LEONARDO GOMES DA FONSECA
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.
- 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.
- Liver decompensation is a frequent cause of treatment discontinuation and prognostic factor in intermediate-advanced HCC(2023) PINEROA, Federico; ANDERS, Margarita; BERMUDEZ, Carla; DEMIRDJIAN, Ezequiel; VARON, Adriana; PALAZZO, Ana; RODRIGUEZ, Jorge; BELTRAN, Oscar; FONSECA, Leonardo Gomes da; RIDRUEJO, Ezequiel; CABALLINI, Pablo; TAMAGNONE, Norberto; REGGIARDO, Virginia; CHEINQUER, Hugo; ARAUJO, Alexandre; ARUFE, Diego; MARIN, Juan Ignacio; RATUSNU, Natalia; MANERO, Estela; PEREZ, Daniela; VILLA, Marina; OROZCO, Federico; MURGA, Dolores; MARCIANO, Sebastian; BESSONE, Fernando; SILVA, Marcelo; MENDIZABAL, ManuelIntroduction and Objectives: With the advent of new therapeutic options for patients with hepatocellular car-cinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real -world data regarding prognostic survival factors are of significant importance. Patients and Methods: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic varia-bles and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, esti-mating hazard ratios (HR) and 95% confidence intervals (95% CI). Results: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enroll-ment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was inde-pendently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initi-ated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first -line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decom-pensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. Conclusions: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists. (c) 2023 Fundacion Clinica Medica Sur, A.C.
bookPart Tumores do trato gastrointestinal(2023) VICTOR, Carolina Ribeiro; SARAGIOTTO, Daniel Fernandes; FONSECA, Leonardo Gomes da; MAK, Milena Perez; TAKAHASHI, Tiago Kenji- 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.
- Current landscape and future directions for systemic treatments of hepatocellular carcinoma(2023) FONSECA, Leonardo G.; CARRILHO, Flair J.
- 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.