학술논문
Plasma-based longitudinal mutation monitoring as a potential predictor of disease progression in subjects with adenocarcinoma in advanced non-small cell lung cancer.
Document Type
Academic Journal
Author
Jiang J; Roche Sequencing Solutions, 4300 Hacienda Dr, Pleasanton & Potsdam, California, 94588, USA.; Adams HP; Signature Diagnostics GmbH, Hermannswerder 20A, 14473, Potsdam, Germany.; Lange M; Signature Diagnostics GmbH, Hermannswerder 20A, 14473, Potsdam, Germany.; Siemann S; Signature Diagnostics GmbH, Hermannswerder 20A, 14473, Potsdam, Germany.; Feldkamp M; Signature Diagnostics GmbH, Hermannswerder 20A, 14473, Potsdam, Germany.; McNamara S; Signature Diagnostics GmbH, Hermannswerder 20A, 14473, Potsdam, Germany.; Froehler S; Signature Diagnostics GmbH, Hermannswerder 20A, 14473, Potsdam, Germany.; Yaung SJ; Roche Sequencing Solutions, 4300 Hacienda Dr, Pleasanton & Potsdam, California, 94588, USA.; Yao L; Roche Sequencing Solutions, 4300 Hacienda Dr, Pleasanton & Potsdam, California, 94588, USA.; Balasubramanyam A; Roche Molecular Systems, 4300 Hacienda Dr., Pleasanton, CA, 94588, USA.; Tikoo N; Roche Molecular Systems, 4300 Hacienda Dr., Pleasanton, CA, 94588, USA.; Ju C; Roche Molecular Systems, 4300 Hacienda Dr., Pleasanton, CA, 94588, USA.; Achenbach HJ; Lungenklinik Lostau, Lindenstraße 2, 39291, Lostau, Germany.; Krügel R; Johanniter Krankenhaus im Fläming, Johanniterstraße 1, 14929, Treuenbrietzen, Germany.; Palma JF; Roche Sequencing Solutions, 4300 Hacienda Dr, Pleasanton & Potsdam, California, 94588, USA. john.palma@roche.com.
Source
Publisher: BioMed Central Country of Publication: England NLM ID: 100967800 Publication Model: Electronic Cited Medium: Internet ISSN: 1471-2407 (Electronic) Linking ISSN: 14712407 NLM ISO Abbreviation: BMC Cancer Subsets: MEDLINE
Subject
Language
English
Abstract
Background: Identifying and tracking somatic mutations in cell-free DNA (cfDNA) by next-generation sequencing (NGS) has the potential to transform the clinical management of subjects with advanced non-small cell lung cancer (NSCLC).
Methods: Baseline tumor tissue (n = 47) and longitudinal plasma (n = 445) were collected from 71 NSCLC subjects treated with chemotherapy. cfDNA was enriched using a targeted-capture NGS kit containing 197 genes. Clinical responses to treatment were determined using RECIST v1.1 and correlations between changes in plasma somatic variant allele frequencies and disease progression were assessed.
Results: Somatic variants were detected in 89.4% (42/47) of tissue and 91.5% (407/445) of plasma samples. The most commonly mutated genes in tissue were TP53 (42.6%), KRAS (25.5%), and KEAP1 (19.1%). In some subjects, the allele frequencies of mutations detected in plasma increased 3-5 months prior to disease progression. In other cases, the allele frequencies of detected mutations declined or decreased to undetectable levels, indicating clinical response. Subjects with circulating tumor DNA (ctDNA) levels above background had significantly shorter progression-free survival (median: 5.6 vs 8.9 months, respectively; log-rank p = 0.0183).
Conclusion: Longitudinal monitoring of mutational changes in plasma has the potential to predict disease progression early. The presence of ctDNA mutations during first-line treatment is a risk factor for earlier disease progression in advanced NSCLC.
Methods: Baseline tumor tissue (n = 47) and longitudinal plasma (n = 445) were collected from 71 NSCLC subjects treated with chemotherapy. cfDNA was enriched using a targeted-capture NGS kit containing 197 genes. Clinical responses to treatment were determined using RECIST v1.1 and correlations between changes in plasma somatic variant allele frequencies and disease progression were assessed.
Results: Somatic variants were detected in 89.4% (42/47) of tissue and 91.5% (407/445) of plasma samples. The most commonly mutated genes in tissue were TP53 (42.6%), KRAS (25.5%), and KEAP1 (19.1%). In some subjects, the allele frequencies of mutations detected in plasma increased 3-5 months prior to disease progression. In other cases, the allele frequencies of detected mutations declined or decreased to undetectable levels, indicating clinical response. Subjects with circulating tumor DNA (ctDNA) levels above background had significantly shorter progression-free survival (median: 5.6 vs 8.9 months, respectively; log-rank p = 0.0183).
Conclusion: Longitudinal monitoring of mutational changes in plasma has the potential to predict disease progression early. The presence of ctDNA mutations during first-line treatment is a risk factor for earlier disease progression in advanced NSCLC.