Prognostic Value of Circulating Mutant DNA in Unresectable Metastatic Colorectal Cancer

Lefebure, B.; Charbonnier, Françoise; Fiore, Frédéric Di; Tuech, Jean Jacques; Pessot, Florence Le; Michot, F; Michel, Pierre; Frébourg, Thierry

doi:10.1097/sla.0b013e3181c35c87

Cited by 48 publications

(41 citation statements)

References 27 publications

(60 reference statements)

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“…Lefebure et al detected, in the serum of unresectable MCRC, KRAS mutation andRASSF2A methylation and they observed that the presence of circulating mutant DNA was predictive of clinical outcome [68]. In a recent study was demonstrated the clinical utility of multiplex digital PCR to screen for multiple KRAS mutations in the plasma samples of MCRC patients [69] suggesting that the "liquid biopsy" is a feasible alternative to a solid tissue biopsy for identifying specific mutations.…”

Section: Colorectal Cancermentioning

confidence: 99%

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Monitoring tumor-derived cell-free DNA in patients with solid tumors: Clinical perspectives and research opportunities

Espósito¹,

Bardelli²,

Criscitiello³

et al. 2014

Cancer Treatment Reviews

101

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Circulating cell-free DNA represents a non-invasive biomarker, as it can be isolated from human plasma, serum and other body fluids. Circulating tumor DNA shed from primary and metastatic cancers may allow the non-invasive analysis of the evolution of tumor genomes during treatment and disease progression through 'liquid biopsies'. The serial monitoring of tumor genotypes, which are instable and prone to changes under selection pressure, is becoming increasingly possible. The "liquid biopsy" provide novel biological insights into the process of metastasis and may elucidate signaling pathways involved in cell invasiveness and metastatic competence. This review will focus on the clinical utility of circulating cell free DNA in main solid tumors, including genetic and epigenetic alterations that can be detected.

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Section: Colorectal Cancermentioning

confidence: 99%

“…This is partly due to KRASmutation, which is currently assessed in the primary tumor. Many studies assessed mutation status in circulating tumor DNA, with the aim to improve patient selection [65], [66], [67] and [68].…”

Section: Colorectal Cancermentioning

confidence: 99%

Monitoring tumor-derived cell-free DNA in patients with solid tumors: Clinical perspectives and research opportunities

Espósito¹,

Bardelli²,

Criscitiello³

et al. 2014

Cancer Treatment Reviews

101

View full text Add to dashboard Cite

show abstract

“…[95][96][97] An analysis of 31 mCRC patients demonstrated that ctDNA detection (KRAS mutation and RASSF2A methylation) was highly predictive of clinical outcome under chemotherapy. 95 Median progression-free survival (PFS) was 5 months in patients positive for ctDNA versus 14 months in patients negative for ctDNA (p = 0.004). Separately, Spindler et al 96,97 developed a sensitive PCR method to quantitatively assess cfDNA as well as KRAS-and BRAF-mutated ctDNA in plasma.…”

Section: Monitoring Tumor Burden or Response During Treatmentmentioning

confidence: 99%

Future perspectives of circulating tumor DNA in colorectal cancer

et al. 2017

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Tumor biopsy is currently the gold standard for diagnosis and in determining cell signaling pathways involved in the development of treatment resistance. However, there are major challenges with this technique, including the need for serial sampling to monitor treatment resistance, which is invasive and also has the potential for selection bias due to intra-tumoral and inter-tumoral heterogeneity. These challenges highlight the need for more effective methods for obtaining Tumor samples. Liquid biopsy analyzes genetic material or tumor cells shed into the blood from the primary tumor and metastatic sites and consequently provides a comprehensive, real-time picture of the tumor burden in an individual patient. Indeed, liquid biopsy has the potential to revolutionize cancer management. Here, we review recent studies on the potential clinical applications of liquid biopsy using circulating tumor DNA in colorectal cancer, including screening, diagnosis, detection of minimal residual disease after surgery, detection of recurrence, prognosis, predicting treatment response, monitoring tumor burden or response during treatment, and tracking resistance. We also discuss recent data demonstrating the utility of detecting KRAS-mutated circulating tumor DNA, both at diagnosis to determine an appropriate treatment strategy and during anti-epidermal growth factor receptor therapy to predict treatment resistance. The future integration of liquid biopsy into clinical practice is discussed, together with alternative approaches and key questions that need to be answered in future clinical studies before this technology can be implemented and used routinely.

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“…These findings may establish the basis for development of new therapies or biomarkers for metastatic non-resectable colorectal cancer. In particular, given the importance of the status of the KRAS gene for cetuximab therapy, it seems possible that other genes whose proteins are known to interact with the KRAS protein, such as C-raf [28] or RALGDS [29], may also be useful as biomarkers or as therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Cetuximab plus chemotherapy as first-line treatment for metastatic colorectal cancer: Effect of KRAS mutation on treatment efficacy in Taiwanese patients

Chen

Chiang²,

Wang³

2013

neo

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Cetuximab, either alone or in combination with chemotherapy, is approved for treatment of patients with metastatic colorectal cancer (mCRC). We reviewed retrospectively records of 50 patients with mCRC from a single center in Taiwan. All patients had ECOG performance status grade 2, histological diagnosis of advanced CRC based on RECIST criteria, and were given at least three cycles of chemotherapy plus cetuximab. We compared the effectiveness of therapy in patients with wild-type and mutant KRAS genes, assessed the overall response (OR) rate of patients with locally advanced or metastatic non-resectable CRC, and assessed the progression-free survival (PFS) time. The ten patients with KRAS mutations had poorer response rates than the 40 patients with the wild-type KRAS gene. Patients with the wild-type and mutant genes had similar progression free survival (PFS) status and median time to PFS. The median overall survival time was significantly greater in patients with the wild-type gene than in those with the mutant gene (28.77 ± 6.43 months vs. 15.13 ± 0.50 months, p = 0.014). Taiwanese patients with mCRC respond better to a cetuximab plus chemotherapy regime if their tumors have the wild-type KRAS gene.

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Prognostic Value of Circulating Mutant DNA in Unresectable Metastatic Colorectal Cancer

Abstract: This study suggests that the presence of circulating mutant DNA in unresectable MCRC patients, which can be detected using simple methods such as methylation-specific PCR or real-time PCR, is highly predictive of clinical outcome.

Cited by 48 publications

References 27 publications

Monitoring tumor-derived cell-free DNA in patients with solid tumors: Clinical perspectives and research opportunities

Monitoring tumor-derived cell-free DNA in patients with solid tumors: Clinical perspectives and research opportunities

Future perspectives of circulating tumor DNA in colorectal cancer

Cetuximab plus chemotherapy as first-line treatment for metastatic colorectal cancer: Effect of KRAS mutation on treatment efficacy in Taiwanese patients

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