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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- The complexity of cholangiocarcinoma goes beyond clinical practice: Challenges in trials design and interpretation(2022) FONSECA, Leonardo G. Da; FORNER, Alejandro
- 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.
- 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.
conferenceObject Irinotecan combined with Panitumumab or cetuximab as third-line treatment for metastatic colorectal cancer.(2022) BRAGHIROLI, Maria Ignez; VICENTINI, Maria Fernanda Batistuzzo; FONSECA, Leonardo Gomes da; SOUZA, Karla Teixeira; BONADIO, Renata Colombo; BRAGHIROLI, Oddone Freitas Melro; MATHIAS, Maria Cecilia Machado; TALANS, Aley; MENDOZA, Maria Elizabeth Zambrano; MARTINS, Juliana Goes; SABAGGA, Jorge; MONIZ, Camila Venchiarutti Motta Venchiarutti; HOFF, Paulo Marcelo- Combination approaches in hepatocellular carcinoma: How systemic treatment can benefit candidates to locoregional modalities(2022) FONSECA, Leonardo Gomes da; ARAUJO, Raphael L. C.The management of hepatocellular carcinoma (HCC) is challenging because most patients have underlying cirrhosis, and the treatment provides, historically, a limited impact on the natural history of patients with advanced-stage disease. Additionally, recurrence rates are high for those patients who receive local and locoregional modalities, such as surgical (resection and transplantation) or image-guided (ablation and intra-arterial) therapies. Translational research has led to new concepts that are reshaping the current clinical practice. Substantial advancements were achieved in the understanding of the hallmarks that drive hepatocarcinogenesis. This has primed a successful incorporation of novel agents with different targets, such as anti-angiogenic drugs, targeted-therapies, and immune-checkpoint inhibitors. Although clinical trials have proven efficacy of systemic agents in advanced stage disease, there is no conclusive evidence to support their use in combination with loco-regional therapy. While novel local modalities are being incorporated (e.g., radioembolization, microwave ablation, and irreversible electroporation), emerging data indicate that locoregional treatments may induce tumor microenvironment changes, such as hyperexpression of growth factors, release of tumor antigens, infiltration of cytotoxic lymphocytes, and modulation of adaptative and innate immune response. Past trials that evaluated the use of antiangiogenic drugs in the adjuvant setting after ablation or chemoembolization fail to demonstrate a substantial improvement. Current efforts are directed to investigate the role of immunotherapy-based regimens in this context. The present review aims to describe the current landscape of systemic and locoregional treatments for HCC, present evidence to support combination approaches, and address future perspectives.
- Immunotherapy-Based Treatments of Hepatocellular Carcinoma: AJR Expert Panel Narrative Review(2022) CANNELLA, Roberto; LEWIS, Sara; FONSECA, Leonardo da; RONOT, Maxime; RIMOLA, JordiThe advent of immunotherapy for patients with hepatocellular carcinoma (HCC) has changed the treatment landscape and conferred a survival benefit on patients with advanced HCC, who typically have a very poor prognosis. The most pronounced improvements in response, as documented by standardized response criteria based on CT or MRI, have been achieved when immunotherapy is combined with other systemic or locoregional therapies. Immune checkpoint inhibitor treatments result in unique patterns on CT and MRI that challenge the application of conventional response criteria such as RECIST, modified RECIST, and European Association for the Study of the Liver criteria. Thus, newer criteria have been developed to gauge therapy response or disease progression for patients receiving immunotherapy, including immune-related RECIST (iRECIST) and immune-modified RECIST (imRECIST), though these remain unvalidated. In this review, we describe the current landscape of immunotherapeutic agents used for HCC, summarize the results of published studies, review the pathobiologic mechanisms that provide a rationale for the use of these agents, and report on the status of response assessment for immunotherapy either alone or in combination with other treatment options. Finally, consensus statements are provided to inform radiologists about essential considerations in the era of a rapidly changing treatment paradigm for patients with HCC.
- 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.