Blood‐based circulating tumor DNA mutations as a diagnostic and prognostic biomarker for lung cancer

Leung, Maurice P.; Freidin, Maxim B.; Фрейдин, Максим Борисович; Crease, C. Von; Sousa, Paulo De; Barbosa, Monica T.; Nicholson, Andrew G.; Lim, Eric

doi:10.1002/cncr.32699

Cited by 17 publications

(6 citation statements)

References 9 publications

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“…There are several techniques to detect ctDNA, including PCR-based (7,23), NGS panel based, and be spoked NGS (10). In this study, using a next-generation sequencing (NGS)-based panel test for cfDNA analysis, we found that detecting mutations in cancer-related genes from postoperative ctDNA (POD 3-12) predicted poor patient outcomes.…”

Section: Discussionmentioning

confidence: 89%

“…Detecting mutations in EGFR, including the T790M resistant mutation, is already used for clinical decision-making in advanced NSCLC patients (6). It has been reported that ctDNA analysis prior to the surgery in early-stage lung cancer patients can detect somatic mutations in tumors at high sensitivity and specificity (7), and that ctDNA analysis is able to detect mutations which will present even in a heterogeneous manner in tumor tissues (8,9). Additionally, recent studies have suggested that ctDNA can be a potential biomarker for the assessment of post-surgical MRD (10), as well as a potential predictor for the disease progression prior to radiological modalities (11).…”

Section: Introductionmentioning

confidence: 99%

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Prognostic implications of preoperative versus postoperative circulating tumor DNA in surgically resected lung cancer patients: a pilot study

Ohara¹,

Suda²,

Sakai³

et al. 2020

Transl Lung Cancer Res

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Background: Recent studies of advanced lung cancer patients have shown that circulating tumor DNA (ctDNA) analysis is useful for molecular profiling, monitoring tumor burden, and predicting therapeutic efficacies and disease progression. However, the usefulness of ctDNA analysis in surgically resected lung cancers is unclear.Methods: This study included 20 lung cancer patients with clinical stage IIA-IIIA disease. Preoperative and postoperative (3-12 days) plasma samples were collected for ctDNA analysis. Cancer personalized profiling by deep sequencing, which can detect mutations in 197 cancer-related genes, was used for ctDNA detection. The cohort consisted of 18 men and 2 women with a median age of 69 (range, 37-88) years.Sixteen patients (80%) had a history of smoking. Histologically, there were four squamous cell carcinomas, 13 adenocarcinomas, two adenosquamous cell carcinomas, and one small cell carcinoma.Results: At the time of data analysis, the 20 patients had been monitored for a median follow-up of 12 months. Eight patients (40%) were positive for preoperative ctDNA, and this was significantly correlated with tumor size (≥5 vs. <5 cm, P=0.018). Four patients (20%) were positive for postoperative ctDNA, and this was significantly correlated with histological grade (3 vs. 1 or 2, P=0.032). Postoperative positivity for ctDNA also predicted shorter recurrence-free survival (RFS) (P=0.015), while pre-and post-operative carcinoembryonic antigen levels (P=0.150 and P=0.533, respectively) and preoperative positivity for ctDNA (P=0.132) were not correlated with RFS.Conclusions: Detecting ctDNA postoperatively was a poor prognostic factor in surgically resected lung cancer patients that may suggest there is minimal residual disease (MRD).

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Section: Discussionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Prognostic implications of preoperative versus postoperative circulating tumor DNA in surgically resected lung cancer patients: a pilot study

Ohara¹,

Suda²,

Sakai³

et al. 2020

Transl Lung Cancer Res

View full text Add to dashboard Cite

show abstract

“…In addition, in a prospective study involving 16,890 participants, the methylation marker cg10673833 was selected and identified as an early diagnostic marker for high-risk patients with colorectal cancer, with high specificity (86.8%) and sensitivity (89.7%). Leung et al [ 91 ] detected the highest frequency of EGFR, KRAS, and TP53 mutations in the ctDNA of 166 patients with lung cancer. In terms of cancer diagnosis, compared with conventional clinicopathological results, the ctDNA diagnosis had a 98% positive predictive ability, 89% specificity, and 85% sensitivity, but the negative predictive value was 35%, which is a serious and urgent problem that should be solved.…”

Section: Clinical Application Of Ctdna During Cancer Progressionmentioning

confidence: 99%

Circulating Tumor DNA—A Novel Biomarker of Tumor Progression and Its Favorable Detection Techniques

Wen

Liu

et al. 2022

Cancers

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Cancer is the second leading cause of death in the world and seriously affects the quality of life of patients. The diagnostic techniques for tumors mainly include tumor biomarker detection, instrumental examination, and tissue biopsy. In recent years, liquid technology represented by circulating tumor DNA (ctDNA) has gradually replaced traditional technology with its advantages of being non-invasive and accurate, its high specificity, and its high sensitivity. ctDNA may carry throughout the circulatory system through tumor cell necrosis, apoptosis, circulating exosome secretion, etc., carrying the characteristic changes in tumors, such as mutation, methylation, microsatellite instability, gene rearrangement, etc. In this paper, ctDNA mutation and methylation, as the objects to describe the preparation process before ctDNA analysis, and the detection methods of two gene-level changes, including a series of enrichment detection techniques derived from PCR, sequencing-based detection techniques, and comprehensive detection techniques, are combined with new materials. In addition, the role of ctDNA in various stages of cancer development is summarized, such as early screening, diagnosis, molecular typing, prognosis prediction, recurrence monitoring, and drug guidance. In summary, ctDNA is an ideal biomarker involved in the whole process of tumor development.

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“…Leung et al [ 28 ] demonstrated the usefulness of ctDNA as a diagnostic test in patients with early stage NSCLC, analyzing the presence of EGFR , KRAS , and p53 mutations, mostly frequent in adenocarcinoma and epidermoid lung carcinoma. When compared to the analysis of neoplastic tissue obtained with standard invasive procedures, this method showed comparable results, with a specificity of 89% in confirming the diagnosis.…”

Section: Diagnostic and Prognostic Value Of Circulating Biomarkersmentioning

confidence: 99%

Diagnostic and prognostic role of liquid biopsy in non-small cell lung cancer: evaluation of circulating biomarkers

Vicidomini

Cascone

Carlucci

et al. 2020

Exploration of Targeted Anti-Tumor Therapy

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Lung cancer is still one of the main causes of cancer-related death, together with prostate and colorectal cancers in males and breast and colorectal cancers in females. The prognosis for non-small cell lung cancer (NSCLC) is strictly dependent on feasibility of a complete surgical resection of the tumor at diagnosis. Since surgery is indicated only in early stages tumors, it is necessary to anticipate the timing of diagnosis in clinical practice. In the diagnostic and therapeutic pathway for NSCLC, sampling of neoplastic tissue is usually obtained using invasive methods that are not free from disadvantages and complications. A valid alternative to the standard biopsy is the liquid biopsy (LB), that is, the analysis of samples from peripheral blood, urine, and other biological fluids, with a simple and non-invasive collection. In particular, it is possible to detect in the blood different tumor derivatives, such as cell-free DNA (cfDNA) with its subtype circulating tumor DNA (ctDNA), cell-free RNA (cfRNA), and circulating tumor cells (CTCs). Plasma-based testing seems to have several advantages over tumor tissue biopsy; firstly, it reduces medical costs, risk of complications related to invasive procedures, and turnaround times; moreover, the analysis of genes alteration, such as EGFR, ALK, ROS1, and BRAF is faster and safer with this method, compared to tissue biopsy. Despite all these advantages, the evidences in literatures indicate that assays performed on liquid biopsies have a low sensitivity, making them unsuitable for screening in lung cancer at the current state. This is caused by lack of standardization in sampling and preparation of specimen and by the low concentration of biomarkers in the bloodstream. Instead, routinely use of LB should be preferred in revaluation of patients with advanced NSCLC resistant to chemotherapy, due to onset of new mutations.

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Blood‐based circulating tumor DNA mutations as a diagnostic and prognostic biomarker for lung cancer

Cited by 17 publications

References 9 publications

Prognostic implications of preoperative versus postoperative circulating tumor DNA in surgically resected lung cancer patients: a pilot study

Prognostic implications of preoperative versus postoperative circulating tumor DNA in surgically resected lung cancer patients: a pilot study

Circulating Tumor DNA—A Novel Biomarker of Tumor Progression and Its Favorable Detection Techniques

Diagnostic and prognostic role of liquid biopsy in non-small cell lung cancer: evaluation of circulating biomarkers

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