RAS Mutations Predict Radiologic and Pathologic Response in Patients Treated with Chemotherapy Before Resection of Colorectal Liver Metastases View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-09-17

AUTHORS

Yoshihiro Mise, Giuseppe Zimmitti, Junichi Shindoh, Scott Kopetz, Evelyne M. Loyer, Andreas Andreou, Amanda B. Cooper, Harmeet Kaur, Thomas A. Aloia, Dipen M. Maru, Jean-Nicolas Vauthey

ABSTRACT

BackgroundRAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. The purpose of this study was to investigate the correlation between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM.MethodsRAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models, including either radiologic morphologic response (model 1) or pathologic response (model 2).ResultsOptimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9 and 58.9 %, respectively) than in patients with RAS mutations (10.5 and 36.8 %; P = 0.006 and 0.015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response [odds ratio (OR), 4.38; 95 % CI 1.45–13.15] and major pathologic response (OR, 2.61; 95 % CI 1.17–5.80). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.57 and 2.30, respectively, in model 1, and 3.19 and 2.09, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified survival in patients with inadequate response to preoperative chemotherapy.ConclusionsRAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy. More... »

PAGES

834-842

Identifiers

URI

http://scigraph.springernature.com/pub.10.1245/s10434-014-4042-6

DOI

http://dx.doi.org/10.1245/s10434-014-4042-6

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1028729249

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25227306


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39 schema:description BackgroundRAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. The purpose of this study was to investigate the correlation between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM.MethodsRAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models, including either radiologic morphologic response (model 1) or pathologic response (model 2).ResultsOptimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9 and 58.9 %, respectively) than in patients with RAS mutations (10.5 and 36.8 %; P = 0.006 and 0.015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response [odds ratio (OR), 4.38; 95 % CI 1.45–13.15] and major pathologic response (OR, 2.61; 95 % CI 1.17–5.80). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.57 and 2.30, respectively, in model 1, and 3.19 and 2.09, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified survival in patients with inadequate response to preoperative chemotherapy.ConclusionsRAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy.
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46 RAS mutational status
47 RAS mutations
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49 chemotherapy
50 colorectal liver metastases
51 correlation
52 criteria
53 curative resection
54 current prognostic indicators
55 different multivariate models
56 factors
57 impact
58 inadequate response
59 inclusion criteria
60 indicators
61 liver metastases
62 major pathologic response
63 meeting inclusion criteria
64 metastasis
65 model
66 modern chemotherapy
67 morphologic response
68 multivariate analysis
69 multivariate model
70 mutational status
71 mutations
72 optimal morphologic response
73 overall survival
74 pathologic response
75 patients
76 patients meeting inclusion criteria
77 potential prognostic factors
78 predictors
79 predictors of survival
80 preoperative chemotherapy
81 prognostic factors
82 prognostic impact
83 prognostic indicator
84 purpose
85 radiologic
86 recurrence
87 relation
88 resection
89 response
90 status
91 strongest predictor
92 study
93 subanalysis
94 survival
95 wild-type RAS
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