Circulating tumor markers: harmonizing the yin and yang of CTCs and ctDNA for precision medicine

Batth, Izhar Singh; Mitra, Abhisek; Manier, Salomon; Ghobrial, Irène M.; Menter, David G.; Kopetz, Scott; Li, Shulin

doi:10.1093/annonc/mdw619

Cited by 64 publications

(45 citation statements)

References 110 publications

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“…However, tumours are not the sole source of cfDNA, and increased levels are also linked to impaired renal clearance and production of white blood cells (WBC) [8] , [9] . Moreover, the mechanisms of cfDNA release are poorly understood, and their prognostic value and relationship to tumour burden are controversial [10] . In particular, the correlation between tumour volume and cfDNA is still under study [11] .…”

Section: Introductionmentioning

confidence: 99%

Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients

Valpione

Gremel

Mundra

et al. 2018

European Journal of Cancer

135

114

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IntroductionTumour burden is a prognostic biomarker in metastatic melanoma. However, tumour burden is difficult to measure and there are currently no reliable surrogate biomarkers to easily and reliably determine it. The aim of this study was to assess the potential of plasma total cell free DNA as biomarker of tumour burden and prognosis in metastatic melanoma patients.Materials and methodsA prospective biomarker cohort study for total plasma circulating cell-free DNA (cfDNA) concentration was performed in 43 metastatic melanoma patients. For 38 patients, paired blood collections and scan assessments were available before treatment and at first response evaluation. Tumour burden was calculated as the sum of volumes from three-dimensional radiological measurements of all metastatic lesions in individual patients.ResultsBaseline cfDNA concentration correlated with pre-treatment tumour burden (ρ = 0.52, P < 0.001). Baseline cfDNA levels correlated significantly with hazard of death and overall survival, and a cut off value of 89 pg/μl identified two distinct prognostic groups (HR = 2.22 for high cfDNA, P = 0.004). Patients with cfDNA ≥89 pg/μl had shorter OS (10.0 versus 22.7 months, P = 0.009; HR = 2.22 for high cfDNA, P = 0.004) and the significance was maintained when compared with lactic dehydrogenase (LDH) in a multivariate analysis. We also found a correlation between the changes of cfDNA and treatment-related changes in tumour burden (ρ = 0.49, P = 0.002). In addition, the ratio between baseline cfDNA and tumour burden was prognostic (HR = 2.7 for cfDNA/tumour volume ≥8 pg/(μl*cm3), P = 0.024).ConclusionsWe have demonstrated that cfDNA is a surrogate marker of tumour burden in metastatic melanoma patients, and that it is prognostic for overall survival.

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Section: Introductionmentioning

confidence: 99%

Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients

Valpione

Gremel

Mundra

et al. 2018

European Journal of Cancer

135

114

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“…At early stages, from the primary tumor after epithelial-to-mesenchymal transition of primary cancer cells, CTCs begin to flow into blood stream at a rate of roughly 10 6 cells per tumor gram [ 6 , 14 , 15 ]. The idea of CTCs was first implemented by Asworth in 1869.…”

Section: Biology Of Ctcsmentioning

confidence: 99%

Circulating tumor cells in clinical research and monitoring patients with colorectal cancer

et al. 2018

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Colorectal cancer remains a frequent disease to which screening and target therapy exist, but despite this is still marked by a high mortality rate. Even though radical surgery may be performed in many cases, patients relapse with metastatic disease. Circulating tumor cells were incriminated for tumor recurrence, that's why vigorous research started on their field. Owning prognostic and predictive value, it was revealed their usefulness in disease monitoring. Moreover, they may serve as liquid biopsies for genetic tests in cases where tissue biopsy is contraindicated or cannot be performed. In spite of these advantages, they were not included in clinical guidelines, despite CellSearch and many other detection methods were developed to ease the identification of circulating tumor cells. This review highlights the implication of circulating tumor cells in metastasis cascade, intrinsic tumor cells mechanisms and correlations with clinical parameters along with their utility for medical practice and detection techniques.

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“…2). This is a novel and minimally invasive technique developed for solid tumors and recently also applied to ACC (Chabre et al 2013, Szabó et al 2014, Creemers et al 2017, Batth et al 2017, Bardelli & Pantel 2017 to identify potential markers to assess malignancy in ACC, even if the predictive power needs to be confirmed on larger cohorts of patients. In addition to its diagnostic/ prognostic value, the liquid biopsy represents a unique tool that can provide informative material to be analyzed and compared to the primary lesion for longitudinal surveillance of clonal evolution and progression of the tumor, also in response to anticancer treatments.…”

Section: The 'Liquid Biopsy' and Circulating Markers Of Malignancymentioning

confidence: 99%

The next step: mechanisms driving adrenocortical carcinoma metastasis

Lalli

Luconi²

2018

Endocrine-Related Cancer

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Endocrine tumors have the peculiarity to become clinically evident not only due to symptoms related to space occupation by the growing lesion, similarly to most other tumors, but also, and most often, because of their specific hormonal secretion, which significantly contributes to their pathological burden. Malignant endocrine tumors, in addition, have the ability to produce distant metastases. Here, we critically review the current knowledge about mechanisms and biomarkers characterizing the metastatic process in adrenocortical carcinoma (ACC), a rare endocrine malignancy with a high risk of relapse and metastatization even when the primary tumor is diagnosed and surgically removed at an early stage. We highlight perspectives of future research in the domain and possible new therapeutic avenues based on targeting factors having an important role in the metastatic process of ACC.

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Circulating tumor markers: harmonizing the yin and yang of CTCs and ctDNA for precision medicine

Cited by 64 publications

References 110 publications

Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients

Plasma total cell-free DNA (cfDNA) is a surrogate biomarker for tumour burden and a prognostic biomarker for survival in metastatic melanoma patients

Circulating tumor cells in clinical research and monitoring patients with colorectal cancer

The next step: mechanisms driving adrenocortical carcinoma metastasis

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