True conversions from RAS mutant to RAS wild-type in circulating tumor DNA from metastatic colorectal cancer patients as assessed by methylation and mutational signature

Nicolazzo, Chiara; Barault, Ludovic; Caponnetto, S; Renzi, Giancarlo; Belardinilli, Francesca; Bottillo, Irene; Bargiacchi, Simone; Macagno, Marco; Grammatico, Paola; Giannini, Giuseppe; Cortesi, Enrico; Nicolantonio, Federica Di; Gazzaniga, Paola

doi:10.1016/j.canlet.2021.03.014

Cited by 19 publications

(22 citation statements)

References 31 publications

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“…Only patients with concordance of RAS mutational status between baseline plasma ctDNA and tumor tissue were included. Plasma samples which resulted in RAS/BRAF wild-type * were further analyzed through methylation test or NGS in order to confirm the presence of ctDNA, as previously described [8]. For both methylation and NGS analysis, ctDNA was extracted from 1 mL and 4 mL of plasma, respectively, using Maxwell 16 system (Promega) according to the manufacturer's instructions.…”

Section: Ras Mutational Analysis In Tissue and Plasma Samplesmentioning

confidence: 99%

“…Bevacizumab induces a consistent improvement in progression free survival (PFS) compared to chemotherapy (CT) alone in first-line treatment (median PFS: 9-10 months), so its use is standard for most patients with no recognized contraindication [3]. Recent studies performed through liquid biopsy have provided evidence that the clonal evolution of RAS mutant CRC may lead to the negative selection of RAS mutant clones, with the appearance of a time window characterized by a RAS wild-type disease in plasma [4][5][6][7][8]. Some studies are currently investigating the efficacy of anti-EGFR therapy in patients with initially RAS mutant mCRC, who convert to RAS wild-type * in plasma with disease progression [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

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RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study

Nicolazzo

Belardinilli

Vestri

et al. 2022

Cancers

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Liquid biopsies have shown that, in RAS mutant colorectal cancer, the conversion to RAS wild-type * status during the course of the disease is a frequent event, supporting the concept that the evolutionary landscape of colorectal cancer can lead to an unexpected negative selection of RAS mutant clones. The aim of the present study was to clarify whether the negative selection of RAS mutation in plasma might be drug-dependent. For this purpose, we used liquid biopsy to compare the rate of conversion from RAS mutant to RAS wild-type * in two groups of originally RAS mutant mCRC patients: the first treated with chemotherapy alone, while the second was treated with chemotherapy combined with bevacizumab. Serial liquid biopsies were performed at 3 months (T1), 6 months (T2), 9 months (T3), and 12 months (T4) after starting first line treatments. We found that the only independent variable significantly associated to RAS status conversion was the use of bevacizumab. RAS conversion was not found associated to tumor burden reduction, although bevacizumab-treated patients who converted to RAS wild-type * had a significantly longer PFS compared to patients who remained RAS mutant. The appearance of a “RAS wild-type * window”, mainly in bevacizumab-treated patients, might present them as candidates for second line treatment with anti-EGFR, which was otherwise precluded.

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Section: Ras Mutational Analysis In Tissue and Plasma Samplesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study

Nicolazzo

Belardinilli

Vestri

et al. 2022

Cancers

Self Cite

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“…The use of blood-based ctDNA assays to characterize alterations in KRAS , BRAF , EGFR , HER2 , and gene fusions as resistance mechanisms to anti-epidermal growth factor receptor (EGFR) therapy and prognosticate in mCRC, particularly in colorectal liver metastases, has been well-described [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 , 83 , 84 , 85 , 86 , 87 , 88 , 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 ]. More recent ctDNA assays have been investigated in mCRC with evidence to suggest varied potential clinical applications in this space.…”

Section: Prediction Of Response To Systemic and Surgical Therapies In Metastatic Colorectal Cancermentioning

confidence: 99%

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer

Gong

Hendifar

Gangi

et al. 2021

Cancers

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Emerging data suggest that circulating tumor DNA (ctDNA) can detect colorectal cancer (CRC)-specific signals across both non-metastatic and metastatic settings. With the development of multiple platforms, including tumor-informed and tumor-agnostic ctDNA assays and demonstration of their provocative analytic performance to detect minimal residual disease, there are now ongoing, phase III randomized clinical trials to evaluate their role in the management paradigm of CRC. In this review, we highlight landmark studies that have formed the basis for ongoing studies on the clinically applicability of plasma ctDNA assays in resected, stage I–III CRC and metastatic CRC. We discuss clinical settings by which ctDNA may have the most immediate impact in routine clinical practice. These include the potential for ctDNA to (1) guide surveillance and intensification or de-intensification strategies of adjuvant therapy in resected, stage I–III CRC, (2) predict treatment response to neoadjuvant therapy in locally advanced rectal cancer inclusive of total neoadjuvant therapy (TNT), and (3) predict response to systemic and surgical therapies in metastatic disease. We end by considering clinical variables that can influence our ability to reliably interpret ctDNA dynamics in the clinic.

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“…When evaluating the potential clinical value of plasma ctDNA levels as a diagnostic tool for early lung cancer, researchers have found that the plasma ctDNA level of patients with NSCLC was significantly higher than that of subjects with chronic respiratory inflammation and healthy individuals. At the same time, when distinguishing NSCLC patients from healthy individuals, the sensitivity and specificity of ctDNA levels were 90 and 80.5%, respectively [ 26 ]. Furthermore, in another study ctDNA was detected in 100% of the plasma specimens taken from patients with stage II–IV NSCLC, 50% of the plasma specimens taken from of the patients with stage I NSCLC, and the 96% specificity of its mutant allele fragment decreased to 0.02%.…”

Section: Introductionmentioning

confidence: 99%

Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring

et al. 2022

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Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.

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True conversions from RAS mutant to RAS wild-type in circulating tumor DNA from metastatic colorectal cancer patients as assessed by methylation and mutational signature

Cited by 19 publications

References 31 publications

RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study

RAS Mutation Conversion in Bevacizumab-Treated Metastatic Colorectal Cancer Patients: A Liquid Biopsy Based Study

Clinical Applications of Minimal Residual Disease Assessments by Tumor-Informed and Tumor-Uninformed Circulating Tumor DNA in Colorectal Cancer

Liquid biopsy in lung cancer: significance in diagnostics, prediction, and treatment monitoring

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