Publications by authors named "Gilberto De Castro"
Purpose: Despite the success of immune checkpoint inhibitors (ICI) across various cancers, their efficacy in metastatic castration-resistant prostate cancer (mCRPC) is modest, except for a subset of patients who experience significant, yet unpredictable, benefits. DNA repair defects (DRD) are associated with higher neoantigen load, which may predict response. Our study explored the potential of DRD for enhanced responsiveness to the ICI nivolumab.
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- IMbrella A is a Phase III study that allowed patients from earlier atezolizumab trials, like IMpower133, to continue receiving treatment for extensive-stage small cell lung cancer (SCLC) with atezolizumab plus chemotherapy after the initial trials closed.
- In IMbrella A, 18 out of 26 eligible patients rolled over for further treatment, and results showed that median follow-up was 59.4 months with estimated three-, four-, and five-year overall survival rates of 16%, 13%, and 12%, respectively.
- The study reported that 16.7% of patients experienced serious adverse events, with only one grade two hypothyroidism noted,
Pembrolizumab Plus Carboplatin and Paclitaxel as First-Line Therapy for Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (KEYNOTE-B10): A Single-Arm Phase IV Trial.
J Clin Oncol
September 2024
Purpose: Standard-of-care first-line treatment for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) is pembrolizumab plus platinum and fluorouracil (FU). However, FU is associated with potential challenges (continuous 4-day infusion, high administration costs, and cardiovascular and gastrointestinal toxicities), creating a clinical need for alternative chemotherapy combinations. We evaluated the efficacy and safety of first-line pembrolizumab plus carboplatin and paclitaxel for R/M HNSCC in the open-label, single-arm, phase IV KEYNOTE-B10 study (ClinicalTrials.
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- Stage III NSCLC accounts for about one-third of lung cancer cases, but detailed data on its distribution and treatment in Brazil is lacking.
- A study, RELANCE/LACOG 0118, analyzed 403 patients with stage III NSCLC across 13 cancer centers, focusing on their demographics, treatment, and survival outcomes from 2015 to 2021.
- Results show that patients with public health insurance face later diagnoses and worse overall survival, indicating a need for improved health policies to ensure timely diagnosis and access to treatment in Brazil.*
Aim: To summarize current knowledge, gaps, quality of the evidence and show main results related to the role of the autonomic nervous system in lung cancer.
Methods: Studies were identified through electronic databases (PubMed, Scopus, Embase and Cochrane Library) in October 2023, and a descriptive analysis was performed. Twenty-four studies were included, and most were observational.
Introduction: The implementation of multidisciplinary teams (MDTs) has been found to be effective for improving outcomes in oncology. Nevertheless, there is still a dearth of robust literature on patients with NSCLC. The aim of this study was to conduct a systematic review regarding the impact of MDTs on patient with NSCLC outcomes.
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- Canakinumab, a monoclonal antibody targeting IL-1β, was tested in a phase III study (CANOPY-1) to see if it could improve survival rates in patients with advanced non-small-cell lung cancer (NSCLC) when combined with pembrolizumab and chemotherapy.
- The study involved 643 patients split between canakinumab and placebo groups, with results showing no significant difference in progression-free survival (PFS) or overall survival (OS) after a median follow-up of 21.2 months.
- While safety profiles were similar, canakinumab treatment led to delays in worsening symptoms like chest pain, coughing, and shortness of breath, suggesting it might
The Clinical and Molecular Profile of Lung Cancer Patients Harboring the R337H Germline Variant in a Brazilian Cancer Center: The Possible Mechanism of Carcinogenesis.
Int J Mol Sci
October 2023
In southern and southeastern Brazil, the founder variant c.1010G>A (R337H) has been previously documented with a prevalence of 0.3% within the general population and linked to a heightened incidence of lung adenocarcinomas (LUADs).
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- Drug resistance in mucoepidermoid carcinomas (MEC) leads to issues like tumor recurrence and metastasis, primarily driven by cancer stem cells (CSCs).
- Previous research indicated that tumors use NFkB signaling for chemotherapy resistance, and targeting the epigenome can help manage CSC populations.
- The study found that using low doses of NFkB inhibitor emetine and HDAC inhibitor SAHA is effective against MEC CSCs; also, combining emetine with Cisplatin (CDDP) is a promising strategy for treating the non-CSC tumor cells in MEC.
Article Synopsis
- The phase 3 NEPTUNE study compared first-line treatment options of durvalumab plus tremelimumab (DT) against chemotherapy for patients with metastatic non-small cell lung cancer (NSCLC), particularly focusing on a cohort from China.
- Among patients with PD-L1 tumor cell expression less than 1%, those treated with DT exhibited a longer overall survival (OS) compared to those receiving chemotherapy, with median OS times of 15.0 months versus 11.7 months, respectively.
- Additionally, while the progression-free survival (PFS) rates were similar between the two groups, DT treatment was associated with fewer severe treatment-related adverse events, indicating a potentially safer profile than conventional chemotherapy.
Article Synopsis
- The phase III KEYNOTE-042 study evaluated the efficacy of pembrolizumab versus chemotherapy in 1,274 patients with advanced non-small-cell lung cancer (NSCLC) who had PD-L1 tumor proportion scores of 1% or higher.
- After 5 years of follow-up, pembrolizumab showed significantly better overall survival rates across different PD-L1 score groups, with 5-year survival rates of 21.9%, 19.4%, and 16.6% for scores ≥ 50%, ≥ 20%, and ≥ 1%, respectively.
- The study confirmed that pembrolizumab has a strong, durable clinical benefit compared to chemotherapy, with no new side effects and a high objective
Background: Cutaneous squamous-cell carcinoma (CSCC) is among the most frequent malignancies worldwide. For those not amenable to treatment with curative intent, immune checkpoint inhibition (ICI) with anti-programmed death receptor 1 (PD-1) antibodies has emerged as a novel therapeutic option. In this study, the authors sought to investigate the activity of the anti-PD-1 agent nivolumab in patients with advanced CSCC (aCSCC).
View Article and Find Full Text PDFIntroduction: 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 tremelimumab (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.
Purpose: Pembrolizumab and pembrolizumab-chemotherapy demonstrated efficacy in recurrent/metastatic head and neck squamous cell carcinoma in KEYNOTE-048. Post hoc analysis of long-term efficacy and progression-free survival on next-line therapy (PFS2) is presented.
Methods: Patients were randomly assigned (1:1:1) to pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy.
Article Synopsis
- Advances in comprehensive genomic profiling (CGP) for lung adenocarcinomas (LUADs) lead to personalized treatment, and a study investigated Brazilian oncologists' attitudes toward CGP when funding is available.
- An online survey assessed oncologists' confidence in interpreting CGP results, treating oncogenic-driven LUAD, and managing tyrosine kinase inhibitor side effects; 67% of respondents felt confident across all areas.
- Despite funding, only 51% of oncologists routinely request CGP for stage IV LUAD, with confidence linked to their willingness to request CGP; challenges include long turnaround times and concerns about treatment delays.
Background: Patients with advanced non-small cell lung cancer (NSCLC) are a heterogeneous population with short lifespan. We aimed to develop methods to better differentiate patients whose survival was >90 days.
Methods: We evaluated 83 characteristics of 106 treatment-naïve, stage IV NSCLC patients with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) >1.
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.
Article Synopsis
- The study aimed to evaluate health-related quality of life (HRQoL) in patients with recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) receiving different treatments: pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy in a phase 3 trial.
- HRQoL was assessed using various questionnaires, with data showing that scores for global health status and quality of life remained stable at week 15, with no significant differences between treatment groups.
- Results suggested that both pembrolizumab alone and in combination therapies not only extended overall survival but also maintained quality of life, supporting their use as first-line treatments for R/M HNSCC.
Purpose: The phase III KEYNOTE-048 (ClinicalTrials.gov identifier: NCT02358031) trial of pembrolizumab in recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) included planned efficacy analyses in the total population and in participants with programmed death ligand-1 (PD-L1) combined positive score (CPS) ≥ 1 and CPS ≥ 20. To further characterize the predictive value of PD-L1 expression on outcome, we conducted efficacy analyses in the PD-L1 CPS < 1 and CPS 1-19 subgroups in KEYNOTE-048.
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- * Biochemical tests confirmed ACTH-dependent Cushing's syndrome, ultimately traced back to ectopic ACTH secretion from the metastatic cancer, and she was treated with ketoconazole and chemotherapy.
- * Despite an initial remission, the Cushing's syndrome recurred after four months, highlighting the importance of monitoring for Cushing's syndrome in patients with aggressive salivary gland tumors, as it affects treatment and outcomes.
The influence of a supervised group exercise intervention combined with active lifestyle recommendations on breast cancer survivors' health, physical functioning, and quality of life indices: study protocol for a randomized and controlled trial.
Trials
December 2021
Article Synopsis
- Many cancer patients remain inactive despite knowing the benefits of exercise, which include better quality of life and reduced cancer recurrence.
- This study investigates a 16-week program for breast cancer survivors that combines supervised group exercise (canoeing) with lifestyle recommendations to boost physical activity.
- The focus is on evaluating various outcomes like aerobic capacity, quality of life, and immune function among participants to determine the program's effectiveness.
Extraoral photobiomodulation for prevention of oral and oropharyngeal mucositis in head and neck cancer patients: interim analysis of a randomized, double-blind, clinical trial.
Support Care Cancer
March 2022
Article Synopsis
- The study aimed to evaluate the safety and effectiveness of a preventive treatment called extraoral photobiomodulation (PBM) for reducing oral and oropharyngeal mucositis (OM) in patients with oral and throat cancer undergoing radiation therapy (RT).
- Patients were randomly assigned to receive either PBM or a placebo; results showed that the PBM group had a delayed onset of OM, lower pain scores, and reduced need for pain and anti-inflammatory medications, along with improved quality of life.
- Despite these benefits, there was no significant difference in overall survival rates between the two groups after one year, suggesting that while PBM may help with symptoms, it doesn't affect long-term cancer
Article Synopsis
- This study evaluated the effectiveness of pembrolizumab compared to chemotherapy in patients with PD-L1-positive non-small-cell lung cancer (NSCLC), focusing on those with and without brain metastases.
- A total of 3,170 patients were analyzed, revealing that pembrolizumab led to better overall survival, progression-free survival, and response rates regardless of brain metastasis presence.
- Additionally, pembrolizumab was associated with fewer treatment-related side effects compared to chemotherapy, making it a safer option for patients with advanced NSCLC.
Background: The influence of age at diagnosis in non-small cell lung cancer (NSCLC) prognosis is unclear.
Objectives: To compare in a Brazilian cohort of NSCLC patients of different age groups: 1) The overall survival; 2) Clinical features and treatment options.
Methods: This is a retrospective cohort study using a hospital-based registry, for NSCLC patients registered in years 2000-2009.
Impact of radiation on tooth loss in patients with head and neck cancer: a retrospective dosimetric-based study.
Oral Surg Oral Med Oral Pathol Oral Radiol
October 2021
Article Synopsis
- A study was conducted to analyze dental problems and tooth loss in patients after receiving head and neck radiation therapy (HNRT), focusing on how different radiation doses affect outcomes.
- The analysis included 66 patients, revealing that radiation caries was the most common dental issue, affecting 67.8% of patients, with maxillary molars near the tumor lost more quickly.
- Results showed that teeth exposed to radiation doses over 60 Gy faced a three-fold higher risk of extraction and also highlighted increased chances of delayed healing and osteoradionecrosis (ORN) at doses above 50 Gy.