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      Manejo atual das metástases hepáticas de câncer colorretal: recomendações do Clube do Fígado de São Paulo Translated title: Current management of liver metastases from colorectal cancer: recommendations of the São Paulo Liver Club

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          Abstract

          Aproximadamente metade dos pacientes portadores de câncer colorretal apresenta metástases hepáticas durante a evolução de sua doença que afetam diretamente o prognóstico e são diretamente responsáveis por 2/3 dos óbitos relacionados à doença. Nas últimas duas décadas o tratamento das metástases hepáticas de câncer colorretal (MHCCR) proporcionou ganho expressivo na sobrevida quando todas as opções terapêuticas são colocadas à disposição do paciente. Nesse contexto, o tratamento cirúrgico persiste como a única possibilidade de cura com índices de sobrevida em cinco anos de 25 a 58%. No entanto, apenas 1/4 dos pacientes tem doença ressecável ao diagnóstico. Por essa razão, um dos pontos fundamentais no manejo atual dos pacientes com MHCCR é o desenvolvimento de estratégias que possibilitem a ressecção completa das lesões hepáticas. O advento e aperfeiçoamento dos métodos ablativos expandiram as possibilidades da terapêutica cirúrgica, além disto, o surgimento de novos esquemas quimioterápicos e a introdução das terapias-alvo proporcionou altas taxas de resposta e alteraram definitivamente o manejo destes pacientes. O tratamento multimodal e a utilização da experiência de diversas especialidades médicas permitiram que o tratamento das MHCCR se aproximasse cada vez mais do tratamento ideal, ou seja, individualizado. Baseado em uma extensa revisão da literatura e na experiência de alguns dos centros especializados mais importantes do Brasil, o Clube do Fígado de São Paulo iniciou um trabalho de discussão multi-institucional que resultou nas recomendações que se seguem. Essas recomendações, no entanto, não visam ser absolutas, mas sim ferramentas úteis no processo de decisão terapêutica desse grupo complexo de pacientes.

          Translated abstract

          Approximately half of patients with colorectal cancer present with liver metastases during the course of their disease, which directly affect prognosis and is responsible for two thirds of deaths related to the disease. In the last two decades the treatment of liver metastases from colorectal cancer (CRCLM) provided significant gain in survival when all treatment options are available to the patient. In this context, surgical treatment remains as the only chance of cure, with five-year survival rates of 25-58%. However, only 1/4 of the patients have resectable disease at diagnosis. For this reason, one of the key points in the current management of patients with CRCLM is the development of strategies that facilitate complete resection of liver lesions. The advent and refinement of ablative methods have expanded the possibilities of surgical therapy. The emergence of new chemotherapy regimens and the introduction of targeted therapies has provided high response rates and has permanently altered the management of these patients. The multimodal therapy and the involvement of different medical specialties has increasingly enabled CRCLM treatment to approached the ideal treatment, i.e., an individualized one. Based on an extensive review of literature and on experience from some of the most important specialized centers of Brazil, the São Paulo Liver Club began a process of multi-institutional discussions that resulted in the recommendations that follow. These recommendations, however, are not intended to be absolute, but useful tools in the therapeutic decision process for this complex group of patients.

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          Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial

          Summary Background Surgical resection alone is regarded as the standard of care for patients with liver metastases from colorectal cancer, but relapse is common. We assessed the combination of perioperative chemotherapy and surgery compared with surgery alone for patients with initially resectable liver metastases from colorectal cancer. Methods This parallel-group study reports the trial's final data for progression-free survival for a protocol unspecified interim time-point, while overall survival is still being monitored. 364 patients with histologically proven colorectal cancer and up to four liver metastases were randomly assigned to either six cycles of FOLFOX4 before and six cycles after surgery or to surgery alone (182 in perioperative chemotherapy group vs 182 in surgery group). Patients were centrally randomised by minimisation, adjusting for centre and risk score. The primary objective was to detect a hazard ratio (HR) of 0·71 or less for progression-free survival. Primary analysis was by intention to treat. Analyses were repeated for all eligible (171 vs 171) and resected patients (151 vs 152). This trial is registered with ClinicalTrials.gov, number NCT00006479. Findings In the perioperative chemotherapy group, 151 (83%) patients were resected after a median of six (range 1–6) preoperative cycles and 115 (63%) patients received a median six (1–8) postoperative cycles. 152 (84%) patients were resected in the surgery group. The absolute increase in rate of progression-free survival at 3 years was 7·3% (from 28·1% [95·66% CI 21·3–35·5] to 35·4% [28·1–42·7]; HR 0·79 [0·62–1·02]; p=0·058) in randomised patients; 8·1% (from 28·1% [21·2–36·6] to 36·2% [28·7–43·8]; HR 0·77 [0·60–1·00]; p=0·041) in eligible patients; and 9·2% (from 33·2% [25·3–41·2] to 42·4% [34·0–50·5]; HR 0·73 [0·55–0·97]; p=0·025) in patients undergoing resection. 139 patients died (64 in perioperative chemotherapy group vs 75 in surgery group). Reversible postoperative complications occurred more often after chemotherapy than after surgery (40/159 [25%] vs 27/170 [16%]; p=0·04). After surgery we recorded two deaths in the surgery alone group and one in the perioperative chemotherapy group. Interpretation Perioperative chemotherapy with FOLFOX4 is compatible with major liver surgery and reduces the risk of events of progression-free survival in eligible and resected patients. Funding Swedish Cancer Society, Cancer Research UK, Ligue Nationale Contre le Cancer, US National Cancer Institute, Sanofi-Aventis.
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            Rescue surgery for unresectable colorectal liver metastases downstaged by chemotherapy: a model to predict long-term survival.

            To evaluate the long-term survival of patients resected for primarily unresectable colorectal liver metastases (CRLM) downstaged by systemic chemotherapy and to use prognostic factors of outcome for a model predictive of survival on a preoperative setting. Surgery of primarily unresectable CRLM after downstaging chemotherapy is still questioned, and prognostic factors of outcome are lacking. From a consecutive series of 1439 patients with CRLM managed in a single institution during an 11-year period (1988-1999), 1104 (77%) initially unresectable (NR) patients were treated by chemotherapy and 335 (23%) resectable were treated by primary liver resection. Chemotherapy mainly consisted of 5-fluorouracil and leucovorin combined to oxaliplatin (70%), irinotecan (7%), or both (4%) given as chronomodulated infusion (87%). NR patients were routinely reassessed every 4 courses. Surgery was reconsidered every time a documented response to chemotherapy was observed. Among 1104 NR patients, 138 "good responders" (12.5%) underwent secondary hepatic resection after an average of 10 courses of chemotherapy. At time of diagnosis, mean number of metastases was 4.4 (1-14) and mean maximum size was 5.2 cm (1-25). Extrahepatic tumor was present in 52 patients (38%). Multinodularity or extrahepatic tumor was the main cause of initial unresectability. All factors likely to be predictive of survival after liver resection were evaluated by uni- and multivariate analysis. Estimation of survival was adjusted on risk factors available preoperatively. Seventy-five percent of procedures were major hepatectomies (> or =3 segments) and 93% were potentially curative. Liver surgery was combined to portal embolization, to ablative treatment, or to a second-stage hepatectomy in 42 patients (30%) and to resection of extrahepatic tumor in 41 patients (30%). Operative mortality within 2 months was 0.7%, and postoperative morbidity was 28%. After a mean follow-up of 48.7 months, 111 of the 138 patients (80%) developed tumor recurrence, 40 of which were hepatic (29%), 12 extrahepatic (9%), and 59 both hepatic and extrahepatic (43%). Recurrence was treated in 52 patients by repeat hepatectomy (71 procedures) and in 42 patients by extrahepatic resection (77 procedures). Survival was 33% and 23% at 5 and 10 years with a disease-free survival of 22% and 17%, respectively. It was decreased as compared with that of patients primarily resected within the same period (48% and 30% respectively, P = 0.01). At the last follow-up, 99 patients had died (72%) and 39 (28%) were alive; 25 were disease free (18%) and 14 had recurrence (10%). At multivariate analysis, 4 preoperative factors were independently associated to decreased survival: rectal primary, > or =3 metastases, maximum tumor size >10 cm, and CA 19-9 >100 UI/L. Mean adjusted 5-year survival according to the presence of 0, 1, 2, 3, or 4 factors was 59%, 30%, 7%, 0%, and 0%. Modern chemotherapy allows 12.5% of patients with unresectable CRLM to be rescued by liver surgery. Despite a high rate of recurrence, 5-year survival is 33% overall, with a wide use of repeat hepatectomies and extrahepatic resections. Four preoperative risk factors could select the patients most likely to benefit from this strategy.
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              Surgical resection of colorectal carcinoma metastases to the liver. A prognostic scoring system to improve case selection, based on 1568 patients. Association Française de Chirurgie.

              Five-year survival rates after resection of liver metastases from colorectal carcinoma are close to 25%. Recurrences occur in two-thirds of the patients after surgery. Selection of patients likely to benefit from surgery remains controversial and subjective. Data from 1568 patients with resected liver metastases from colorectal carcinoma were collected. The prognostic value of different factors was studied through uni- and multivariate analyses. A scoring system was developed including the most relevant factors. Two- and 5-year survival rates were 64% and 28%, respectively, and were affected by: age; size of largest metastasis or CEA level; stage of the primary tumor; disease free interval; number of liver nodules; and resection margin. Giving one point to each factor, the population was divided into three risk groups three risk groups with different 2-year survival rates: 0-2 (79%), 3-4 (60%), 5-7 (43%). A simple prognostic scoring system was proposed to evaluate the chances for cure of patients after resection of liver metastases from colorectal carcinoma. The comparison between expected survival and estimated operative risk can help determine on an objective basis whether surgery is worthwhile. This system needs further prospective validation.
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                Author and article information

                Journal
                rcbc
                Revista do Colégio Brasileiro de Cirurgiões
                Rev. Col. Bras. Cir.
                Colégio Brasileiro de Cirurgiões (Rio de Janeiro, RJ, Brazil )
                0100-6991
                1809-4546
                June 2013
                : 40
                : 3
                : 251-260
                Affiliations
                [01] orgnameUniversidade de São Paulo orgdiv1Faculdade de Medicina
                [03] orgnameSanta Casa de São Paulo orgdiv1Faculdade de Ciências Médicas
                [02] orgnameUniversidade Federal de São Paulo orgdiv1Escola Paulista de Medicina
                Article
                S0100-69912013000300016 S0100-6991(13)04000300016
                10.1590/S0100-69912013000300016
                23912376
                ac2a40dd-f17f-4293-aa08-ee25282a0b1a

                This work is licensed under a Creative Commons Attribution 4.0 International License.

                History
                : 01 July 2012
                : 01 October 2012
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 54, Pages: 10
                Product

                SciELO Brazil

                Categories
                Artigo Especial

                Neoplasm metastasis,Colorectal neoplasms,Terapêutica,Neoplasms,Neoplasias colorretais,Therapeutics,Neoplasias,Liver neoplasms,Neoplasias hepáticas,Metástase neoplásica

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