Validation of Microsatellite Instability Detection Using a Comprehensive Plasma-Based Genotyping Panel
| Autor: | Catalin Barbacioru, Jason Willis, M. Benavides, Marwan Fakih, Jinchul Kim, Jing Zhao, Kabir Mody, Timmy Nguyen, Richard B. Lanman, Jeeyun Lee, Seung Tae Kim, Kyoung-Mee Kim, Daniel V.T. Catenacci, Hyuk Lee, Yoshiaki Nakamura, Ramez N. Eskander, Nir Peled, Danielle Gavino, Darya Chudova, Scott Kopetz, Alexander Artyomenko, Pashtoon Murtaza Kasi, Takayuki Yoshino, Marcin Sikora, Victoria M. Raymond, Georges Azzi, Justin I. Odegaard, Stephen R. Fairclough, Martina I. Lefterova, Mike Cusnir, Kimberly C. Banks, Amir Ali Talasaz |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Oncology Cancer Research medicine.medical_specialty Plasma samples business.industry Concordance Case-control study Microsatellite instability Cancer medicine.disease digestive system diseases 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Microsatellite Stable 030220 oncology & carcinogenesis Internal medicine Genotype Medicine business neoplasms Genotyping |
| Zdroj: | Clinical Cancer Research. 25:7035-7045 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-19-1324 |
| Popis: | Purpose:To analytically and clinically validate microsatellite instability (MSI) detection using cell-free DNA (cfDNA) sequencing.Experimental Design:Pan-cancer MSI detection using Guardant360 was analytically validated according to established guidelines and clinically validated using 1,145 cfDNA samples for which tissue MSI status based on standard-of-care tissue testing was available. The landscape of cfDNA-based MSI across solid tumor types was investigated in a cohort of 28,459 clinical plasma samples. Clinical outcomes for 16 patients with cfDNA MSI-H gastric cancer treated with immunotherapy were evaluated.Results:cfDNA MSI evaluation was shown to have high specificity, precision, and sensitivity, with a limit of detection of 0.1% tumor content. In evaluable patients, cfDNA testing accurately detected 87% (71/82) of tissue MSI-H and 99.5% of tissue microsatellite stable (863/867) for an overall accuracy of 98.4% (934/949) and a positive predictive value of 95% (71/75). Concordance of cfDNA MSI with tissue PCR and next-generation sequencing was significantly higher than IHC. Prevalence of cfDNA MSI for major cancer types was consistent with those reported for tissue. Finally, robust clinical activity of immunotherapy treatment was seen in patients with advanced gastric cancer positive for MSI by cfDNA, with 63% (10/16) of patients achieving complete or partial remission with sustained clinical benefit.Conclusions:cfDNA-based MSI detection using Guardant360 is highly concordant with tissue-based testing, enabling highly accurate detection of MSI status concurrent with comprehensive genomic profiling and expanding access to immunotherapy for patients with advanced cancer for whom current testing practices are inadequate.See related commentary by Wang and Ajani, p. 6887 |
| Databáze: | OpenAIRE |
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