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Hepatocellular carcinoma (HCC) is the most common primary malignancy in the liver and is the third cause of cancer-related death worldwide. Surveillance with abdominal ultrasound should be offered to individuals at high risk for developing HCC. Accurate diagnosis, staging, and liver function are crucial when determining the optimal therapeutic approach. The BCLC staging system is widely endorsed in Western countries. Managing this pathology requires a multidisciplinary, personalized approach, generally with a multimodal strategy. Surgery remains the only curative option, albeit local and systemic therapy may also increase survival when surgery is not suitable. In advanced disease, systemic treatment should be offered to patients with ECOG/PS 0-1 and Child-Pugh class A.
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Background: The prospective phase IV AVAMET study was undertaken to correlate response evaluation criteria in solid tumors (RECIST)-defined response rates with computed tomography-based morphological criteria (CTMC) and pathological response after liver resection of colorectal cancer metastases. Methods: Eligible patients were aged ≥18 years, with Eastern Cooperative Oncology Group (ECOG) performance status 0/1 and histologically-confirmed colon or rectal adenocarcinoma with measurable liver metastases. Preoperative treatment was bevacizumab (7.5 mg on day 1) + XELOX (oxaliplatin 130 mg/m2, capecitabine 1000 mg/m2 bid on days 1-14 q3w). After three cycles, response was evaluated by a multidisciplinary team. Patients who were progression-free and metastasectomy candidates received one cycle of XELOX before undergoing surgery 3-5 weeks later, followed by four cycles of bevacizumab + XELOX. Results: A total of 83 patients entered the study; 68 were eligible for RECIST, 67 for CTMC, and 51 for pathological response evaluation. Of these patients, 49% had a complete or partial RECIST response, 91% had an optimal or incomplete CTMC response, and 81% had a complete or major pathological response. CTMC response predicted 37 of 41 pathological responses versus 23 of 41 responses predicted using RECIST (p = 0.008). Kappa coefficients indicated a lack of correlation between the results of RECIST and morphological responses and between morphological and pathological response rates. Conclusion: CTMC may represent a better marker of pathological response to bevacizumab + XELOX than RECIST in patients with potentially-resectable CRC liver metastases.
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INTRODUCTION: Mutational analysis of RAS is required for anti-epidermal growth factor receptor (EGFR) treatment for patients with metastatic colorectal cancer (mCRC). However, most patients with KRAS wild-type tumors still do not respond. Other molecules downstream of the EGFR may also play a role in resistance to EGFR therapies. OBJECTIVE: Our objective was to investigate the clinical importance of biomarkers in relation to response, progression-free survival, and overall survival in patients with mCRC receiving first-line treatment with anti-EGFR therapy plus chemotherapy. METHODS: We studied the EGFR pathway [EGFR, NRAS, BRAF, PIK3CA, phosphatase and tensin homolog (PTEN), amphiregulin (AREG), and epiregulin (EREG)] in 105 patients with mCRC KRAS codon 12 wild type. We analysed objective response, progression-free survival, and overall survival in molecularly defined subgroups of the patients receiving anti-EGFR therapy plus chemotherapy as first-line treatment. RESULTS: We found a significant association between RAS wild-type, BRAF wild-type, EREG, and AREG overexpression and response to anti-EGFR therapy (p = 0.003, p = 0.015, p = 0.05, and p = 0.009, respectively). Progression-free survival and overall survival were lower in patients with RAS (p = 0.36 and p ≤ 0.001, respectively) or BRAF (p = 0.003 and p = 0.002, respectively) mutant tumors. Patients with EREG and AREG messenger RNA (mRNA) expression had longer survival than those with low-expression tumors; progression-free survival and overall survival were significant for AREG (p = 0.001 and p = 0.05, respectively). Patients with EGFR amplification tumors responded better to treatment and had better survival rates, although this was not significant. PIK3CA and PTEN were not associated with either response or survival. The multivariate logistic regression model for response showed only BRAF as a significant predictor after adjustment for the other covariates (p = 0.04, odds ratio 8.3, 95 % confidence interval 0.81-86.0). CONCLUSIONS: RAS, BRAF, AREG, and EREG predict for efficacy of first-line anti-EGFR therapy in patients with mCRC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/genética , Variaciones en el Número de Copia de ADN , Adulto , Anciano , Anciano de 80 o más Años , Anfirregulina , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Fosfatidilinositol 3-Quinasa Clase I , Codón , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Familia de Proteínas EGF/genética , Familia de Proteínas EGF/metabolismo , Epirregulina/genética , Epirregulina/metabolismo , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Femenino , Dosificación de Gen , Expresión Génica , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mutación Missense , Metástasis de la Neoplasia , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Fosfatidilinositol 3-Quinasas/genética , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas B-raf/genética , Proteínas Proto-Oncogénicas p21(ras)/genética , Curva ROC , Estudios Retrospectivos , Resultado del TratamientoAsunto(s)
Tumor de Células de la Granulosa/tratamiento farmacológico , Cetoconazol/uso terapéutico , Neoplasias Ováricas/tratamiento farmacológico , Esteroide 17-alfa-Hidroxilasa/antagonistas & inhibidores , Inhibidores de 14 alfa Desmetilasa/administración & dosificación , Inhibidores de 14 alfa Desmetilasa/uso terapéutico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Secuencia de Bases , Femenino , Proteína Forkhead Box L2 , Factores de Transcripción Forkhead/genética , Factores de Transcripción Forkhead/metabolismo , Tumor de Células de la Granulosa/enzimología , Tumor de Células de la Granulosa/genética , Humanos , Hidrocortisona/administración & dosificación , Cetoconazol/administración & dosificación , Datos de Secuencia Molecular , Mutación Missense , Neoplasias Ováricas/enzimología , Neoplasias Ováricas/genética , Esteroide 17-alfa-Hidroxilasa/metabolismo , Resultado del TratamientoRESUMEN
BACKGROUND: Determining life expectancy in terminally ill cancer patients is a difficult task. We aimed to develop and validate a nomogram to predict the length of survival in patients with terminal disease. METHODS: From February 1, 2003, to December 31, 2005, 406 consecutive terminally ill patients were entered into the study. We analyzed 38 features prognostic of life expectancy among terminally ill patients by multivariable Cox regression and identified the most accurate and parsimonious model by backward variable elimination according to the Akaike information criterion. Five clinical and laboratory variables were built into a nomogram to estimate the probability of patient survival at 15, 30, and 60 days. We validated and calibrated the nomogram with an external validation cohort of 474 patients who were treated from June 1, 2006, through December 31, 2007. RESULTS: The median overall survival was 29.1 days for the training set and 18.3 days for the validation set. Eastern Cooperative Oncology Group performance status, lactate dehydrogenase levels, lymphocyte levels, albumin levels, and time from initial diagnosis to diagnosis of terminal disease were retained in the multivariable Cox proportional hazards model as independent prognostic factors of survival and formed the basis of the nomogram. The nomogram had high predictive performance, with a bootstrapped corrected concordance index of 0.70, and it showed good calibration. External independent validation revealed 68% predictive accuracy. CONCLUSIONS: We developed a highly accurate tool that uses basic clinical and analytical information to predict the probability of survival at 15, 30, and 60 days in terminally ill cancer patients. This tool can help physicians making decisions on clinical care at the end of life.