LEONARDO GOMES DA FONSECA

(Fonte: Lattes)
Índice h a partir de 2011
11
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

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  • article 29 Citação(ões) na Scopus
    Return to work after breast cancer diagnosis: An observational prospective study in Brazil
    (2018) LANDEIRO, Luciana C. G.; GAGLIATO, Debora M.; FEDE, Angelo B.; FRAILE, Natalia M.; LOPEZ, Rossana M.; FONSECA, Leonardo G. da; PETRY, Vanessa; TESTA, Laura; HOFF, Paulo M.; MANO, Max S.
    Background In North America and Europe, return-to-work (RTW) rates vary among breast cancer (BC) survivors, from 24% to 66% and from 53% to 82% at 6 and 36 months after diagnosis, respectively. To date, there is a lack of data on RTW rates after BC diagnosis in Latin America. Therefore, the primary objectives of this study were to define RTW rates at 12 and 24 months after BC diagnosis and to identify the factors associated with RTW in this population. Methods In total, 125 employed women from a single institution with newly diagnosed BC were interviewed by telephone at 6, 12, and 24 months after diagnosis. Those who had inoperable or metastatic disease were excluded. Results Overall, RTW rates were 30.3% and 60.4% at 12 and 24 months after BC diagnosis, respectively. Most women reported that they received support from their employer, but only 29.1% reported having been offered work adjustments. In multivariate analysis, the factors associated with positive RTW outcomes included higher household income (odds ratio [OR], 17.76; 95% confidence interval [CI], 3.33-94.75; P = .001), breast-conserving surgery (OR, 9.77; 95% CI, 2.03-47.05; P = .004), and work adjustments (OR, 37.62; 95% CI, 2.03-47.05; P = .004). The factors associated with negative RTW outcomes included adjuvant endocrine therapy (OR, 0.11; 95% CI, 0.02-0.74; P = .023), and depression diagnosed after BC (OR, 0.07; 95% CI, 0.01-0.63; P = .017). Conclusions RTW rates in the current study were lower than those observed in developed countries but similar to the rates among low-income Americans. Workplace adjustments, higher income, breast-conserving surgery, endocrine therapy, and depression after BC played an important role in the RTW decision. Cancer 2018;124:4700-4710. (C) 2018 American Cancer Society.
  • article 12 Citação(ões) na Scopus
    Young-age onset colorectal cancer in Brazil: Analysis of incidence, clinical features, and outcomes in a tertiary cancer center
    (2019) SILVA, Andrea C. B.; VICENTINI, Maria Fernanda B.; MENDOZA, Elizabeth Z.; FUJIKI, Fernanda K.; FONSECA, Leonardo G. da; BRAGHIROLI, Maria Ignez F. M.; HOFF, Paulo M.
    Background: Recent studies report increasing incidence of colorectal cancer (CRC) in the young-age population, but data concerning clinical behavior, pathologic findings, and prognosis are controversial for this group. Early recognition of CRC in young patients is a challenge and diagnosis at advanced stage is clearly associated with worse outcomes. Materials and methods: We retrospectively reviewed medical records of 5806 patients diagnosed with CRC between January/2011 and November/2016 and identified 781 patients aged less than 50-years-old. Results: We found an absolute increasing in the incidence of CRC in patients <50 years old of 1.88%-2.23% annually, with a relative increasing of 35.3% between 2011 and 2016. Median age was 42 years, 57.4% were female and 20.9% reported family history of CRC. Left-sided tumors were more frequent and the majority of patients were symptomatic. The most common stages at diagnosis were III (34.1%) and IV (37.3%). The median overall survival (OS) for stage IV was 25 months (95% Cl 20.7-29.3) and was not reached for Stages I-III (P < 0.001). Family history of CRC was independently associated with better OS in stage IV(P= 0.02). For stages I-III, wild-type KRAS, family history of CRC, and absence of angiolymphatic invasion were associated with better OS (P.0.02, P=0.01 and P < 0.001, respectively). Conclusions: In our cohort, the incidence of early-onset CRC is increasing over the past years. Young patients were more likely to be diagnosed with metastatic disease, left-sided and/or rectum site and symptoms at presentation. These findings highlight the emerging importance of young-age onset CRC and the need to discuss strategies to early diagnosis.
  • article 6 Citação(ões) na Scopus
    Response to Paclitaxel in an Adult Patient with Advanced Kaposiform Hemangioendothelioma
    (2016) MOTA, Jose Mauricio; SCARANTI, Mariana; FONSECA, Leonardo G.; TOLOI, Diego Araujo; CAMARGO, Veridiana Pires de; MUNHOZ, Rodrigo Ramella; FEHER, Olavo; HOFF, Paulo M.
    Background: Kaposiform hemangioendothelioma (KHE) is a rare neoplasm of vascular origin that typically arises from the skin or soft tissues as a solitary tumor. The optimal therapy for this disease is still unknown. We report the case of an adult patient presenting with metastatic KHE of the spleen, who had a partial response after treatment with paclitaxel. Case Presentation: A 36-year-old man presented in November 2012 with a nontraumatic rupture of the spleen. A splenectomy was performed, and the pathology was consistent with a nonspecific vascular proliferation. Follow-up scans revealed lytic bone lesions and liver metastasis. A biopsy of the liver was performed and confirmed KHE. The decision was made to proceed with treatment with gemcitabine and docetaxel, which was discontinued due to myelotoxicity. The patient was then transferred to our institution, and a pathology review supported the diagnosis of metastatic KHE. His disease remained stable until February 2014, when he developed progression in the liver. Chemotherapy was restarted with paclitaxel, and a partial response was documented after 3 cycles. Unfortunately, disease progression occurred after 24 weeks, and subsequent treatments included prednisone, doxorubicin, interferon-a, gemcitabine, and ifosfamide, without any response. The patient developed Kasabach-Merritt phenomenon and passed away 1 week later due to a major gastrointestinal bleeding. Conclusions: This case report suggests that paclitaxel could be considered as a treatment option for advanced KHE, a rare condition for which no standard treatment exists. (C) 2016 The Author(s) Published by S. Karger AG, Basel
  • article 1 Citação(ões) na Scopus
    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 Jose
    Prognostic 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.
  • article
    Safety and efficacy of sorafenib in patients with Child-Pugh B advanced hepatocellular carcinoma
    (2015) FONSECA, Leonardo Gomes Da; BARROSO-SOUSA, Romualdo; BENTO, Afonso Da Silva Alves; BLANCO, Bruna Paccola; VALENTE, Gabriel Luis; PFIFFER, Tulio Eduardo Flesch; HOFF, Paulo Marcelo; SABBAGA, Jorge
    Sorafenib demonstrated a survival benefit in the treatment of advanced hepatocellular carcinoma (HCC) in phase III trials. However, almost all the patients included in those trials exhibited well-preserved liver function (Child-Pugh A). The aim of this study was to describe our experience with sorafenib in Child-Pugh B HCC patients. A database of patients with advanced HCC treated with sorafenib was retrospectively evaluated. The median overall survival of Child-Pugh B patients (n=20) was 2.53 months [95% confidence interval (CI): 0.33-5.92 months] and of Child-Pugh A patients (n=100) 9.71 months (95% CI: 6.22-13.04). Child-Pugh B patients had a significantly poorer survival compared to Child-Pugh A patients (P=0.002). The toxicities were similar between the two groups. Metastasis, vascular invasion and alpha-fetoprotein level >1,030 ng/ml were not associated with survival among Child-Pugh B patients (P=0.281, 0.189 and 0.996, respectively). Although the survival outcomes were worse in Child-Pugh B patients treated with sorafenib, the toxicity profile was manageable. Therefore, there remains the question of whether to treat this subgroup of patients and more data are required to define the role of sorafenib in the context of liver dysfunction.
  • article 14 Citação(ões) na Scopus
    Regorafenib in Patients with Antiangiogenic-Naive and Chemotherapy-Refractory Advanced Colorectal Cancer: Results from a Phase IIb Trial
    (2019) RIECHELMANN, Rachel P.; LEITE, Luiz S.; BARIANI, Giovanni M.; GLASBERG, Joao; RIVELLI, Thomas G.; FONSECA, Leonardo Gomes da; NEBULONI, Daniela R.; I, Maria Braghiroli; QUEIROZ, Marcelo A.; ISEJIMA, Alice M.; KAPPELER, Christian; KIKUCHI, Luciana; HOFF, Paulo M.
    Background Regorafenib is a multikinase inhibitor with antiangiogenic effects that improves overall survival (OS) in metastatic colorectal cancer (mCRC) after failure of standard therapies. We investigated the efficacy and safety of regorafenib in antiangiogenic therapy-naive chemotherapy-refractory advanced colorectal cancer. Patients and Methods This single-center, single-arm, phase IIb study (NCT02465502) enrolled adults with mCRC whose disease had progressed on, or who were intolerant to, standard therapy, but who were antiangiogenic therapy-naive. Patients received regorafenib 160 mg once daily for 3 weeks per 4-week cycle. The primary endpoint was progression-free survival (PFS) rate at week 8. Results Of 59 treated patients, almost half had received at least four prior lines of therapy. Patients received a median of 86% of the planned dose. The week 8 PFS rate was 53% (95% confidence interval [CI], 39.1-64.3); median PFS was 3.5 months (95% CI, 1.8-3.6). Median OS was 7.4 months (95% CI, 5.3-8.9). Tumor response (RECIST version 1.1) was 2%, and metabolic response rate (criteria from the European Organisation for Research and Treatment of Cancer) was 41%. The most frequently reported regorafenib-related grade >= 3 adverse events were hypertension (36%), hand-foot skin reaction (HFSR, 25%), and hypophosphatemia (24%). There were no regorafenib-related deaths. An exploratory analysis showed that patients with grade >= 2 HFSR had longer OS (10.2 months) with regorafenib treatment versus those with grades 0-1 (5.4 months). Conclusion These findings support the antitumor activity of regorafenib in antiangiogenic-naive patients with chemotherapy-refractory mCRC. Implications for Practice The multikinase inhibitor regorafenib improved overall survival in the phase III CORRECT and CONCUR trials in heavily pretreated patients with treatment-refractory metastatic colorectal cancer (mCRC). Exploratory subgroup analysis from CONCUR suggested that regorafenib treatment prior to targeted therapy (including bevacizumab) may improve outcomes. In this single-center, single-arm phase IIb study, regorafenib demonstrated antitumor activity in 59 antiangiogenic-naive patients with chemotherapy-refractory mCRC. Further studies should assess the efficacy of regorafenib in this patient population, as well as explore the reasons behind improved outcomes among patients who had a metabolic response and those who developed hand-foot skin reaction.
  • article 14 Citação(ões) na Scopus
    Metronomic oral cyclophosphamide plus prednisone in docetaxel-pretreated patients with metastatic castration-resistant prostate cancer
    (2015) BARROSO-SOUSA, Romualdo; FONSECA, Leonardo Gomes da; SOUZA, Karla Teixeira; CHAVES, Ana Carolina Ribeiro; KANN, Ariel Galapo; CASTRO JR., Gilberto de; DZIK, Carlos
    We evaluated the efficacy and safety of metronomic oral cyclophosphamide (CTX) and prednisone in metastatic castration-resistant prostate cancer (mCRPC) patients. We analyzed retrospectively patients with mCRPC previously treated with docetaxel, and who received metronomic CTX (from 50 mg PO daily to 150 mg PO, 14 days/7 days off) and prednisone 10 mg PO daily between September 2009 and April 2014 were analyzed. The primary endpoint was prostate-specific antigen (PSA) decrease >= 50 %. Secondary analysis included PSA decrease >= 30 %, time-to-treatment failure (TTF) and toxicity. Demographics and baseline characteristics were summarized using descriptive statistics. PSA response and adverse events were reported as relative rates. Kaplan-Meier estimates were calculated and plotted for time-to-event endpoints. Forty patients were evaluated. The median age was 69 years old (52-86), 12 (30.0 %) patients presented a Karnofsky performance status (KPS) of <80 %, and 34 (85 %) presented with bone with or without nodal metastases. Median pretreatment PSA was 192 ng/dL (7-2696 ng/dL). All patients were previously exposed to docetaxel, including 33 (82.5 %) with docetaxel-refractory disease. PSA response rate was achieved in eight (20.0 %) out of 40 patients. Additionally, PSA declines of >= 30 % occurred in 14 (35.0 %) patients. The median TTF was 3 months (95 % confidence interval 2.5-3.5). The treatment was well tolerated. Grade 3/4 lymphopenia was reported in 11 (27.5 %) patients and was the only grade 3-4 toxicity reported. Metronomic oral CTX showed activity and safety in docetaxel-pretreated mCRPC patients. This regimen deserves further investigation in this setting.
  • article 10 Citação(ões) na Scopus
    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, Maria
    Background & 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.
  • article 0 Citação(ões) na Scopus
    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 Jose
    Objective: 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.
  • article 0 Citação(ões) na Scopus
    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 Jose
    Purpose: 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.