Circulating tumor DNA in early response assessment and monitoring of advanced colorectal cancer treated with a multi-kinase inhibitor

Vandeputte, Caroline; Kehagias, Pashalina; Housni, Hakim El; Ameye, Lieveke; Laes, Jean-François; Desmedt, Christine; Sotiriou, Christos; Deleporte, Amélie; Puleo, Francesco; Geboes, Karen; Delaunoit, Thierry; Demolin, Gauthier; Peeters, Marc; D’Hondt, Lionel; Janssens, Jos; Carrasco, Javier; Maréchal, Raphaël; Galdón, María Gómez; Heimann, Pierre; Paesmans, Marianne; Flamen, Patrick; Hendlisz, Alain

doi:10.18632/oncotarget.24879

Cited by 30 publications

(44 citation statements)

References 25 publications

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“…Finally, Vandeputte et al showed the prognostic value of monitoring genetic alterations in the ctDNA of a small cohort of 20 patients. This approach implied next generation sequencing of patient primary tumors and optimization of personalized assays for mutation tracking in plasma (12).…”

Section: Introductionmentioning

confidence: 99%

“…Inspired by data of two recent studies (11, 12) with limited number of patients and using exclusively genetic alterations, we hypothesized that dynamics of circulating methylated DNA (cmDNA) may stratify mCRC patients treated with regorafenib according to their clinical outcome sparing a subgroup of unresponsive patients from prolonged drug exposure.…”

Section: Introductionmentioning

confidence: 99%

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High Circulating Methylated DNA Is a Negative Predictive and Prognostic Marker in Metastatic Colorectal Cancer Patients Treated With Regorafenib

et al. 2019

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Background: Regorafenib improves progression free survival (PFS) in a subset of metastatic colorectal cancer (mCRC) patients, although no biomarkers of efficacy are available. Circulating methylated DNA (cmDNA) assessed by a five-gene panel was previously associated with outcome in chemotherapy treated mCRC patients. We hypothesized that cmDNA could be used to identify cases most likely to benefit from regorafenib (i.e., patients with PFS longer than 4 months). Methods: Plasma samples from mCRC patients were collected prior to (baseline samples N = 60) and/or during regorafenib treatment ( N = 62) for the assessment of cmDNA and total amount of cell free DNA (cfDNA). Results: In almost all patients, treatment with regorafenib increased the total cfDNA, but decreased cmDNA warranting the normalization of cmDNA to the total amount of circulating DNA (i.e., cmDNA/ml). We report that cmDNA/ml dynamics reflects clinical response with an increase in cmDNA/ml associated with higher risk of progression (HR for progression = 1.78 [95%CI: 1.01–3.13], p = 0.028). Taken individually, high baseline cmDNA/ml (above median) was associated with worst prognosis (HR for death = 3.471 [95%CI: 1.83–6.57], p < 0.0001) and also predicted shorter PFS (<16 weeks with PPV 86%). In addition, high cmDNA/ml values during regorafenib treatment predicted with higher accuracy shorter PFS (<16 weeks with a PPV of 96%), therefore associated with increased risk of progression (HR for progression = 2.985; [95%CI: 1.63–5.46; p < 0.0001). Conclusions: Our data highlight the predictive and prognostic value of cmDNA/ml in mCRC patients treated with regorafenib.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

High Circulating Methylated DNA Is a Negative Predictive and Prognostic Marker in Metastatic Colorectal Cancer Patients Treated With Regorafenib

et al. 2019

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“…In patients with targetable alterations, response to therapy can be monitored in this way; utilizing this technology to guide therapeutic options has not been widely implemented. As described above, clinical studies to explore this strategy are ongoing (211)(212)(213)(214)(215)…”

Section: Engineering Principles To Control the Multifactorial Basis Omentioning

confidence: 99%

“…Multiple groups have identified important axioms that need to be considered to implement this type of anticipatory, instead of reactive, treatment strategy in cancer (184). Incorporation of "liquid biopsy"-based information shows promise in monitoring response and relapse to treatment in lung, gynecologic, colon, and hematologic malignancies (211)(212)(213)(214)(215).…”

Section: Reviewmentioning

confidence: 99%

Engineering Multidimensional Evolutionary Forces to Combat Cancer

McCoach

Bivona

2019

Cancer Discovery

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With advances in technology and bioinformatics, we are now positioned to view and manage cancer through an evolutionary lens. This perspective is critical as our appreciation for the role of tumor heterogeneity, tumor immune compartment, and tumor microenvironment on cancer pathogenesis and evolution grows. Here, we explore recent knowledge on the evolutionary basis of cancer pathogenesis and progression, viewing tumors as multilineage, multicomponent organisms whose growth is regulated by subcomponent fi tness relationships. We propose reconsidering some current tenets of the cancer management paradigm in order to take better advantage of crucial fi tness relationships to improve outcomes of patients with cancer. Signifi cance: Tumor and tumor immune compartment and microenvironment heterogeneity, and their evolution, are critical disease features that affect treatment response. The impact and interplay of these components during treatment are viable targets to improve clinical response. In this article, we consider how tumor cells, the tumor immune compartment and microenvironment, and epigenetic factors interact and also evolve during treatment. We evaluate the convergence of these factors and suggest innovative treatment concepts that leverage evolutionary relationships to limit tumor growth and drug resistance. Research.

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“…Résistance primaire aux anti-EGFR (cetuximab et panitumumab) [43,44] x Résistance acquise au cetuximab ou panitumumab [46,47] x…”

Section: Analyse De La Méthylation De L'adnunclassified

Development of molecular analyzes by digital PCR for clinical practice: positioning, current applications and perspectives

Denis¹,

Perrier

Nectoux

et al. 2019

Annales De Biologie Clinique

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This review is the second part of the workshop on digital PCR (dPCR) proposed by the working group of the French society of clinical biology. The first part of the paper discusses the advantages and limitations of dPCR for the search of different molecular abnormalities such as point mutations, copy number variants, DNA methylation, RNA analysis and a more innovative application, the single-cell dPCR. This synthesis makes it possible to propose a positioning of the dPCR compared to the other available technologies in a medical laboratory. In a second part, the main current applications of the dPCR will be addressed including the oncology of solid tumors and liquid biopsies, oncohematology and the follow-up of hemopathies treatments by hematopoietic stem cell transplantation. We will also detail non-invasive prenatal diagnosis and diagnosis of mosaic genetic disease, using the example of McCune-Albright syndrome. Several French specialists in the field who have implemented these

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Circulating tumor DNA in early response assessment and monitoring of advanced colorectal cancer treated with a multi-kinase inhibitor

Cited by 30 publications

References 25 publications

High Circulating Methylated DNA Is a Negative Predictive and Prognostic Marker in Metastatic Colorectal Cancer Patients Treated With Regorafenib

High Circulating Methylated DNA Is a Negative Predictive and Prognostic Marker in Metastatic Colorectal Cancer Patients Treated With Regorafenib

Engineering Multidimensional Evolutionary Forces to Combat Cancer

Development of molecular analyzes by digital PCR for clinical practice: positioning, current applications and perspectives

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