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The gut microbiome is interlinked with renal cell carcinoma (RCC) and its response to systemic treatment. Mounting data suggests that certain elements of the gut microbiome may correlate with improved outcomes. New generation sequencing techniques and advanced bioinformatic data curation are accelerating the investigation of specific markers and metabolites that could predict treatment response. A variety of new therapeutic strategies, such as fecal microbiota transplantation, probiotic supplements, and dietary interventions, are currently being developed to modify the gut microbiome and improve anticancer therapies in patients with RCC. This review discusses the preliminary evidence indicating the role of the microbiome in cancer treatment, the techniques and tools necessary for its proper study and some of the current forms with which the microbiome can be modulated to improve patient outcomes.
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PURPOSE: Patients with no evidence of disease (NED) after metastasectomy for renal cell carcinoma are at high risk of recurrence. Pazopanib is an inhibitor of vascular endothelial growth factor receptor and other kinases that improves progression-free survival in patients with metastatic RCC (mRCC). We conducted a randomized, double-blind, placebo-controlled multicenter study to test whether pazopanib would improve disease-free survival (DFS) in patients with mRCC rendered NED after metastasectomy. PATIENTS AND METHODS: Patients with NED after metastasectomy were randomly assigned 1:1 to receive pazopanib 800 mg once daily versus placebo for 52 weeks. The study was designed to observe an improvement in DFS from 25% to 45% with pazopanib at 3 years, corresponding to 42% reduction in the DFS event rate. RESULTS: From August 2012 to July 2017, 129 patients were enrolled. The study was unblinded after 83 DFS events (92% information). The study did not meet its primary end point. An updated analysis at 60.5-month median follow-up from random assignment (95% CI, 59.3 to 71.0) showed that the 3-year DFS was 27.4% (95% CI, 17.9 to 41.7) for pazopanib and 21.9% (95% CI, 13.3 to 36.2) for placebo. Hazard ratio (HR) for DFS was 0.90 ([95% CI, 0.60 to 1.34]; Pone-sided = .29) in favor of pazopanib. Three-year overall survival (OS) was 81.9% (95% CI, 72.7 to 92.2) for pazopanib and 91.4% (95% CI, 84.4 to 98.9) for placebo. The HR for OS was 2.55 (95% CI, 1.23 to 5.27) in favor of placebo (Ptwo-sided = .012). Health-related quality-of-life measures deteriorated in the pazopanib group during the treatment period. CONCLUSION: Pazopanib did not improve DFS as the primary end point compared with blinded placebo in patients with mRCC with NED after metastasectomy. In addition, there was a concerning trend favoring placebo in OS.
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Carcinoma de Células Renais , Indazóis , Neoplasias Renais , Metastasectomia , Pirimidinas , Sulfonamidas , Humanos , Indazóis/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/cirurgia , Carcinoma de Células Renais/mortalidade , Pirimidinas/uso terapêutico , Pirimidinas/farmacologia , Sulfonamidas/uso terapêutico , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacologia , Neoplasias Renais/patologia , Neoplasias Renais/tratamento farmacológico , Método Duplo-Cego , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Inibidores da Angiogênese/uso terapêutico , Intervalo Livre de Doença , Idoso de 80 Anos ou maisRESUMO
PURPOSE: To assess the effect of clinical and pathological variables on cancer-specific and overall survival (OS) in de novo metastatic patients from a collaborative of primarily Latin American countries. PATIENTS AND METHODS: Of 4,060 patients with renal cell carcinoma diagnosed between 1990 and 2015, a total of 530 (14.5%) had metastasis at clinical presentation. Relationships between clinical and pathological parameters and treatment-related outcomes were analyzed by Cox regression and the log-rank method. RESULTS: Of 530 patients, 184 (90.6%) had died of renal cell carcinoma. The median OS of the entire cohort was 24 months. American Society of Anesthesiology classification 3-4 (hazard ratio [HR]: 1.64), perirenal fat invasion (HR: 2.02), and ≥ 2 metastatic organ sites (HR: 2.19) were independent prognostic factors for 5-year OS in multivariable analyses. We created a risk group stratification with these variables: no adverse risk factors (favorable group), median OS not reached; one adverse factor (intermediate group), median OS 33 months (HR: 2.04); and two or three adverse factors (poor risk group), median OS 14 months (HR: 3.58). CONCLUSION: Our study defines novel prognostic factors that are relevant to a Latin American cohort. With external validation, these easily discerned clinical variables can be used to offer prognostic information across low- and middle-income countries.
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Carcinoma de Células Renais , Neoplasias Renais , Humanos , América Latina/epidemiologia , Prognóstico , Resultado do Tratamento , Estados UnidosRESUMO
OBJECTIVE: Emotional symptoms are frequently reported among patients with cancer. We evaluated the association between emotional symptoms and problem-related distress in a sample of patients with cancer about to initiate chemotherapy within a private hospital in Brazil. METHODS: Patients were assessed before initiating chemotherapy, treatment mid-point, and on the last day of treatment for anxiety and depression (Hospital Anxiety and Depression Scale [HADS]) and for problem-related distress (Distress Thermometer Problem List). Problem-related distress variable was computed as the sum of practical, physical, spiritual and familial problems. Mixed-model analysis was applied to determine the association between HADS and problem-related distress, adjusting for age and gender. RESULTS: A total of 655 consecutive patients were enrolled. There was a significant main effect of time (F = 8.99, p = 0.0001), showing that emotional symptoms improve over time. A significant main effect was observed for problem-related distress (F = 371.56, p < 0.0001) revealing that patients with elevated problem-related distress at baseline tend to have higher HADS across the three time points, compared to patients with lower problem-related distress. There was an interaction effect between problem-related distress and time (F = 85.22, p < 0.0001), suggesting that HADS scores decreased differently over time, depending on patients' initial level of problem-related distress. CONCLUSION: Overall, emotional symptoms, while decreasing over time, remained associated with problem-related distress after chemotherapy in Brazil. The potential benefit of implementing a psychosocial intervention remains high throughout cancer treatment.
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Ansiedade/psicologia , Depressão/psicologia , Neoplasias/psicologia , Angústia Psicológica , Estresse Psicológico/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transtornos de Ansiedade , Brasil/epidemiologia , Hospitais , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Neoplasias/epidemiologia , Estudos Prospectivos , Escala Visual AnalógicaRESUMO
In the era of precision oncology, liquid biopsy techniques, especially the use of plasma circulating tumour DNA (ctDNA) analysis, represent a paradigm shift in the use of genomic biomarkers with considerable implications for clinical practice. Compared with tissue-based tumour DNA analysis, plasma ctDNA is more convenient to test, more readily accessible, faster to obtain and less invasive, minimizing procedure-related risks and offering the opportunity to perform serial monitoring. Additionally, genomic profiles of ctDNA have been shown to reflect tumour heterogeneity, which has important implications for the identification of resistant clones and selection of targeted therapy well before clinical and radiographic changes occur. Moreover, plasma ctDNA testing can also be applied to cancer screening, risk stratification and quantification of minimal residual disease. These features provide an unprecedented opportunity for early treatment of patients, improving the chances of treatment success.
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Ácidos Nucleicos Livres/sangue , Neoplasias Renais/genética , Neoplasias Renais/patologia , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Ensaios Clínicos como Assunto , Humanos , Biópsia Líquida , MasculinoRESUMO
Renal cell carcinoma (RCC) is a commonly diagnosed and histologically diverse urologic malignancy. Clear cell RCC (ccRCC) is by far the most common, followed by the papillary and chromophobe subtypes. Sarcomatoid differentiation is a morphologic change that can be seen in all subtypes that typically portends a poor prognosis. In the past, treatment options for RCC were limited to cytokine-based therapy with a high-toxicity profile and low response rate. An increased understanding of the molecular basis of RCC has led to substantial improvement in treatment options in the form of targeted therapy and immunotherapy. A significant early discovery in RCC was frequent inactivation of the Von Hippel Lindau gene in ccRCC, which ultimately led to the development of vascular endothelial growth factor and mammalian target of rapamycin inhibitors. Further genomic sequencing of ccRCC tumors has identified other common mutations including BAP-1, PBRM1, SETD2, and PIK3CA. Many recent studies have explored how these mutations can affect prognosis and response to treatment. Likewise, papillary RCC has also been studied at the molecular level, which has shown a high level of mutations in the MET gene; early clinical data suggest the utility of MET targeted therapy. Finally, regarding the rarer sarcomatoid tumors, mutations in TP53 and NF2 may be important to their development. As we continue to learn more about what drives RCC at the molecular level, treatment options for RCC patients are diversifying.