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INTRODUCTION: Fibroblast growth factor receptor (FGFR) mutations and fusions are relevant biomarkers in metastatic urothelial carcinoma (mUC). However, the prevalence of genomic alterations and their impact on clinical outcomes in a Latin American population remains unknown. This study aimed to explore the prevalence of FGFR mutations and/or fusions in patients with mUC in Latin America (LATAM) and its association with clinicopathological characteristics, Bellmunt's prognostic model, and survival outcomes. PATIENTS AND METHODS: A multicenter retrospective cohort study from 2016 to 2019 of patients with mUC from several LACOG LATAM institutions. FGFR alterations were analyzed by real-time PCR and/or next-generation sequencing in tumor samples and clinicopathologic characteristics and survival outcomes data were collected. The prevalence of FGFR, patient characteristics, and treatment in real-world settings were summarized. Kaplan-Meier survival estimates and Cox regression analyses were used to evaluate the associations of FGFR mutation and/or fusion status with median overall survival (mOS), median time to treatment failure (mTTF), and clinicopathological characteristics. RESULTS: In total, 222 patients were screened. Of these, 196 patients were considered eligible and were included in the analysis. FGFR mutations and/or fusions were found in 35 (17.9%) patients. There was no statistical difference in mOS and mTTF in FGFR-altered and non-altered patients (13.1 vs. 16.8 months, P = .20 and 3.9 vs. 4.1 months, P = .96, respectively). Bellmunt's prognostic model correctly predicted overall survival (P = .049). CONCLUSIONS: This is the largest study evaluating the prevalence of FGFR alterations in patients with mUC in the LATAM population. FGFR alterations in mUC were found in 17.9% of the patients, and the presence of this biomarker was not associated with OS. We validated Bellmunt's prognostic model in this cohort.
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PURPOSE: Renal cell carcinoma is an aggressive disease with a high mortality rate. Management has drastically changed with the new era of immunotherapy, and novel strategies are being developed; however, identifying systemic treatments is still challenging. This paper presents an update of the expert panel consensus from the Latin American Cooperative Oncology Group and the Latin American Renal Cancer Group on advanced renal cell carcinoma management in Brazil. METHODS: A panel of 34 oncologists and experts in renal cell carcinoma discussed and voted on the best options for managing advanced disease in Brazil, including systemic treatment of early and metastatic renal cell carcinoma as well as nonclear cell tumours. The results were compared with the literature and graded according to the level of evidence. RESULTS: Adjuvant treatments benefit patients with a high risk of recurrence after surgery, and the agents used are pembrolizumab and sunitinib, with a preference for pembrolizumab. Neoadjuvant treatment is exceptional, even in initially unresectable cases. First-line treatment is mainly based on tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs); the choice of treatment is based on the International Metastatic Database Consortium (IMCD) risk score. Patients at favourable risk receive ICIs in combination with TKIs. Patients classified as intermediate or poor risk receive ICIs, without preference for ICI + ICIs or ICI + TKIs. Data on nonclear cell renal cancer treatment are limited. Active surveillance has a place in treating favourable-risk patients. Either denosumab or zoledronic acid can be used for treating metastatic bone disease. CONCLUSION: Immunotherapy and targeted therapy are the standards of care for advanced disease. The utilization and sequencing of these therapeutic agents hinge upon individual risk scores and responses to previous treatments. This consensus reflects a commitment to informed decision-making, drawn from professional expertise and evidence in the medical literature.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , América Latina , Consenso , SunitinibeRESUMO
INTRODUCTION: Non-metastatic, castration-resistant prostate cancer (nmCRPC) is an important clinical stage of prostate cancer, prior to morbidity and mortality from clinical metastases. In particular, the introduction of novel androgen-receptor signaling inhibitors (ARSi) has changed the therapeutic landscape in nmCRPC. Given recent developments in this field, we update our recommendations for the management of nmCRPC. METHODS: A panel of 51 invited medical oncologists and urologists convened in May of 2021 with the aim of discussing and providing recommendations regarding the most relevant issues concerning staging methods, antineoplastic therapy, osteoclast-targeted therapy, and patient follow-up in nmCRPC. Panel members considered the available evidence and their practical experience to address the 73 multiple-choice questions presented. RESULTS: Key recommendations and findings include the reliance on prostate-specific antigen doubling time for treatment decisions, the absence of a clear preference between conventional and novel (i.e., positron-emission tomography-based) imaging techniques, the increasing role of ARSis in various settings, the general view that ARSis have similar efficacy. Panelists highlighted the slight preference for darolutamide, when safety is of greater concern, and a continued need to develop high-level evidence to guide the intensity of follow-up in this subset of prostate cancer. DISCUSSION: Despite the limitations associated with a consensus panel, the topics addressed are relevant in current practice, and the recommendations can help practicing clinicians to provide state-of-the-art treatment to patients with nmCRPC in Brazil and other countries with similar healthcare settings.
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Neoplasias de Próstata Resistentes à Castração , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/terapia , Humanos , Masculino , Estadiamento de Neoplasias , Antineoplásicos/uso terapêutico , Antagonistas de Receptores de Andrógenos/uso terapêutico , Consenso , Brasil , OsteoclastosRESUMO
PURPOSE: To present a summary of the recommendations for the treatment and follow-up for metastatic castration-resistant prostate cancer (mCRPC) as acquired through a questionnaire administered to 99 physicians working in the field of prostate cancer in developing countries who attended the Prostate Cancer Consensus Conference for Developing Countries. METHODS: A total of 106 questions out of more than 300 questions addressed the use of imaging in staging mCRPC, treatment recommendations across availability and response to prior drug treatments, appropriate drug treatments, and follow-up, and those same scenarios when limited resources needed to be considered. Responses were compiled and the percentages were presented by clinicians to support each response. Most questions had five to seven relevant options for response including abstain and/or unqualified to answer, or in the case of yes or no questions, the option to abstain was offered. RESULTS: Most of the recommendations from this panel were in line with prior consensus, including the preference of a new antiandrogen for first-line therapy of mCRPC. Important aspects highlighted in the scenario of limited resources included the option of docetaxel as treatment preference as first-line treatment in several scenarios, docetaxel retreatment, consideration for reduced doses of abiraterone, and alternative schedules of an osteoclast-targeted therapy. CONCLUSION: There was wide-ranging consensus in the treatment for men with mCRPC in both optimal and limited resource settings.
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Neoplasias de Próstata Resistentes à Castração , Antagonistas de Androgênios/uso terapêutico , Países em Desenvolvimento , Docetaxel/uso terapêutico , Seguimentos , Humanos , Masculino , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológicoRESUMO
BACKGROUND: Non-metastatic castration resistant prostate cancer (M0 CRPC) has seen important developments in drugs and diagnostic tools in the last two years. New hormonal agents have demonstrated improvement in metastasis free survival in M0 CRPC patients and have been approved by regulatory agencies in Brazil. Additionally, newer and more sensitive imaging tools are able to detect metastasis earlier than before, which will impact the percentage of patients staged as M0 CRPC. Based on the available international guidelines, a group of Brazilian urology and medical oncology experts developed and completed a survey on the diagnosis and treatment of M0 CRPC in Brazil. These results are reviewed and summarized and associated recommendations are provided. OBJECTIVE: To present survey results on management of M0 CRPC in Brazil. DESIGN, SETTING, AND PARTICIPANTS: A panel of six Brazilian prostate cancer experts determined 64 questions concerning the main areas of interest: 1) staging tools, 2) treatments, 3) side effects of systemic treatment/s, and 4) osteoclast-targeted therapy. A larger panel of 28 Brazilian prostate cancer experts answered these questions in order to create country-specific recommendations discussed in this manuscript. Outcome measurements and statistical analysis: The panel voted publicly but anonymously on the predefined questions. These answers are the panelists' opinions, not a literature review or meta-analysis. Therapies not yet approved in Brazil were excluded from answer options. Each question had five to seven relevant answers including two non-answers. Results were tabulated in real time. CONCLUSIONS: The results and recommendations presented can be used by Brazilian physicians to support the management of M0 CRPC patients. Individual clinical decision making should be supported by available data, however, for Brazil, guidelines for diagnosis and management of M0 CRPC patients have not been developed. This document will serve as a point of reference when confronting this disease stage.
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Consenso , Médicos , Neoplasias de Próstata Resistentes à Castração , Brasil , Humanos , Masculino , Seleção de Pacientes , Percepção , Neoplasias de Próstata Resistentes à Castração/diagnóstico , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , Resultado do TratamentoRESUMO
PURPOSE: The outcome of RCC has improved considerably in the last few years, and the treatment options have increased. LACOG-GU and LARCG held a consensus meeting to develop guidelines to support the clinical decisions of physicians and other health professionals involved in the care of RCC patients. METHODS: Eighty questions addressing relevant advanced RCC treatments were previously formulated by a panel of experts. The voting panel comprised 26 specialists from the LACOG-GU/LARCG. Consensus was determined as 75% agreement. For questions with less than 75% agreement, a new discussion was held, and consensus was determined by the majority of votes after the second voting session. RESULTS: The recommendations were based on the highest level of scientific evidence or by the opinion of the RCC experts when no relevant research data were available. CONCLUSION: This manuscript provides guidance for advanced RCC treatment according to the LACOG-GU/LARCG expert recommendations.
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Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/terapia , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Tomada de Decisão Clínica , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Gerenciamento Clínico , Prova Pericial , Humanos , América Latina , Metastasectomia/métodos , Nefrectomia/métodos , Guias de Prática Clínica como Assunto , Padrão de CuidadoRESUMO
BACKGROUND: Renal cell cancer (RCC) is one of the 10 most common cancers in the world, and its incidence is increasing, whereas mortality is declining only in developed countries. Therefore, two collaborative groups, The Latin American Oncology Cooperative Group-Genitourinary Section (LACOG-GU) and the Latin American Renal Cancer Group (LARCG), held a consensus meeting to develop this guideline. METHODS: Issues (134) related to the treatment of RCC were previously formulated by a panel of experts. The voting panel comprised 26 specialists (urologists and medical oncologists) from the LACOG-GU/LARCG. A consensus was reached if 75% agreement was achieved. If there was less concordance, a new discussion was undertaken, and a consensus was determined by the most votes after a second voting session. RESULTS: The expert meeting provided recommendations that were in line with the global literature; 75.0% of the recommendations made by the panel of experts were evidence-based level A, 22.5% of the recommendations were level B, and 2.5% of the recommendations were level D. CONCLUSIONS: This review suggests recommendations for the surgical treatment of RCC according to the LACOG-GU/LARCG experts.
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Diffuse intrinsic pontine glioma is a pediatric oncologic disease with dismal prognosis and no effective treatment. Since 2007, our patients have been using valproic acid as prophylactic anticonvulsant. We have undertaken a retrospective study in order to evaluate the influence of valproate in the outcomes of children with this disease in our center. Patients were treated with weekly carboplatin and vincristine and received conformal radiotherapy, either concurrent or sequential. Event-free survival and overall survival of patients not treated with valproic acid were 6.5 and 7.8 months. Accelerated failure time model (a parametric multivariate regression test for time-to-failure data) showed a statistically significant superiority of the median event-free survival of treated patients (6.5 vs. 9.5 months in treated patients; HR 0.54-95 % CI 0.33-0.87; p < 0.05) and also of overall survival (7.8 vs. 13.4 months in treated patients; HR 0.60-95 % CI 0.37-0.98; p = 0.05).
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Antineoplásicos/uso terapêutico , Neoplasias do Tronco Encefálico/tratamento farmacológico , Neoplasias do Tronco Encefálico/radioterapia , Glioma/tratamento farmacológico , Glioma/radioterapia , Ácido Valproico/uso terapêutico , Adolescente , Carboplatina/uso terapêutico , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Imageamento por Ressonância Magnética , Masculino , Estudos Retrospectivos , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Vincristina/uso terapêuticoRESUMO
Although substantial progress has been made in pediatric brain tumor management, patients with brainstem tumors and high-grade gliomas, as well as patients less than 3 years of age with high-risk malignant tumors, have a poorer prognosis. The authors have been treating these patients with radiotherapy and standard carboplatin and vincristine chemotherapy. Since January 2007 the authors have been using valproate as anticonvulsant for prophylaxis. The authors performed a retrospective cohort analysis of pediatric patients with high-risk brain tumors treated with chemotherapy, radiotherapy, and valproate prophylaxis, comparing this group with a historical control. The 2007-2008 group was comprised of 22 patients, 15 with brainstem tumors (7 diffuse intrinsic pontine glioma [DIPG], 3 focal, the remaining infiltrating with a solid portion), 4 with diencephalic tumors (2 thalamic), and 3 with supratentorial high-grade tumors (1 glioblastoma, 1 recurrent grade III ependymoma, 1 with gliomatosis). There were 15 patients alive (68%) after a mean follow-up time of 19 months. Survival function comparison by log rank test was highly significant (P = .004) with a hazard ratio of 0.31 (0.14-0.70). Radiological response showed 3 complete responses (14%), 8 partial responses (36%), 5 stable diseases (23%), and 5 progresssive diseases (23%). The authors hypothesize that valproate may have potentiated the antiangiogenic effect of vincristine, diminished expression of resistance to carboplatin, and sensitized tumor cells to radiotherapy. The authors suggest that clinical trials of carboplatin and vincristine associated with oral continuous low-dose valproate are indicated for pediatric patients with high-risk brain tumor.