ALINE LOPES CHAGAS
Projetos de Pesquisa
Unidades Organizacionais
Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
LIM/07 - Laboratório de Gastroenterologia Clínica e Experimental, Hospital das Clínicas, Faculdade de Medicina
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- Early variation of inflammatory indexes refines prognostic prediction in patients with hepatocellular carcinoma under systemic treatment(2023) FONSECA, Leonardo G. Da; URATANI, Lucas Fernando; SOARES, Gabriella Fernandes; AMARAL, Paulo Siqueira Do; ALENCAR, Regiane Saraiva De Souza Melo; CHAGAS, Aline Lopes; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JosePrognostic markers in advanced hepatocellular carcinoma (HCC) are relevant for clinical decisions. Variations in inflammatory indexes, such as neutrophil-to-lymphocyte ratio (NLR) or platelet-to-lymphocyte ratio (PLR), may correlate with outcomes. In the present study, it was aimed to assess the prognostic role of inflammation indexes in patients with HCC and the evolutionary behavior of these variables within the first month of treatment in a cohort of patients treated with sorafenib from 2009-2021. Subgroups were divided based on the median of each variable ('low' or 'high)'. Survival was estimated using the Kaplan-Meier method. Hazard Ratio (HR) with 95% confidence interval (CI) were estimated using Cox regression models. A total of 373 patients were included, most Child-Pugh-A (83.1%) and BCLC-C (74%). Child-Pugh-A (P=0.011), performance status 0 (P<0.001), no ascites (P<0.001) and NLR<2.6 (P<0.001) were independently associated with improved survival. Baseline PLR was not correlated with survival (P=0.137). Patients who maintained low NLR at baseline and at 1 month (reference subgroup) had improved survival (18.6 months, 95% CI:15.4-22.0) compared with the subgroup that maintained high NLR at baseline and at 1 month (4.2 months, 95% CI:3.6-5.9), with HR: 3.80 (95% CI: 2.89-4.96). The subgroup with low NLR at baseline and high NLR at 1 month had a worse prognosis compared with the reference group (HR:1.4, 95% CI: 1.1-2.0), whereas the subgroup with high NLR at baseline and low at 1 month had similar outcome (HR:1.2, 95% CI: 0.8-1.6). It was concluded that evolutionary variation of NLR has a prognostic role in HCC patients under systemic therapy. This finding suggested that systemic inflammation and early modulation of the immune environment during treatment may correlate with outcomes.
- Epidemiology of Liver Cancer in Latin America: Current and Future Trends(2020) CARRILHO, Flair Jose; PARANAGUA-VEZOZZO, Denise Cerqueira; CHAGAS, Aline Lopes; ALENCAR, Regiane Saraiva de Souza Melo; FONSECA, Leonardo Gomes daOver 38,000 cases of hepatocellular carcinoma (HCC) are estimated to occur in Latin America annually. The region is characterized by sociocultural heterogeneity and economic disparities, which impose barriers in addressing this major health issue. A significant proportion of patients are still diagnosed in the later stages of the disease, although efforts to implement effective screening programs have been reported by referral centers. While viral hepatitis remains the predominant etiology of liver disease among HCC cases in Latin America, a high prevalence of fatty liver disease in the region is a matter of concern, reflecting the current scenario in many Western countries. In addition, other risk factors such as alcohol, aflatoxin, and early-onset HCC in hepatitis B virus infection contribute to the burden of HCC in Latin America. Interventions to increase screening coverage, expand healthcare access, and implement continuing medical training are key challenges to be overcome.
- Management of Hepatocellular Carcinoma during the COVID-19 Pandemic - S(a)over-tildeo Paulo Clinicas Liver Cancer Group Multidisciplinary Consensus Statement (vol 75, e2192, 2020)(2021) ABADALA, Edson; CHAGAS, A. L.; FONSECA, L. G. da; COELHO, F. F.; SAUD, L. R. C.; ABADALA, E.; ANDRAUS, W.
- Hepatocellular carcinoma (HCC) in patients with Non-Alcoholic Fatty Liver Disease (NAFLD): screening, treatment and survival analysis in a Brazilian series(2022) ALENCAR, Regiane Saraiva de Souza Melo; OLIVEIRA, Claudia P.; CHAGAS, Aline Lopes; FONSECA, Leonardo Gomes da; MACCALI, Claudia; SAUD, Lisa Rodrigues da Cunha; XERFAN, Mariana Pinheiro; STEFANO, Jose Tadeu; HERMAN, Paulo; D'ALBUQUERQUE, Luiz Augusto Carneiro; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JoseObjective: The aim of the present study was to evaluate the clinical features, Hepatocellular Carcinoma (HCC) screening, treatment modalities, and Overall Survival (OS) in a series of Non-Alcoholic Fatty Liver Disease-Related Hepatocellular Carcinoma (NAFLD-HCC) Brazilian patients. Methods: This was a cross-sectional study at the Instituto do Cancer do Estado de Sao Paulo, at the Faculdade de Medicina da Universidade de Sao Paulo with the approval of the local research ethics committee. NAFLD patients with HCC diagnosed, from May 2010 to May 2019, were included. Results: A total of 131 patients were included. Risk factors for NAFLD were present in 94.7% of the patients. Only 29% of patients were in the HCC screening program before diagnosis. HCC treatment was performed in 84.7% of patients. Cumulative survival at the end of the first year was 72%, second-year 52%, and fifth-year 32%. HCC screening before diagnosis was not significantly associated with higher cumulative survival. The independent factors associated with shorter general survival were BCLC C-D, p < 0.001, and the size of the largest nodule > 42 mm, p = 0.039. Conclusions: Although the efficacy of screening in our population regarding overall survival was hampered due to the sample size (29% had screening), BCLC stages C-D and the size of the largest nodule larger than 42 mm were identified as independent factors of worse prognosis.
- Treatment Outcomes in Patients with Advanced Fibrolamellar Hepatocellular Carcinoma Under Systemic Treatment: Analysis of Clinical Characteristics, Management, and Radiomics(2023) FONSECA, Leonardo Da; YAMAMOTO, Victor Junji; CUNHA, Mateus Trinconi; TORRE, Giovanna Sawaya; ARAUJO, Raphael L. C.; FONSECA, Gilton Marques; CHEN, Andre Tsin Chih; CHAGAS, Aline Lopes; HERMAN, Paulo; ALVES, Venancio Avancini Ferreira; CARRILHO, Flair JosePurpose: Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare primary liver malignancy often diagnosed at advanced stages. While there are limited data on the efficacy of specific agents, we aim to report outcomes of patients treated with systemic therapies and explore prognostic factors.Patients and Methods: Medical records of patients treated between 2010 and 2022 were reviewed. Treatments were defined after multidisciplinary assessment. Descriptive statistics were used for baseline demographics. Time-to-event outcomes were estimated using the Kaplan-Meier method, compared by log-rank and adjusted by a regression model. Radiomic features (including size, shape, and texture) of the primary lesion were extracted and dimensionality reduced. An unsupervised Gaussian Mixture Model (GMM) clustering was performed, and survival was compared between clusters.Results: We identified 23 patients: 12 males, with a median age of 23.6 years. At diagnosis, 82.6% had metastases, most frequently to the lungs (39.1%), lymph nodes (39.1%), and peritoneum (21.7%). Patients received a median of three lines (1-8) of treatment, including different regimens. Sorafenib (39.1%), capecitabine (30.4%), and capecitabine/interferon (13%) were the most used first-line regimens. The median time-to-failure was 3.8 months (95% CI: 3.2-8.7). Capecitabine + interferon (42.1%) and platinum combinations (39.1%) were the most used second-line regimens, with a time-to-failure of 3.5 months (95% CI: 1.5-11.6). Median overall survival was 26.7 months (95% CI: 15.1-40.4). A high baseline neutrophil-to-lymphocyte ratio (NLR) was associated with worse survival (p=0.02). Radiomic features identified three clusters, with one cluster (n=6) having better survival (40.4 vs 22.6 months, p=0.039). Tumor sphericity in the arterial phase was the most relevant characteristic associated with a better prognosis (accuracy=0.93).Conclusion: FLHCC has unique features compared to conventional HCC, including young onset, gender balance, and absence of hepatopathy. Systemic therapies can provide encouraging survival, but lack of uniformity precludes defining a preferable regimen. Radiomics and NLR were suggested to correlate with prognosis and warrant further validation.
conferenceObject A multicenter international study of sorafenib treatment in patients with hepatocellular carcinoma and chronic kidney disease undergoing hemodialysis(2019) DIAZ-GONZALEZ, Alvaro; SANDUZZI-ZAMPARELLI, Marco; FONSECA, Leonardo Gomes da; COSTANZO, Giovan Giuseppe Di; ALVES, Rogerio; IAVARONE, Massimo; LEAL, Cassia Regina G.; SACCO, Rodolfo; MATILLA, Ana M.; GUERRA, Manuel Hernandez; SOTERAS, Gabriel Alejandro Aballay; MARCUS, Worns; PINTER, Matthias; VARELA, Maria; LADEKARL, Morten; CHAGAS, Aline Lopes; MINGUEZ, Beatriz; RUIZ-TAPIADOR, Juan Ignacio Arenas; GRANITO, Alessandro; SANCHEZ, Yolanda; ROJAS, Angela; LOPE, Carlos Rodriguez De; ALVARES-DA-SILVA, Mario Reis; PASCUAL, Sonia; RIMASSA, Lorenza; LLEDO, Jose Luis; HUERTAS, Carlos; SANGRO, Bruno; GIANNINI, Edoardo Giovanni; DELGADO, Manuel; GOMEZ, Mercedes Vergara; PERELLO, Christie; LUE, Alberto; SALA, Margarita; MOYA, Adolfo Gallego; COLL, Susana; ALSINA, Tania Hernaez; PINERO, Federico; PEREIRA, Gustavo; FRANCA, Alex Vianey Callado; MARIN, Juan; ANDERS, Maria Margarita; MELLO, Vivianne; LOZANO, Maria Del Mar; NAULT, Jean Charles; MENENDEZ, Jose Maria; JUAREZ, Ignacio Garcia; BRUIX, Jordi; REIG, Maria- BRAZILIAN SOCIETY OF HEPATOLOGY UPDATED RECOMMENDATIONS FOR SYSTEMIC TREATMENT OF HEPATOCELLULAR CARCINOMA(2023) CHAGAS, Aline Lopes; LEAL, Cassia Regina Guedes; MELLO, Vivianne Barreto de; BARROS, Fábio Marinho Do Rego; BITTENCOURT, Paulo Lisboa; MATTOS, Angelo A; AROUCHA, Dayse; FONSECA, Leonardo G da; SILVA, Joyce Roma Lucas de; DOTTORI, Mariana Fonseca; TEIXEIRA, Rosangela; MENDES, Liliana Sampaio Costa; REZENDE, Rosamar Eulira Fontes; FILGUEIRA, Norma Arteiro; COUTINHO, Anelisa K; ARAÚJO NETO, João Marcello de; COELHO, Henrique Sergio Moraes; PESSOA, Mario Guimarães; CHEINQUER, Hugo; PARISE, Edison Roberto; FRANÇA, Alex; ÁLVARES-DA-SILVA, Mário Reis; CARRILHO, Flair José; CORAL, Gabriela P; PINTO, Paulo de Tarso Aparecida; PEREIRA, Leila M M Beltrão; PARANÁ, Raymundo; ALVES, Rogério Camargo Pinheiro; BRANDÃO-MELLO, Carlos EduardoABSTRACT Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related mortality worldwide. The Brazilian Society of Hepatology (SBH) published in 2020 the updated recommendations for the diagnosis and treatment of HCC. Since then, new data have emerged in the literature, including new drugs approved for the systemic treatment of HCC that were not available at the time. The SBH board conducted an online single-topic meeting to discuss and review the recommendations on the systemic treatment of HCC. The invited experts were asked to conduct a systematic review of the literature on each topic related to systemic treatment and to present the summary data and recommendations during the meeting. All panelists gathered together for discussion of the topics and elaboration of the updated recommendations. The present document is the final version of the reviewed manuscript containing the recommendations of SBH and its aim is to assist healthcare professionals, policy-makers, and planners in Brazil and Latin America with systemic treatment decision-making of patients with HCC.
- Safety and efficacy of cytotoxic chemotherapy in hepatocellular carcinoma after first-line treatment with sorafenib(2018) FONSECA, Leonardo Gomes da; MARTA, Guilherme Nader; BRAGHIROLI, Maria Ignez Freitas Melro; CHAGAS, Aline Lopes; CARRILHO, Flair Jose; HOFF, Paulo Marcelo; SABBAGA, JorgeBackgroundBefore the targeted therapies era, cytotoxic chemotherapy (CCT) was an option for advanced hepatocellular carcinoma (HCC), even with the lack of supporting evidence. Since the last decade, sorafenib has been established as the first-line therapy. Although new agents are being incorporated, CCT is still considered in regions where new drugs are not available or for patients who progressed through the approved therapies and remain in good clinical condition. We aimed to describe our experience regarding the use of CCT as second-line treatment after sorafenib.MethodsA database of 273 patients was evaluated. Patients that received CCT after sorafenib progression were selected for the analysis. Descriptive statistics was used for categorical and continue variables. Median survival was estimated with Kaplan-Meier curves. Variables were found to be significant if the two-sided p value was 0.05 on multivariate testing using the Cox regression model.ResultsForty-five patients received CCT; 33 (73.3%) had Child-Pugh classification A, and 34 (75.6%) had stage C according to the Barcelona Clinic Liver Cancer (BCLC) staging system. The most used regimen was doxorubicin in 25 patients (55.6%). Median overall survival (OS) was 8.05 months (95% confidence interval [CI] 2.73 - 9.88 months). The 6-month and 1-year survival probability was 52.4% and 27.36%, respectively. Eastern Cooperative Oncology Group performance status (ECOG PS) 0-1 and disease control with sorafenib was independently associated with better OS in patients treated with CCT. Any-grade toxicities were observed in 82.2% and grade 3-4 in 44.4% of the patients.ConclusionIn accordance with previous studies, CCT had a notable rate of adverse events. The poor prognosis of this cohort suggests that CCT may not alter the natural history of HCC after sorafenib progression.
- Management of Hepatocellular Carcinoma during the COVID-19 Pandemic - Sao Paulo Clinicas Liver Cancer Group Multidisciplinary Consensus Statement(2020) CHAGAS, Aline Lopes; FONSECA, Leonardo Gomes; COELHO, Fabricio Ferreira; SAUD, Lisa Rodrigues Cunha; ABADALA, Edson; ANDRAUS, Wellington; FIORE, Lucas; MOREIRA, Airton Mota; MENEZES, Marcos Roberto; CARNEVALE, Francisco Cesar; TANI, Claudia Megumi; ALENCAR, Regiane S. S. M.; D'ALBUQUERQUE, Luiz Augusto Carneiro; HERMAN, Paulo; CARRILHO, Flair JoseMore than 18 million people in 188 countries have been diagnosed as having coronavirus disease (COVID-19), and COVID-19 has been responsible for more than 600,000 deaths worldwide. Brazil is now the second most affected country globally. Faced with this scenario, various public health measures and changes in the daily routines of hospitals were implemented to stop the pandemic. Patients with hepatocellular carcinoma (HCC) are at an increased risk for severe COVID-19 as they present with two major diseases: cancer and concomitant chronic liver disease. The COVID-19 pandemic can significantly impact the management of HCC patients from diagnosis to treatment strategies. These patients need special attention and assistance at this time, especially since treatment for tumors cannot be delayed in most cases. The aim of this guideline was to standardize the management of HCC patients during the COVID-19 pandemic. This document was developed, on the basis of the best evidence available, by a multidisciplinary team from Instituto do Cancer do Estado de Sao Paulo (ICESP), and Instituto Central of the Hospital das Clinicas da Universidade de Sao Paulo (HC-FMUSP), which are members of the Sao Paulo Cli ' nicas Liver Cancer Group.
- Brazilian Landscape of Hepatocellular Carcinoma(2023) FONSECA, Leonardo G.; CHEN, Andre T. C.; OLIVEIRA, Irai S. de; CHAGAS, Aline L.; KRUGER, Jaime A. P.; CARRILHO, Flair J.The incidence of hepatocellular carcinoma (HCC) is expected to increase in the coming years, and strategies to mitigate the burden of this disease are needed in different regions. Geographic variations in epidemiology and risk factors, such as viral hepatitis and metabolic disease, pose challenges in adopting programs for early detection programs and management of patients with HCC. Brazil, like other countries, has high economic and social inequality, with heterogeneous access to health care. Viral hepatitis is themain risk factor but there is growing awareness of fatty liver disease. Risk factor monitoring and screening programs are unmet priorities because patients are often diagnosed at later stages. Advances in the management of patients with HCC have been made in recent years, including new tools for selecting patients for liver transplantation, sophisticated surgical techniques, and new systemic agents. High-volume academic centers often achieve favorable results through the adoption and application of established treatments, but this is not a reality in most regions of Brazil, because of disparities in wealth and resources. As HCC management requires a coordinated and multidisciplinary team, the role of local referral centers in decentralizing access to treatments and promoting health education in different regions should be encouraged and supported.