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Published in: BMC Surgery 1/2020

Open Access 01-12-2020 | Metastasis | Research article

Tumor response and outcome after reverse treatment for patients with synchronous colorectal liver metastasis: a cohort study

Authors: Céline Du Pasquier, Didier Roulin, Pierre Bize, Christine Sempoux, Caterina Rebecchini, Michael Montemurro, Markus Schäfer, Nermin Halkic, Nicolas Demartines

Published in: BMC Surgery | Issue 1/2020

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Abstract

Background

The reverse treatment of patients with synchronous colorectal liver metastases (CRLM) is a sequential approach with systemic chemotherapy first, followed by liver resection, and finally, primary tumor resection. The aim of this study was to assess the feasibility, the radiological and pathological tumor response to neoadjuvant therapy, recurrence rates and long-term survival after reverse treatment in a cohort study.

Methods

Data from patients with CRLM who underwent a reverse treatment from August 2008 to October 2016 were extracted from our prospective hepato-biliary database and retrospectively analyzed for response rates and survival outcomes. Radiological tumor response was assessed by RECIST (Response Evaluation Criteria In Solid Tumor) criteria and pathological response according to TRG (Tumor Regression Grade). Disease-free and overall survival were estimated with Kaplan-Meier survival curves.

Results

There were 44 patients with 19 rectal and 25 colonic tumors. The reverse treatment was fully completed until primary tumor resection in 41 patients (93%). Radiological assessment after chemotherapy showed 61% of complete/partial response. Pathological tumor response was major or partial in 52% of patients (TRG 1–3). Median disease-free survival after primary tumor resection was 10 months (95% CI 5–15 months). Disease-free survival at 3 and 5 years was 25% and 25%, respectively. Median overall survival was 50 months (95% CI 42–58 months). Overall survival at 3 and 5 years was 59% and 39%, respectively.

Conclusion

The reverse treatment approach was feasible with a high rate of patients with complete treatment sequence and offers promising long-term survival for selected patients with advanced simultaneous colorectal liver metastases.
Literature
1.
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):465–74.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):465–74.CrossRef
2.
go back to reference Pawlik TM, Schulick RD, Choti MA. Expanding criteria for Resectability of colorectal liver metastases. Oncologist. 2008;13(1):51–64.CrossRef Pawlik TM, Schulick RD, Choti MA. Expanding criteria for Resectability of colorectal liver metastases. Oncologist. 2008;13(1):51–64.CrossRef
3.
go back to reference Klinger M, Tamandl D, Eipeldauer S, Hacker S, Herberger B, Kaczirek K, et al. Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX. Ann Surg Oncol. 2010;17(8):2059–65.CrossRef Klinger M, Tamandl D, Eipeldauer S, Hacker S, Herberger B, Kaczirek K, et al. Bevacizumab improves pathological response of colorectal cancer liver metastases treated with XELOX/FOLFOX. Ann Surg Oncol. 2010;17(8):2059–65.CrossRef
4.
go back to reference Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, 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. Lancet. 2008;371(9617):1007–16.CrossRef Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, 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. Lancet. 2008;371(9617):1007–16.CrossRef
5.
go back to reference Suenaga M, Fujimoto Y, Matsusaka S, Shinozaki E, Akiyoshi T, Nagayama S, et al. Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01). OncoTargets Ther. 2015;8:1111–8.CrossRef Suenaga M, Fujimoto Y, Matsusaka S, Shinozaki E, Akiyoshi T, Nagayama S, et al. Perioperative FOLFOX4 plus bevacizumab for initially unresectable advanced colorectal cancer (NAVIGATE-CRC-01). OncoTargets Ther. 2015;8:1111–8.CrossRef
6.
go back to reference Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609–18.CrossRef Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, et al. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014;371(17):1609–18.CrossRef
7.
go back to reference Tabernero J, Van Cutsem E, Díaz-Rubio E, Cervantes A, Humblet Y, André T, et al. Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the first-line treatment of metastatic colorectal cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(33):5225–32.CrossRef Tabernero J, Van Cutsem E, Díaz-Rubio E, Cervantes A, Humblet Y, André T, et al. Phase II trial of cetuximab in combination with fluorouracil, leucovorin, and oxaliplatin in the first-line treatment of metastatic colorectal cancer. J Clin Oncol Off J Am Soc Clin Oncol. 2007;25(33):5225–32.CrossRef
8.
go back to reference Mentha G, Majno PE, Andres A, Rubbia-Brandt L, Morel P, Roth AD. Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary. Br J Surg. 2006;93(7):872–8.CrossRef Mentha G, Majno PE, Andres A, Rubbia-Brandt L, Morel P, Roth AD. Neoadjuvant chemotherapy and resection of advanced synchronous liver metastases before treatment of the colorectal primary. Br J Surg. 2006;93(7):872–8.CrossRef
9.
go back to reference Kelly ME, Spolverato G, Lê GN, Mavros MN, Doyle F, Pawlik TM, et al. Synchronous colorectal liver metastasis: a network meta-analysis review comparing classical, combined, and liver-first surgical strategies: synchronous colorectal liver metastasis. J Surg Oncol. 2015;111(3):341–51.CrossRef Kelly ME, Spolverato G, Lê GN, Mavros MN, Doyle F, Pawlik TM, et al. Synchronous colorectal liver metastasis: a network meta-analysis review comparing classical, combined, and liver-first surgical strategies: synchronous colorectal liver metastasis. J Surg Oncol. 2015;111(3):341–51.CrossRef
10.
go back to reference Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRef Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45(2):228–47.CrossRef
11.
go back to reference Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRef Dindo D, Demartines N, Clavien P-A. Classification of surgical complications: a new proposal with evaluation in a cohort of 6336 patients and results of a survey. Ann Surg. 2004;240(2):205–13.CrossRef
12.
go back to reference Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien P-A. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013;258(1):1–7.CrossRef Slankamenac K, Graf R, Barkun J, Puhan MA, Clavien P-A. The comprehensive complication index: a novel continuous scale to measure surgical morbidity. Ann Surg. 2013;258(1):1–7.CrossRef
13.
go back to reference Rubbia-Brandt L, Giostra E, Brezault C, Roth AD, Andres A, Audard V, et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol Off J Eur Soc Med Oncol. 2007;18(2):299–304.CrossRef Rubbia-Brandt L, Giostra E, Brezault C, Roth AD, Andres A, Audard V, et al. Importance of histological tumor response assessment in predicting the outcome in patients with colorectal liver metastases treated with neo-adjuvant chemotherapy followed by liver surgery. Ann Oncol Off J Eur Soc Med Oncol. 2007;18(2):299–304.CrossRef
14.
go back to reference Rubbia-Brandt L. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15(3):460–6.CrossRef Rubbia-Brandt L. Severe hepatic sinusoidal obstruction associated with oxaliplatin-based chemotherapy in patients with metastatic colorectal cancer. Ann Oncol. 2004;15(3):460–6.CrossRef
15.
go back to reference Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. the METAVIR cooperative study group. Hepatol Baltim Md. 1996;24(2):289–93.CrossRef Bedossa P, Poynard T. An algorithm for the grading of activity in chronic hepatitis C. the METAVIR cooperative study group. Hepatol Baltim Md. 1996;24(2):289–93.CrossRef
16.
go back to reference Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic Correlations Cancer. 1994;73(11):2680–6.PubMed Mandard AM, Dalibard F, Mandard JC, Marnay J, Henry-Amar M, Petiot JF, et al. Pathologic assessment of tumor regression after preoperative chemoradiotherapy of esophageal carcinoma. Clinicopathologic Correlations Cancer. 1994;73(11):2680–6.PubMed
17.
go back to reference Lam VWT, Laurence JM, Pang T, Johnston E, Hollands MJ, Pleass HCC, et al. A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases. HPB. 2014;16(2):101–8.CrossRef Lam VWT, Laurence JM, Pang T, Johnston E, Hollands MJ, Pleass HCC, et al. A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases. HPB. 2014;16(2):101–8.CrossRef
18.
go back to reference Tanaka K, Murakami T, Matsuo K, Hiroshima Y, Endo I, Ichikawa Y, et al. Preliminary results of “liver-first” reverse management for advanced and aggressive synchronous colorectal liver metastases: a propensity-matched analysis. Dig Surg. 2015;32(1):16–22.CrossRef Tanaka K, Murakami T, Matsuo K, Hiroshima Y, Endo I, Ichikawa Y, et al. Preliminary results of “liver-first” reverse management for advanced and aggressive synchronous colorectal liver metastases: a propensity-matched analysis. Dig Surg. 2015;32(1):16–22.CrossRef
19.
go back to reference Welsh FKS, Chandrakumaran K, John TG, Cresswell AB, Rees M. Propensity score-matched outcomes analysis of the liver-first approach for synchronous colorectal liver metastases. Br J Surg. 2016;103(5):600–6.CrossRef Welsh FKS, Chandrakumaran K, John TG, Cresswell AB, Rees M. Propensity score-matched outcomes analysis of the liver-first approach for synchronous colorectal liver metastases. Br J Surg. 2016;103(5):600–6.CrossRef
20.
go back to reference Sturesson C, Valdimarsson VT, Blomstrand E, Eriksson S, Nilsson JH, Syk I, et al. Liver-first strategy for synchronous colorectal liver metastases - an intention-to-treat analysis. HPB. 2017;19(1):52–8.CrossRef Sturesson C, Valdimarsson VT, Blomstrand E, Eriksson S, Nilsson JH, Syk I, et al. Liver-first strategy for synchronous colorectal liver metastases - an intention-to-treat analysis. HPB. 2017;19(1):52–8.CrossRef
21.
go back to reference Mentha G, Roth AD, Terraz S, Giostra E, Gervaz P, Andres A, et al. “Liver first” approach in the treatment of colorectal cancer with synchronous liver metastases. Dig Surg. 2008;25(6):430–5.CrossRef Mentha G, Roth AD, Terraz S, Giostra E, Gervaz P, Andres A, et al. “Liver first” approach in the treatment of colorectal cancer with synchronous liver metastases. Dig Surg. 2008;25(6):430–5.CrossRef
22.
go back to reference Brouquet A, Mortenson MM, Vauthey J-N, Rodriguez-Bigas MA, Overman MJ, Chang GJ, et al. Surgical strategies for synchronous colorectal liver metastases in 156 consecutive patients: classic, combined or reverse strategy? J Am Coll Surg. 2010;210(6):934–41.CrossRef Brouquet A, Mortenson MM, Vauthey J-N, Rodriguez-Bigas MA, Overman MJ, Chang GJ, et al. Surgical strategies for synchronous colorectal liver metastases in 156 consecutive patients: classic, combined or reverse strategy? J Am Coll Surg. 2010;210(6):934–41.CrossRef
23.
go back to reference de Jong MC, van Dam RM, Maas M, Bemelmans MHA, Olde Damink SWM, Beets GL, et al. The liver-first approach for synchronous colorectal liver metastasis: a 5-year single-Centre experience. HPB. 2011;13(10):745–52.CrossRef de Jong MC, van Dam RM, Maas M, Bemelmans MHA, Olde Damink SWM, Beets GL, et al. The liver-first approach for synchronous colorectal liver metastasis: a 5-year single-Centre experience. HPB. 2011;13(10):745–52.CrossRef
24.
go back to reference de Rosa A, Gomez D, Hossaini S, Duke K, Fenwick SW, Brooks A, et al. Stage IV colorectal cancer: outcomes following the liver-first approach. J Surg Oncol. 2013;108(7):444–9.CrossRef de Rosa A, Gomez D, Hossaini S, Duke K, Fenwick SW, Brooks A, et al. Stage IV colorectal cancer: outcomes following the liver-first approach. J Surg Oncol. 2013;108(7):444–9.CrossRef
25.
go back to reference Mayo SC, Pulitano C, Marques H, Lamelas J, Wolfgang CL, de Saussure W, et al. Surgical management of patients with synchronous colorectal liver metastasis: a multicenter international analysis. J Am Coll Surg. 2013;216(4):707–16 discussion 716–8.CrossRef Mayo SC, Pulitano C, Marques H, Lamelas J, Wolfgang CL, de Saussure W, et al. Surgical management of patients with synchronous colorectal liver metastasis: a multicenter international analysis. J Am Coll Surg. 2013;216(4):707–16 discussion 716–8.CrossRef
26.
go back to reference Okuno M, Hatano E, Kasai Y, Nishio T, Seo S, Taura K, et al. Feasibility of the liver-first approach for patients with initially unresectable and not optimally resectable synchronous colorectal liver metastases. Surg Today. 2016;46(6):721–8.CrossRef Okuno M, Hatano E, Kasai Y, Nishio T, Seo S, Taura K, et al. Feasibility of the liver-first approach for patients with initially unresectable and not optimally resectable synchronous colorectal liver metastases. Surg Today. 2016;46(6):721–8.CrossRef
27.
go back to reference Lim C, Doussot A, Osseis M, Salloum C, Gomez Gavara C, Compagnon P, et al. Primary tumor versus liver-first strategy in patients with stage IVA colorectal Cancer: a propensity score analysis of long-term outcomes and recurrence pattern. Ann Surg Oncol. 2016;23(9):3024–32.CrossRef Lim C, Doussot A, Osseis M, Salloum C, Gomez Gavara C, Compagnon P, et al. Primary tumor versus liver-first strategy in patients with stage IVA colorectal Cancer: a propensity score analysis of long-term outcomes and recurrence pattern. Ann Surg Oncol. 2016;23(9):3024–32.CrossRef
28.
go back to reference Esposito F, Lim C, Sa Cunha A, Pessaux P, Navarro F, Azoulay D, et al. Primary tumor versus liver-first approach for synchronous colorectal liver metastases: an association Française de Chirurgie (AFC) multicenter-based study with propensity score analysis. World J Surg. 2018;42(12):4046–53. Esposito F, Lim C, Sa Cunha A, Pessaux P, Navarro F, Azoulay D, et al. Primary tumor versus liver-first approach for synchronous colorectal liver metastases: an association Française de Chirurgie (AFC) multicenter-based study with propensity score analysis. World J Surg. 2018;42(12):4046–53.
29.
go back to reference Vallance AE, van der Meulen J, Kuryba A, Charman SC, Botterill ID, Prasad KR, et al. The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a population-based study of current practice and survival. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2018;20(6):486–95. Vallance AE, van der Meulen J, Kuryba A, Charman SC, Botterill ID, Prasad KR, et al. The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a population-based study of current practice and survival. Colorectal Dis Off J Assoc Coloproctology G B Irel. 2018;20(6):486–95.
30.
go back to reference Verhoef C, van der Pool AEM, Nuyttens JJ, Planting AST. Eggermont AMM, de wilt JHW the “liver-first approach” for patients with locally advanced rectal cancer and synchronous liver metastases. Dis Colon Rectum. 2009;52(1):23–30.CrossRef Verhoef C, van der Pool AEM, Nuyttens JJ, Planting AST. Eggermont AMM, de wilt JHW the “liver-first approach” for patients with locally advanced rectal cancer and synchronous liver metastases. Dis Colon Rectum. 2009;52(1):23–30.CrossRef
31.
go back to reference Gervaz P, Rubbia-Brandt L, Andres A, Majno P, Roth A, Morel P, et al. Neoadjuvant chemotherapy in patients with stage IV colorectal cancer: a comparison of histological response in liver metastases, primary tumors, and regional lymph nodes. Ann Surg Oncol. 2010;17(10):2714–9.CrossRef Gervaz P, Rubbia-Brandt L, Andres A, Majno P, Roth A, Morel P, et al. Neoadjuvant chemotherapy in patients with stage IV colorectal cancer: a comparison of histological response in liver metastases, primary tumors, and regional lymph nodes. Ann Surg Oncol. 2010;17(10):2714–9.CrossRef
32.
go back to reference Reding D, Pestalozzi BC, Breitenstein S, Stupp R, Clavien P-A, Slankamenac K, et al. Treatment strategies and outcome of surgery for synchronous colorectal liver metastases. Swiss Med Wkly. 2017;05(147):w14486. Reding D, Pestalozzi BC, Breitenstein S, Stupp R, Clavien P-A, Slankamenac K, et al. Treatment strategies and outcome of surgery for synchronous colorectal liver metastases. Swiss Med Wkly. 2017;05(147):w14486.
33.
go back to reference Andres A, Toso C, Adam R, Barroso E, Hubert C, Capussotti L, et al. A survival analysis of the liver-first reversed management of advanced simultaneous colorectal liver metastases: a LiverMetSurvey-based study. Ann Surg. 2012;256(5):772–8 discussion 778–9.CrossRef Andres A, Toso C, Adam R, Barroso E, Hubert C, Capussotti L, et al. A survival analysis of the liver-first reversed management of advanced simultaneous colorectal liver metastases: a LiverMetSurvey-based study. Ann Surg. 2012;256(5):772–8 discussion 778–9.CrossRef
Metadata
Title
Tumor response and outcome after reverse treatment for patients with synchronous colorectal liver metastasis: a cohort study
Authors
Céline Du Pasquier
Didier Roulin
Pierre Bize
Christine Sempoux
Caterina Rebecchini
Michael Montemurro
Markus Schäfer
Nermin Halkic
Nicolas Demartines
Publication date
01-12-2020
Publisher
BioMed Central
Published in
BMC Surgery / Issue 1/2020
Electronic ISSN: 1471-2482
DOI
https://doi.org/10.1186/s12893-020-00738-3

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