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
    Canakinumab with Standard of Care for Patients with Advanced NSCLC: T-cell Infiltration Analysis in CANOPY-1
    (2023) TAN, D. S.; FELIP, E.; CASTRO JUNIOR, G. de; SOLOMON, B. J.; GREYSTOKE, A.; CHO, B. C.; COBO, M.; KIM, T. M.; GANGULY, S.; WU, J.; DEMANSE, D.; BUTLER, A. A.; BRASE, J. C.; BOSSEN, C.; JOHNSON, B. E.
  • bookPart
    Câncer de pulmão
    (2023) FêDE, Angelo Bezerra de Souza; TAKAHASHI, Tiago Kenji; MAK, Milena Perez; CASTRO JUNIOR, Gilberto de
  • article 0 Citação(ões) na Scopus
    Time to Recurrence as a Prognostic Factor in Parathyroid Carcinoma
    (2023) MAGNABOSCO, Felipe Ferraz; BRESCIA, Marilia D'Elboux Guimaraes; NASCIMENTO JUNIOR, Climerio Pereira; MASSONI NETO, Ledo Mazzei; ARAP, Sergio Samir; CASTRO JUNIOR, Gilberto de; LEDESMA, Felipe Lourenco; ALVES, Venancio Avancini Ferreira; KOWALSKI, Luiz Paulo; MARTIN, Regina Matsunaga; MONTENEGRO, Fabio Luiz de Menezes
    Background Parathyroid carcinoma (PC) is a rare and challenging disease without clearly understood prognostic factors. Adequate management can improve outcomes. Characteristics of patients treated for PC over time and factors affecting prognosis were analyzed. Methods Retrospective cohort study including surgically treated patients for PC between 2000 and 2021. If malignancy was suspected, free-margin resection was performed. Demographic, clinical, laboratory, surgical, pathological, and follow-up characteristics were assessed. Results Seventeen patients were included. Mean tumor size was 32.5 mm, with 64.7% staged as pT1/pT2. None had lymph node involvement at admission, and 2 had distant metastases. Parathyroidectomy with ipsilateral thyroidectomy was performed in 82.2%. Mean postoperative calcium levels were different between patients who developed recurrence vs those who did not (P = .03). Six patients (40%) had no recurrence during follow-up, 2 (13.3%) only regional, 3 (20%) only distant, and 4 (26.6%) both regional and distant. At 5 and 10 years, 79% and 56% of patients were alive, respectively. Median disease-free survival was 70 months. Neither Tumor, Nodule, Metastasis system nor largest tumor dimension (P = .29 and P = .74, respectively) were predictive of death. En bloc resection was not superior to other surgical modalities (P = .97). Time between initial treatment and development of recurrence negatively impacted overall survival rate at 36 months (P = .01). Conclusion Patients with PC can survive for decades and have indolent disease course. Free margins seem to be the most important factor in initial surgery. Recurrence was common (60%), but patients with disease recurrence within 36 months of initial surgery had a lower survival rate.
  • article
    Repurposing NF kappa B and HDAC inhibitors to individually target cancer stem cells and non-cancer stem cells from mucoepidermoid carcinomas
    (2023) SILVA, Luan Cesar; BORGATO, Gabriell Bonifacio; WAGNER, Vivian Petersen; MARTINS, Manoela Domingues; SANTOS-SILVA, Alan Roger; JR, Gilberto de Castro; KOWALSKI, Luiz Paulo; SQUARIZE, Cristiane Helena; VARGAS, Pablo Agustin; CASTILHO, Rogerio Moraes
    Drug resistance remains a major obstacle in the treatment of mucoepidermoid carcinomas (MEC) lead-ing to tumor recurrence, disease progression, and metastasis. Emerging evidence suggests that drug resistance is mediated by the presence of a highly adaptative subpopulation of cancer cells known as cancer stem cells (CSC). We have previously reported that solid tumors use NFkB signaling as a chemotherapy-resistant mechanism. We have also shown that interfering with the epigenome of solid tumors is an effective strategy to control the popula-tion of CSC. Here, we sought to investigate the effects of the NFkB inhibitor emetine and the HDAC inhibitor SAHA on the biology of MEC CSC and assessed whether this combination therapy would favor the standard of care therapy comprised of the administration of Cisplatin (CDDP). Our findings suggested that the administration of low concen-trations of emetine and SAHA is more effective in disrupting CSC in MEC, while the administration of emetine in combination with CDDP constitutes an effective therapy to target non-CSC MEC tumor cells.
  • conferenceObject
    AVANZAR: Phase III Study of Datopotamab Deruxtecan (Dato-DXd) plus Durvalumab plus Carboplatin as 1L Treatment of Advanced/mNSCLC
    (2023) AGGARWAL, C.; CHEEMA, P.; ARRIETA, O.; BONANNO, L.; BORGHAEI, H.; HU, Y.; KIM, D. -W.; CASTRO JUNIOR, G. de; HEPNER, A.; DENG, C.; RIEGO, M. Gonzalez del; KATO, T.
  • article 0 Citação(ões) na Scopus
    NEPTUNE China cohort: First-line durvalumab plus tremelimumab in Chinese patients with metastatic non-small-cell lung cancer
    (2023) CHENG, Ying; ZHOU, Qing; HAN, Baohui; FAN, Yun; SHAN, Li; CHANG, Jianhua; SUN, Si; FANG, Jian; CHEN, Yuan; SUN, Jianguo; WU, Gang; MANN, Helen; NAICKER, Kirsha; SHIRE, Norah; MOK, Tony; JR, Gilberto de Castro
    Objectives: The phase 3 NEPTUNE study (NCT02542293) evaluated first-line durvalumab plus tremelimumab (DT) versus chemotherapy for metastatic NSCLC. Prespecified exploratory analyses were conducted in an extended cohort enrolled in China. Materials and methods: Patients were randomized (1:1) to DT or standard chemotherapy, stratified by PD-L1 tumor cell (TC) expression (>= 25 % vs < 25 %), histology, and smoking history. The primary analysis for this cohort was overall survival (OS) in patients with PD-L1 TC < 1 %. Secondary analyses included OS and progression-free survival (PFS) in the ITT population and PD-L1 subgroups, and safety. No alpha was allocated to these cohort analyses (data cut-off, 21-September-2020). Results: 78 and 82 patients were randomized to DT and chemotherapy, respectively; 26 and 29 had PD-L1 TC < 1 % (median follow-up, 31.2 and 29.7 months [censored patients]). Among patients with PD-L1 TC < 1 %, OS favored DT versus chemotherapy (HR 0.60; 95 % CI, 0.32-1.11), with medians of 15.0 months (95 % CI, 10.5-27.4) and 11.7 months (95 % CI, 8.6-20.5), respectively; 24-month rates were 36.0 % (95 % CI, 18.2-54.2) and 17.9 % (95 % CI, 6.5-33.7). In the ITT population, OS was prolonged with DT versus chemotherapy (HR 0.70; 95 % CI, 0.48-1.02); medians were 20.0 and 14.1 months and 24-month rates were 44.2 % and 30.4 %. PFS was similar in the PD-L1 TC < 1 % (HR 1.13; 95 % CI, 0.59-2.14) and ITT (HR 0.95; 95 % CI, 0.66-1.36) populations; 12-month rates were 15.6 % versus 11.3 % and 23.9 % versus 16.6 %. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 31.2 % with DT and 52.6 % with chemotherapy; 3.9 % versus 10.3 % discontinued due to TRAEs. Conclusions: In exploratory analyses, first-line DT showed a trend towards improved OS versus chemotherapy among Chinese patients in the PD-L1 TC < 1 % population and ITT population, with 24-month OS and 12-month PFS rates indicating benefit in survival curve tails. DT was well tolerated with no new safety signals.
  • article 1 Citação(ões) na Scopus
    EGFR Mutation Detection in Brazilian Patients With Non-Small-Cell Lung Cancer: Lessons From Real-World Data Scenario of Molecular Testing
    (2023) MONTELLA, Tatiane; ZALIS, Mariano; ZUKIN, Mauro; LIMA, Vladmir Claudio Cordeiro de; BALDOTTO, Clarissa; MARCHI, Pedro De; SALLES, Paulo; MATHIAS, Clarissa; BARRIOS, Carlos; KAWAMURA, Carolina; CALABRICH, Aknar; ARAUJO, Luiz Henrique; CASTRO, Gilberto; BUSTAMANTE, Carolina; MARIA, Andre Santa; REIS, Marcelo; FERREIRA, Carlos Gil
    PURPOSE There is a paucity of consistent data concerning genetic mutations in Brazilian patients with lung cancer. The aim of this study was to retrospectively analyze epidermal growth factor receptor (EGFR) mutations detected in a real-world scenario using a large cohort of Brazilian patients with non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS This was a cross-sectional, observational, descriptive study on the basis of a database of EGFR molecular analysis from tumor samples of patients with a confirmatory histopathological diagnosis of primary lung cancer. Specimens were collected from 2013 to 2017 and were tested using cobas, next-generation sequencing, and Sanger sequencing platforms. RESULTS A total of 7,413 tumor specimens were tested. The patients were predominantly women with a median age of 67.0 years. Patients with at least one mutation represented 24.2% of the total sample. Among the positive patients, the majority had just one mutation, but two or more simultaneous mutations were observed in 1.52% of patients. Exon 19 deletion was the most prevalent alteration in the sample (12.8%), followed by exon 21 L858R (6.9%) and exon 20 insertion (1.6%). All others were considered uncommon mutations and were observed in 18.5% of all mutated patients and 4.0% of the total sample (2.3%18.7% depending on the sequencing method). CONCLUSION This study examined the prevalence of EGFR mutations in Brazilian patients with NSCLC using different technologies, suggesting that the type of method used, directed or nondirected against specific mutations, influences the analysis, particularly for uncommon mutations, which will be missed by mutation-specific approaches such as cobas testing. Our estimates are the largest in Latin America and are consistent with previous reports from other parts of the world. Besides the variability in methods described here as technology incorporation advances in a nonhomogeneous manner, it is probably like the real-world clinical setting Brazilian oncologists face in their daily practice.
  • conferenceObject
    Five-Year Survival in Patients with ES-SCLC Treated with Atezolizumab in IMpower133: Imbrella a Extension Study Results
    (2023) LIU, S. V.; DZIADZIUSZKO, R.; SUGAWARA, S.; KAO, S.; HOCHMAIR, M.; HUEMER, F.; CASTRO JR., G.; HAVEL, L.; CARO, R. B.; LOSONCZY, G.; LEE, J. -S.; KOWALSKI, D.; ANDRIC, Z.; CALIFANO, R.; VEATCH, A.; GERSTNER, G.; BATUS, M.; MORRIS, S.; KAUL, M.; SIDDIQUI, M.; LI, H.; ZHANG, W.; NABET, B.; RECK, M.
  • article 21 Citação(ões) na Scopus
    NEPTUNE: Phase 3 Study of First-Line Durvalumab Plus Tremelimumab in Patients With Metastatic NSCLC
    (2023) JR, Gilberto de Castro; RIZVI, Naiyer A.; SCHMID, Peter; SYRIGOS, Konstantinos; MARTIN, Claudio; YAMAMOTO, Nobuyuki; CHENG, Ying; MOISEYENKO, Vladimir; SUMMERS, Yvonne; VYNNYCHENKO, Ihor; LEE, Sung Yong; BRYL, Maciej; ZER, Alona; ERMAN, Mustafa; TIMCHEVA, Constanta; RAJA, Rajiv; NAICKER, Kirsha; SCHEURING, Urban; WALKER, Jill; MANN, Helen; CHAND, Vikram; MOK, Tony; NEPTUNE Investigators
    Introduction: NEPTUNE, a phase 3, open-label study, evaluated first-line durvalumab plus tremelimumab versus chemotherapy in metastatic NSCLC (mNSCLC).Methods: Eligible patients with EGFR and ALK wild-type mNSCLC were randomized (1:1) to first-line durvalumab (20 mg/kg every 4 weeks until progression) plus trem-elimumab (1 mg/kg every 4 weeks for up to four doses) or standard chemotherapy. Randomization was stratified by tumor programmed death-ligand 1 expression (>= 25% versus <25%), tumor histologic type, and smoking history. The amended primary end point was overall survival (OS) in patients with blood tumor mutational burden (bTMB) greater than or equal to 20 mutations per megabase (mut/ Mb). Secondary end points included progression-free sur-vival (PFS) in patients with bTMB greater than or equal to 20 mut/Mb and safety and tolerability in all treated patients. Results: As of June 24, 2019, 823 patients were randomized (intention-to-treat [ITT]); 512 (62%) were bTMB-evaluable, with 129 of 512 (25%) having bTMB greater than or equal to 20 mut/Mb (durvalumab plus tremelimumab [n = 69]; chemotherapy [n = 60]). Baseline characteristics were balanced in the intention-to-treat. Among patients with bTMB greater than or equal to 20 mut/Mb, OS improvement with durvalumab plus tremelimumab versus chemotherapy did not reach statistical significance (hazard ratio 0.71 [95% confidence interval: 0.49-1.05; p = 0.081]; median OS, 11.7 versus 9.1 months); the hazard ratio for PFS was 0.77 (95% confidence interval, 0.51-1.15; median PFS, 4.2 versus 5.1 months). In the overall safety population, incidence of grade 3 or 4 treatment-related adverse events was 20.7% (durva-lumab plus tremelimumab) and 33.6% (chemotherapy).Conclusions: NEPTUNE did not meet its primary end point of improved OS with durvalumab plus tremelimumab versus chemotherapy in patients with mNSCLC and bTMB greater than or equal to 20 mut/Mb. Despite the amended study design, with a resultant small primary analysis pop-ulation, therapeutic activity was aligned with expectations based on mechanistic biology and previous studies.(c) 2022 International Association for the Study of Lung Cancer.
  • article 3 Citação(ões) na Scopus
    Patient's perceptions of oral and oropharyngeal cancer diagnosis disclosure: communication aspects based on SPIKES protocol
    (2023) ALVES, Carolina G. B.; RIBEIRO, Ana Carolina Prado; BRANDAO, Thais Bianca; TONAKI, Juliana O.; PEDROSO, Caique Mariano; RIVERA, Cesar; EPSTEIN, Joel B.; MIGLIORATI, Cesar Augusto; KOWALSKI, Luiz Paulo; MAK, Milena Perez; CASTRO, Gilberto; LOPES, Marcio Ajudarte; SANTOS-SILVA, Alan Roger
    Objective. Breaking bad medical news is a complex task of clinical practice. The manner in which this is done has a significant impact on patients. This study aimed to assess patient's perceptions regarding oral and oropharyngeal cancer diagnosis disclosure according to the ""SPIKES"" protocol. Study Design. This cross-sectional study used a questionnaire with 21 SPIKES-based items. The questionnaire was administered to 100 patients with recently diagnosed oral and oropharyngeal squamous cell carcinoma who evaluated each item according to their preference and experience. Results. Nineteen items showed a significant difference between patient's preference and recalled experience. Eighteen of these items showed lower experience scores primarily related to the amount of information desired by patients, presence of a compan-ion, time to express feelings, and summary of information. Most patients preferred receiving as much information as possible about the diagnosis. However, only 35% reported that they had obtained sufficient information. Patients who were aware of can-cer diagnostic suspicion had better communication experiences. Conclusions. Protocols may be useful to guide health professionals to support patient-centered strategies to disclose oral cancer diagnoses. (Oral Surg Oral Med Oral Pathol Oral Radiol 2023;135:518-529)