TY - JOUR
T1 - Prognostic significance of K-Ras mutation rate in metastatic colorectal cancer patients
AU - Bronte, Giuseppe
AU - Russo, Antonio
AU - Pantano, Francesco
AU - Loupakis, Fotios
AU - Zoccoli, Alice
AU - Imperatori, Marco
AU - Russo, Antonio
AU - Dell'Aquila, Emanuela
AU - Onetti-Muda, Andrea
AU - Ongaro, Elena
AU - Onetti-Muda, Andrea
AU - Rossini, Daniele
AU - Perrone, Giuseppe
AU - Mannavola, Francesco
AU - Bonazzina, Erica
AU - Cremolini, Chiara
AU - Maglio, Giovanna De
AU - Aprile, Giuseppe
AU - Vincenzi, Bruno
AU - Maglio, Giovanna De
AU - Fontanini, Gabriella
AU - Falcone, Alfredo
AU - Siena, Salvatore
AU - Natoli, Clara
AU - Tonini, Giuseppe
AU - Santini, Daniele
AU - Bronte, Giuseppe
AU - Sartore-Bianchi, Andrea
AU - Santini, Daniele
AU - Perrone, Giuseppe
PY - 2015
Y1 - 2015
N2 - Introduction: Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/ tumor sample, are available. We aimed to evaluate the prognostic value of K-Ras mutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. Patients and Methods: This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. Results: At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Discussion: Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set.
AB - Introduction: Activating mutations of K-Ras gene have a well-established role as predictors of resistance to anti-EGFR monoclonal antibodies in metastatic colorectal cancer (mCRC) patients. Their prognostic value is controversial, and no data regarding the prognostic value of mutation rate, defined as the percentage of mutated alleles/ tumor sample, are available. We aimed to evaluate the prognostic value of K-Ras mutation rate in a homogenous cohort of mCRC patients receiving first-line doublet plus bevacizumab. Patients and Methods: This retrospective study enrolled 397 K-Ras mutant mCRC patients from 6 Italian centers, and 263 patients were fully evaluable for our analysis. K-Ras mutation rate was assessed by pyrosequencing. Patients with less than 60% of cancer cells in tumor tissue were excluded. No patients received anti-EGFR containing anticancer therapy, at any time. Median mutation rate was 40% and was adopted as cut-off. The primary and secondary endpoints were PFS and OS respectively. Results: At univariate analysis, K-Ras mutation rate higher than 40% was significantly associated with lower PFS (7.3 vs 9.1 months; P < 0.0001) and OS (21 vs 31 months; P = 0.004). A multivariate model adjusted for age at diagnosis, site of origin of tumor tissue (primary vs metastases), referral center, number of metastatic sites, and first-line chemotherapy backbone, showed that K-Ras mutation rate remained a significant predictor of PFS and OS in the whole population. Discussion: Our data demonstrate an association between K-Ras mutation rate and prognosis in mCRC patients treated with bevacizumab-containing first-line therapy. These data deserve to be verified in an independent validation set.
KW - Bevacizumab; Colorectal cancer; K-Ras; Mutation rate; Prognosis; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Middle Aged; Mutation; Neoplasm Staging; Prognosis; Proto-Onco
KW - Cultured; Oncology
KW - Bevacizumab; Colorectal cancer; K-Ras; Mutation rate; Prognosis; Antineoplastic Combined Chemotherapy Protocols; Colorectal Neoplasms; Female; Follow-Up Studies; Humans; Liver Neoplasms; Male; Middle Aged; Mutation; Neoplasm Staging; Prognosis; Proto-Onco
KW - Cultured; Oncology
UR - http://hdl.handle.net/10447/291790
UR - http://www.impactjournals.com/oncotarget/index.php?journal=oncotarget&page=article&op=download&path%5B%5D=5231&path%5B%5D=12173
M3 - Article
VL - 6
SP - 31604
EP - 31612
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
ER -