Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer

Abstract Pancreatic cancer (PDAC) is still lacking of reliable markers to monitor tumor response. CA 19-9 is the only biomarker approved, despite it has several limitations in sensitivity and specificity. Since mutations of KRAS occur in more than 90% of tumors, its detection in circulating free tum...

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Autores principales:	Marzia Del Re, Caterina Vivaldi, Eleonora Rofi, Enrico Vasile, Mario Miccoli, Chiara Caparello, Paolo Davide d’Arienzo, Lorenzo Fornaro, Alfredo Falcone, Romano Danesi
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fb7d73f047fa494fa1acb5333118a956
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spelling	oai:doaj.org-article:fb7d73f047fa494fa1acb5333118a9562021-12-02T11:40:59ZEarly changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer10.1038/s41598-017-08297-z2045-2322https://doaj.org/article/fb7d73f047fa494fa1acb5333118a9562017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08297-zhttps://doaj.org/toc/2045-2322Abstract Pancreatic cancer (PDAC) is still lacking of reliable markers to monitor tumor response. CA 19-9 is the only biomarker approved, despite it has several limitations in sensitivity and specificity. Since mutations of KRAS occur in more than 90% of tumors, its detection in circulating free tumor DNA (cftDNA) could represent a biomarker to monitor chemotherapy response. Twenty-seven advanced PDAC patients given first-line 5-fluorouracil, irinotecan and oxaliplatin or gemcitabine and nab-paclitaxel were enrolled. Three ml of plasma were collected: 1) before starting chemotherapy (baseline); 2) at day 15 of treatment; and 3) at each clinical follow-up. cftDNA was extracted and analysed for KRAS mutations (mutKRAS) by digital droplet PCR. Nineteen patients displayed a mutKRAS in baseline plasma samples. There was a statistically significant difference in progression-free survival (PFS) and overall survival (OS) in patients with increase vs. stability/reduction of cftDNA in the sample collected at day 15 (median PFS 2.5 vs 7.5 months, p = 0.03; median OS 6.5 vs 11.5 months, p = 0.009). The results of this study demonstrate that cftDNA mutKRAS changes are associated with tumor response to chemotherapy and support the evidence that mutKRAS in plasma may be used as a new marker for monitoring treatment outcome and disease progression in PDAC.Marzia Del ReCaterina VivaldiEleonora RofiEnrico VasileMario MiccoliChiara CaparelloPaolo Davide d’ArienzoLorenzo FornaroAlfredo FalconeRomano DanesiNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marzia Del Re Caterina Vivaldi Eleonora Rofi Enrico Vasile Mario Miccoli Chiara Caparello Paolo Davide d’Arienzo Lorenzo Fornaro Alfredo Falcone Romano Danesi Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer
description	Abstract Pancreatic cancer (PDAC) is still lacking of reliable markers to monitor tumor response. CA 19-9 is the only biomarker approved, despite it has several limitations in sensitivity and specificity. Since mutations of KRAS occur in more than 90% of tumors, its detection in circulating free tumor DNA (cftDNA) could represent a biomarker to monitor chemotherapy response. Twenty-seven advanced PDAC patients given first-line 5-fluorouracil, irinotecan and oxaliplatin or gemcitabine and nab-paclitaxel were enrolled. Three ml of plasma were collected: 1) before starting chemotherapy (baseline); 2) at day 15 of treatment; and 3) at each clinical follow-up. cftDNA was extracted and analysed for KRAS mutations (mutKRAS) by digital droplet PCR. Nineteen patients displayed a mutKRAS in baseline plasma samples. There was a statistically significant difference in progression-free survival (PFS) and overall survival (OS) in patients with increase vs. stability/reduction of cftDNA in the sample collected at day 15 (median PFS 2.5 vs 7.5 months, p = 0.03; median OS 6.5 vs 11.5 months, p = 0.009). The results of this study demonstrate that cftDNA mutKRAS changes are associated with tumor response to chemotherapy and support the evidence that mutKRAS in plasma may be used as a new marker for monitoring treatment outcome and disease progression in PDAC.
format	article
author	Marzia Del Re Caterina Vivaldi Eleonora Rofi Enrico Vasile Mario Miccoli Chiara Caparello Paolo Davide d’Arienzo Lorenzo Fornaro Alfredo Falcone Romano Danesi
author_facet	Marzia Del Re Caterina Vivaldi Eleonora Rofi Enrico Vasile Mario Miccoli Chiara Caparello Paolo Davide d’Arienzo Lorenzo Fornaro Alfredo Falcone Romano Danesi
author_sort	Marzia Del Re
title	Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer
title_short	Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer
title_full	Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer
title_fullStr	Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer
title_full_unstemmed	Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer
title_sort	early changes in plasma dna levels of mutant kras as a sensitive marker of response to chemotherapy in pancreatic cancer
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/fb7d73f047fa494fa1acb5333118a956
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Early changes in plasma DNA levels of mutant KRAS as a sensitive marker of response to chemotherapy in pancreatic cancer

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