An ultrasensitive method for quantitating circulating tumor DNA with broad patient coverage
By Aaron M. Newman, S. Bratman, Jacqueline To, J. Wynne, N. Eclov, L. Modlin, C. Liu, J. Neal, H. Wakelee, R. Merritt and 4 more. Nature Medicine, 2014
2,063 citations recorded by the source corpus.
Circulating tumor DNA (ctDNA) is a promising biomarker for noninvasive assessment of cancer burden, but existing ctDNA detection methods have insufficient sensitivity or patient coverage for broad clinical applicability. Here we introduce cancer personalized profiling by deep sequencing (CAPP-Seq), an economical and ultrasensitive method for quantifying ctDNA. We implemented CAPP-Seq for non–small-cell lung cancer (NSCLC) with a design covering multiple classes of somatic alterations that identified mutations in >95% of tumors. We detected ctDNA in 100% of patients with stage II–IV NSCLC and in 50% of patients with stage I, with 96% specificity for mutant allele fractions down to ∼0.02%. Levels of ctDNA were highly correlated with tumor volume and distinguished between residual disease and treatment-related imaging changes, and measurement of ctDNA levels allowed for earlier response assessment than radiographic approaches. Finally, we evaluated biopsy-free tumor screening and genotyping with CAPP-Seq. We envision that CAPP-Seq could be routinely applied clinically to detect and monitor diverse malignancies, thus facilitating personalized cancer therapy.
Subfields: Cancer Research, Pathology and Forensic Medicine, Pulmonary and Respiratory Medicine
View Paper: https://www.semanticscholar.org/paper/e1bb162b12f43cb4bf66b67e6eca44e80ff4f4d5
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Citations in the corpus
- Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA (2015, methodology): “2% specificity this latter method was only tested on a single gene, KRAS, in a single cancer (colorectal) [28,29].”
- ESMO recommendations on the use of circulating tumour DNA assays for patients with cancer: a report from the ESMO Precision Medicine Working Group. (2022, background): “75-77 Across multiple different tumour types, and type of treatment (chemotherapy, targeted therapy and immunotherapy), patients who respond to treatment drop ctDNA levels within weeks of starting therapy.”
- Early Detection of Molecular Residual Disease in Localized Lung Cancer by Circulating Tumor DNA Profiling (2017, methodology): “05 it was classified as detected, in accordance with our prior publications (9,10).”
- AfterQC: automatic filtering, trimming, error removing and quality control for fastq data (2017, result): “Typically the somatic mutation rate in ctDNA is near 1% for advanced tumour patients, and can be as low as 1% for early stage tumour patients [3], which is very close to the error rate of mainstream NGS platforms.”
- Circulating Tumor DNA Analysis in Patients With Cancer: American Society of Clinical Oncology and College of American Pathologists Joint Review. (2018, background): “The large number of potential genetic driver events in advanced cancers has raised interest in NGS-based panel ctDNA assays, with the potential to detect a wide range of simple and complex genomic events, including targetable gene rearrangements (eg, ALK and ROS1).(60,61) Determination of clinical v”
- Liquid biopsy: a step closer to transform diagnosis, prognosis and future of cancer treatments (2022, methodology): “RNA-Seq analyses of platelet-derived RNA were reported to detect both early- and late-stage NSCLC with an accuracy of nearly 80 percent [201].”