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1.
Urol Clin North Am ; 47(4): 419-431, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33008493

RESUMO

The management of metastatic renal cell carcinoma (RCC) has evolved rapidly in recent years with several immunotherapy-based combinations of strategies approved as first-line therapies. Targeted strategies, including systemic antiangiogenesis agents and immune checkpoint blockade, form the basis of a therapeutic approach. With rising rates of recurrence after first-line treatment, it is increasingly important to not only adopt a personalized treatment plan with minimal adverse events but also develop predictive biomarkers for response. This review discusses currently available first-line and second-line therapies in RCC and their pivotal data, with specific focus on ongoing clinical trials in the adjuvant setting, including those involving novel agents.


Assuntos
Produtos Biológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Imunoterapia/métodos , Neoplasias Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Ensaios Clínicos Fase II como Assunto , Terapia Combinada , Quimioterapia Combinada , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Nefrectomia/métodos , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos
2.
Cochrane Database Syst Rev ; 10: CD012796, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33058158

RESUMO

BACKGROUND: Several comparative randomised controlled trials (RCTs) have been performed including combinations of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors since the publication of a Cochrane Review on targeted therapy for metastatic renal cell carcinoma (mRCC) in 2008. This review represents an update of that original review. OBJECTIVES: To assess the effects of targeted therapies for clear cell mRCC in patients naïve to systemic therapy. SEARCH METHODS: We performed a comprehensive search with no restrictions on language or publication status. The date of the latest search was 18 June 2020. SELECTION CRITERIA: We included randomised controlled trials, recruiting patients with clear cell mRCC naïve to previous systemic treatment. The index intervention was any TKI-based targeted therapy. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the included studies and extracted data for the primary outcomes: progression-free survival (PFS), overall survival (OS) and serious adverse events (SAEs); and the secondary outcomes: health-related quality of life (QoL), response rate and minor adverse events (AEs). We performed statistical analyses using a random-effects model and rated the certainty of evidence according to the GRADE approach. MAIN RESULTS: We included 18 RCTs reporting on 11,590 participants randomised across 18 comparisons. This abstract focuses on the primary outcomes of select comparisons. 1. Pazopanib versus sunitinib Pazopanib may result in little to no difference in PFS as compared to sunitinib (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.90 to 1.23; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 420 per 1000 in this trial at 12 months, this corresponds to 18 fewer participants experiencing PFS (95% CI 76 fewer to 38 more) per 1000 participants. Pazopanib may result in little to no difference in OS compared to sunitinib (HR 0.92, 95% CI 0.80 to 1.06; 1 study, 1110 participants; low-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 27 more OSs (95% CI 19 fewer to 70 more) per 1000 participants. Pazopanib may result in little to no difference in SAEs as compared to sunitinib (risk ratio (RR) 1.01, 95% CI 0.94 to 1.09; 1 study, 1102 participants; low-certainty evidence). Based on the control event risk of 734 per 1000 in this trial, this corresponds to 7 more participants experiencing SAEs (95% CI 44 fewer to 66 more) per 1000 participants. 2. Sunitinib versus avelumab and axitinib Sunitinib probably reduces PFS as compared to avelumab plus axitinib (HR 1.45, 95% CI 1.17 to 1.80; 1 study, 886 participants; moderate-certainty evidence). Based on the control event risk of 550 per 1000 in this trial at 12 months, this corresponds to 130 fewer participants experiencing PFS (95% CI 209 fewer to 53 fewer) per 1000 participants. Sunitinib may result in little to no difference in OS (HR 1.28, 95% CI 0.92 to 1.79; 1 study, 886 participants; low-certainty evidence). Based on the control event risk of 890 per 1000 in this trial at 12 months, this would result in 29 fewer OSs (95% CI 78 fewer to 8 more) per 1000 participants. Sunitinib may result in little to no difference in SAEs (RR 1.01, 95% CI 0.93 to 1.10; 1 study, 873 participants; low-certainty evidence). Based on the control event risk of 705 per 1000 in this trial, this corresponds to 7 more SAEs (95% CI 49 fewer to 71 more) per 1000 participants.  3. Sunitinib versus pembrolizumab and axitinib Sunitinib probably reduces PFS as compared to pembrolizumab plus axitinib (HR 1.45, 95% CI 1.19 to 1.76; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 590 per 1000 in this trial at 12 months, this corresponds to 125 fewer participants experiencing PFS (95% CI 195 fewer to 56 fewer) per 1000 participants. Sunitinib probably reduces OS (HR 1.90, 95% CI 1.36 to 2.65; 1 study, 861 participants; moderate-certainty evidence). Based on the control event risk of 880 per 1000 in this trial at 12 months, this would result in 96 fewer OSs (95% CI 167 fewer to 40 fewer) per 1000 participants. Sunitinib may reduce SAEs as compared to pembrolizumab plus axitinib (RR 0.90, 95% CI 0.81 to 1.02; 1 study, 854 participants; low-certainty evidence) although the CI includes the possibility of no effect. Based on the control event risk of 604 per 1000 in this trial, this corresponds to 60 fewer SAEs (95% CI 115 fewer to 12 more) per 1000 participants.  4. Sunitinib versus nivolumab and ipilimumab Sunitinib may reduce PFS as compared to nivolumab plus ipilimumab (HR 1.30, 95% CI 1.11 to 1.52; 1 study, 847 participants; low-certainty evidence). Based on the control event risk of 280 per 1000 in this trial at 30 months' follow-up, this corresponds to 89 fewer PFSs (95% CI 136 fewer to 37 fewer) per 1000 participants. Sunitinib reduces OS (HR 1.52, 95% CI 1.23 to 1.89; 1 study, 847 participants; high-certainty evidence). Based on the control event risk 600 per 1000 in this trial at 30 months, this would result in 140 fewer OSs (95% CI 219 fewer to 67 fewer) per 1000 participants. Sunitinib probably increases SAEs (RR 1.37, 95% CI 1.22 to 1.53; 1 study, 1082 participants; moderate-certainty evidence). Based on the control event risk of 457 per 1000 in this trial, this corresponds to 169 more SAEs (95% CI 101 more to 242 more) per 1000 participants. AUTHORS' CONCLUSIONS: Based on the low to high certainty of evidence, several combinations of immune checkpoint inhibitors appear to be superior to single-agent targeted therapy in terms of PFS and OS, and with a favourable AE profile. Some single-agent targeted therapies demonstrated a similar or improved oncological outcome compared to others; minor differences were observed for AE within this group. The certainty of evidence was variable ranging from high to very low and all comparisons were based on single trials.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Adulto , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Axitinibe/efeitos adversos , Axitinibe/uso terapêutico , Bevacizumab/efeitos adversos , Bevacizumab/uso terapêutico , Viés , Carcinoma de Células Renais/mortalidade , Everolimo/efeitos adversos , Everolimo/uso terapêutico , Humanos , Ipilimumab/efeitos adversos , Ipilimumab/uso terapêutico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Intervalo Livre de Progressão , Inibidores de Proteínas Quinases/efeitos adversos , Pirimidinas/efeitos adversos , Pirimidinas/uso terapêutico , Qualidade de Vida , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Sirolimo/efeitos adversos , Sirolimo/análogos & derivados , Sirolimo/uso terapêutico , Sorafenibe/efeitos adversos , Sorafenibe/uso terapêutico , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Sunitinibe/efeitos adversos , Sunitinibe/uso terapêutico
3.
J Comput Assist Tomogr ; 44(5): 737-743, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32842065

RESUMO

PURPOSE: The aim of the study was to investigate associations between computed tomography (CT) imaging characteristics, DNA methylation subtyping, and overall survival in renal cell carcinomas. METHODS: Survival curves were calculated using the Kaplan-Meier analysis. The CT data from 212 patients generated with The Cancer Imaging Archive (TCIA) were reviewed. Identified were 70 (33.0%) M1 subtype, 17 (8.0%) M2 subtype, and 125 (59.0%) M3 subtype. Univariate and multivariate analyses were performed using the logistic regression model. RESULTS: Patients with M1 subtype had the shortest median overall survival (P < 0.001). On univariate analysis, long axis of 70 mm, intratumoral calcifications, enhancement, long axis > median, short axis > median, and intratumoral vascularity were associated with a significantly higher incidence of M1 subtype (P < 0.05). Short axis ≤ median, absence of necrosis, absence of intratumoral vascularity, and nodular enhancement were associated with M2 subtype (P < 0.05). Short axis ≤ median, long axis ≤ median, long axis of less than 70 mm, and necrosis were associated with a significantly higher incidence of M3 subtype (P < 0.05). On multivariate logistic regression analysis, long axis of greater than 70 mm (odds ratio [OR] = 2.452, P = 0.004; 95% confidence interval [CI] = 1.332-4.514) and necrosis (OR = 4.758, P = 0.041, 95% CI = 1.065-21.250) were associated with M1 subtype (area under the curve [AUC] = 0. 664). Necrosis (OR = 0.047, P < 0.001, 95% CI = 0.012-0.178) and enhancement (OR = 0.083, P = 0.024, 95% CI = 0.010-0.716) were associated with M2 subtype (AUC = 0.909). Long axis > median (OR = 0.303, P < 0.001, 95% CI = 0.164-0.561) and necrosis (OR = 3.256, P = 0.003, 95% CI = 1.617-10.303) were associated with M3 subtype (AUC = 0. 664). CONCLUSIONS: The shortest survival was observed in patients with M1 subtype. This preliminary radiogenomics analysis of renal cell carcinoma demonstrated associations between CT imaging characteristic and DNA methylation subtyping.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/genética , Metilação de DNA , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/genética , Carcinoma de Células Renais/mortalidade , Estudos de Coortes , Feminino , Genômica , Humanos , Neoplasias Renais/mortalidade , Modelos Logísticos , Masculino , Tomografia Computadorizada por Raios X
4.
Medicine (Baltimore) ; 99(34): e21693, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846785

RESUMO

The role of immune cell infiltration in the prognosis of clear cell renal cell carcinoma (ccRCC) has received increasing attention. However, immune scores have not yet been introduced into routine clinical practice of ccRCC patients. The principal objective of our research was to study the correlation between immune scores and overall survival (OS) of ccRCC.In this study, Cox regression analyses were used to identify risk factors associated with OS of ccRCC based on the Cancer Genome Atlas datasets. Furthermore, an integrated nomogram combining immune scores and clinicopathologic factors was built for predicting 3- and 5-year OS of ccRCC patients. The receiver operating characteristic curve, concordance index, and calibration curves were used for the evaluation of our nomogram. Also, Kaplan-Meier (KM) survival analysis of immune scores, stromal scores, and different clinicopathological factors was performed.A total of 514 patients were divided into the low- or high-immune scores group. KM and multivariate Cox regression analyses demonstrated that ccRCC patients with high-immune scores had significantly poor OS compared with those with low-immune scores. Calibration curves showed good consistency between the predicted OS and the actual OS probability. Areas under the receiver operating characteristic curves for 3- and 5-year OS were 0.816 and 0.769, and the concordance index was 0.775, indicating that our nomogram had good accuracy for predicting OS of ccRCC patients. Additionally, KM analysis showed that older age, later T stage, distant metastasis, advanced tumor lymph node metastasis stage, higher tumor grade, left site, and low stromal scores were associated with worse OS in ccRCC patients.High-immune scores show a significant correlation with unsatisfactory prognosis in ccRCC patients. Furthermore, the immune scores-based nomogram may be helpful in predicting ccRCC prognosis.


Assuntos
Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/imunologia , Neoplasias Renais/mortalidade , Nomogramas , Idoso , Idoso de 80 Anos ou mais , Correlação de Dados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida
5.
Asia Pac J Clin Oncol ; 16 Suppl 3: 12-17, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32852898

RESUMO

Adjuvant treatment with VEGFR tyrosine kinase inhibitor in renal cell carcinoma after nephrectomy has been reported through four clinical trials: S-TRAC, ASSURE, PROTECT and ATLAS. Only S-TRAC has been significantly positive on primary endpoint DFS under sunitinib compared to placebo, whereas ASSURE, PROTECT and ATLAS did not show any gain under sunitinib, sorafenib, pazopanib or axitinib, respectively. Nevertheless, there are arguments for a trend for the impact of anti-angiogenic therapy on outcome of patients with high-risk renal cell carcinoma cancer following nephrectomy, allowing for a fair discussion with patients to decide for or against an adjuvant treatment.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Quimioterapia Adjuvante/métodos , Neoplasias Renais/tratamento farmacológico , Nefrectomia/métodos , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Humanos , Neoplasias Renais/mortalidade
6.
Anticancer Res ; 40(8): 4395-4400, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32727768

RESUMO

BACKGROUND/AIM: The therapeutic outcomes of patients with metastatic renal cell carcinoma (mRCC) have dramatically improved with the introduction of molecular-targeted agents. The observational multicenter study was conducted to develop a novel stratification system for the intermediate risk group of the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) model. PATIENTS AND METHODS: The present study included 252 Japanese patients with mRCC who received first-line molecular-targeted therapy at four institutions. RESULTS: The 252 patients were classified into the favorable, intermediate, and poor risk groups by the IMDC model. For the intermediate risk group, multivariate analysis of the six factors included in the IMDC model revealed that a low performance status, anemia, and a high platelet count were independent predictors of poor overall survival (OS). The intermediate risk group was subsequently divided into the following two groups (int -group 1 and 2) by the three independent OS predictors. Significant differences in the OS were noted among the IMDC favorable risk group, int-group 1, int-group 2, and poor risk group. CONCLUSION: The novel stratification presented in this study could be a useful tool for further prognostication of patients with mRCC classified into the intermediate risk group according to the IMDC model after first-line molecular-targeted therapy.


Assuntos
Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Terapia de Alvo Molecular/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Prognóstico , Estudos Retrospectivos , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
8.
Medicine (Baltimore) ; 99(24): e20742, 2020 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-32541526

RESUMO

The present study aimed to detect the A-kinase interacting protein 1 (AKIP1) expression in clear cell renal cell carcinoma (ccRCC) tumor tissues and adjacent tissues, and further investigate the correlation of tumor AKIP1 expression with clinicopathological features and survival profile in ccRCC patients.Totally 210 ccRCC patients who underwent resection were retrospectively reviewed, and their tumor and adjacent tissue specimens were acquired for immunohistochemical detection of AKIP1 expression. The survival data of patients were collected for overall survival (OS) assessment.AKIP1 was upregulated in ccRCC tumor tissues compared with adjacent tissues (P < .001). Tumor AKIP1 expression was positively associated with T stage (P = .019), N stage (P = .032), and TNM stage (P = .005) in ccRCC patients. According to AKIP1 expression in tumor tissues, all patients were grouped as AKIP1 low and high expression (AKIP1 high expression were further divided into AKIP1 high+, high++, and high+++ expression). OS was the lowest in the patients with AKIP1 high+++ expression, followed by those with AKIP1 high++ expression and AKIP1 high+ expression, and then patients with AKIP1 low expression (P < .001). Furthermore, multivariate Cox regression exhibited tumor AKIP1 high expression (P = .017), age (>60 years) (P = .030), pathological grade (G2/G3 vs G1) (P = .037), and TNM stage (II/III vs I) (P < .001) were independent predictive factors for decreased OS in ccRCC patients.AKIP1 presents potency to be a novel biomarker for tumor progression and prognosis surveillance in ccRCC.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/biossíntese , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Proteínas Nucleares/biossíntese , Idoso , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Correlação de Dados , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Taxa de Sobrevida
9.
Anticancer Res ; 40(6): 3485-3489, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32487648

RESUMO

BACKGROUND/AIM: Despite early detection by widespread use of abdominal imaging more than 40% of patients with conventional renal cell carcinoma (RCC) will die due to metastatic disease. Small kinase inhibitors for AXL receptor tyrosine kinase may delay the progression of metastatic cRCC. PATIENTS AND METHODS: We analysed AXL expression by immunohistochemistry on tissue multi arrays of 691 conventional RCC without metastasis at the time of nephrectomy. RESULTS: The Kaplan-Meier survival analysis indicated a poor disease-specific survival rates for patients with tumour showing cytoplasmic AXL staining, whereas expression on the cell membrane is associated with excellent disease outcome. Multivariate Cox regression analysis identified cytoplasmic AXL expression as an independent prognostic factor indicating a five-times higher risk of postoperative tumour progression (RR=5.048; 95% CI=2.391-10.657; p<0.001). CONCLUSION: Detecting cytoplasmic expression of AXL can be used to define a subset of conventional RCC with high risk of progression, thus identifying patients for more aggressive surveillance and adjuvant AXL inhibitor treatment as early as possible.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/patologia , Neoplasias Renais/metabolismo , Neoplasias Renais/patologia , Proteínas Proto-Oncogênicas/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/cirurgia , Citoplasma/metabolismo , Progressão da Doença , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Proteínas Proto-Oncogênicas/genética , Receptores Proteína Tirosina Quinases/genética , Recidiva , Resultado do Tratamento , Adulto Jovem
10.
Int J Clin Oncol ; 25(9): 1678-1686, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32488547

RESUMO

BACKGROUND: Sequential treatment starting with target therapy is still the standard care for metastatic renal cell carcinoma (mRCC), even in the era of immune checkpoint inhibitors. Our objective was to compare the clinical outcomes between axitinib and nivolumab as second-line therapy following prior targeted therapy in mRCC patients. METHODS: We identified 41 patients treated with axitinib and 39 patients treated with nivolumab as a second-line regimen after targeted therapy, and retrospectively compared the treatment efficacy and safety in these patients. RESULTS: The clinical benefit rate of axitinib was significantly higher than that of nivolumab (82.9% versus 56.4%; p = 0.014) and patients who received axitinib tended to show longer progression-free survival (PFS) than those who received nivolumab (10.3 months versus 7.3 months; p = 0.067). There was no difference in the overall survival (OS) of the two groups (both not reached; p = 0.581). The incidence of grade ≥ 3 adverse events (AEs) was similar between the two groups, but one patient in the nivolumab group died due to an immune-related AE. In addition, a Cox proportional hazards model showed that the pre-treatment KPS, the baseline neutrophil-to-lymphocyte ratio (NLR), and an objective response in second-line therapy were significantly associated with PFS, while the pre-treatment KPS, the number of metastatic organs, and an objective response in second-line therapy significantly contributed to the predicted OS. CONCLUSIONS: Although the prognosis did not differ markedly between the two groups, axitinib resulted in a better tumor response rate. Further randomized prospective studies are needed for the ideal order of this sequential treatment.


Assuntos
Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Axitinibe/efeitos adversos , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Prognóstico , Intervalo Livre de Progressão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
11.
Int J Clin Oncol ; 25(8): 1551-1561, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32504136

RESUMO

BACKGROUND: The objective of this study was to provide more definitive information about the prognostic impact of perioperative blood transfusion (PBT) on patients with surgically treated renal cell carcinoma (RCC). METHODS: A database of 4019 patients with clear cell RCC, all of whom underwent radical or partial nephrectomy as primary therapy as part of a multi-institutional Korean collaboration between 1988 and 2015, was analyzed retrospectively. PBT was defined as transfusion of allogeneic red blood cells during surgery or postsurgical period. Receipt of a PBT, as well as the amount and time of blood transfusion (BT), was compared. RESULTS: Overall, 335 (8.3%) patients received a PBT: 84 received postoperative BT, 202 received intraoperative BT, and 49 received both intraoperative and postoperative BT. Patients receiving a PBT had a poor preoperative immuno-nutritional status, and aggressive tumor characteristics. Multivariate analyses identified PBT as an independent predictor of recurrence-free survival and cancer-specific survival. Prognostic impact of PBT was restricted to those with locally advanced stage (pT3-4), and who underwent radical nephrectomy. Among patients who received a PBT, intraoperative (but not postoperative) BT was a prognostic factor for survival. Among patients who received intraoperative BT, those receiving three or more transfusion units had a significantly worse survival. CONCLUSION: Receipt of a PBT was an independent predictor of RFS and CSS in patients with surgically treated RCC, specifically locally advanced disease. Regarding the prognostic impact of timing or dose of PBT on survival, intraoperative BT and ≥ 3 pRBC units were associated with adverse oncological outcomes.


Assuntos
Carcinoma de Células Renais/cirurgia , Cuidados Intraoperatórios/métodos , Neoplasias Renais/cirurgia , Adulto , Idoso , Transfusão de Sangue , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nefrectomia/efeitos adversos , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
12.
Int J Clin Oncol ; 25(8): 1533-1542, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32519026

RESUMO

BACKGROUND: In a phase III clinical trial, CheckMate 025, treatment of metastatic renal cell carcinoma (mRCC) with nivolumab demonstrated superior efficacy over everolimus. However, as the clinical trial excluded patients with specific complications and poor performance status (PS), the effectiveness and safety of nivolumab in clinical practice, in which patients with various clinical complications are treated, is unclear. This study explored real-world nivolumab treatment in Japanese mRCC patients. METHODS: This is an interim analysis of a multicenter, non-interventional, medical record review study (minimum follow-up: 9 months). All eligible Japanese mRCC patients who first received nivolumab between February and October 2017 were included; data cut-off was April 2019. We analyzed nivolumab treatment patterns, efficacy (including overall survival, progression-free survival, objective response rate, and duration of response) and safety (including immune-related adverse events). RESULTS: Of 208 evaluable patients, 31.7% received nivolumab as fourth- or later line of treatment. At data cut-off, 26.9% of patients were continuing nivolumab treatment. The major reason for discontinuation was disease progression (n = 100, 65.8%). Median overall survival was not reached; the 12-month survival rate was 75.6%. Median progression-free survival was 7.1 months, the objective response rate was 22.6%, and median duration of response was 13.3 months. Patients who were excluded or limited in number in CheckMate 025, such as those with non-clear cell RCC or poor PS, also received benefits from nivolumab treatment. Immune-related adverse events occurred in 27.4% of patients (grade ≥ 3, 10.1%). CONCLUSION: Nivolumab was effective and well-tolerated in real-world Japanese mRCC patients. TRIAL REGISTRATION: UMIN000033312.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Idoso , Antineoplásicos Imunológicos/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Sistema de Registros , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
13.
Cancer Sci ; 111(7): 2460-2471, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32402135

RESUMO

The present study aimed to evaluate the efficacy of the real-world use of axitinib and to develop a prognostic model for stratifying patients who could derive long-term benefit from axitinib. This was a retrospective, descriptive study evaluating the efficacy of axitinib in patients with metastatic renal cell carcinoma that had been treated with 1 or 2 systemic antiangiogenic therapy regimens at 1 of 36 hospitals belonging to the Japan Urologic Oncology Group between January 2012 and February 2019. The primary outcome was overall survival (OS). Using a split-sample method, candidate variables that exhibited significant relationships with OS were chosen to create a model. The new model was validated using the rest of the cohort. In total, 485 patients were enrolled. The median OS was 34 months in the entire study population, whereas it was not reached, 27 months, and 14 months in the favorable, intermediate, and poor risk groups, respectively, according to the new risk classification model. The following 4 variables were included in the final risk model: the disease stage at diagnosis, number of metastatic sites at the start of axitinib therapy, serum albumin level, and neutrophil : lymphocyte ratio. The adjusted area under the curve values of the new model at 12, 36, and 60 months were 0.77, 0.82, and 0.82, respectively. The efficacy of axitinib in routine practice is comparable or even superior to that reported previously. The patients in the new model's favorable risk group might derive a long-term survival benefit from axitinib treatment.


Assuntos
Antineoplásicos/uso terapêutico , Axitinibe/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Axitinibe/administração & dosagem , Axitinibe/efeitos adversos , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Curva ROC , Retratamento , Resultado do Tratamento
14.
Nat Med ; 26(5): 693-698, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32405063

RESUMO

Although elevated plasma interleukin-8 (pIL-8) has been associated with poor outcome to immune checkpoint blockade 1, this has not been comprehensively evaluated in large randomized studies. Here we analyzed circulating pIL-8 and IL8 gene expression in peripheral blood mononuclear cells and tumors of patients treated with atezolizumab (anti-PD-L1 monoclonal antibody) from multiple randomized trials representing 1,445 patients with metastatic urothelial carcinoma (mUC) and metastatic renal cell carcinoma. High levels of IL-8 in plasma, peripheral blood mononuclear cells and tumors were associated with decreased efficacy of atezolizumab in patients with mUC and metastatic renal cell carcinoma, even in tumors that were classically CD8+ T cell inflamed. Low baseline pIL-8 in patients with mUC was associated with increased response to atezolizumab and chemotherapy. Patients with mUC who experienced on-treatment decreases in pIL-8 exhibited improved overall survival when treated with atezolizumab but not with chemotherapy. Single-cell RNA sequencing of the immune compartment showed that IL8 is primarily expressed in circulating and intratumoral myeloid cells and that high IL8 expression is associated with downregulation of the antigen-presentation machinery. Therapies that can reverse the impacts of IL-8-mediated myeloid inflammation will be essential for improving outcomes of patients treated with immune checkpoint inhibitors.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antígeno B7-H1/antagonistas & inibidores , Interleucina-8/metabolismo , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados/uso terapêutico , Antígeno B7-H1/imunologia , Biomarcadores Farmacológicos/sangue , Biomarcadores Farmacológicos/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/tratamento farmacológico , Carcinoma de Células de Transição/metabolismo , Carcinoma de Células de Transição/mortalidade , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Interleucina-8/sangue , Neoplasias Renais/diagnóstico , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Masculino , Neoplasias/metabolismo , Neoplasias/mortalidade , Prognóstico , Análise de Sobrevida , Falha de Tratamento , Neoplasias Urológicas/diagnóstico , Neoplasias Urológicas/tratamento farmacológico , Neoplasias Urológicas/metabolismo , Neoplasias Urológicas/mortalidade
15.
Int J Clin Oncol ; 25(7): 1356-1363, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32361824

RESUMO

OBJECTIVE: The only one established prognostic nomogram for patients with sarcomatoid renal cell carcinoma (sRCC) was based on a small sample-sized study without external validation, and a nomogram can be applied to western sRCC patients has not yet been developed. Therefore, our study aimed to construct and validate an effective nomogram to predict overall survival (OS) for these patients. METHODS: The independent predictors for OS were identified and the nomogram was constructed on the basis of a retrospective study of a training cohort consisted of 428 non-Hispanic white sRCC patients registered in the Surveillance, Epidemiology and End Results (SEER) database from January 2010 to December 2015. Then, the discriminative performance of the nomogram was assessed by the concordance index (C-index). OS calibrations of the nomogram were also performed by comparing the nomogram-predicted probability to the observed survival rate. Furthermore, our nomogram was externally validated using two independent cohorts consisted of 71 non-Hispanic black patients and 82 Hispanic patients, respectively. RESULTS: Age at diagnosis, T stage, N stage, bone metastases, liver metastases, lung metastases and nephrectomy were identified as independent predictors for OS. In the training cohort and two validation cohorts, the C-indexes of the nomogram were 0.737, 0.801 and 0.764, respectively. Besides, excellent agreements between the nomogram prediction and the actual observation were achieved in all cohorts. CONCLUSIONS: The current study constructed and validated an effective prognostic nomogram for patients with sRCC, which can be used to perform accurate predictions of the 0.5-, 1-, and 2-year possibilities of OS.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/patologia , Neoplasias Ósseas/secundário , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Programa de SEER , Taxa de Sobrevida
16.
Int J Surg ; 79: 66-73, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32417461

RESUMO

BACKGROUND: To date, there remain uncertainties over the prognostic role of serum lactate dehydrogenase (LDH) in patients with metastatic renal cell carcinoma (mRCC). A systematic review and meta-analysis was performed. MATERIALS AND METHODS: Eligible studies were retrieved from PubMed, Embase, Cochrane Library and Web of Science databases up to October 2019. The endpoints included overall survival (OS) and progression-free survival (PFS). Multivariable adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were used to evaluate each endpoint. RESULTS: Thirty observational studies of low to moderate risk of bias embracing 6754 patients with mRCC were included. The results showed that patients with a high pretreatment serum LDH had an inferior OS (HR: 2.15, 95% CI: 1.85-2.51; P < 0.001) and PFS (HR: 1.76, 95% CI: 1.49-2.10; P < 0.001). Subgroup analyses according to year of publication, study design, patient population, geographic region, sample size and NOS score did not alter the direction of results. There was significant publication bias for OS, but not for PFS. Sensitivity analyses further confirmed the robustness of the results. CONCLUSION: Our findings indicated that a high level of pretreatment serum LDH was associated with an inferior OS and DFS in patients with mRCC. Methodological limitations should be considered while interpreting these results.


Assuntos
Carcinoma de Células Renais/mortalidade , Neoplasias Renais/mortalidade , L-Lactato Desidrogenase/sangue , Carcinoma de Células Renais/enzimologia , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/enzimologia , Neoplasias Renais/patologia , Metástase Neoplásica , Prognóstico
17.
Medicine (Baltimore) ; 99(19): e20191, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384514

RESUMO

Patients with renal cell carcinoma (RCC), the most common malignant renal epithelial tumor, usually present with advanced disease and unpredicted clinical behavior. The receptor tyrosine kinase, ephrin type-A receptor 2 (EphA2) was found to be overexpressed in several malignancies and its expression was found to be associated with poor prognostic features.Our study is an observational study with the aim of investigating the prognostic value of EphA2 in RCC patients and its association with clinicopathological parameters as well as Ki-67 expression, which is a well-known proliferative and prognostic marker in RCC.EphA2 and Ki-67 immunohistochemical staining was performed on whole sections representative of 50 patients diagnosed with primary RCC from 2013 to 2018. In addition, the association between EphA2 mRNA expression and clinicopathological parameters as well as the patients' outcome was also evaluated using two large publicly available databases.Our results showed a significant association between EphA2 immunohistochemical expression and tumor size, nuclear grade, tumor stage, patients' outcome and Ki-67 expression (P < .05 for all). The same trend was also observed with EphA2 mRNA expression using larger patients' cohorts in 2 publicly available databases. Notably, EphA2 protein expression showed higher levels of co-expression with the proliferative marker Ki-67.Our results suggested that higher expression of EphA2 and Ki-67 in tumor tissues predicts a locally aggressive behaviour and poor outcome of patients with RCC. Moreover, our results give a rationale for the potential benefits of using novel therapeutic strategies with the aim of targeting EphA2 receptor in RCC patients that might help in improving their outcome.


Assuntos
Carcinoma de Células Renais/patologia , Antígeno Ki-67/biossíntese , Neoplasias Renais/patologia , Receptor EphA2/biossíntese , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma de Células Renais/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , RNA Mensageiro , Carga Tumoral
18.
Tunis Med ; 98(2): 131-137, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32395802

RESUMO

INTRODUCTION: The subdivision into two entities of papillary renal cell carcinoma (PRCC) was established on histological criteria. It's in fact possible to distinguish the two subtypes by the means of radiological and progressive data. The subtype 1 is associated with the favorable profile. The ultrasound and especially CT urography ensure an accurate diagnostic approach with substantial therapeutic and prognostic involvement. The aim of the study is to define the radiological features that distinguish the two subtypes of renal papillary carcinoma, and to study the radiological predictive factors of locoregional recurrence, metastases free survival and specific survival. METHODS: It's about a monocentric, retrospective study led between January 2005 and June 2017, gathering 49 cases of operated PRCC. The study concerned patients over the age of 18, who were diagnosed after anatomopathological examination of the operative specimen (enlarged nephrectomy or conservative surgery). Cases in which diagnosis was made by renal biopsy were excluded. The comparative study concerned ultrasound and CT scan data. Univariate and multivariate analysis were performed to determine factors having a prognostic value in terms of locoregional recurrence, metastases-free and specific survival. RESULTS: On the ultrasound, the subtype 1 tumors were significantly homogenous with regular contours. Tumors were globally spontaneously hypodense and hypo vascular in 97,8% of cases. Enhancement was significantly more heterogonous for subtype 2 (p=0,01). Intratumoral necrosis and adenomegalies were associated with subtype 2 (p=0,0001 and 0,005). The predictive factors of locoregional recurrence, metastases-free survival and specific survival in univariate analysis were the contours' aspect, moderate enhancement and the presence of adenomegalies. On multivariate analysis, only the irregular contours were retained for locoregional recurrence-free survival and specific survival. CONCLUSIONS: Significant differences between the PRCC subtypes were observed when studying the radiological data. Irregular contours, adenomegalies and enhancement degree seemed to predict the progression of PRCC after curative surgery.


Assuntos
Carcinoma de Células Renais/diagnóstico , Diagnóstico por Imagem/métodos , Neoplasias Renais/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/cirurgia , Tratamento Conservador/efeitos adversos , Tratamento Conservador/métodos , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/diagnóstico , Recidiva Local de Neoplasia/etiologia , Estadiamento de Neoplasias , Nefrectomia/efeitos adversos , Nefrectomia/métodos , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Tomografia/métodos , Ultrassonografia/métodos , Adulto Jovem
19.
Int J Clin Oncol ; 25(8): 1543-1550, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32394047

RESUMO

PURPOSE: Despite nivolumab being increasingly used for treating metastatic renal cell carcinoma (mRCC), differing findings have been reported about its efficacy and safety in elderly patients. Thus, this study was aimed at evaluating nivolumab's efficacy and safety for treating mRCC in Japanese patients aged ≥ 75 years. METHODS: From March 2013 to August 2019, 118 mRCC patients (89 men and 29 women) were treated with nivolumab. The objective response rates (ORRs) were compared between patients aged ≥ 75 and < 75 years. Progression-free survival (PFS), overall survival (OS), and adverse events (AEs) were also compared between the two age-groups. RESULTS: The median follow-up duration after nivolumab initiation was 10 months. At the time of nivolumab initiation, 22 and 96 patients were aged ≥ 75 and < 75 years, respectively. Intergroup differences in patient characteristics except for age were not significant. Furthermore, intergroup differences in ORR (14 vs 23%; P = 0.367), PFS (HR 0.74, 95% CI 0.37-1.51; P = 0.414), and median OS (HR 1.29, 95% CI 0.68-2.46; P = 0.433) were not significant. The incidence of nivolumab discontinuation due to AEs was significantly higher in the ≥ 75 years group (27% vs 7%; P = 0.028), although the intergroup difference in the AE incidence rate was not significant (55% vs 43.8%; P = 0.535). CONCLUSIONS: Nivolumab's effectiveness was comparable between the two patient groups, except for early AE-related discontinuation in the ≥ 75 year group.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Nivolumabe/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Imunológicos/efeitos adversos , Grupo com Ancestrais do Continente Asiático , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Feminino , Humanos , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Nivolumabe/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
20.
Aging (Albany NY) ; 12(8): 6518-6535, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: covidwho-140657

RESUMO

Angiotensin-converting enzyme 2 (ACE2) is a member of the renin-angiotension system, however, the correlation between ACE2 and prognosis in UCEC (Uterine Corpus Endometrial Carcinoma) and KIRP (Kidney Renal Papillary Cell Carcinoma) is not clear. We analyzed the expression levels of ACE2 in the Oncomine and TIMER databases, the correlation between ACE2 and overall survival in the PrognoScan, GEPIA and Kaplan-Meier plotter databases. The correlation between ACE2 and immune infiltration level and the type markers of immune cells was investigated in TIMER database. A prognosis analysis based on the expression levels of ACE2 was further performed in related immune cells subgroup. The ACE2 promoter methylation profile was tested in the UALCAN database. In addition, we used GSE30589 and GSE52920 databases to elucidate the changes of ACE2 expression in vivo and in vitro after SARS-CoV infection. ACE2 was elevated in UCEC and KIRP, and high ACE2 had a favorable prognosis. The expression of ACE2 was positively correlated with the level of immune infiltration of macrophage in KIRP, B cell, CD4+T cell, neutrophil and dendritic cell immune infiltration levels in UCEC. ACE2 was significantly positively correlated with the type markers of B cells and neutrophils, macrophages in UCEC, while ACE2 in KIRP was positively correlated with the type markers of macrophages. High ACE2 expression level had a favorable prognosis in different enriched immune cells subgroups in UCEC and KIRP. And the promoter methylation levels of ACE2 in UCEC and KIRP were significantly reduced. What's more, we found that the expression of ACE2 decreased in vivo and in vitro after SARS-CoV infection. In conclusion, ACE2 expression increased significantly in UCEC and KIRP, elevated ACE2 was positively correlated with immune infiltration and prognosis. Moreover, tumor tissues may be more susceptible to SARS-CoV-2 infection in COVID-19 patients with UCEC and KIRP, which may worsen the prognosis.


Assuntos
Betacoronavirus , Carcinoma de Células Renais , Infecções por Coronavirus , Neoplasias do Endométrio , Imunidade Celular , Neoplasias Renais , Pandemias , Peptidil Dipeptidase A/biossíntese , Pneumonia Viral , Biomarcadores Tumorais , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/mortalidade , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Neoplasias do Endométrio/imunologia , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/mortalidade , Feminino , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/metabolismo , Neoplasias Renais/mortalidade , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Prognóstico
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