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.
- 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.
- Outcome of liver cancer patients with SARS-CoV-2 infection: An International, Multicentre, Cohort Study(2022) MUNOZ-MARTINEZ, Sergio; SAPENA, Victor; FORNER, Alejandro; BRUIX, Jordi; SANDUZZI-ZAMPARELLI, Marco; RIOS, Jose; BOUATTOUR, Mohamed; EL-KASSAS, Mohamed; LEAL, Cassia R. G.; MOCAN, Tudor; NAULT, Jean-Charles; ALVES, Rogerio C. P.; REEVES, Helen L.; FONSECA, Leonardo da; GARCIA-JUAREZ, Ignacio; PINATO, David J.; VARELA, Maria; ALQAHTANI, Saleh A.; ALVARES-DA-SILVA, Mario R.; BANDI, Juan C.; RIMASSA, Lorenza; LOZANO, Mar; SANTIAGO, Jesus M. Gonzalez; TACKE, Frank; SALA, Margarita; ANDERS, Maria; LACHENMAYER, Anja; PINERO, Federico; FRANCA, Alex; GUARINO, Maria; ELVEVI, Alessandra; CABIBBO, Giuseppe; PECK-RADOSAVLJEVIC, Markus; ROJAS, Angela; VERGARA, Mercedes; BRACONI, Chiara; PASCUAL, Sonia; PERELLO, Christie; MELLO, Vivianne; RODRIGUEZ-LOPE, Carlos; ACEVEDO, Juan; VILLANI, Rosanna; HOLLANDE, Clemence; VILGRAIN, Valerie; TAWHEED, Ahmed; THEODORO, Carmem Ferguson; SPARCHEZ, Zeno; BLAISE, Lorraine; VIERA-ALVES, Daniele E.; WATSON, Robyn; CARRILHO, Flair J.; MOCTEZUMA-VELAZQUEZ, Carlos; D'ALESSIO, Antonio; IAVARONE, Massimo; REIG, MariaBackground & Aims Information about the impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in patients with liver cancer is lacking. This study characterizes the outcomes and mortality risk in this population. Methods Multicentre retrospective, cross-sectional, international study of liver cancer patients with SARS-CoV-2 infection registered between February and December 2020. Clinical data at SARS-CoV-2 diagnosis and outcomes were registered. Results Two hundred fifty patients from 38 centres were included, 218 with hepatocellular carcinoma (HCC) and 32 with intrahepatic cholangiocarcinoma (iCCA). The median age was 66.5 and 64.5 years, and 84.9% and 21.9% had cirrhosis in the HCC and iCCA cohorts respectively. Patients had advanced cancer stage at SARS-CoV-2 diagnosis in 39.0% of the HCC and 71.9% of the iCCA patients. After a median follow-up of 7.20 (IQR: 1.84-11.24) months, 100 (40%) patients have died, 48% of the deaths were SARS-CoV-2-related. Forty (18.4%) HCC patients died within 30-days. The death rate increase was significantly different according to the BCLC stage (6.10% [95% CI 2.24-12.74], 11.76% [95% CI 4.73-22.30], 20.69% [95% CI 11.35-31.96] and 34.52% [95% CI 17.03-52.78] for BCLC 0/A, B, C and D, respectively; p = .0017). The hazard ratio was 1.45 (95% CI 0.49-4.31; p = .5032) in BCLC-B versus 0/A, and 3.13 (95% CI 1.29-7.62; p = .0118) in BCLC-C versus 0/A in the competing risk Cox regression model. Nineteen out of 32 iCCA (59.4%) died, and 12 deaths were related to SARS-CoV-2 infection. Conclusions This is the largest cohort of liver cancer patients infected with SARS-CoV-2. It characterizes the 30-day mortality risk of SARS-CoV-2 infected patients with HCC during this period.
- 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.
- Association between Metabolic Disorders and Cholangiocarcinoma: Impact of a Postulated Risk Factor with Rising Incidence(2022) FONSECA, Leonardo G. Da; HASHIZUME, Pedro H.; OLIVEIRA, Irai Santana de; IZQUIERDO-SANCHEZ, Laura; SAUD, Lisa Rodrigues da Cunha; XERFAN, Mariana Pinheiro; ALVES, Venancio Avancini Ferreira; MELLO, Evandro Sobroza de; HERMAN, Paulo; BANALES, Jesus M.; OLIVEIRA, Claudia P.; CARRILHO, Flair J.Simple Summary A potential relationship between cholangiocarcinoma and metabolic disorders has been suggested, but there is a lack of published data. This study aimed to describe the prevalence of metabolic disorders in a cohort of 122 patients with cholangiocarcinoma and report clinical outcomes. We found a prevalence of 42.6% of metabolic disorders. There was no significant difference in overall survival between patients with or without metabolic disorders, although there was a better survival in the subgroup of patients undergoing surgical resection. This indicates a need to better explore the association between cholangiocarcinoma in a metabolic background. Introduction and objectives: The incidence of cholangiocarcinoma (CCA) has been increasing globally. Although a concomitant increase in the incidence of metabolic disorders might suggest a causal relationship, the data are scarce. We aimed to describe the prevalence of metabolic disorders in patients with CCA and report the clinical features and outcomes. Patients and Methods: Retrospective study including patients with CCA. Patients were divided into: (1) past history of diabetes or/and overweight/obesity (""metabolic disorder group"") and (2) without any of these features (""non-metabolic-disorder group""). A Cox regression model was used to determine the prognostic factors. Results: 122 patients were included. In total, 36 (29.5%) had overweight/obesity, 24 (19.7%) had diabetes, and 8 (6.6%) had both. A total of 29 (23.8%) patients had resectable disease and received upfront surgery. A total of 104 (85.2%) received chemotherapy for advanced/recurrent disease. The overall survival of the cohort was 14.3 months (95% CI: 10.1-17.3). ECOG-PS 0 (p < 0.0001), resectable disease (p = 0.018) and absence of vascular invasion (p = 0.048) were independently associated with better prognosis. The ""metabolic disorder group"" (n = 52) had a median survival of 15.5 months (95% CI 10.9-33.9) vs. 11.5 months (95% CI 8.4-16.5) in the ""non-metabolic-disorder group"" (n = 70) (HR: 1.10; 95% CI 0.62-1.94). Patients with resectable disease in the ""metabolic group"" had longer survival than patients in the ""non-metabolic group"" (43.4 months (95% CI 33.9-NR) vs. 21.8 months (95% CI 8.6-26.9); HR = 0.12, 95% CI 0.03-0.59). Conclusion: Metabolic disorders are frequent among CCA patients. Underlying metabolic comorbidities may be associated with prognosis in resectable CCA. There is a need to explore the mechanism that drives CCA carcinogenesis in a metabolic background.
- A multidisciplinary approach to peritoneal metastasis from hepatocellular carcinoma: clinical features, management and outcomes(2022) FONSECA, Leonardo G. Da; LEONARDI, Paulo C.; HASHIZUME, Pedro H.; SANSONE, Francesco; SAUD, Lisa R.; CARRILHO, Flair J.; HERMAN, PauloAim of the study: Hepatocellular carcinoma (HCC) is a lethal malignancy with heterogeneous behavior determined by liver function, clinical presentation and treatment response. Peritoneal metastasis (PM) from HCC is rare and management is challenging. We aim to report a cohort of patients with advanced HCC and describe demographic characteristics, treatment and outcomes of patients with PM. Material and methods: We analyzed data from a retrospective cohort of patients with HCC. Patients with PM were analyzed individually. Baseline characteristics, treatment strategy and median overall survival (OS) with 95% confidence interval (CI) were reported. Results: 238 patients with advanced HCC were evaluated. Eleven patients had PM: 7 patients were treated with systemic treatment and 4 were treated with upfront peritonectomy followed by systemic treatment at recurrence. These 4 patients had well-preserved liver function and low disease burden and were younger compared to the total cohort. The median time to recurrence after peritonectomy was 30.25 months (interquartile range [IQR]: 13.53-46.92): 3 of them presented peritoneal recurrence (2 with diffuse peritoneal spread and 1 with concomitant hepatic recurrence) and 1 presented pulmonary recurrence. Overall, patients with PM showed similar OS compared to patients with other metastatic sites (11.8 months; 95% CI: 1.5-19.8 vs. 8 months; 95% CI: 6.7-10, p = 0.901). Patients with PM treated with upfront surgery had a median OS of 60 months (95% CI: 16.7-not reached). Conclusions: Resection of PM from HCC may provide long-term survival in selected patients. A multidisciplinary approach is the optimal strategy for managing PM from HCC.
- 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.
- 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.