RAS Mutation Predicts Positive Resection Margins and Narrower Resection Margins in Patients Undergoing Resection of Colorectal Liver Metastases View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2016-03-25

AUTHORS

Kristoffer Watten Brudvik, Yoshihiro Mise, Michael Hsiang Chung, Yun Shin Chun, Scott E. Kopetz, Guillaume Passot, Claudius Conrad, Dipen M. Maru, Thomas A. Aloia, Jean-Nicolas Vauthey

ABSTRACT

BackgroundIn patients undergoing resection of colorectal liver metastases (CLM), resection margin status is a significant predictor of survival, particularly in patients with suboptimal response to preoperative therapy. RAS mutations have been linked to more invasive and migratory tumor biology and poor response to modern chemotherapy.ObjectiveThe aim of this study was to evaluate the relationship between RAS mutation and resection margin status in patients undergoing resection of CLM.MethodsPatients who underwent curative resection of CLM from 2005 to 2013 with known RAS mutation status were identified from a prospectively maintained database. A positive margin was defined as tumor cells <1 mm from the parenchymal transection line.ResultsThe study included 633 patients, of whom 229 (36.2 %) had mutant RAS. The positive margin rate was 11.4 % (26/229) for mutant RAS and 5.4 % (22/404) for wild-type RAS (p = 0.007). In multivariate analysis, the only factors associated with a positive margin were RAS mutation (hazard ratio [HR] 2.439; p = 0.005) and carcinoembryonic antigen level 4.5 ng/mL or greater (HR 2.060; p = 0.026). Among patients presenting with liver-first recurrence during follow-up, those with mutant RAS had narrower margins at initial CLM resection (median 4 mm vs. 7 mm; p = 0.031). A positive margin (HR 3.360; p < 0.001) and RAS mutation (HR 1.629; p = 0.044) were independently associated with worse overall survival.ConclusionRAS mutations are associated with positive margins in patients undergoing resection of CLM. Tumors with RAS mutation should prompt careful efforts to achieve negative resection margins. More... »

PAGES

2635-2643

Identifiers

URI

http://scigraph.springernature.com/pub.10.1245/s10434-016-5187-2

DOI

http://dx.doi.org/10.1245/s10434-016-5187-2

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https://app.dimensions.ai/details/publication/pub.1050206513

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/27016292


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34 schema:description BackgroundIn patients undergoing resection of colorectal liver metastases (CLM), resection margin status is a significant predictor of survival, particularly in patients with suboptimal response to preoperative therapy. RAS mutations have been linked to more invasive and migratory tumor biology and poor response to modern chemotherapy.ObjectiveThe aim of this study was to evaluate the relationship between RAS mutation and resection margin status in patients undergoing resection of CLM.MethodsPatients who underwent curative resection of CLM from 2005 to 2013 with known RAS mutation status were identified from a prospectively maintained database. A positive margin was defined as tumor cells <1 mm from the parenchymal transection line.ResultsThe study included 633 patients, of whom 229 (36.2 %) had mutant RAS. The positive margin rate was 11.4 % (26/229) for mutant RAS and 5.4 % (22/404) for wild-type RAS (p = 0.007). In multivariate analysis, the only factors associated with a positive margin were RAS mutation (hazard ratio [HR] 2.439; p = 0.005) and carcinoembryonic antigen level 4.5 ng/mL or greater (HR 2.060; p = 0.026). Among patients presenting with liver-first recurrence during follow-up, those with mutant RAS had narrower margins at initial CLM resection (median 4 mm vs. 7 mm; p = 0.031). A positive margin (HR 3.360; p < 0.001) and RAS mutation (HR 1.629; p = 0.044) were independently associated with worse overall survival.ConclusionRAS mutations are associated with positive margins in patients undergoing resection of CLM. Tumors with RAS mutation should prompt careful efforts to achieve negative resection margins.
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41 CLM resection
42 MethodsPatients
43 Patients Undergoing Resection
44 RA
45 RAS
46 RAS mutation status
47 RAS mutations
48 ResultsThe study
49 aim
50 analysis
51 biology
52 careful efforts
53 cells
54 chemotherapy
55 colorectal liver metastases
56 curative resection
57 database
58 efforts
59 factors
60 levels 4.5
61 lines
62 liver metastases
63 margin
64 margin rate
65 margin status
66 metastasis
67 modern chemotherapy
68 multivariate analysis
69 mutant RAS
70 mutation status
71 mutations
72 narrow margin
73 negative resection margins
74 only factor
75 overall survival
76 parenchymal transection line
77 patients
78 poor response
79 positive margin rate
80 positive margins
81 positive resection margins
82 predictors
83 preoperative therapy
84 rate
85 recurrence
86 relationship
87 resection
88 resection margin status
89 resection margins
90 resection of CRLM
91 response
92 significant predictors
93 status
94 study
95 suboptimal response
96 survival
97 therapy
98 transection line
99 tumor biology
100 tumor cells
101 tumors
102 undergoing resection
103 wild-type Ras
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