Lung Cancer
Research Institute, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Published: April 2016
Objectives: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have dramatic effects on EGFR-mutant non-small-cell lung cancer (NSCLC). However, most patients experience disease recurrences, approximately half of which are T790M-mediated. Monitoring EGFR status with re-biopsy has spatiotemporal limitations.
Patients And Methods: EGFR circulating tumor DNA (ctDNA) in serial plasma samples was amplified and 10(5) of them were sequenced with a next-generation sequencer. Plasma mutation (PM) score was defined as the number of reads containing deletions/substitutions in 10(5)EGFR cell free DNA (cfDNA).
Results: PM scores of various EGFR mutations showed dynamic, case-specific changes during EGFR-TKI treatments in 52 patients. The effects of the treatment on EGFR ctDNA were evaluated in 38 patients with elevated pre-treatment PM scores. The ctDNA responses correlated well with radiologic responses in radiologic good responders, whereas correlation was poor in non-responders. In addition to the peaks for the most prevalent ctDNA, small peaks of ctDNA with different types of activating EGFR mutations or the T790M mutation (early T790M ctDNA) appeared transiently in 10.5% and 26.3%, respectively. Early T790M ctDNA disappeared in all patients, including 7 who eventually developed acquired resistance accompanied by elevated levels of T790M ctDNA.
Conclusions: Monitoring ctDNA is useful in evaluating treatment responses and monitoring driver oncogene status in NSCLC. ctDNA revealed clonal heterogeneity and genetic processes of cancer evolution in individual patients. The simple presence of the T790M mutation may be insufficient to confer EGFR-TKI resistance to tumor cells.
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http://dx.doi.org/10.1016/j.lungcan.2016.01.023 | DOI Listing |
Chem Biodivers
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SRM Institute of Science and Technology - NCR Campus, chemistry, Department of Chemistry, SRM Institute of Science and Technology, Delhi NCR Camp, India, 241405, Modinagar, INDIA.
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Division of Hematology/Oncology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
The management of early-stage colon cancer involves surgical resection of the primary tumor with or without chemotherapy, depending on pathological staging. The benefit of adjuvant chemotherapy for stage II and III colon cancer is approximately 5% and 15%, indicating the need for optimization for risk stratification and patient selection. Several studies have revealed that current clinicopathological factors lack precision.
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Clinical Measurement Sciences, Global Research & Development, EMD Serono, Billerica, MA, USA.
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Department of Surgery, Los Angeles General Medical Center, Los Angeles, California, USA.
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January 2025
Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, and Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
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