare cancers supports the use of comprehensive&nbsp;NGS&nbsp;profiling at diagnosis for these patients. Nevertheless, the authors highlight that assessing the clinical utility of&nbsp;NGS&nbsp;testing in oncology remains a challenge that requires large-scale precision oncology studies with access to a wide range of targeted therapies. An accompanying&nbsp;<a href=\"https:\/\/jamanetwork.com\/journals\/jamaoncology\/article-abstract\/2776756\" target=\"_blank\" rel=\"noreferrer noopener\">editorial<\/a>&nbsp;acknowledges the \u201celegant work\u201d presented by the study investigators and commends their detailed molecular profiling efforts. The authors note that operational challenges of interpreting and returning germline&nbsp;PGV&nbsp;testing results is an important issue, as is the need to consider cost-effectiveness of large-scale genomic profiling.&nbsp;&nbsp;<\/p>\n\n\n\n<p><strong>References<\/strong>&nbsp;<\/p>\n\n\n\n<p>Cobain EF, et al.&nbsp;<em>JAMA Oncology&nbsp;<\/em>2021; Feb 25. [Online ahead of print].&nbsp;<br>Yap TA, Johnson A,&nbsp;Meric-Bernstam F.&nbsp;<em>JAMA&nbsp;<\/em>Oncology; Feb 25. [Online ahead of print].&nbsp;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Developments in next-generation sequencing (NGS) and ot [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":1634,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-1633","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-article-highlights"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.8 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>The Clinical Utility of Genomic Testing in Advanced Solid Tumors - ACE Oncology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/aceoncology.org\/zh-hans\/the-clinical-utility-of-genomic-testing-in-advanced-solid-tumors\/\" \/>\n<meta property=\"og:locale\" content=\"zh_CN\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"The Clinical Utility of Genomic Testing in Advanced Solid Tumors - 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