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Published in: Annals of Surgical Oncology 9/2020

01-09-2020 | Metastasis | Hepatobiliary Tumors

Survival Outcomes of Resected BRAF V600E Mutant Colorectal Liver Metastases: A Multicenter Retrospective Cohort Study in Japan

Authors: Shin Kobayashi, MD, PhD, Shinichiro Takahashi, MD, PhD, Naoki Takahashi, MD, PhD, Toshiki Masuishi, MD, PhD, Hirokazu Shoji, MD, PhD, Eiji Shinozaki, MD, PhD, Tatsuro Yamaguchi, MD, PhD, Motohiro Kojima, MD, PhD, Naoto Gotohda, MD, PhD, Shogo Nomura, MD, PhD, Takayuki Yoshino, MD, PhD, Hiroya Taniguchi, MD, PhD

Published in: Annals of Surgical Oncology | Issue 9/2020

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Abstract

Background

Although the prognosis for patients with resected BRAF mutant colorectal liver metastases (CRLM) is poor, the survival impact of the BRAF V600E mutation in such cases remains unclear.

Methods

A multicenter retrospective cohort study was performed to investigate the survival outcomes of patients who underwent initial hepatectomy for histologically confirmed BRAF V600E mutant CRLM between January 2005 and December 2017.

Results

Thirty-three patients from 6 institutions were included in this study. During the median duration of the post-hepatectomy follow-up period of 49.2 months, 31 patients (93.9%) developed recurrence after a median period of 5.3 months and the 1-year recurrence-free survival (RFS) rate was 24.2%. Only two patients underwent repeated surgery for recurrence. The other 29 patients had unresectable recurrent lesions, and 27 of them received systemic chemotherapy. The median overall survival (OS) period was 31.1 months and the 5-year OS rate was 18.2%. The factors for a poor RFS prognosis were an elevated serum CA19-9 level (≥ 37 IU/ml) at hepatectomy (HR: 2.139, 95% CI: 1.009–4.534, P = 0.047) and R1 resection (HR: 5.827, 95% CI: 1.585–21.42, P = 0.008), and that for OS was R1 resection only (HR: 4.129, 95% CI: 1.104–15.45, P = 0.035).

Conclusions

Since the early onset unresectable recurrence rate was very high, systemic chemotherapy should be considered for resectable BRAF V600E mutant CRLM. A novel perioperative treatment strategy is needed to improve the survival of such patients.
Literature
1.
go back to reference Weitz J, Koch M, Debus J, Höhler T, Galle PR, Büchler MW. Colorectal cancer. The Lancet. 2005; 365(9454): 153–165.CrossRef Weitz J, Koch M, Debus J, Höhler T, Galle PR, Büchler MW. Colorectal cancer. The Lancet. 2005; 365(9454): 153–165.CrossRef
2.
go back to reference Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A.: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018; 68(6): 394–424.CrossRef Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A.: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin. 2018; 68(6): 394–424.CrossRef
3.
go back to reference Leporrier J, Maurel J, Chiche L, Bara S, Segol P, Launoy G. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br. J. Surg. 2006;93(4):465–474.CrossRef Leporrier J, Maurel J, Chiche L, Bara S, Segol P, Launoy G. A population-based study of the incidence, management and prognosis of hepatic metastases from colorectal cancer. Br. J. Surg. 2006;93(4):465–474.CrossRef
4.
go back to reference Weiss L, Grundmann E, Torhorst J, et al. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J. Pathol. 1986;150(3):195–203.CrossRef Weiss L, Grundmann E, Torhorst J, et al. Haematogenous metastatic patterns in colonic carcinoma: an analysis of 1541 necropsies. J. Pathol. 1986;150(3):195–203.CrossRef
5.
go back to reference Sadahiro S, Suzuki T, Ishikawa K, et al. Recurrence patterns after curative resection of colorectal cancer in patients followed for a minimum of ten years. Hepatogastroenterology. 2003;50(53):1362–1366.PubMed Sadahiro S, Suzuki T, Ishikawa K, et al. Recurrence patterns after curative resection of colorectal cancer in patients followed for a minimum of ten years. Hepatogastroenterology. 2003;50(53):1362–1366.PubMed
6.
go back to reference 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(8): 1386–1422.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(8): 1386–1422.CrossRef
8.
go back to reference Sakamoto K, Honda G, Beppu T, et al. Comprehensive data of 3,820 patients newly diagnosed with colorectal liver metastasis between 2005 and 2007: report of a nationwide survey in Japan. J. Hepatobiliary Pancreat. Sci. 2018; 25(2): 115–123.CrossRef Sakamoto K, Honda G, Beppu T, et al. Comprehensive data of 3,820 patients newly diagnosed with colorectal liver metastasis between 2005 and 2007: report of a nationwide survey in Japan. J. Hepatobiliary Pancreat. Sci. 2018; 25(2): 115–123.CrossRef
9.
go back to reference Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. The Lancet. 2008;371(9617):1007–1016.CrossRef Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. The Lancet. 2008;371(9617):1007–1016.CrossRef
10.
go back to reference Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. The Lancet Oncology. 2013;14(12):1208–1215.CrossRef Nordlinger B, Sorbye H, Glimelius B, et al. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. The Lancet Oncology. 2013;14(12):1208–1215.CrossRef
11.
go back to reference Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N. Engl. J. Med. 24 2019;381(17):1632–1643.CrossRef Kopetz S, Grothey A, Yaeger R, et al. Encorafenib, Binimetinib, and Cetuximab in BRAF V600E-Mutated Colorectal Cancer. N. Engl. J. Med. 24 2019;381(17):1632–1643.CrossRef
13.
go back to reference 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(12):1921–1928.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(12):1921–1928.CrossRef
14.
go back to reference 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
15.
go back to reference Margonis GA, Buettner S, Andreatos N, et al. Association of BRAF Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer. JAMA Surg. 18 2018;153(7):e180996. Margonis GA, Buettner S, Andreatos N, et al. Association of BRAF Mutations With Survival and Recurrence in Surgically Treated Patients With Metastatic Colorectal Liver Cancer. JAMA Surg. 18 2018;153(7):e180996.
16.
go back to reference Bachet JB, Moreno-Lopez N, Vigano L, et al. BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases. Br J Surg 2019;106(9):1237–1247.CrossRef Bachet JB, Moreno-Lopez N, Vigano L, et al. BRAF mutation is not associated with an increased risk of recurrence in patients undergoing resection of colorectal liver metastases. Br J Surg 2019;106(9):1237–1247.CrossRef
17.
go back to reference Gagniere J, Dupre A, Gholami SS, et al. Is Hepatectomy Justified for BRAF Mutant Colorectal Liver Metastases?: A Multi-institutional Analysis of 1497 Patients. Ann Surg 2020;271(1):147–154.CrossRef Gagniere J, Dupre A, Gholami SS, et al. Is Hepatectomy Justified for BRAF Mutant Colorectal Liver Metastases?: A Multi-institutional Analysis of 1497 Patients. Ann Surg 2020;271(1):147–154.CrossRef
18.
go back to reference Jones JC, Renfro LA, Al-Shamsi HO, et al. (Non-V600) BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer. J Clin Onco. 10 2017;35(23):2624–2630.CrossRef Jones JC, Renfro LA, Al-Shamsi HO, et al. (Non-V600) BRAF mutations define a clinically distinct molecular subtype of metastatic colorectal cancer. J Clin Onco. 10 2017;35(23):2624–2630.CrossRef
19.
go back to reference Cremolini C, Di Bartolomeo M, Amatu A, et al. BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann Oncol 2015;26(10):2092–2097.CrossRef Cremolini C, Di Bartolomeo M, Amatu A, et al. BRAF codons 594 and 596 mutations identify a new molecular subtype of metastatic colorectal cancer at favorable prognosis. Ann Oncol 2015;26(10):2092–2097.CrossRef
20.
go back to reference JSCCR Guidelines 2016 for the Treatment of Colorectal Cancer. Tokyo: Kanehara publishing Co.Ltd; 2016 JSCCR Guidelines 2016 for the Treatment of Colorectal Cancer. Tokyo: Kanehara publishing Co.Ltd; 2016
21.
go back to reference Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment 4th edition. Tokyo: Kanehara Publishing Co.Ltd; 2019. Japanese Society of Medical Oncology Clinical Guidelines: Molecular Testing for Colorectal Cancer Treatment 4th edition. Tokyo: Kanehara Publishing Co.Ltd; 2019.
22.
go back to reference Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013; 48(3): 452–458.CrossRef Kanda Y. Investigation of the freely available easy-to-use software ‘EZR’ for medical statistics. Bone Marrow Transplant. 2013; 48(3): 452–458.CrossRef
23.
go back to reference Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015;16(13):1306–1315.CrossRef Cremolini C, Loupakis F, Antoniotti C, et al. FOLFOXIRI plus bevacizumab versus FOLFIRI plus bevacizumab as first-line treatment of patients with metastatic colorectal cancer: updated overall survival and molecular subgroup analyses of the open-label, phase 3 TRIBE study. Lancet Oncol. 2015;16(13):1306–1315.CrossRef
24.
go back to reference de la Fouchardiere C, Cohen R, Malka D, et al. Characteristics of BRAF (V600E) Mutant, Deficient Mismatch Repair/Proficient Mismatch Repair, Metastatic Colorectal Cancer: A Multicenter Series of 287 Patients. Oncologist. 2019;24(12):e1331–e1340.CrossRef de la Fouchardiere C, Cohen R, Malka D, et al. Characteristics of BRAF (V600E) Mutant, Deficient Mismatch Repair/Proficient Mismatch Repair, Metastatic Colorectal Cancer: A Multicenter Series of 287 Patients. Oncologist. 2019;24(12):e1331–e1340.CrossRef
25.
go back to reference Thomsen M, Skovlund E, Sorbye H, et al. Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome. Br. J. Cancer. 2018;118(12):1609–1616.CrossRef Thomsen M, Skovlund E, Sorbye H, et al. Prognostic role of carcinoembryonic antigen and carbohydrate antigen 19-9 in metastatic colorectal cancer: a BRAF-mutant subset with high CA 19-9 level and poor outcome. Br. J. Cancer. 2018;118(12):1609–1616.CrossRef
26.
go back to reference Loupakis F, Intini R, Cremolini C, et al. A validated prognostic classifier for (V600E)BRAF-mutated metastatic colorectal cancer: the ‘BRAF BeCool’ study. Eur. Cance. 2019; 118: 121–130.CrossRef Loupakis F, Intini R, Cremolini C, et al. A validated prognostic classifier for (V600E)BRAF-mutated metastatic colorectal cancer: the ‘BRAF BeCool’ study. Eur. Cance. 2019; 118: 121–130.CrossRef
Metadata
Title
Survival Outcomes of Resected BRAF V600E Mutant Colorectal Liver Metastases: A Multicenter Retrospective Cohort Study in Japan
Authors
Shin Kobayashi, MD, PhD
Shinichiro Takahashi, MD, PhD
Naoki Takahashi, MD, PhD
Toshiki Masuishi, MD, PhD
Hirokazu Shoji, MD, PhD
Eiji Shinozaki, MD, PhD
Tatsuro Yamaguchi, MD, PhD
Motohiro Kojima, MD, PhD
Naoto Gotohda, MD, PhD
Shogo Nomura, MD, PhD
Takayuki Yoshino, MD, PhD
Hiroya Taniguchi, MD, PhD
Publication date
01-09-2020
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 9/2020
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-020-08817-8

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