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I BRAZILIAN CONSENSUS ON MULTIMODAL TREATMENT OF COLORECTAL LIVER METASTASES. MODULE 2: APPROACH TO RESECTABLE METASTASES Translated title: I CONSENSO BRASILEIRO DE TRATAMENTO MULTIDISCIPLINAR DE METÁSTASE HEPÁTICA COLORRETAIS MÓDULO 2: MANEJO DAS METÁSTASES RESSECÁVEIS

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Arquivos Brasileiros de Cirurgia Digestiva : ABCD

Colégio Brasileiro de Cirurgia Digestiva

Colorectal cancer, Liver metastases, Brazilian consensus, Resectable metastases, Metachronous metastases, Synchronous metastases, Missing metastases

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      Abstract

      Background:

      Liver metastases of colorectal cancer are frequent and potentially fatal event in the evolution of patients.

      Aim:

      In the second module of this consensus, management of resectable liver metastases was discussed.

      Method:

      Concept of synchronous and metachronous metastases was determined, and both scenarius were discussed separately according its prognostic and therapeutic peculiarities.

      Results:

      Special attention was given to the missing metastases due to systemic preoperative treatment response, with emphasis in strategies to avoid its reccurrence and how to manage disappeared lesions.

      Conclusion:

      Were presented validated ressectional strategies, to be taken into account in clinical practice.

      Translated abstract

      Racional:

      As metástases hepáticas de câncer colorretal são evento frequente e potencialmente fatal na evolução dos pacientes.

      Objetivo:

      No segundo módulo desse consenso, foi discutido o manejo de metástases hepáticas ressecáveis.

      Método:

      Foi definido o conceito de metástases síncrônicas e metacrônicas, e ambos os cenários foram discutidos separadamente de acordo com as suas peculiaridades prognósticas e terapêuticas.

      Resultados:

      Foi dada especial atenção às missing metástases em resposta ao tratamento pré-operatório sistêmico, com ênfase em estratégias para evitar sua recorrência e como gerenciar as lesões desaparecidas.

      Conclusão:

      Foram apresentadas e validadas estratégias de ressecção em várias circunstâncias, para serem aplicadas na prática clínica.

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      Most cited references 86

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      Clinical score for predicting recurrence after hepatic resection for metastatic colorectal cancer: analysis of 1001 consecutive cases.

      There is a need for clearly defined and widely applicable clinical criteria for the selection of patients who may benefit from hepatic resection for metastatic colorectal cancer. Such criteria would also be useful for stratification of patients in clinical trials for this disease. Clinical, pathologic, and outcome data for 1001 consecutive patients undergoing liver resection for metastatic colorectal cancer between July 1985 and October 1998 were examined. These resections included 237 trisegmentectomies, 394 lobectomies, and 370 resections encompassing less than a lobe. The surgical mortality rate was 2.8%. The 5-year survival rate was 37%, and the 10-year survival rate was 22%. Seven factors were found to be significant and independent predictors of poor long-term outcome by multivariate analysis: positive margin (p = 0.004), extrahepatic disease (p = 0.003), node-positive primary (p = 0.02), disease-free interval from primary to metastases 1 (p = 0.0004), largest hepatic tumor >5 cm (p = 0.01), and carcinoembryonic antigen level >200 ng/ml (p = 0.01). When the last five of these criteria were used in a preoperative scoring system, assigning one point for each criterion, the total score was highly predictive of outcome (p < 0.0001). No patient with a score of 5 was a long-term survivor. Resection of hepatic colorectal metastases may produce long-term survival and cure. Long-term outcome can be predicted from five criteria that are readily available for all patients considered for resection. Patients with up to two criteria can have a favorable outcome. Patients with three, four, or five criteria should be considered for experimental adjuvant trials. Studies of preoperative staging techniques or of adjuvant therapies should consider using such a score for stratification of patients.
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        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.

        Previous results of the EORTC intergroup trial 40983 showed that perioperative chemotherapy with FOLFOX4 (folinic acid, fluorouracil, and oxaliplatin) increases progression-free survival (PFS) compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Here we present overall survival data after long-term follow-up. This randomised, controlled, parallel-group, phase 3 study recruited patients from 78 hospitals across Europe, Australia, and Hong Kong. Eligible patients aged 18-80 years who had histologically proven colorectal cancer and up to four liver metastases were randomly assigned (1:1) to either perioperative FOLFOX4 or surgery alone. Perioperative FOLFOX4 consisted of six 14-day cycles of oxaliplatin 85mg/m(2), folinic acid 200 mg/m(2) (DL form) or 100 mg/m(2) (L form) on days 1-2 plus bolus, and fluorouracil 400 mg/m(2) (bolus) and 600 mg/m(2) (continuous 22 h infusion), before and after surgery. Patients were centrally randomised by minimisation, adjusting for centre and risk score and previous adjuvant chemotherapy to primary surgery for colorectal cancer, and the trial was open label. Analysis of overall survival was by intention to treat in all randomly assigned patients. Between Oct 10, 2000, and July 5, 2004, 364 patients were randomly assigned to a treatment group (182 patients in each group, of which 171 per group were eligible and 152 per group underwent resection). At a median follow-up of 8·5 years (IQR 7·6-9·5), 107 (59%) patients in the perioperative chemotherapy group had died versus 114 (63%) in the surgery-only group (HR 0·88, 95% CI 0·68-1·14; p=0·34). In all randomly assigned patients, median overall survival was 61·3 months (95% CI 51·0-83·4) in the perioperative chemotherapy group and 54·3 months (41·9-79·4) in the surgery alone group. 5-year overall survival was 51·2% (95% CI 43·6-58·3) in the perioperative chemotherapy group versus 47·8% (40·3-55·0) in the surgery-only group. Two patients in the perioperative chemotherapy group and three in the surgery-only group died from complications of protocol surgery, and one patient in the perioperative chemotherapy group died possibly as a result of toxicity of protocol treatment. We found no difference in overall survival with the addition of perioperative chemotherapy with FOLFOX4 compared with surgery alone for patients with resectable liver metastases from colorectal cancer. However, the previously observed benefit in PFS means that perioperative chemotherapy with FOLFOX4 should remain the reference treatment for this population of patients. Norwegian and Swedish Cancer Societies, Cancer Research UK, Ligue Nationale Contre Cancer, US National Cancer Institute, Sanofi-Aventis. Copyright © 2013 Elsevier Ltd. All rights reserved.
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          Tumour response and secondary resectability of colorectal liver metastases following neoadjuvant chemotherapy with cetuximab: the CELIM randomised phase 2 trial.

          Neoadjuvant chemotherapy for unresectable colorectal liver metastases can downsize tumours for curative resection. We assessed the effectiveness of cetuximab combined with chemotherapy in this setting. Between Dec 2, 2004, and March 27, 2008, 114 patients were enrolled from 17 centres in Germany and Austria; three patients receiving FOLFOX6 alone were excluded from the analysis. Patients with non-resectable liver metastases (technically non-resectable or > or =5 metastases) were randomly assigned to receive cetuximab with either FOLFOX6 (oxaliplatin, fluorouracil, and folinic acid; group A) or FOLFIRI (irinotecan, fluorouracil, and folinic acid; group B). Randomisation was not blinded, and was stratified by technical resectability and number of metastases, use of PET staging, and EGFR expression status. They were assessed for response every 8 weeks by CT or MRI. A local multidisciplinary team reassessed resectability after 16 weeks, and then every 2 months up to 2 years. Patients with resectable disease were offered liver surgery within 4-6 weeks of the last treatment cycle. The primary endpoint was tumour response assessed by Response Evaluation Criteria In Solid Tumours (RECIST), analysed by modified intention to treat. A retrospective, blinded surgical review of patients with radiological images at both baseline and during treatment was done to assess objectively any changes in resectability. The study is registered with ClinicalTrials.gov, number NCT00153998. 56 patients were randomly assigned to group A and 55 to group B. One patient in each group were excluded from the analysis of the primary endpoint because they discontinued treatment before first full dose, one patient in group B was excluded because of early pulmonary embolism. A confirmed partial or complete response was noted in 36 (68%) of 53 patients in group A, and 30 (57%) of 53 patients in group B (difference 11%, 95% CI -8 to 30; odds ratio [OR] 1.62, 0.74-3.59; p=0.23). The most frequent grade 3 and 4 toxicities were skin toxicity (15 of 54 patients in group A, and 22 of 55 patients in group B), and neutropenia (13 of 54 patients in group A and 12 of 55 patients in group B). R0 resection was done in 20 (38%) of 53 patients in group A and 16 (30%) of 53 of patients in group B. In a retrospective analysis of response by KRAS status, a partial or complete response was noted in 47 (70%) of 67 patients with KRAS wild-type tumours versus 11 (41%) of 27 patients with KRAS-mutated tumours (OR 3.42, 1.35-8.66; p=0.0080). According to the retrospective review, resectability rates increased from 32% (22 of 68 patients) at baseline to 60% (41 of 68) after chemotherapy (p<0.0001). Chemotherapy with cetuximab yields high response rates compared with historical controls, and leads to significantly increased resectability. Merck-Serono, Sanofi-Aventis, and Pfizer. Copyright (c) 2010 Elsevier Ltd. All rights reserved.
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            Author and article information

            Affiliations
            [1 ]Brazilian Chapter of the International Hepato-Pancreato-Biliary Association - CB-IHPBA
            [2 ]Brazilian Society of Surgical Oncology - SBCO
            [3 ]Brazilian Society of Clinical Oncology - SBOC
            [4 ]Brazilian College of Digestive Surgery - CBCD
            [5 ]Brazilian College of Surgeons - CBC
            [6 ]Americas Hepato-Pancreato-Biliary Association - AHPBA, Brazil
            [* ]Sociedade Brasileira de Radioterapia
            [** ]Colégio Brasileiro de Cirurgiões
            Author notes
            Correspondence: Héber Salvador de Castro Ribeiro E-mail: hsalvadorcr@ 123456gmail.com

            Conflicts of interest: none

            Journal
            Arq Bras Cir Dig
            Arq Bras Cir Dig
            abcd
            Arquivos Brasileiros de Cirurgia Digestiva : ABCD
            Colégio Brasileiro de Cirurgia Digestiva
            0102-6720
            2317-6326
            Jan-Mar 2016
            Jan-Mar 2016
            : 29
            : 1
            : 9-13
            27120731 4851142 10.1590/0102-6720201600010003

            This is an open-access article distributed under the terms of the Creative Commons Attribution License

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