Quantification of circulating cell-free DNA to predict patient survival in non-small-cell lung cancer

Hyun, Myung Han; Sung, Jae Sook; Kang, Eun Joo; Choi, Yoon Ji; Park, Kyong Hwa; Shin, Sang Won; Lee, Sung Yong; Kim, Yeul Hong

doi:10.18632/oncotarget.21769

Cited by 29 publications

(22 citation statements)

References 39 publications

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“…Moreover, we observed an apparent joint effect between CTC and ccfDNA levels on patient outcomes. The joint effect was much more prominent on OS than PFS (Table 3), which seems to be reasonable because both CTC and ccfDNA provide more values that are prognostic of eventual survival but not predictive of response to specific treatments [31, 48–52]. Nonetheless, the multiplicative interaction between CTC and ccfDNA on OS was borderline significant, which could be due to the smaller number of deceased patients in each risk group and insufficient power in interaction analysis, and thus needs to be further confirmed.…”

Section: Discussionmentioning

confidence: 99%

Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA

Wang

Wan

et al. 2019

European Journal of Cancer

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Background: Both circulating tumor cell (CTC) and total circulating cell-free DNA (ccfDNA) predict cancer patient prognosis. However, no study has explored the prognostic value of the combined use of CTC and ccfDNA. We aimed to investigate individual and joint effects of CTC and ccfDNA on clinical outcomes of metastatic breast cancer (MBC) patients. Methods: We collected 227 blood samples from 117 MBC patients. CTCs were enumerated using the CellSearch System. ccfDNAs were quantified by quantitative real-time PCR and Qubit fluorometer. The individual and joint effects of CTC and ccfDNA levels on patient progression-free survival (PFS) and overall survival (OS) were analyzed using Cox proportional hazards models. Results: Compared to patients with < 5 CTCs, patients with ≥ 5 CTCs had a 2.58-fold increased risk of progression and 3.63-fold increased risk of death. High level of ccfDNA was associated with a 2.05-fold increased risk of progression and 3.56-fold increased risk of death. These associations remained significant after adjusting for other important clinical covariates and CTC/ccfDNA levels. CTC and ccfDNA levels had a joint effect on patient outcomes. Compared to patients with low levels of both CTC and ccfDNA, those with high levels of both markers exhibited a > 17-fold increased death risk (P < 0.001). Moreover, longitudinal analysis of 132 samples from 22 patients suggested that the inconsistency between CTC level and outcome in some patients could possibly be explained by ccfDNA level. Conclusions: CTC and total ccfDNA levels were individually and jointly associated with PFS and OS in MBC patients.

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Section: Discussionmentioning

confidence: 99%

Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA

Wang

Wan

et al. 2019

European Journal of Cancer

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“…Currently, a number of studies have shown that a high concentration of cfDNA at baseline represents a negative prognostic factor in terms of PFS and OS, irrespectively of patient characteristics like age and smoking habits, treatments and tumor histological type [13,[30][31][32][33]. In this regard, Cargnin et al performed a systematic review and meta-analysis to evaluate the impact of baseline cfDNA levels on the progression and survival of lung cancer patients.…”

Section: Circulating Cell-free Dnamentioning

confidence: 99%

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Rijavec

Coco

Genova

et al. 2019

Cancers

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Non-small cell lung cancer is one leading cause of death worldwide, and patients would greatly benefit from an early diagnosis. Since targeted and immunotherapies have emerged as novel approaches for more tailored treatments, repeated assessments of the tumor biology have become pivotal to drive clinical decisions. Currently, tumor tissue biopsy is the gold standard to investigate potentially actionable biomarkers, but this procedure is invasive and may prove inadequate to represent the whole malignancy. In this regard, liquid biopsy represents a minimally invasive and more comprehensive option for early detection and investigation of this tumor. Today, cell-free DNA is the only approved circulating marker to select patients for a targeted therapy. Conversely, the other tumor-derived markers (i.e., circulating tumor cells, miRNAs, exosomes, and tumor educated platelets) are still at a pre-clinical phase, although they show promising results for their application in screening programs or as prognostic/predictive biomarkers. The main challenges for their clinical translation are the lack of reliable cutoffs and, especially for miRNAs, the great variability among the studies. Moreover, no established tool has been approved for circulating tumor cells and exosome isolation. Finally, large prospective clinical trials are mandatory to provide evidence of their clinical utility.

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“…A recent study on 177 NSCLC highlighted that high ctDNA concentration was and independent prognostic factor for progression-free survival and overall survival. However, concentration changes during treatment did not correlate with radiological CT response [ 111 ]. We analyzed prospectively the clinical impact of ctDNA independently of molecular profiles and first line treatment, we found that ctDNA at baseline was an independent marker of poor prognosis, with a median OS of 13.6 versus 21.5 months and a median PFS of 4.9 versus 10.4 months.…”

Section: -Lung Cancer Molecular Screenings Update On Validated Mmentioning

confidence: 99%

Current and Future Molecular Testing in NSCLC, What Can We Expect from New Sequencing Technologies?

Garinet

Laurent‐Puig

Blons

et al. 2018

JCM

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Recent changes in lung cancer care, including new approvals in first line and the introduction of high-throughput molecular technologies in routine testing led us to question ourselves on how deeper molecular testing may be helpful for the optimal use of targeted drugs. In this article, we review recent results in the scope of personalized medicine in lung cancer. We discuss biomarkers that have a therapeutic predictive value in lung cancer with a focus on recent changes and on the clinical value of large scale sequencing strategies. We review the use of second- and third-generation EGFR and ALK inhibitors with a focus on secondary resistance alterations. We discuss anti-BRAF and anti-MEK combo, emerging biomarkers as NRG1 and NTRKs fusions and immunotherapy. Finally, we discuss the different technical issues of comprehensive molecular profiling and show how large screenings might refine the prediction value of individual markers. Based on a review of recent publications (2012–2018), we address promising approaches for the treatment of patients with lung cancers and the technical challenges associated with the identification of new predictive markers.

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Quantification of circulating cell-free DNA to predict patient survival in non-small-cell lung cancer

Cited by 29 publications

References 39 publications

Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA

Association of clinical outcomes in metastatic breast cancer patients with circulating tumour cell and circulating cell-free DNA

Liquid Biopsy in Non-Small Cell Lung Cancer: Highlights and Challenges

Current and Future Molecular Testing in NSCLC, What Can We Expect from New Sequencing Technologies?

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