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BACKGROUND: Post-hoc analyses of AFP response and progression and their relationship with objective measures of response and survival were performed in patients from REACH. METHODS: Serum AFP was measured at baseline and every 3 cycles (2 weeks/cycle). Associations between AFP and radiographic progression and efficacy end points were analysed. RESULTS: Median percent AFP increase from baseline was smaller in the ramucirumab than in the placebo arm throughout treatment. Time to AFP progression (HR 0.621; P < 0.0001) and to radiographic progression (HR 0.613; P < 0.0001) favoured ramucirumab. Association between AFP and radiographic progression was shown at 6 (OR 6.44, 95% CI 4.03, 10.29; P < 0.0001) and 12 weeks (OR 2.28, 95% CI 1.47, 3.53; P = 0.0002). AFP response was higher with ramucirumab compared with placebo (P < 0.0001). More patients in the ramucirumab arm experienced tumour shrinkage and AFP response compared with placebo. Survival was longer in patients with AFP response (13.6 months) than in patients without (6.2 months), irrespective of treatment (HR 0.457, P < 0.0001). CONCLUSIONS: Treatment with ramucirumab prolonged time to AFP progression, slowed AFP increase and was more likely to induce AFP response. Similar benefits in radiographic progression and response correlated with AFP changes.
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Anticorpos Monoclonais/administração & dosagem , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , alfa-Fetoproteínas/metabolismo , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Radiografia/métodos , RamucirumabRESUMO
BACKGROUND AND AIMS: The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response, which can be evaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. MATERIAL AND METHODS: This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil. Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database. RESULTS: Cirrhosis was present in 94% of patients, 85.6% were Child-Pugh A, 80.3%BCLC-C, 81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1.The median duration of treatment was 10.1 months (range: 0.1-47 months).The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%).The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. CONCLUSION: This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.
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Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Toxidermias/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Toxidermias/diagnóstico , Toxidermias/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Niacinamida/efeitos adversos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Sorafenibe , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: VEGF and VEGF receptor-2-mediated angiogenesis contribute to hepatocellular carcinoma pathogenesis. Ramucirumab is a recombinant IgG1 monoclonal antibody and VEGF receptor-2 antagonist. We aimed to assess the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma following first-line therapy with sorafenib. METHODS: In this randomised, placebo-controlled, double-blind, multicentre, phase 3 trial (REACH), patients were enrolled from 154 centres in 27 countries. Eligible patients were aged 18 years or older, had hepatocellular carcinoma with Barcelona Clinic Liver Cancer stage C disease or stage B disease that was refractory or not amenable to locoregional therapy, had Child-Pugh A liver disease, an Eastern Cooperative Oncology Group performance status of 0 or 1, had previously received sorafenib (stopped because of progression or intolerance), and had adequate haematological and biochemical parameters. Patients were randomly assigned (1:1) to receive intravenous ramucirumab (8 mg/kg) or placebo every 2 weeks, plus best supportive care, until disease progression, unacceptable toxicity, or death. Randomisation was stratified by geographic region and cause of liver disease with a stratified permuted block method. Patients, medical staff, investigators, and the funder were masked to treatment assignment. The primary endpoint was overall survival in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT01140347. FINDINGS: Between Nov 4, 2010, and April 18, 2013, 565 patients were enrolled, of whom 283 were assigned to ramucirumab and 282 were assigned to placebo. Median overall survival for the ramucirumab group was 9·2 months (95% CI 8·0-10·6) versus 7·6 months (6·0-9·3) for the placebo group (HR 0·87 [95% CI 0·72-1·05]; p=0·14). Grade 3 or greater adverse events occurring in 5% or more of patients in either treatment group were ascites (13 [5%] of 277 patients treated with ramucirumab vs 11 [4%] of 276 patients treated with placebo), hypertension (34 [12%] vs ten [4%]), asthenia (14 [5%] vs five [2%]), malignant neoplasm progression (18 [6%] vs 11 [4%]), increased aspartate aminotransferase concentration (15 [5%] vs 23 [8%]), thrombocytopenia (13 [5%] vs one [<1%]), hyperbilirubinaemia (three [1%] vs 13 [5%]), and increased blood bilirubin (five [2%] vs 14 [5%]). The most frequently reported (≥1%) treatment-emergent serious adverse event of any grade or grade 3 or more was malignant neoplasm progression. INTERPRETATION: Second-line treatment with ramucirumab did not significantly improve survival over placebo in patients with advanced hepatocellular carcinoma. No new safety signals were noted in eligible patients and the safety profile is manageable. FUNDING: Eli Lilly and Co.
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Anticorpos Monoclonais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalos de Confiança , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/uso terapêutico , Seleção de Pacientes , Modelos de Riscos Proporcionais , Indução de Remissão , Sorafenibe , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , RamucirumabRESUMO
Oesophageal cancer is among the ten most common types of cancer worldwide. More than 80% of the cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of oesophageal and oesophagogastric junction (OGJ) carcinomas. The Brazilian Group of Gastrointestinal Tumours invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy (including checkpoint inhibitors) and follow-up, which was followed by presentation, discussion and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of oesophageal and OGJ carcinomas in several scenarios and clinical settings.
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Gastric cancer is among the ten most common types of cancer worldwide. Most cases and deaths related to the disease occur in developing countries. Local socio-economic, epidemiologic and healthcare particularities led us to create a Brazilian guideline for the management of gastric carcinomas. The Brazilian Group of Gastrointestinal Tumors (GTG) invited 50 physicians with different backgrounds, including radiology, pathology, endoscopy, nuclear medicine, genetics, oncological surgery, radiotherapy and clinical oncology, to collaborate. This document was prepared based on an extensive review of topics related to heredity, diagnosis, staging, pathology, endoscopy, surgery, radiation, systemic therapy and follow-up, which was followed by presentation, discussion, and voting by the panel members. It provides updated evidence-based recommendations to guide clinical management of gastric carcinomas in several scenarios and clinical settings.
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BACKGROUND: Small cell lung cancer (SCLC) and high-grade extrapulmonary neuroendocrine carcinomas (EPNEC) share similar histopathological features and treatment, but outcomes may differ. We evaluated in our study the expression of biomarkers associated with response rate (RR) to chemotherapy and overall survival (OS) for these entities. MATERIALS AND METHODS: This is a multicentre retrospective analysis of advanced EPNEC and SCLC patients treated with platinum-based chemotherapy. Paraffin-embedded tumour samples were reviewed by a single pathologist and tested for immunohistochemistry (IHC) expression of Ki-67, ERCC1, Bcl-2, and Lin28a. All images were evaluated by the same radiologist and RR was determined by RECIST 1.1. RESULTS: From July, 2006 to July, 2014, 142 patients were identified, being 82 (57.7%) SCLC and 60 (42.3%) EPNEC. Clinical characteristics and median Ki-67 (SCLC: 60%; EPNEC: 50%; p = 0.86) were similar between the groups. RR was higher for SCLC patients (86.8% versus 44.6%; p<0.001), but median OS was similar (10.3 months in SCLC and 11.1 months in EPNEC; HR 0.69, p = 0.07). Bcl-2 expression was higher in SCLC patients (46.3% versus 28.3%, p = 0.03) and was associated with worse prognosis in EPNEC (median OS 8.0 months versus 14.7 months; HR 0.47, p = 0.02). CONCLUSION: EPNEC patients presented inferior RR to platinum-based chemotherapy than SCLC but tended to live longer. Neither ERCC1, Lin28, or Ki-67 were prognostic or predictive for RR in EPNEC or SCLC. High Bcl-2 expression was associated with poor prognosis in EPNEC patients.
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Neuroendocrine tumours are a heterogeneous group of diseases with a significant variety of diagnostic tests and treatment modalities. Guidelines were developed by North American and European groups to recommend their best management. However, local particularities and relativisms found worldwide led us to create Brazilian guidelines. Our consensus considered the best feasible strategies in an environment involving more limited resources. We believe that our recommendations may be extended to other countries with similar economic standards.
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OBJECTIVES: Spirituality is related to the care and the quality of life of cancer patients. Thus, it is very important to assess their needs. The objective of this study was the translation and cultural adjustment of the Spiritual Needs Assessment for Patients (SNAP) questionnaire to the Brazilian Portuguese language. METHODOLOGY: The translation and cultural adjustment of the SNAP questionnaire involved six stages: backtranslation, revision of backtranslation, translation to the original language and adjustments, pre-test on ten patients, and test and retest with 30 patients after three weeks. Adult patients, with a solid tumour and literate with a minimum of four years schooling were included. For analysis and consistency we used the calculation of the Cronbach alpha coefficient and the Pearson linear correlation. RESULTS: The final questionnaire had some language and content adjustments compared to the original version in English. The correlation analysis of each item with the total score of the questionnaire showed coefficients above 0.99. The calculation of the Cronbach alpha coefficient was 0.9. The calculation of the Pearson linear correlation with the test and retest of the questionnaire was equal to 0.95. CONCLUSION: The SNAP questionnaire translated into Brazilian Portuguese is adequately reliable and consistent. This instrument allows adequate access to spiritual needs and can help patient care.
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The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.
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Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Neoplasias dos Ductos Biliares/patologia , Colangiocarcinoma/patologia , Gerenciamento Clínico , Medicina Baseada em Evidências , Humanos , Estadiamento de Neoplasias , Guias de Prática Clínica como AssuntoRESUMO
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.
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Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/cirurgia , Brasil , Terapia Combinada , HumanosRESUMO
BACKGROUND AND AIMS: Schistosomiasis is a major chronic disease of humans in endemic regions, and infected individuals may develop a spectrum of pathology, including hepatic fibrosis, hepatosplenomegaly, and portal hypertension. Hepatocellular carcinoma (HCC) is considered the fifth most common cancer in the world, and there is limited and controversial evidence suggesting that Schistosoma mansoni infection may be a possible risk factor for HCC. The aim of this study was to report a case series of patients with HCC and S. mansoni infection and to conduct a literature review on the topic. METHODS: From January 2002 to January 2015, an institutional database was screened retrospectively to identify patients with HCC and S. mansoni infection at a single center in the Department of Gastroenterology of University of São Paulo School of Medicine and Hospital das Clínicas, Brazil. RESULTS: Seven cases were included. The mean age of patients was 62.1±10.3 years; six (85.7%) were male and one (14.3%) was female. All cases had positive epidemiology, coming from endemic areas of S. mansoni infection in Brazil, and four (57.1%) had previous complications (upper gastrointestinal bleeding) related to portal hypertension or surgery intervention (splenectomy) performed more than 10 years before the HCC diagnosis. Nontumoral portal vein thrombosis was identified in five (71.4%) patients. All patients had negative serology for HCV, and four (57.1%) had positivity of HBVcore antibodies without evidence of viral replication. According to BCLC staging, one (14.3%) patient was BCLC A and received TACE instead of RFA because HCC size was >30 mm; three (42.8%) BCLC B patients received sorafenib instead of local regional treatment due to the presence of nontumoral TPV. During follow-up, all patients developed tumoral progression and died. CONCLUSIONS: It remains unclear if S. mansoni infection alone has carcinogenic potential. The available literature indicates that S. Mansoni, in the presence of HBV and HCV infections, likely acts as a cofactor for the hepatic lesion and potentiates injury.
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Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33-5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22-13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and α-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction.
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BACKGROUND: In patients with adenocarcinoma of the pancreas, there are no standard second-line regimens. Many pre-clinical studies have shown that metformin alone or when combined with paclitaxel has antitumour effects on this tumour. We have tested here the combination of paclitaxel and metformin for patients with gemcitabine-refractory pancreatic cancer. METHODS: An uncontrolled phase II trial was carried out based on a two-stage Simon's design, with metformin and paclitaxel for patients with locally advanced or metastatic pancreatic cancer whose disease had progressed during first line treatment with a gemcitabine-based regimen. The primary endpoint was the disease control rate at eight weeks as per response evaluation criteria in solid tumours (RECIST) 1.1. Patients received paclitaxel 80 mg/m(2) weekly for three weeks every 28 days and metformin 850 mg p.o. t.i.d. continuously until progression or intolerance state was reached. RESULTS: Twenty patients were enrolled from July 2011 to January 2014: N = 6 (31.6%) achieved the primary endpoint, with all presenting stable disease. Median overall survival (OS) was 128 days (range 17-697) and the median progression free survival (PFS) was 44 days (range 14-210). Eight patients (40%) presented treatment-related G3-4 toxicities with the most common one being diarrhoea. CONCLUSIONS: Despite the encouraging pre-clinical evidence of the antitumour activity of metformin in adenocarcinoma of the pancreas, the primary endpoint of the disease control rate was not met. Besides, the treatment combination was poorly tolerated and could not be studied further. This study highlights the importance of performing clinical trials to reassure preclinical or observational data.
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OBJECTIVE: To analyze the predictors of operative treatment in patients sustaining bleeding peptic ulcers. METHODS: Retrospective analysis of the patients admitted owing to bleeding peptic ulcers from 1998 to 2001. Vital signs upon admission, associated diseases, endoscopy data, evolution and definitive care were evaluated. Patients who underwent surgery were compared with the others in order to identify the predictors of the operative treatment. Student's t and chi squared test were employed for statistical analysis, considering p< 0,05 as significant. RESULTS: Two hundred patients were included in the study group. The age ranged between 17 and 97 years (mean 52 + 18), and 153 patients (76.5%) were male. Shock upon admission was present in 27 (13.5%). The endoscopic exam performed at admission showed that 101 patients sustained ulcers in the duodenum and 99 in the stomach, which were classified as Forrest Ia in 5 (2.5%), Ib in 20 (10%), IIa in 48 (24%) and IIb in 48 (24%). Twenty five (12.5%) patients needed operation, and 23 (92%) were submitted to gastrectomy with Billroth's II reconstruction. The operative treatment were more frequently performed in patients sustaining chronic alcoholic intake (p=0.002), cigarette smoking (p=0.02), diabetes mellitus (p=0.01), chronic peptic disease (p=0.05), shock upon admission (p<0.001) and spurting activity at the endoscopy (p<0.001). Forrest IIb lesions which did not receive any form of endoscopic treatment at admission were more likely to rebleed (p=0.012). CONCLUSIONS: The predictors of operative treatment were chronic alcoholic intake, smoke addiction, diabetes mellitus, chronic peptic disease, shock upon admission and Forrest Ia ulcers.
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Úlcera Péptica Hemorrágica/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Endoscopia Gastrointestinal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Úlcera Péptica Hemorrágica/etiologia , Úlcera Péptica Hemorrágica/patologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Úlcera Gástrica/complicações , Úlcera Gástrica/patologia , Resultado do TratamentoRESUMO
Sorafenib is the first systemic therapy to demonstrate survival benefit in advanced hepatocellular carcinoma (HCC) in randomized controlled trials with rigorous patient selection. Neutrophil-to-lymphocyte ratio (NLR) has been shown to be associated with poor survival in various solid tumors. Our aim is to evaluate the prognostic role of NLR in HCC patients treated with sorafenib. A total of 105 advanced HCC patients treated with sorafenib were retrospectively reviewed, and relevant data from the clinical records were collected. Univariate and multivariate analysis were carried out to identify factors associated with survival. The median age of the cohort was 59.7 years, and 84.8 % were Child-Pugh class A, and 86.7 % had ECOG performance status 0 or 1. Median duration of sorafenib treatment was 100 days. Median overall survival (OS) of the entire cohort was 8.03 months. Median OS was 5.23 months (95 % CI 2.96-7.50 months) and 10.05 months (95 % IC 2.52-18.47 months) for patients with NLR > 3.5 and NLR ≤ 3.5, respectively (p = 0.002). Alpha-fetoprotein >1,030 ng/mL and serum albumin ≤3.8 g/dL were also associated with worse prognosis (p = 0.006 and p = 0.042, respectively). The subgroup of patients with high alpha-fetoprotein, low albumin and NLR > 3.5 had median OS of 1.7 months, whereas the subgroup with none of these parameters had median OS of 16.5 months (p < 0.001). NLR affects survival in advanced HCC patients treated with sorafenib. Selecting HCC patients based on the laboratorial features may improve the therapeutic effectiveness of sorafenib.
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Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/tratamento farmacológico , Linfócitos/metabolismo , Neutrófilos/metabolismo , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/mortalidade , Feminino , Humanos , Neoplasias Hepáticas/mortalidade , Linfócitos/efeitos dos fármacos , Masculino , Pessoa de Meia-Idade , Neutrófilos/efeitos dos fármacos , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Compostos de Fenilureia/farmacologia , Estudos Retrospectivos , Sorafenibe , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemRESUMO
Extrapulmonary poorly differentiated neuroendocrine carcinoma (PDNEC) is a rare and highly aggressive neoplasm for which the optimal chemotherapy remains unclear. The objective of this study was to evaluate the outcomes of patients with PDNEC treated with cisplatin and irinotecan (IP) and perform a review of the literature. From 2008 to 2012, patients with advanced PDNEC (Ki67≥20%) who received the IP combination were selected for analysis. Radiologic responses were determined through Response Evaluation Criteria In Solid Tumors criteria. Twenty-eight patients were included. The median age at diagnosis was 57 years and the most common presentation was pancreatic PDNEC. Twenty-five patients (89%) received chemotherapy with cisplatin and irinotecan and three received carboplatin and irinotecan. Forty-six percent of the patients achieved objective response and the median time to tumor progression was 3.7 months. The median overall survival was 11.7 months. Thirteen patients (46%) had treatment interruptions or dose reductions due to grade 3/4 toxicity. This retrospective cohort of advanced extrapulmonary PDNEC patients suggests that the IP combination is feasible and resulted in similar response rate and median survival to other treatments previously reported.
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ABSTRACT Background and Aims. The presence of dermatologic reaction as an adverse event to sorafenib treatment in patients with unresectable hepatocellular carcinoma has been indicated as a prognostic factor for survival in a recent prospective analysis. To date, this is the only clinical predictor of treatment response, which can be evaluated earlier in the treatment and, therefore, contribute to a better and more individualized patient management. Material and methods. This retrospective study included 127 patients treated with sorafenib under real-life practice conditions in two hepatology reference centers in Brazil. Demographic data, disease/medical history and time of sorafenib administration as well as adverse events related to the medication were recorded in a database. Results. Cirrhosis was present in 94% of patients, 85.6% were Child-Pugh A, 80.3%BCLC-C, 81% had vascular invasion and/or extrahepatic spread and 95% had a performance status 0 to 1.The median duration of treatment was 10.1 months (range: 0.1-47 months).The most common adverse event within the first 60 days of treatment were diarrhea (62.2%) and dermatological reaction (42%).The median overall survival for the cohort was 20 months, and it was higher for patients who developed dermatological reactions within the first 60 days compared to those who did not present this adverse event. Conclusion. This retrospective analysis showed the use of sorafenib in patients selected according to BCLC staging, and it is the first external validation of early dermatologic adverse events as a predictor of overall survival in patients with advanced hepatocellular carcinoma.
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Humanos , Compostos de Fenilureia/efeitos adversos , Niacinamida/análogos & derivados , Toxidermias/etiologia , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Antineoplásicos/efeitos adversos , Fatores de Tempo , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Niacinamida/efeitos adversos , Toxidermias/diagnóstico , Toxidermias/mortalidade , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Estimativa de Kaplan-Meier , Sorafenibe , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Estadiamento de NeoplasiasRESUMO
BACKGROUND: A growing number of patients with hepatocellular carcinoma undergo liver transplantation, but there is little data on recurrence and its treatment in the posttransplant setting. METHODS: This article presents a retrospective analysis of adult hepatocellular carcinoma patients. The aim of the study was to characterize the clinical pattern of posttransplant hepatocellular carcinoma recurrence, treatment options in recurrence and overall survival after liver transplantation and after recurrence. RESULTS: A total of 139 patients with histological proven hepatocellular carcinoma was included in the study. The median follow-up after liver transplantation was 37.2 months. Twenty-four of 139 patients experienced a recurrence. In 72.7% of the cases, the hepatocellular carcinoma recurred outside the transplant. Median overall survival after recurrence was 23.1 months. A total of 68.2% of patients received a mean of 2.2 treatments for posttransplant hepatocellular carcinoma recurrence. While on treatment with sorafenib, the use of mTOR inhibitors and radiotherapy had no statistically significant effect on overall survival, complete surgical resection of metastatic lesions significantly improved overall survival. Non-resectable patients with isolated hepatic relapse also benefited from local control strategies. CONCLUSIONS: Posttransplant hepatocellular carcinoma recurrence frequently is located outside the transplant, and despite the proven efficacy of sorafenib, complete surgical resection of metastatic lesions remains the hallmark of treatment.
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Carcinoma Hepatocelular/terapia , Ablação por Cateter , Quimioembolização Terapêutica , Hepatectomia , Neoplasias Hepáticas/terapia , Transplante de Fígado , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/terapia , Adulto , Idoso , Antineoplásicos/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Feminino , Seguimentos , Humanos , Imunossupressores/administração & dosagem , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/cirurgia , Niacinamida/análogos & derivados , Compostos de Fenilureia , Modelos de Riscos Proporcionais , Piridinas/uso terapêutico , Radioterapia Adjuvante , Recidiva , Estudos Retrospectivos , Fatores de Risco , Sorafenibe , Análise de Sobrevida , Serina-Treonina Quinases TOR/antagonistas & inibidores , Fatores de Tempo , Resultado do TratamentoRESUMO
ABSTRACT The Brazilian Gastrointestinal Tumor Group developed guidelines for the surgical and clinical management of patients with billiary cancers. The multidisciplinary panel was composed of experts in the field of radiology, medical oncology, surgical oncology, radiotherapy, endoscopy and pathology. The panel utilized the most recent literature to develop a series of evidence-based recommendations on different treatment and diagnostic strategies for cholangiocarcinomas and gallbladder cancers.
RESUMO O Grupo Brasileiro de Tumores Gastrointestinais desenvolveu diretrizes de tratamento cirúrgico e clínico de pacientes com tumores de vias biliares. O painel multidisciplinar foi composto de especialistas nas áreas radiologia, oncologia, cirurgia, radioterapia, endoscopia e anatomia patológica. O painel utilizou literatura atual para desenvolver recomendações baseadas em evidência científica para as diferentes estratégias terapêuticas e diagnósticas dos colangiocarcinomas e tumores de vesícula biliar.
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Humanos , Neoplasias dos Ductos Biliares/terapia , Colangiocarcinoma/terapia , Neoplasias dos Ductos Biliares/patologia , Guias de Prática Clínica como Assunto , Colangiocarcinoma/patologia , Medicina Baseada em Evidências , Gerenciamento Clínico , Estadiamento de NeoplasiasRESUMO
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.
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.