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01.12.2021 | Hepatobiliary Tumors

Limited Prognostic Value of KRAS in Patients Undergoing Hepatectomy for Colorectal Liver Metastases

verfasst von: Yoshinori Takeda, MD, PhD, Yoshihiro Mise, MD, PhD, Yu Takahashi, MD, PhD, Hiromichi Ito, MD, FACS, Yosuke Inoue, MD, PhD, Ryuji Yoshioka, MD, PhD, Yoshihiro Ono, MD, PhD, Akio Saiura, MD, PhD

Erschienen in: Annals of Surgical Oncology | Ausgabe 4/2022

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Abstract

Background

RAS mutation status is considered a powerful prognostic factor in patients undergoing hepatectomy for colorectal liver metastases (CLM). However, whether its prognostic power is robust regardless of administration of preoperative chemotherapy or tumor burden remains unclear.

Methods

Consecutive patients who underwent initial hepatectomy for CLM from April 2010 through March 2017 in two hospitals were included. The prognostic value of KRAS was compared based on whether patients received preoperative chemotherapy and their tumor burden score (TBS).

Results

We included 409 patients (median follow-up 38 months). In the preoperative chemotherapy group, patients with mutant KRAS (mt-KRAS) CLM had poorer overall survival (OS) than those with wild KRAS (wt-KRAS; 5-year OS: 37.7% vs 53.8%, p = 0.024), although their OS was not different from patients undergoing upfront surgery. Similarly, patients with mt-KRAS had poorer OS than those with wt-KRAS in TBS of 3–9 (5-year OS: 33.1% vs 63.2%, p = 0.001), although their OS was not different from patients with TBS < 3 or ≥ 9. In multivariate analysis, mt-KRAS was an independent prognostic factor of OS among patients receiving preoperative chemotherapy (hazard ratio [HR] 1.61, 95% confidence interval [CI]: 1.034–2.491; p = 0.035) and patients with TBS of 3–9 (HR 1.836, 95% CI 1.176–2.866; p = 0.008). However, it was not a prognostic factor in patients who underwent upfront surgery or with TBS > 3 or ≥ 9.

Conclusions

In patients undergoing hepatectomy for CLM, the prognostic value of KRAS depends on their history of preoperative chemotherapy or tumor burden.
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Literatur
1.
Zurück zum Zitat Brudvik KW, Jones RP, Giuliante F, et al. RAS mutation clinical risk score to predict survival after resection of colorectal liver metastases. Ann Surg. 2019;269:120–6.CrossRef Brudvik KW, Jones RP, Giuliante F, et al. RAS mutation clinical risk score to predict survival after resection of colorectal liver metastases. Ann Surg. 2019;269:120–6.CrossRef
2.
Zurück zum Zitat Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–422.CrossRef Van Cutsem E, Cervantes A, Adam R, et al. ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol. 2016;27:1386–422.CrossRef
3.
Zurück zum Zitat Zimmitti G, Shindoh J, Mise Y, et al. RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases. Ann Surg Oncol. 2015;22:834–42.CrossRef Zimmitti G, Shindoh J, Mise Y, et al. RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases. Ann Surg Oncol. 2015;22:834–42.CrossRef
4.
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;258:619–26 ((discussion 626-617)).CrossRef 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;258:619–26 ((discussion 626-617)).CrossRef
5.
Zurück zum Zitat Yamashita S, Chun YS, Kopetz SE, Vauthey JN. Biomarkers in colorectal liver metastases. Br J Surg. 2018;105:618–27.CrossRef Yamashita S, Chun YS, Kopetz SE, Vauthey JN. Biomarkers in colorectal liver metastases. Br J Surg. 2018;105:618–27.CrossRef
6.
Zurück zum Zitat Soreide K, Sandvik OM, Soreide JA. KRAS mutation in patients undergoing hepatic resection for colorectal liver metastasis: a biomarker of cancer biology or a byproduct of patient selection? Cancer. 2014;120:3862–5.CrossRef Soreide K, Sandvik OM, Soreide JA. KRAS mutation in patients undergoing hepatic resection for colorectal liver metastasis: a biomarker of cancer biology or a byproduct of patient selection? Cancer. 2014;120:3862–5.CrossRef
7.
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.CrossRef 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.CrossRef
8.
Zurück zum Zitat Sasaki K, Morioka D, Conci S, et al. The tumor burden score: a new, “metro-ticket” prognostic tool for colorectal liver metastases based on tumor size and number of tumors. Ann Surg. 2018;267:132–41.CrossRef Sasaki K, Morioka D, Conci S, et al. The tumor burden score: a new, “metro-ticket” prognostic tool for colorectal liver metastases based on tumor size and number of tumors. Ann Surg. 2018;267:132–41.CrossRef
9.
Zurück zum Zitat Matsumura M, Mise Y, Saiura A, et al. Parenchymal-sparing hepatectomy does not increase intrahepatic recurrence in patients with advanced colorectal liver metastases. Ann Surg Oncol. 2016;23:3718–26.CrossRef Matsumura M, Mise Y, Saiura A, et al. Parenchymal-sparing hepatectomy does not increase intrahepatic recurrence in patients with advanced colorectal liver metastases. Ann Surg Oncol. 2016;23:3718–26.CrossRef
10.
Zurück zum Zitat Imai K, Allard MA, Castro Benitez C, et al. Nomogram for prediction of prognosis in patients with initially unresectable colorectal liver metastases. Br J Surg. 2016;103:590–9.CrossRef Imai K, Allard MA, Castro Benitez C, et al. Nomogram for prediction of prognosis in patients with initially unresectable colorectal liver metastases. Br J Surg. 2016;103:590–9.CrossRef
11.
Zurück zum Zitat Passot G, Kim BJ, Glehen O, et al. Impact of RAS mutations in metastatic colorectal cancer after potentially curative resection: does site of metastases matter? Ann Surg Oncol. 2018;25:179–87.CrossRef Passot G, Kim BJ, Glehen O, et al. Impact of RAS mutations in metastatic colorectal cancer after potentially curative resection: does site of metastases matter? Ann Surg Oncol. 2018;25:179–87.CrossRef
12.
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.CrossRef 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.CrossRef
13.
Zurück zum Zitat Karagkounis G, Torbenson MS, Daniel HD, et al. Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer. 2013;119:4137–44.CrossRef Karagkounis G, Torbenson MS, Daniel HD, et al. Incidence and prognostic impact of KRAS and BRAF mutation in patients undergoing liver surgery for colorectal metastases. Cancer. 2013;119:4137–44.CrossRef
14.
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;112:1921–8.CrossRef 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;112:1921–8.CrossRef
15.
Zurück zum Zitat Shindoh J, Nishioka Y, Yoshioka R, et al. KRAS mutation status predicts site-specific recurrence and survival after resection of colorectal liver metastases irrespective of location of the primary lesion. Ann Surg Oncol. 2016;23:1890–6.CrossRef Shindoh J, Nishioka Y, Yoshioka R, et al. KRAS mutation status predicts site-specific recurrence and survival after resection of colorectal liver metastases irrespective of location of the primary lesion. Ann Surg Oncol. 2016;23:1890–6.CrossRef
16.
Zurück zum Zitat Umeda Y, Nagasaka T, Mori Y, et al. Poor prognosis of KRAS or BRAF mutant colorectal liver metastasis without microsatellite instability. J Hepatobiliary Pancreat Sci. 2013;20:223–33.CrossRef Umeda Y, Nagasaka T, Mori Y, et al. Poor prognosis of KRAS or BRAF mutant colorectal liver metastasis without microsatellite instability. J Hepatobiliary Pancreat Sci. 2013;20:223–33.CrossRef
17.
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.CrossRef 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.CrossRef
18.
Zurück zum Zitat Lin Q, Ye Q, Zhu D, et al. Determinants of long-term outcome in patients undergoing simultaneous resection of synchronous colorectal liver metastases. PLoS ONE. 2014;9:e105747.CrossRef Lin Q, Ye Q, Zhu D, et al. Determinants of long-term outcome in patients undergoing simultaneous resection of synchronous colorectal liver metastases. PLoS ONE. 2014;9:e105747.CrossRef
19.
Zurück zum Zitat Teng HW, Huang YC, Lin JK, et al. BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy. J Surg Oncol. 2012;106:123–9.CrossRef Teng HW, Huang YC, Lin JK, et al. BRAF mutation is a prognostic biomarker for colorectal liver metastasectomy. J Surg Oncol. 2012;106:123–9.CrossRef
20.
Zurück zum Zitat Kemeny NE, Chou JF, Capanu M, et al. KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases. Cancer. 2014;120:3965–71.CrossRef Kemeny NE, Chou JF, Capanu M, et al. KRAS mutation influences recurrence patterns in patients undergoing hepatic resection of colorectal metastases. Cancer. 2014;120:3965–71.CrossRef
21.
Zurück zum Zitat Rose JS, Serna DS, Martin LK, et al. Influence of KRAS mutation status in metachronous and synchronous metastatic colorectal adenocarcinoma. Cancer. 2012;118:6243–52.CrossRef Rose JS, Serna DS, Martin LK, et al. Influence of KRAS mutation status in metachronous and synchronous metastatic colorectal adenocarcinoma. Cancer. 2012;118:6243–52.CrossRef
22.
Zurück zum Zitat Russo A, Migliavacca M, Bazan V, et al. Prognostic significance of proliferative activity, DNA-ploidy, p53 and Ki-ras point mutations in colorectal liver metastases. Cell Prolif. 1998;31:139–53.CrossRef Russo A, Migliavacca M, Bazan V, et al. Prognostic significance of proliferative activity, DNA-ploidy, p53 and Ki-ras point mutations in colorectal liver metastases. Cell Prolif. 1998;31:139–53.CrossRef
23.
Zurück zum Zitat Margonis GA, Kim Y, Sasaki K, et al. Activating KRAS mutation is prognostic only among patients who receive preoperative chemotherapy before resection of colorectal liver metastases. J Surg Oncol. 2016;114:361–7.CrossRef Margonis GA, Kim Y, Sasaki K, et al. Activating KRAS mutation is prognostic only among patients who receive preoperative chemotherapy before resection of colorectal liver metastases. J Surg Oncol. 2016;114:361–7.CrossRef
24.
Zurück zum Zitat Adam R, Bhangui P, Poston G, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252:774–87.CrossRef Adam R, Bhangui P, Poston G, et al. Is perioperative chemotherapy useful for solitary, metachronous, colorectal liver metastases? Ann Surg. 2010;252:774–87.CrossRef
25.
Zurück zum Zitat Okuno M, Goumard C, Kopetz S, et al. RAS mutation is associated with unsalvageable recurrence following hepatectomy for colorectal cancer liver metastases. Ann Surg Oncol. 2018;25:2457–66.CrossRef Okuno M, Goumard C, Kopetz S, et al. RAS mutation is associated with unsalvageable recurrence following hepatectomy for colorectal cancer liver metastases. Ann Surg Oncol. 2018;25:2457–66.CrossRef
26.
Zurück zum Zitat Cremolini C, Casagrande M, Loupakis F, et al. Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: a pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest. Eur J Cancer. 2017;73:74–84.CrossRef Cremolini C, Casagrande M, Loupakis F, et al. Efficacy of FOLFOXIRI plus bevacizumab in liver-limited metastatic colorectal cancer: a pooled analysis of clinical studies by Gruppo Oncologico del Nord Ovest. Eur J Cancer. 2017;73:74–84.CrossRef
27.
Zurück zum Zitat Margonis GA, Sasaki K, Gholami S, et al. Genetic and morphological evaluation (GAME) score for patients with colorectal liver metastases. Br J Surg. 2018;105:1210–20.CrossRef Margonis GA, Sasaki K, Gholami S, et al. Genetic and morphological evaluation (GAME) score for patients with colorectal liver metastases. Br J Surg. 2018;105:1210–20.CrossRef
28.
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 (discussion 318–321).CrossRef 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 (discussion 318–321).CrossRef
29.
Zurück zum Zitat De Roock W, Claes B, Bernasconi D, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11:753–62.CrossRef De Roock W, Claes B, Bernasconi D, et al. Effects of KRAS, BRAF, NRAS, and PIK3CA mutations on the efficacy of cetuximab plus chemotherapy in chemotherapy-refractory metastatic colorectal cancer: a retrospective consortium analysis. Lancet Oncol. 2010;11:753–62.CrossRef
Metadaten
Titel
Limited Prognostic Value of KRAS in Patients Undergoing Hepatectomy for Colorectal Liver Metastases
verfasst von
Yoshinori Takeda, MD, PhD
Yoshihiro Mise, MD, PhD
Yu Takahashi, MD, PhD
Hiromichi Ito, MD, FACS
Yosuke Inoue, MD, PhD
Ryuji Yoshioka, MD, PhD
Yoshihiro Ono, MD, PhD
Akio Saiura, MD, PhD
Publikationsdatum
01.12.2021
Verlag
Springer International Publishing
Erschienen in
Annals of Surgical Oncology / Ausgabe 4/2022
Print ISSN: 1068-9265
Elektronische ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-021-11015-9

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