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Erschienen in: Journal of Gastrointestinal Surgery 11/2016

06.07.2016 | Original Article

Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases

verfasst von: Georgios Antonios Margonis, Kazunari Sasaki, Yuhree Kim, Mario Samaha, Stefan Buettner, Neda Amini, Efstathios Antoniou, Timothy M. Pawlik

Erschienen in: Journal of Gastrointestinal Surgery | Ausgabe 11/2016

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Abstract

Introduction

The interplay of tumor biology and surgical margin status after resection for colorectal liver metastasis (CRLM) remains controversial. Consequently, we sought to determine the impact of surgical margin status on overall survival (OS) stratified by KRAS mutational status.

Materials and Methods

Four hundred eighty-five patients with known KRAS mutational status were identified. Clinicopathologic and long-term survival data were collected and assessed.

Results

On pathology, most patients (n = 380; 78.3 %) had an R0 margin, while 105 (21.7 %) had an R1. Roughly two thirds of tumors were KRAS wild type (wtKRAS) (n = 307, 63.3 %), while 36.7 % (n = 178) had KRAS mutations (mutKRAS). Median and 5-year OS of the entire cohort was 65.8 months and 53.8 %, respectively. An R1 resection was associated with worse 5-year OS compared with R0 (42.4 % vs. 57.1 %; hazard ratio (HR) 1.82, 95 % CI 1.28–2.57; P = 0.001). After controlling for KRAS status, the survival benefit associated with an R0 resection persisted only among patients with wtKRAS tumors (HR 2.16, 95 % CI 1.42–3.30; P < 0.001). In contrast, surgical margin had no impact on OS among patients with mutKRAS tumors (5-year OS R0, 40.7 % vs. R1, 46.7 %; HR 1.34, 95 % CI 0.73–2.48; P = 0.348).

Conclusion

The impact of margin status differed by KRAS mutation status. An R0 margin only provided a survival benefit to patients with wtKRAS tumors. Tumor biology and not surgical technique determined prognosis.
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Literatur
1.
Zurück zum Zitat Leung U, Gonen M, Allen PJ et al. Colorectal Cancer Liver Metastases and Concurrent Extrahepatic Disease Treated With Resection. Ann Surg.2016. Leung U, Gonen M, Allen PJ et al. Colorectal Cancer Liver Metastases and Concurrent Extrahepatic Disease Treated With Resection. Ann Surg.2016.
2.
Zurück zum Zitat Tzeng CW, Aloia TA. Colorectal liver metastases. J Gastrointest Surg.2013;17:195-201; quiz p 201-192. Tzeng CW, Aloia TA. Colorectal liver metastases. J Gastrointest Surg.2013;17:195-201; quiz p 201-192.
3.
Zurück zum Zitat Abbas S, Lam V, Hollands M. Ten-year survival after liver resection for colorectal metastases: systematic review and meta-analysis. ISRN Oncol.2011;2011:763245.PubMedPubMedCentral Abbas S, Lam V, Hollands M. Ten-year survival after liver resection for colorectal metastases: systematic review and meta-analysis. ISRN Oncol.2011;2011:763245.PubMedPubMedCentral
4.
Zurück zum Zitat Pawlik TM, Schulick RD, Choti MA. Expanding criteria for resectability of colorectal liver metastases. Oncologist.2008;13:51-64.CrossRefPubMed Pawlik TM, Schulick RD, Choti MA. Expanding criteria for resectability of colorectal liver metastases. Oncologist.2008;13:51-64.CrossRefPubMed
5.
Zurück zum Zitat Dhir M, Sasson AR. Surgical Management of Liver Metastases From Colorectal Cancer. J Oncol Pract.2016;12:33-39.CrossRefPubMed Dhir M, Sasson AR. Surgical Management of Liver Metastases From Colorectal Cancer. J Oncol Pract.2016;12:33-39.CrossRefPubMed
6.
Zurück zum Zitat Cady B, Stone MD, McDermott WV, Jr. et al. Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases. Arch Surg.1992;127:561-568; discussion 568-569.CrossRefPubMed Cady B, Stone MD, McDermott WV, Jr. et al. Technical and biological factors in disease-free survival after hepatic resection for colorectal cancer metastases. Arch Surg.1992;127:561-568; discussion 568-569.CrossRefPubMed
7.
Zurück zum Zitat Ekberg H, Tranberg KG, Andersson R et al. Determinants of survival in liver resection for colorectal secondaries. Br J Surg.1986;73:727-731.CrossRefPubMed Ekberg H, Tranberg KG, Andersson R et al. Determinants of survival in liver resection for colorectal secondaries. Br J Surg.1986;73:727-731.CrossRefPubMed
8.
9.
Zurück zum Zitat Dhir M, Lyden ER, Wang A et al. Influence of margins on overall survival after hepatic resection for colorectal metastasis: a meta-analysis. Ann Surg.2011;254:234-242.CrossRefPubMed Dhir M, Lyden ER, Wang A et al. Influence of margins on overall survival after hepatic resection for colorectal metastasis: a meta-analysis. Ann Surg.2011;254:234-242.CrossRefPubMed
10.
Zurück zum Zitat Hamady ZZ, Lodge JP, Welsh FK et al. One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach. Ann Surg.2014;259:543-548.CrossRefPubMed Hamady ZZ, Lodge JP, Welsh FK et al. One-millimeter cancer-free margin is curative for colorectal liver metastases: a propensity score case-match approach. Ann Surg.2014;259:543-548.CrossRefPubMed
11.
Zurück zum Zitat Kokudo N, Miki Y, Sugai S et al. Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection. Arch Surg.2002;137:833-840.CrossRefPubMed Kokudo N, Miki Y, Sugai S et al. Genetic and histological assessment of surgical margins in resected liver metastases from colorectal carcinoma: minimum surgical margins for successful resection. Arch Surg.2002;137:833-840.CrossRefPubMed
12.
Zurück zum Zitat Mbah NA, Scoggins C, McMasters K et al. Impact of hepatectomy margin on survival following resection of colorectal metastasis: the role of adjuvant therapy and its effects. Eur J Surg Oncol.2013;39:1394-1399.CrossRefPubMed Mbah NA, Scoggins C, McMasters K et al. Impact of hepatectomy margin on survival following resection of colorectal metastasis: the role of adjuvant therapy and its effects. Eur J Surg Oncol.2013;39:1394-1399.CrossRefPubMed
13.
Zurück zum Zitat Truant S, Sequier C, Leteurtre E et al. Tumour biology of colorectal liver metastasis is a more important factor in survival than surgical margin clearance in the era of modern chemotherapy regimens. HPB (Oxford).2015;17:176-184. Truant S, Sequier C, Leteurtre E et al. Tumour biology of colorectal liver metastasis is a more important factor in survival than surgical margin clearance in the era of modern chemotherapy regimens. HPB (Oxford).2015;17:176-184.
14.
Zurück zum Zitat Eveno C, Karoui M, Gayat E et al. Liver resection for colorectal liver metastases with peri-operative chemotherapy: oncological results of R1 resections. HPB (Oxford).2013;15:359-364. Eveno C, Karoui M, Gayat E et al. Liver resection for colorectal liver metastases with peri-operative chemotherapy: oncological results of R1 resections. HPB (Oxford).2013;15:359-364.
15.
Zurück zum Zitat Pawlik TM, Scoggins CR, Zorzi D et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg.2005;241:715-722, discussion 722-714.CrossRefPubMedPubMedCentral Pawlik TM, Scoggins CR, Zorzi D et al. Effect of surgical margin status on survival and site of recurrence after hepatic resection for colorectal metastases. Ann Surg.2005;241:715-722, discussion 722-714.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat de Haas RJ, Wicherts DA, Flores E et al. R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg.2008;248:626-637.PubMed de Haas RJ, Wicherts DA, Flores E et al. R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg.2008;248:626-637.PubMed
17.
Zurück zum Zitat Brudvik KW, Passot G, Vauthey JN. Colorectal Liver Metastases: A Changing Treatment Landscape. J Oncol Pract.2016;12:40-41.CrossRefPubMed Brudvik KW, Passot G, Vauthey JN. Colorectal Liver Metastases: A Changing Treatment Landscape. J Oncol Pract.2016;12:40-41.CrossRefPubMed
18.
Zurück zum Zitat Spolverato G, Ejaz A, Azad N et al. Surgery for colorectal liver metastases: The evolution of determining prognosis. World J Gastrointest Oncol.2013;5:207-221.CrossRefPubMedPubMedCentral Spolverato G, Ejaz A, Azad N et al. Surgery for colorectal liver metastases: The evolution of determining prognosis. World J Gastrointest Oncol.2013;5:207-221.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat Brudvik KW, Kopetz SE, Li L et al. Meta-analysis of KRAS mutations and survival after resection of colorectal liver metastases. Br J Surg.2015;102:1175-1183.CrossRefPubMed Brudvik KW, Kopetz SE, Li L et al. Meta-analysis of KRAS mutations and survival after resection of colorectal liver metastases. Br J Surg.2015;102:1175-1183.CrossRefPubMed
20.
Zurück zum Zitat Margonis GA, Spolverato G, Kim Y et al. Effect of KRAS Mutation on Long-Term Outcomes of Patients Undergoing Hepatic Resection for Colorectal Liver Metastases. Ann Surg Oncol.2015;22:4158-4165.CrossRefPubMed Margonis GA, Spolverato G, Kim Y et al. Effect of KRAS Mutation on Long-Term Outcomes of Patients Undergoing Hepatic Resection for Colorectal Liver Metastases. Ann Surg Oncol.2015;22:4158-4165.CrossRefPubMed
21.
Zurück zum Zitat Margonis GA, Kim Y, Spolverato G et al. Association Between Specific Mutations in KRAS Codon 12 and Colorectal Liver Metastasis. JAMA Surg.2015;150:722-729.CrossRefPubMedPubMedCentral Margonis GA, Kim Y, Spolverato G et al. Association Between Specific Mutations in KRAS Codon 12 and Colorectal Liver Metastasis. JAMA Surg.2015;150:722-729.CrossRefPubMedPubMedCentral
22.
Zurück zum Zitat Vauthey JN, Zimmitti G, Kopetz SE et al. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg.2013;258:619-626; discussion 626-617.CrossRefPubMed Vauthey JN, Zimmitti G, Kopetz SE et al. RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases. Ann Surg.2013;258:619-626; discussion 626-617.CrossRefPubMed
23.
Zurück zum Zitat Schirripa M, Bergamo F, Cremolini C et al. BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection. Br J Cancer.2015;112:1921-1928.CrossRefPubMedPubMedCentral Schirripa M, Bergamo F, Cremolini C et al. BRAF and RAS mutations as prognostic factors in metastatic colorectal cancer patients undergoing liver resection. Br J Cancer.2015;112:1921-1928.CrossRefPubMedPubMedCentral
24.
Zurück zum Zitat Sadot E, Groot Koerkamp B, Leal JN et al. Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Ann Surg.2015;262:476-485; discussion 483-475.CrossRefPubMedPubMedCentral Sadot E, Groot Koerkamp B, Leal JN et al. Resection margin and survival in 2368 patients undergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Ann Surg.2015;262:476-485; discussion 483-475.CrossRefPubMedPubMedCentral
25.
Zurück zum Zitat Andreou A, Aloia TA, Brouquet A et al. Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy. Ann Surg.2013;257:1079-1088.CrossRefPubMedPubMedCentral Andreou A, Aloia TA, Brouquet A et al. Margin status remains an important determinant of survival after surgical resection of colorectal liver metastases in the era of modern chemotherapy. Ann Surg.2013;257:1079-1088.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Angelsen JH, Horn A, Eide GE et al. Surgery for colorectal liver metastases: the impact of resection margins on recurrence and overall survival. World J Surg Oncol.2014;12:127.CrossRefPubMedPubMedCentral Angelsen JH, Horn A, Eide GE et al. Surgery for colorectal liver metastases: the impact of resection margins on recurrence and overall survival. World J Surg Oncol.2014;12:127.CrossRefPubMedPubMedCentral
27.
Zurück zum Zitat Ayez N, Lalmahomed ZS, Eggermont AM et al. Outcome of microscopic incomplete resection (R1) of colorectal liver metastases in the era of neoadjuvant chemotherapy. Ann Surg Oncol.2012;19:1618-1627.CrossRefPubMed Ayez N, Lalmahomed ZS, Eggermont AM et al. Outcome of microscopic incomplete resection (R1) of colorectal liver metastases in the era of neoadjuvant chemotherapy. Ann Surg Oncol.2012;19:1618-1627.CrossRefPubMed
28.
Zurück zum Zitat Tranchart H, Chirica M, Faron M et al. Prognostic impact of positive surgical margins after resection of colorectal cancer liver metastases: reappraisal in the era of modern chemotherapy. World J Surg.2013;37:2647-2654.CrossRefPubMed Tranchart H, Chirica M, Faron M et al. Prognostic impact of positive surgical margins after resection of colorectal cancer liver metastases: reappraisal in the era of modern chemotherapy. World J Surg.2013;37:2647-2654.CrossRefPubMed
29.
Zurück zum Zitat Siriwardena AK, Mason JM, Mullamitha S et al. Management of colorectal cancer presenting with synchronous liver metastases. Nat Rev Clin Oncol.2014;11:446-459.CrossRefPubMed Siriwardena AK, Mason JM, Mullamitha S et al. Management of colorectal cancer presenting with synchronous liver metastases. Nat Rev Clin Oncol.2014;11:446-459.CrossRefPubMed
30.
Zurück zum Zitat Bodingbauer M, Tamandl D, Schmid K et al. Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases. Br J Surg.2007;94:1133-1138.CrossRefPubMed Bodingbauer M, Tamandl D, Schmid K et al. Size of surgical margin does not influence recurrence rates after curative liver resection for colorectal cancer liver metastases. Br J Surg.2007;94:1133-1138.CrossRefPubMed
31.
Zurück zum Zitat Muratore A, Ribero D, Zimmitti G et al. Resection margin and recurrence-free survival after liver resection of colorectal metastases. Ann Surg Oncol.2010;17:1324-1329.CrossRefPubMed Muratore A, Ribero D, Zimmitti G et al. Resection margin and recurrence-free survival after liver resection of colorectal metastases. Ann Surg Oncol.2010;17:1324-1329.CrossRefPubMed
32.
Zurück zum Zitat Welsh FK, Tekkis PP, O’Rourke T et al. Quantification of risk of a positive (R1) resection margin following hepatic resection for metastatic colorectal cancer: an aid to clinical decision-making. Surg Oncol.2008;17:3-13.CrossRefPubMed Welsh FK, Tekkis PP, O’Rourke T et al. Quantification of risk of a positive (R1) resection margin following hepatic resection for metastatic colorectal cancer: an aid to clinical decision-making. Surg Oncol.2008;17:3-13.CrossRefPubMed
33.
Zurück zum Zitat Yamamoto J, Shimada K, Kosuge T et al. Factors influencing survival of patients undergoing hepatectomy for colorectal metastases. Br J Surg.1999;86:332-337.CrossRefPubMed Yamamoto J, Shimada K, Kosuge T et al. Factors influencing survival of patients undergoing hepatectomy for colorectal metastases. Br J Surg.1999;86:332-337.CrossRefPubMed
34.
Zurück zum Zitat Van Cutsem E, Nordlinger B, Adam R et al. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer.2006;42:2212-2221.CrossRefPubMed Van Cutsem E, Nordlinger B, Adam R et al. Towards a pan-European consensus on the treatment of patients with colorectal liver metastases. Eur J Cancer.2006;42:2212-2221.CrossRefPubMed
35.
Zurück zum Zitat Brunner SM, Kesselring R, Rubner C et al. Prognosis according to histochemical analysis of liver metastases removed at liver resection. Br J Surg.2014;101:1681-1691.CrossRefPubMed Brunner SM, Kesselring R, Rubner C et al. Prognosis according to histochemical analysis of liver metastases removed at liver resection. Br J Surg.2014;101:1681-1691.CrossRefPubMed
36.
Zurück zum Zitat Nielsen K, Rolff HC, Eefsen RL et al. The morphological growth patterns of colorectal liver metastases are prognostic for overall survival. Mod Pathol.2014;27:1641-1648.CrossRefPubMed Nielsen K, Rolff HC, Eefsen RL et al. The morphological growth patterns of colorectal liver metastases are prognostic for overall survival. Mod Pathol.2014;27:1641-1648.CrossRefPubMed
37.
Zurück zum Zitat Rekhtman N, Ang DC, Riely GJ et al. KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma. Mod Pathol.2013;26:1307-1319.CrossRefPubMedPubMedCentral Rekhtman N, Ang DC, Riely GJ et al. KRAS mutations are associated with solid growth pattern and tumor-infiltrating leukocytes in lung adenocarcinoma. Mod Pathol.2013;26:1307-1319.CrossRefPubMedPubMedCentral
38.
Zurück zum Zitat Santini D, Loupakis F, Vincenzi B et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist.2008;13:1270-1275.CrossRefPubMed Santini D, Loupakis F, Vincenzi B et al. High concordance of KRAS status between primary colorectal tumors and related metastatic sites: implications for clinical practice. Oncologist.2008;13:1270-1275.CrossRefPubMed
39.
Zurück zum Zitat Knijn N, Mekenkamp LJ, Klomp M et al. KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients. Br J Cancer.2011;104:1020-1026.CrossRefPubMedPubMedCentral Knijn N, Mekenkamp LJ, Klomp M et al. KRAS mutation analysis: a comparison between primary tumours and matched liver metastases in 305 colorectal cancer patients. Br J Cancer.2011;104:1020-1026.CrossRefPubMedPubMedCentral
40.
Zurück zum Zitat Italiano A, Hostein I, Soubeyran I et al. KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: biological and clinical implications. Ann Surg Oncol.2010;17:1429-1434.CrossRefPubMed Italiano A, Hostein I, Soubeyran I et al. KRAS and BRAF mutational status in primary colorectal tumors and related metastatic sites: biological and clinical implications. Ann Surg Oncol.2010;17:1429-1434.CrossRefPubMed
41.
Zurück zum Zitat Etienne-Grimaldi MC, Formento JL, Francoual M et al. K-Ras mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy. Clin Cancer Res.2008;14:4830-4835.CrossRefPubMed Etienne-Grimaldi MC, Formento JL, Francoual M et al. K-Ras mutations and treatment outcome in colorectal cancer patients receiving exclusive fluoropyrimidine therapy. Clin Cancer Res.2008;14:4830-4835.CrossRefPubMed
42.
Zurück zum Zitat Margonis GA, Spolverato G, Kim Y et al. Intraoperative surgical margin re-resection for colorectal liver metastasis: is it worth the effort? J Gastrointest Surg.2015;19:699-707.CrossRefPubMed Margonis GA, Spolverato G, Kim Y et al. Intraoperative surgical margin re-resection for colorectal liver metastasis: is it worth the effort? J Gastrointest Surg.2015;19:699-707.CrossRefPubMed
43.
Zurück zum Zitat Nuzzo G, Giuliante F, Ardito F et al. Influence of surgical margin on type of recurrence after liver resection for colorectal metastases: a single-center experience. Surgery.2008;143:384-393.CrossRefPubMed Nuzzo G, Giuliante F, Ardito F et al. Influence of surgical margin on type of recurrence after liver resection for colorectal metastases: a single-center experience. Surgery.2008;143:384-393.CrossRefPubMed
Metadaten
Titel
Tumor Biology Rather Than Surgical Technique Dictates Prognosis in Colorectal Cancer Liver Metastases
verfasst von
Georgios Antonios Margonis
Kazunari Sasaki
Yuhree Kim
Mario Samaha
Stefan Buettner
Neda Amini
Efstathios Antoniou
Timothy M. Pawlik
Publikationsdatum
06.07.2016
Verlag
Springer US
Erschienen in
Journal of Gastrointestinal Surgery / Ausgabe 11/2016
Print ISSN: 1091-255X
Elektronische ISSN: 1873-4626
DOI
https://doi.org/10.1007/s11605-016-3198-8

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