GILBERTO DE CASTRO JUNIOR

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Instituto do Câncer do Estado de São Paulo, Hospital das Clínicas, Faculdade de Medicina - Médico
LIM/24 - Laboratório de Oncologia Experimental, Hospital das Clínicas, Faculdade de Medicina - Líder

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  • conferenceObject
    Pooled Analysis of Outcomes with Second-Course Pembrolizumab Across 5 Phase 3 Studies of Non-Small-Cell Lung Cancer
    (2022) RODRIGUEZ-ABREU, D.; WU, Y. -L.; BOYER, M.; GARASSINO, M. C.; MOK, T. S. K.; CHENG, Y.; HUI, R.; KOWALSKI, D. M.; ROBINSON, A. G.; BRAHMER, J. R.; LEAL, T. A.; LOPES, G.; CHO, B. C.; NOGAMI, N.; NOVELLO, S.; PELED, N.; CASTRO JR., G. de; LEIBY, M. A.; CHIROVSKY, D.; LIN, J.; PIETANZA, M. C.; RECK, M.
  • conferenceObject
    Performance of the 2021 CKD-EPI equations without a race coefficient in a multi-racial population of adults with solid tumors: A prospective cross-sectional study.
    (2022) SILVA, Veronica Torres Costa E; GIL- JR., Luiz A.; INKER, Lesley; CAIRES, Renato; COSTALONGA, Elerson; COURA-FILHO, George; ESTEVEZ-DIZ, Maria Del Pilar; CASTRO, Gilberto; MATHEW, Paul; LEVEY, Andrew; BURDMANN, Emmanuel de Almeida
  • article 20 Citação(ões) na Scopus
    A prospective cross-sectional study estimated glomerular filtration rate from creatinine and cystatin C in adults with solid tumors
    (2022) SILVA, Veronica T. Costa e; JR, Luiz A. Gil; INKER, Lesley A.; CAIRES, Renato A.; COSTALONGA, Elerson; COURA-FILHO, George; SAPIENZA, Marcelo T.; JR, Gilberto Castro; ESTEVEZ-DIZ, Maria Dp; ZANETTA, Dirce Maria T.; ANTONANGELO, Leila; MARCAL, Lia; TIGHIOUART, Hocine; MIAO, Shiyuan; MATHEW, Paul; LEVEY, Andrew S.; BURDMANN, Emmanuel A.
    Current guidelines recommend estimating glomerular filtration rate (eGFR) using creatinine (eGFRcr) with the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation as the first test for GFR evaluation, but the Cockcroft-Gault (CG) equation is still commonly used in oncology practice and clinical trials despite increasing evidence of its inaccuracy compared to measured GFR (mGFR). Guidelines recommend eGFR using cystatin C (eGFRcys) or both markers (eGFRcr-cys) as a confirmatory test, but neither was carefully evaluated in cancer patients. Therefore, we compared performance of the CKD-EPI equations and others to the CG equation in adults with a variety of solid tumors. The mGFR was determined by plasma clearance of Cr-51-EDTA. Bias was defined as the median of the differences between mGFR and eGFR while accuracy was defined as the percentage of estimates that differed by more than 30% from the measured GFR (1-P30). We prospectively recruited 1,200 patients between April 2015 and September 2017 with a mean age and mGFR of 58.8 years and 78.4 ml/min/1.73m 2 , respectively. Bias among eGFRcr equations varied from -8.1 to +6.1 ml/min/1.73 m(2). CG was the least accurate, 1-P30 (95% confidence interval) was 24.9 (22.4- 27.3)%; CKD-EPI had 1-P30 of 19.1 (16.8-21.2)% while eGFRcr-cys had the best performance: bias -2.0 (-2.6 to -1.1) ml/min/1.73m(2) and 1-P30 7.8 (6.3-9.4)%. Thus, the CG equation should not be preferred over CKD-EPI equation, and eGFRcr-cys can be used as a confirmatory test in adults with solid tumors. Hence, a major policy implication would be to adopt general practice guideline-recommended methods for GFR evaluation in oncology practice and clinical trials.
  • article 7 Citação(ões) na Scopus
    Rationale and design of ON TRK: a novel prospective non-interventional study in patients with TRK fusion cancer treated with larotrectinib
    (2022) YANG, James C. H.; BROSE, Marcia S.; CASTRO, Gilberto; KIM, Edward S.; LASSEN, Ulrik N.; LEYVRAZ, Serge; PAPPO, Alberto; LOPEZ-RIOS, Fernando; REEVES, John A.; FELLOUS, Marc; PENAULT-LLORCA, Frederique; RUDZINSKI, Erin R.; TABATABAI, Ghazaleh; VASSAL, Gilles; DRILON, Alexander; TRENT, Jonathan
    Background: Tropomyosin receptor kinase (TRK) fusion proteins resulting from neurotrophic tyrosine receptor kinase (NTRK) gene fusions are rare primary oncogenic drivers in a wide array of tumors. Larotrectinib is a first-in-class, highly selective, central nervous system-active TRK inhibitor approved by the US Food and Drug Administration (FDA), European Medicines Agency (EMA), and over 40 countries for the treatment of TRK fusion solid tumors in adult and pediatric patients. Due to the rarity of TRK fusion cancer, larotrectinib was granted accelerated approval based on a relatively small number of patients enrolled in three early phase trials. ON-TRK aims to evaluate the safety profile of larotrectinib in a broader population and over extended time periods. Methods: ON-TRK is a prospective, non-interventional, open-label, multicenter, multi-cohort, post-approval study in adult and pediatric patients with locally advanced or metastatic TRK fusion cancer treated with larotrectinib that will describe the safety and effectiveness of larotrectinib in real-world practice conditions. Adult patients will be grouped by tumor type and followed for at least 2 years. Patients <18 years old will be enrolled under a 'pediatric' cohort regardless of tumor type and will be followed for 5 years to evaluate the risk of potential long-term adverse effects of larotrectinib on their growth and development. The effectiveness of larotrectinib in the overall study population as well as in patient subgroups will also be evaluated. Procedures avoided in patients with infantile fibrosarcoma (e.g., amputation) and the number of patients who were able to undergo surgery with a curative intent (excluding amputation) because of the use of larotrectinib will be described. Larotrectinib treatment patterns in real-world practice, including dosing and duration of treatment, will be described. Discussion: The FDA Accelerated Approval Program allows for earlier approval of and patient access to drugs that treat serious conditions and fill an unmet medical need. This study is designed to fulfill post-approval requirements set by the FDA as well as post-marketing requirements set forth by local regulatory bodies and is part of the risk management plan for the EMA.
  • bookPart
    Protocolo de preservação de órgão não cirúrgico
    (2022) CASTRO JUNIOR, Gilberto de
  • article 0 Citação(ões) na Scopus
    Assessing Oncologists’ Attitudes Concerning Comprehensive Genomic Profiling in Stage IV Lung Adenocarcinoma in Brazil
    (2022) FARES, A. F.; MARTINEZ, P. H.; FARINA, P. H.; SOUZA, I. Bicalho de; ARAúJO, D. V.; PAIVA, N. S.; ORLANDO, L. F.; COLOMBO, T. E.; MASCARENHAS, E.; GELATTI, A. C. Z.; BALDOTTO, C.; ZUKIN, M.; ARAUJO, L. H.; MATHIAS, C.; WERUTSKY, G.; CASTRO, G. Jr. de; LIMA, V. C. Cordeiro de
    Introduction: Advances in comprehensive genomic profiling (CGP) of lung adenocarcinomas (LUADs) led to personalized treatment for patients. This study evaluated medical oncologists’ attitudes toward CGP in a scenario where sponsored funding for CGP was available. Methods: We designed an online survey assessing CGP use and treating physicians’ confidence, composed of three self-confidence domains, which are as follows: confidence in interpreting CGP results, confidence in treating oncogenic-driven LUAD, and confidence in managing tyrosine kinase inhibitor adverse events. The survey was distributed to medical oncologists who treat lung cancer in Brazil. Comparisons between groups were performed using the chi-square or Fisher's exact test. Univariable and multivariable (adjusted OR) analyses were performed. Results: Among 104 respondents who treat patients with lung cancer, 55% were from the Southeast region, 28% had high lung cancer clinical load, and 33% had in-house molecular testing. More than half (51%) of the participants request CGP systematically to stage IV LUAD. As for provider confidence, 67% stated being confident in all three domains: 76% confident in interpreting CGP, 84% confident in treating oncogenic-driven LUAD, and 81% in managing tyrosine kinase inhibitor adverse events. Providers’ confidence was associated with systematically requesting CGP to stage IV LUAD (p = 0.013). After controlling for the variables of interest, systematic requesting CGP for stage IV LUAD revealed a significant association with the provider's confidence (adjusted OR = 0.35, p = 0.028, 95% CI: 0.14–0.84). The major challenge for properly requesting CGP was the long turnaround time and the fear of treatment delays. Conclusions: Even though CGP for stage IV LUAD in Brazil is fully sponsored, only half of the oncologists in our survey systematically request it. Requesting CGP was associated with providers’ confidence. Improving access and promoting providers’ awareness of CGP utility is necessary to increase CGP use and better inform treatment decisions. © 2022 The Authors
  • conferenceObject
    KeyVibe-003: Randomized, double-blind, phase 3 study of first-line pembrolizumab with and without vibostolimab (anti-TIGIT) in patients with PD-L1-positive metastatic NSCLC
    (2022) CHO, Byoung Chul; JUERGENS, Rosalyn A.; CHENG, Ying; CASTRO JR., Gilberto de; ERMAN, Mustafa; BAUMAN, Jessica R.; TAKAHASHI, Toshiaki; SCHWARZENBERGER, Paul; LI, Chengxiang; PIETANZA, M. Catherine; YANG, James Chih-Hsin
  • article 13 Citação(ões) na Scopus
    Cephaeline is an inductor of histone H3 acetylation and inhibitor of mucoepidermoid carcinoma cancer stem cells
    (2022) SILVA, Luan Cesar; BORGATO, Gabriell Bonifacio; WAGNER, Vivian Petersen; MARTINS, Manoela Domingues; ROCHA, Guilherme Zweig; LOPES, Marcio Ajudarte; SANTOS-SILVA, Alan Roger; CASTRO JUNIOR, Gilberto de; KOWALSKI, Luiz Paulo; NOR, Jacques E.; SQUARIZE, Cristiane H.; CASTILHO, Rogerio Moraes; VARGAS, Pablo Agustin
    Aim To evaluate the potential use of Cephaeline as a therapeutic strategy to manage mucoepidermoid carcinomas (MEC) of the salivary glands. Material and Methods UM-HMC-1, UM-HMC-2, and UM-HMC-3A MEC cell lines were used to establish the effects of Cephaeline over tumor viability determined by MTT assay. In vitro wound healing scratch assays were performed to address cellular migration while immunofluorescence staining for histone H3 lysine 9 (H3k9ac) was used to identify the acetylation status of tumor cells upon Cephaeline administration. The presence of cancer stem cells was evaluated by the identification of ALDH enzymatic activity by flow cytometry and through functional assays using in vitro tumorsphere formation. Results A single administration of Cephaeline resulted in reduced viability of MEC cells along with the halt on tumor growth and cellular migration potential. Administration of Cephaeline resulted in chromatin histone acetylation as judged by the increased levels of H3K9ac and disruption of tumorspheres formation. Interestingly, ALDH levels were increased in UM-HMC-1 and UM-HMC-3A cell lines, while UM-HMC-2 showed a reduced enzymatic activity. Conclusion Cephaeline has shown anti-cancer properties in all MEC cell lines tested by regulating tumor cells' viability, migration, proliferation, and disrupting the ability of cancer cells to generate tumorspheres.
  • conferenceObject
    EGFR Tyrosine Kinase Inhibitors and Combination Strategies in First-line Treatment of Advanced NSCLC: A Network Meta-analysis
    (2022) CASTRO, G. de; STOCK, G. T.; HARADA, G.; PEREIRA, A. A. L.; SADEGHIRAD, B.
  • article 5 Citação(ões) na Scopus
    Non-Small-Cell Lung Cancer With CNS Metastasis: Disparities From a Real-World Analysis (GBOT-LACOG 0417)
    (2022) COELHO, Juliano Ce; CARVALHO, Giselle de Souza; CHAVES, Fabio; MARCHI, Pedro de; JR, Gilberto de Castro; BALDOTTO, Clarissa; MASCARENHAS, Eldsamira; PACHECO, Patricia; GOMES, Rafaela; WERUTSKY, Gustavo; ARAUJO, Luiz H.
    PURPOSE Despite the advances in the approach to non-small-cell lung cancer (NSCLC) with CNS metastasis, access to timely diagnosis and treatment may not be optimal in many instances. Our main objective was to describe a cohort of patients with NSCLC with brain metastases from public and private cancer centers, and the differences between patients' presentation, treatment, and outcomes. METHODS GBOT-LACOG 0417 is a multi-institutional retrospective cohort study of patients diagnosed with NSCLC and CNS metastasis in Brazil. All patients had confirmed diagnosis of NSCLC between January 2010 and December 2015. CNS metastases were identified by imaging. RESULTS A total of 273 patients were included. Patients treated at public institutions were more often Black or Brown (38.8% v 15.4%), current or former smoker (88.6% v 60.0%), of squamous cell histology (25.0% v 9.1%), EGFR- and ALK-negative (95.9% v 74.9%), and were less frequently assessed by using brain magnetic resonance imaging (38.8% v 83.6%). At public institutions, patients were more often symptomatic (78.1% v 44.6%) and had worse performance status (Eastern Cooperative Oncology Group 2 or higher 61.5% v 10.3%). CNS metastases were larger (median size 25 v 15 mm) and more often surrounded by edema (67.7% v 55.2%) at public institutions. Patients at public institutions were more frequently treated with whole-brain radiation therapy (72.9% v 45.4%) and less frequently with radiosurgery (6.3% v 24.1%). Among patients from private care, median overall survival was 24.2 months (95% CI, 20.0 to 30.6), significantly higher than in public care (median 12.1 months; 95% CI, 6.7 to 13.6; P < .001). CONCLUSION Our results demonstrate the discrepancy between public and private health care system in the critical setting of patients with CNS metastasis from NSCLC. (C) 2022 by American Society of Clinical Oncology