G12V and G12A KRAS mutations are associated with poor outcome
in patients with metastatic colorectal cancer treated with
bevacizumab

J 2016

G12V and G12A KRAS mutations are associated with poor outcome in patients with metastatic colorectal cancer treated with bevacizumab

FIALA, Ondrej; Tomas BUCHLER; Beatrice MOHELNIKOVA-DUCHONOVA; Bohuslav MELICHAR; Vit Martin MATEJKA et al.

Základní údaje

Originální název

G12V and G12A KRAS mutations are associated with poor outcome in patients with metastatic colorectal cancer treated with bevacizumab

Autoři

Vydání

Tumor Biology, Dordrecht, Springer, 2016, 1010-4283

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

30200 3.2 Clinical medicine

Stát vydavatele

Nizozemské království

Utajení

není předmětem státního či obchodního tajemství

Impakt faktor

Impact factor: 3.650

Označené pro přenos do RIV

Ano

Kód RIV

RIV/00216224:14110/16:00090376

Organizační jednotka

Lékařská fakulta

Klíčová slova anglicky

Colorectal cancer; Bevacizumab; Chemotherapy; KRAS; Mutation

Štítky

EL OK

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 3. 8. 2016 14:48, Ing. Mgr. Věra Pospíšilíková

Anotace

V originále

The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 35-45 % of colorectal cancer (CRC) cases, Although the association between the RAS signaling and angiogenesis is well known, the negative predictive value of KRAS mutation has not been established in patients treated with bevacizumab. The aim of this study was to evaluate the association between specific KRAS mutation types and outcome of patients with metastatic CRC treated with bevacizumab. The study included 404 patients with metastatic CRC (mCRC) treated with bevacizumab. Clinical data obtained from the clinical registry CORECT were retrospectively analyzed. The shortest survival was observed in patients with tumors harboring G12V or G12A KRAS mutation (G12V/A). The median progression-free survival (PFS) and overall survival (OS) for patients with tumors harboring G12V/A KRAS mutation was 6.6 and 16.8 compared to 11.6 and 26.3 months for patients with tumors harboring other KRAS mutation type (p<0.001 and p<0.001), while the survival of patients harboring other KRAS mutation types was comparable to those with tumors harboring wild-type KRAS gene. In the Cox multivariable analysis, KRAS G12V/A mutation type remains a significant factor predicting both PFS (HR=2.18,p<0.001) and OS (HR=2.58,p<0.001). In conclusion, the results of the present study indicate that there is a significant difference in biological behavior between tumors harboring G12V/A and other KRAS mutations. Moreover, comparison of the survival of patients with tumors harboring G12V/A KRAS mutations with those harboring wild type KRAS gene revealed that G12V/A KRAS mutations are prognostic biomarker for inferior PFS and OS in patients with mCRC treated with bevacizumab in univariate as well as multivariable analyses.

Citovat

FIALA, Ondrej; Tomas BUCHLER; Beatrice MOHELNIKOVA-DUCHONOVA; Bohuslav MELICHAR; Vit Martin MATEJKA; Lubos HOLUBEC; Jana KULHANKOVA; Zbyněk BORTLÍČEK; Marie BARTOUSKOVA; Vaclav LISKA; Ondrej TOPOLCAN; Monika SEDIVCOVA a Jindrich FINEK. G12V and G12A KRAS mutations are associated with poor outcome in patients with metastatic colorectal cancer treated with bevacizumab. Tumor Biology. Dordrecht: Springer, 2016, roč. 37, č. 5, s. 6823-6830. ISSN 1010-4283. Dostupné z: https://doi.org/10.1007/s13277-015-4523-7.

@article{1349622,
   author = {Fiala, Ondrej and Buchler, Tomas and MohelnikovaandDuchonova, Beatrice and Melichar, Bohuslav and Matejka, Vit Martin and Holubec, Lubos and Kulhankova, Jana and Bortlíček, Zbyněk and Bartouskova, Marie and Liska, Vaclav and Topolcan, Ondrej and Sedivcova, Monika and Finek, Jindrich},
   article_location = {Dordrecht},
   article_number = {5},
   doi = {https://doi.org/10.1007/s13277-015-4523-7},
   keywords = {Colorectal cancer; Bevacizumab; Chemotherapy; KRAS; Mutation},
   language = {eng},
   issn = {1010-4283},
   journal = {Tumor Biology},
   title = {G12V and G12A KRAS mutations are associated with poor outcome in patients with metastatic colorectal cancer treated with bevacizumab},
   volume = {37},
   year = {2016}
}

TY  - JOUR
ID  - 1349622
AU  - Fiala, Ondrej - Buchler, Tomas - Mohelnikova-Duchonova, Beatrice - Melichar, Bohuslav - Matejka, Vit Martin - Holubec, Lubos - Kulhankova, Jana - Bortlíček, Zbyněk - Bartouskova, Marie - Liska, Vaclav - Topolcan, Ondrej - Sedivcova, Monika - Finek, Jindrich
PY  - 2016
TI  - G12V and G12A KRAS mutations are associated with poor outcome in patients with metastatic colorectal cancer treated with bevacizumab
JF  - Tumor Biology
VL  - 37
IS  - 5
SP  - 6823-6830
EP  - 6823-6830
PB  - Springer
SN  - 10104283
KW  - Colorectal cancer
KW  - Bevacizumab
KW  - Chemotherapy
KW  - KRAS
KW  - Mutation
N2  - The v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations are found in 35-45 % of colorectal cancer (CRC) cases, Although the association between the RAS signaling and angiogenesis is well known, the negative predictive value of KRAS mutation has not been established in patients treated with bevacizumab. The aim of this study was to evaluate the association between specific KRAS mutation types and outcome of patients with metastatic CRC treated with bevacizumab. The study included 404 patients with metastatic CRC (mCRC) treated with bevacizumab. Clinical data obtained from the clinical registry CORECT were retrospectively analyzed. The shortest survival was observed in patients with tumors harboring G12V or G12A KRAS mutation (G12V/A). The median progression-free survival (PFS) and overall survival (OS) for patients with tumors harboring G12V/A KRAS mutation was 6.6 and 16.8 compared to 11.6 and 26.3 months for patients with tumors harboring other KRAS mutation type (p<0.001 and p<0.001), while the survival of patients harboring other KRAS mutation types was comparable to those with tumors harboring wild-type KRAS gene. In the Cox multivariable analysis, KRAS G12V/A mutation type remains a significant factor predicting both PFS (HR=2.18,p<0.001) and OS (HR=2.58,p<0.001). In conclusion, the results of the present study indicate that there is a significant difference in biological behavior between tumors harboring G12V/A and other KRAS mutations. Moreover, comparison of the survival of patients with tumors harboring G12V/A KRAS mutations with those harboring wild type KRAS gene revealed that G12V/A KRAS mutations are prognostic biomarker for inferior PFS and OS in patients with mCRC treated with bevacizumab in univariate as well as multivariable analyses.
ER  -

FIALA, Ondrej; Tomas BUCHLER; Beatrice MOHELNIKOVA-DUCHONOVA; Bohuslav MELICHAR; Vit Martin MATEJKA; Lubos HOLUBEC; Jana KULHANKOVA; Zbyněk BORTLÍČEK; Marie BARTOUSKOVA; Vaclav LISKA; Ondrej TOPOLCAN; Monika SEDIVCOVA a Jindrich FINEK. G12V and G12A KRAS mutations are associated with poor outcome in patients with metastatic colorectal cancer treated with bevacizumab. \textit{Tumor Biology}. Dordrecht: Springer, 2016, roč.~37, č.~5, s.~6823-6830. ISSN~1010-4283. Dostupné z: https://doi.org/10.1007/s13277-015-4523-7.

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