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Thématique :
- Cancer colorectal (CCR)
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| Doit faire évoluer notre pratique : |
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Dans certains cas
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Nom du veilleur :
Professeur David TOUGERON
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Annals of oncology
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2017/09
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2017 Sep ;28(9):2149-2159.
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doi: 10.1093/annonc/mdx330.
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Clinical utility of circulating DNA analysis for rapid detection of actionable mutations to select metastatic colorectal patients for anti-EGFR treatment.
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Thierry AR, El Messaoudi S, Mollevi C, Raoul JL, Guimbaud R, Pezet D, Artru P, Assenat E, Borg C, Mathonnet M, De La Fouchardière C, Bouché O, Gavoille C, Fiess C, Auzemery B, Meddeb R, Lopez-Crapez E, Sanchez C, Pastor B, Ychou M
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https://www.ncbi.nlm.nih.gov/pubmed/28911069
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Abstract
BACKGROUND:
While tumor-tissue remains the 'gold standard' for genetic analysis in cancer patients, it is challenged with the advent of circulating cell-free tumor DNA (ctDNA) analysis from blood samples. Here, we broaden our previous study on the clinical validation of plasma DNA in metastatic colorectal cancer patients, by evaluating its clinical utility under standard management care.
PATIENTS AND METHODS:
Concordance and data turnaround-time of ctDNA when compared with tumor-tissue analysis were studied in a real-time blinded prospective multicenter clinical study (n = 140 metastatic colorectal patients). Results are presented according to STARD criteria and were discussed in regard with clinical outcomes of patients.
RESULTS:
Much more mutations were found by ctDNA analysis: 59%, 11.8% and 14.4% of the patients were found KRAS, NRAS and BRAF mutant by ctDNA analysis instead of 44%, 8.8% and 7.2% by tumor-tissue analysis. Median tumor-tissue data turnaround-time was 16 days while 2 days for ctDNA analysis. Discordant samples analysis revealed that use of biopsy, long delay between tumor-tissue and blood collection and resection of the tumor at time of blood draw, tumor site, or type of tissue analyzed seem to affect concordance. Altogether, the clinical data with respect to the anti-epidermal growth factor receptor response (RAS status) and the prognosis (BRAF status) of those discordant patients do not appear contradictory to the mutational status as determined by plasma analysis. Lastly, we present the first distribution profile of the RAS and BRAF hotspot mutations as determined by ctDNA analysis (n = 119), revealing a high proportion of patients with multiple mutations (45% of the population and up to 5 mutations) and only 24% of WT scored patients for both genes. Mutation profile as determined from ctDNA analysis with using various detection thresholds highlights the importance of the test sensitivity.
CONCLUSION:
Our study showed that ctDNA could replace tumor-tissue analysis, and also clinical utility of ctDNA analysis by considerably reducing data turnaround time.
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Cette étude s’intéresse à la détection des mutations RAS et BRAF à partir de l’ADN tumoral circulant dans les cancers colorectaux métastatiques.
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Les taux de mutations RAS et BRAF détectés à partir de l’ADN tumoral circulant sont plus élevés que ceux détectés à partir de la tumeur primitive. Les pourcentages de discordance sont de l’ordre de 25% et 45% des patients ont des mutations multiples dans le sang circulant.
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Ces discordances peuvent s’expliquer par l’hétérogénéité tumorale et l’évolution du statut moléculaire au cours de temps. Le statut RAS déterminé à partir de l’ADN tumoral circulant pourrait être plus fiable que celui déterminé à partir de la tumeur primitive, et donc mieux prédire la réponse aux anti-EGFR. Cela doit être validé dans un essai prospectif avant une utilisation en pratique courante.
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