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Erschienen in: Annals of Surgical Oncology 1/2017

30.09.2016 | Hepatobiliary Tumors

KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases

verfasst von: Georgios A. Margonis, MD, PhD, Kazunari Sasaki, MD, Nikolaos Andreatos, MD, Yuhree Kim, MD, MPH, Katiuscha Merath, MD, Doris Wagner, MD, Ana Wilson, MD, Stefan Buettner, MD, Neda Amini, MD, Efstathios Antoniou, MD, PhD, Timothy M. Pawlik, MD, MPH, PhD, FACS

Erschienen in: Annals of Surgical Oncology | Ausgabe 1/2017

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Abstract

Background

The optimal tumor-free margin width remains controversial and may be inappropriate to investigate without considering differences in the underlying tumor biology.

Methods

R1 resection was defined as margin clearance less than 1 mm. R0 resection was further divided into 3 groups: 1–4, 5–9, and ≥10 mm. The impact of margin width on overall survival (OS) relative to KRAS status [wild type (wtKRAS) vs. mutated (mutKRAS)] was assessed.

Results

A total of 411 patients met inclusion criteria. Median patient age was 58 years (interquartile range, 49.7–66.7); most patients were male (n = 250; 60.8 %). With a median follow-up of 28.3 months, median and 5-year OS were 69.8 months and 55.1 %. Among patients with wtKRAS tumors, although margin clearance of 1–4 mm or more was associated with improved OS compared to R1 (all P < 0.05), no difference in OS was observed when comparing margin clearance of 1–4 mm to the 5–9 mm and the ≥10 mm groups (all P > 0.05). In contrast, among patients with mutKRAS tumors, all three groups of margin clearance (1–4, 5–9, and ≥10 mm) fared no better in terms of 5-year survival compared to R1 resection (all P > 0.05).

Conclusions

While a 1–4 mm margin clearance in patients with wtKRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status—including a 1 cm margin—did not improve survival among patients with mutKRAS tumors.
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Literatur
1.
Zurück zum Zitat Postriganova N, Kazaryan AM, Rosok BI, Fretland A, Barkhatov L, Edwin B. Margin status after laparoscopic resection of colorectal liver metastases: does a narrow resection margin have an influence on survival and local recurrence? HPB (Oxford). 2014;16:822–9.CrossRefPubMed Postriganova N, Kazaryan AM, Rosok BI, Fretland A, Barkhatov L, Edwin B. Margin status after laparoscopic resection of colorectal liver metastases: does a narrow resection margin have an influence on survival and local recurrence? HPB (Oxford). 2014;16:822–9.CrossRefPubMed
2.
Zurück zum Zitat Mattar RE, Al-Alem F, Simoneau E, Hassanain M. Preoperative selection of patients with colorectal cancer liver metastasis for hepatic resection. World J Gastroenterol. 2016;22:567–81.CrossRefPubMedPubMedCentral Mattar RE, Al-Alem F, Simoneau E, Hassanain M. Preoperative selection of patients with colorectal cancer liver metastasis for hepatic resection. World J Gastroenterol. 2016;22:567–81.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Kassahun WT. Unresolved issues and controversies surrounding the management of colorectal cancer liver metastasis. World J Surg Oncol. 2015;13:61.CrossRefPubMedPubMedCentral Kassahun WT. Unresolved issues and controversies surrounding the management of colorectal cancer liver metastasis. World J Surg Oncol. 2015;13:61.CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244:254–9.CrossRefPubMedPubMedCentral Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier AM. Epidemiology and management of liver metastases from colorectal cancer. Ann Surg. 2006;244:254–9.CrossRefPubMedPubMedCentral
6.
Zurück zum Zitat Adam R, Delvart V, Pascal G, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240:644–57.CrossRefPubMedPubMedCentral Adam R, Delvart V, Pascal G, et al. Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival. Ann Surg. 2004;240:644–57.CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230:309–18.CrossRefPubMedPubMedCentral Fong Y, Fortner J, Sun RL, Brennan MF, Blumgart LH. Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases. Ann Surg. 1999;230:309–18.CrossRefPubMedPubMedCentral
8.
Zurück zum Zitat Minagawa M, Makuuchi M, Torzilli G, et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg. 2000;231:487–99.CrossRefPubMedPubMedCentral Minagawa M, Makuuchi M, Torzilli G, et al. Extension of the frontiers of surgical indications in the treatment of liver metastases from colorectal cancer: long-term results. Ann Surg. 2000;231:487–99.CrossRefPubMedPubMedCentral
9.
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;241:715–22.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;241:715–22.CrossRefPubMedPubMedCentral
10.
Zurück zum Zitat Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg. 1995;19:59–71.CrossRefPubMed Scheele J, Stang R, Altendorf-Hofmann A, Paul M. Resection of colorectal liver metastases. World J Surg. 1995;19:59–71.CrossRefPubMed
11.
Zurück zum Zitat Nordlinger B, Van Cutsem E, Rougier P, et al. Does chemotherapy prior to liver resection increase the potential for cure in patients with metastatic colorectal cancer? A report from the European Colorectal Metastases Treatment Group. Eur J Cancer. 2007;43:2037–45.CrossRefPubMed Nordlinger B, Van Cutsem E, Rougier P, et al. Does chemotherapy prior to liver resection increase the potential for cure in patients with metastatic colorectal cancer? A report from the European Colorectal Metastases Treatment Group. Eur J Cancer. 2007;43:2037–45.CrossRefPubMed
12.
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
13.
Zurück zum Zitat Mise Y, Aloia TA, Brudvik KW, Schwarz L, Vauthey JN, Conrad C. Parenchymal-sparing hepatectomy in colorectal liver metastasis improves salvageability and survival. Ann Surg. 2016;263:146–52.CrossRefPubMed Mise Y, Aloia TA, Brudvik KW, Schwarz L, Vauthey JN, Conrad C. Parenchymal-sparing hepatectomy in colorectal liver metastasis improves salvageability and survival. Ann Surg. 2016;263:146–52.CrossRefPubMed
14.
Zurück zum Zitat Schnitzbauer AA, Lang SA, Goessmann H, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012;255:405–14.CrossRefPubMed Schnitzbauer AA, Lang SA, Goessmann H, et al. Right portal vein ligation combined with in situ splitting induces rapid left lateral liver lobe hypertrophy enabling 2-staged extended right hepatic resection in small-for-size settings. Ann Surg. 2012;255:405–14.CrossRefPubMed
15.
Zurück zum Zitat Gold JS, Are C, Kornprat P, et al. Increased use of parenchymal-sparing surgery for bilateral liver metastases from colorectal cancer is associated with improved mortality without change in oncologic outcome: trends in treatment over time in 440 patients. Ann Surg. 2008;247:109–17.CrossRefPubMed Gold JS, Are C, Kornprat P, et al. Increased use of parenchymal-sparing surgery for bilateral liver metastases from colorectal cancer is associated with improved mortality without change in oncologic outcome: trends in treatment over time in 440 patients. Ann Surg. 2008;247:109–17.CrossRefPubMed
16.
Zurück zum Zitat Cady B, Jenkins RL, Steele GD Jr, et al. Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome. Ann Surg. 1998;227:566–71.CrossRefPubMedPubMedCentral Cady B, Jenkins RL, Steele GD Jr, et al. Surgical margin in hepatic resection for colorectal metastasis: a critical and improvable determinant of outcome. Ann Surg. 1998;227:566–71.CrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Ekberg H, Tranberg KG, Andersson R, et al. Determinants of survival in liver resection for colorectal secondaries. Br J Surg. 1986;73:727–31.CrossRefPubMed Ekberg H, Tranberg KG, Andersson R, et al. Determinants of survival in liver resection for colorectal secondaries. Br J Surg. 1986;73:727–31.CrossRefPubMed
18.
Zurück zum Zitat de Haas RJ, Wicherts DA, Flores E, Azoulay D, Castaing D, Adam R. R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg. 2008;248:626–37.PubMed de Haas RJ, Wicherts DA, Flores E, Azoulay D, Castaing D, Adam R. R1 resection by necessity for colorectal liver metastases: is it still a contraindication to surgery? Ann Surg. 2008;248:626–37.PubMed
19.
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;262:476–85.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;262:476–85.CrossRefPubMedPubMedCentral
20.
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;257:1079–88.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;257:1079–88.CrossRefPubMedPubMedCentral
21.
Zurück zum Zitat Margonis GA, Spolverato G, Kim Y, Karagkounis G, Choti MA, Pawlik TM. Effect of KRAS mutation on long-term outcomes of patients undergoing hepatic resection for colorectal liver metastases. Ann Surg Oncol. 2015;22:4158–65.CrossRefPubMed Margonis GA, Spolverato G, Kim Y, Karagkounis G, Choti MA, Pawlik TM. Effect of KRAS mutation on long-term outcomes of patients undergoing hepatic resection for colorectal liver metastases. Ann Surg Oncol. 2015;22:4158–65.CrossRefPubMed
22.
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;150:722–9.CrossRefPubMedPubMedCentral Margonis GA, Kim Y, Spolverato G, et al. Association between specific mutations in KRAS codon 12 and colorectal liver metastasis. JAMA Surg. 2015;150:722–9.CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Elias D, Lasser P, Rougier P, Debaene B. Another failure in the attempt of definition of the indications to the resection of liver metastases of colorectal origin. J Chir (Paris). 1992;129:59–65.PubMed Elias D, Lasser P, Rougier P, Debaene B. Another failure in the attempt of definition of the indications to the resection of liver metastases of colorectal origin. J Chir (Paris). 1992;129:59–65.PubMed
24.
Zurück zum Zitat Cucchetti A, Ercolani G, Cescon M, et al. Impact of subcentimeter margin on outcome after hepatic resection for colorectal metastases: a meta-regression approach. Surgery. 2012;151:691–9.CrossRefPubMed Cucchetti A, Ercolani G, Cescon M, et al. Impact of subcentimeter margin on outcome after hepatic resection for colorectal metastases: a meta-regression approach. Surgery. 2012;151:691–9.CrossRefPubMed
25.
Zurück zum Zitat Cejas P, Lopez-Gomez M, Aguayo C, et al. KRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasis. PLoS One. 2009;4:e8199.CrossRefPubMedPubMedCentral Cejas P, Lopez-Gomez M, Aguayo C, et al. KRAS mutations in primary colorectal cancer tumors and related metastases: a potential role in prediction of lung metastasis. PLoS One. 2009;4:e8199.CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Cully M, Downward J. SnapShot: Ras signaling. Cell. 2008;133:1292–1292.e1. Cully M, Downward J. SnapShot: Ras signaling. Cell. 2008;133:1292–1292.e1.
27.
Zurück zum Zitat Brudvik KW, Mise Y, Chung MH, et al. RAS mutation predicts positive resection margins and narrower resection margins in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol. 2016;23:2635–43.CrossRefPubMed Brudvik KW, Mise Y, Chung MH, et al. RAS mutation predicts positive resection margins and narrower resection margins in patients undergoing resection of colorectal liver metastases. Ann Surg Oncol. 2016;23:2635–43.CrossRefPubMed
28.
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;137:833–40.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;137:833–40.CrossRefPubMed
29.
Zurück zum Zitat Holdhoff M, Schmidt K, Diehl F, et al. Detection of tumor DNA at the margins of colorectal cancer liver metastasis. Clin Cancer Res. 2011;17:3551–7.CrossRefPubMedPubMedCentral Holdhoff M, Schmidt K, Diehl F, et al. Detection of tumor DNA at the margins of colorectal cancer liver metastasis. Clin Cancer Res. 2011;17:3551–7.CrossRefPubMedPubMedCentral
30.
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;17:176–84.CrossRefPubMed 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;17:176–84.CrossRefPubMed
31.
Zurück zum Zitat Wakai T, Shirai Y, Sakata J, et al. Appraisal of 1 cm hepatectomy margins for intrahepatic micrometastases in patients with colorectal carcinoma liver metastasis. Ann Surg Oncol. 2008;15:2472–81.CrossRefPubMed Wakai T, Shirai Y, Sakata J, et al. Appraisal of 1 cm hepatectomy margins for intrahepatic micrometastases in patients with colorectal carcinoma liver metastasis. Ann Surg Oncol. 2008;15:2472–81.CrossRefPubMed
32.
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;13:1270–5.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;13:1270–5.CrossRefPubMed
33.
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;104:1020–6.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;104:1020–6.CrossRefPubMedPubMedCentral
34.
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;17:1429–34.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;17:1429–34.CrossRefPubMed
35.
Zurück zum Zitat Margonis GA, Spolverato G, Kim Y, Ejaz A, Pawlik TM. 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, Ejaz A, Pawlik TM. Intraoperative surgical margin re-resection for colorectal liver metastasis: is it worth the effort? J Gastrointest Surg. 2015;19:699–707.CrossRefPubMed
36.
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;143:384–93.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;143:384–93.CrossRefPubMed
Metadaten
Titel
KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases
verfasst von
Georgios A. Margonis, MD, PhD
Kazunari Sasaki, MD
Nikolaos Andreatos, MD
Yuhree Kim, MD, MPH
Katiuscha Merath, MD
Doris Wagner, MD
Ana Wilson, MD
Stefan Buettner, MD
Neda Amini, MD
Efstathios Antoniou, MD, PhD
Timothy M. Pawlik, MD, MPH, PhD, FACS
Publikationsdatum
30.09.2016
Verlag
Springer International Publishing
Erschienen in
Annals of Surgical Oncology / Ausgabe 1/2017
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-016-5609-1

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