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1.
Nat Commun ; 12(1): 5262, 2021 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-34489456

RESUMO

TFE3-translocation renal cell carcinoma (TFE3-tRCC) is a rare and heterogeneous subtype of kidney cancer with no standard treatment for advanced disease. We describe comprehensive molecular characteristics of 63 untreated primary TFE3-tRCCs based on whole-exome and RNA sequencing. TFE3-tRCC is highly heterogeneous, both clinicopathologically and genotypically. ASPSCR1-TFE3 fusion and several somatic copy number alterations, including the loss of 22q, are associated with aggressive features and poor outcomes. Apart from tumors with MED15-TFE3 fusion, most TFE3-tRCCs exhibit low PD-L1 expression and low T-cell infiltration. Unsupervised transcriptomic analysis reveals five molecular clusters with distinct angiogenesis, stroma, proliferation and KRAS down signatures, which show association with fusion patterns and prognosis. In line with the aggressive nature, the high angiogenesis/stroma/proliferation cluster exclusively consists of tumors with ASPSCR1-TFE3 fusion. Here, we describe the genomic and transcriptomic features of TFE3-tRCC and provide insights into precision medicine for this disease.


Assuntos
Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Adolescente , Adulto , Idoso , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Criança , Pré-Escolar , Feminino , Regulação Neoplásica da Expressão Gênica , Fusão Gênica , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Prognóstico , Análise de Sequência de RNA , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Sequenciamento Completo do Exoma , Adulto Jovem
2.
Zhonghua Er Ke Za Zhi ; 59(10): 836-840, 2021 Oct 02.
Artigo em Chinês | MEDLINE | ID: mdl-34587679

RESUMO

Objective: To further understand the clinical features, treatment efficacy and risk factors for poor prognosis in infantile-onset renal tumors. Methods: Clinical data of 45 cases of infantile-onset renal tumors from June 2011 to November 2019 in Peking University First Hospital, Beijing Children's Hospital, Beijing Tongren Hospital and Beijing Shijitan Hospital were analyzed retrospectively. The clinical features were summarized and the prognoses were evaluated. Multi-disciplinary diagnosis and treatment was used, including surgery, chemotherapy and radiotherapy. Kaplan-Meier analysis was used to calculate the overall survival rate and the event-free survival rate, while the chi-square test was used to analyze the risk factors for poor prognosis. Results: Among 45 patients, 24 were males and 21 females. The age of onset was 7 (ranged 3-11) months, and the length of tumor at initial diagnosis was 9.7 (ranged 4.9-25.0)cm. The International Society of Pediatric Oncology (SIOP) staging: 5 cases (11%) were in stage Ⅰ, 22 cases in stage Ⅱ (49%), 8 cases in stage Ⅲ (18%), 6 cases in stage Ⅳ (13%), and 4 cases in stage Ⅴ (9%). Risk groups included 5 cases (11%) in the low-risk group, 22 cases (49%) in the intermediate-risk group, and 18 cases (40%) in the high-risk group. Forty-four cases (98%) did not receive preoperative biopsy, 26 cases (58%) received preoperative chemotherapy, 39 cases (87%) received postoperative chemotherapy, and 2 cases (4%) received three-dimensional conformal radiotherapy. The 5-year overall survival rate was (83±7)%, and the 5-year event-free survival rate was (76±8)%. Hematuria as the first symptom (3/8 vs. 83% (30/36), χ²=7.005, P=0.024), tumor long diameter≤8 cm (5/11 vs. 85% (28/33), χ²=5.606, P=0.027) and high-risk pathological group (7/18 vs.100% (26/26), χ²=21.928, P<0.01) were risk factors for poor prognosis of children with renal tumors in this group. Conclusion: The prognosis of children with infantile-onset renal tumors is fairly well, nevertheless the prognosis is poor in patients with hematuria as the first symptom and in high-risk pathological group.


Assuntos
Neoplasias Renais , Feminino , Humanos , Lactente , Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Masculino , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento
3.
Aktuelle Urol ; 52(5): 474-480, 2021 09.
Artigo em Alemão | MEDLINE | ID: mdl-34428827

RESUMO

The Response Evaluation Criteria in Solid Tumours (RECIST 1.1) currently represent the most widely established evaluation criteria for standardised therapy monitoring in solid tumours treated with traditional cytostatic and cytotoxic tumour therapies. The increasing use of immune checkpoint inhibitors in the therapy of metastatic renal cell carcinoma poses special challenges for radiological therapy monitoring due to the presence of atypical response patterns and immunotherapy-specific side-effects. Adapted criteria such as immune RECIST (iRECIST) can help in the follow-up assessment of renal cell carcinoma to detect atypical courses of disease under immune checkpoint inhibitor therapy both within and outside of clinical trials.


Assuntos
Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/terapia , Humanos , Imunoterapia , Neoplasias Renais/terapia , Critérios de Avaliação de Resposta em Tumores Sólidos
4.
Am J Hum Genet ; 108(9): 1590-1610, 2021 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-34390653

RESUMO

Our study investigated the underlying mechanism for the 14q24 renal cell carcinoma (RCC) susceptibility risk locus identified by a genome-wide association study (GWAS). The sentinel single-nucleotide polymorphism (SNP), rs4903064, at 14q24 confers an allele-specific effect on expression of the double PHD fingers 3 (DPF3) of the BAF SWI/SNF complex as assessed by massively parallel reporter assay, confirmatory luciferase assays, and eQTL analyses. Overexpression of DPF3 in renal cell lines increases growth rates and alters chromatin accessibility and gene expression, leading to inhibition of apoptosis and activation of oncogenic pathways. siRNA interference of multiple DPF3-deregulated genes reduces growth. Our results indicate that germline variation in DPF3, a component of the BAF complex, part of the SWI/SNF complexes, can lead to reduced apoptosis and activation of the STAT3 pathway, both critical in RCC carcinogenesis. In addition, we show that altered DPF3 expression in the 14q24 RCC locus could influence the effectiveness of immunotherapy treatment for RCC by regulating tumor cytokine secretion and immune cell activation.


Assuntos
Carcinoma de Células Renais/genética , Cromossomos Humanos Par 14 , Proteínas de Ligação a DNA/genética , Loci Gênicos , Neoplasias Renais/genética , Fator de Transcrição STAT3/genética , Fatores de Transcrição/genética , Carcinogênese/genética , Carcinogênese/imunologia , Carcinogênese/patologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/terapia , Linhagem Celular Tumoral , Cromatina/química , Cromatina/imunologia , Montagem e Desmontagem da Cromatina/imunologia , Citocinas/genética , Citocinas/imunologia , Proteínas de Ligação a DNA/imunologia , Regulação da Expressão Gênica , Predisposição Genética para Doença , Genoma Humano , Estudo de Associação Genômica Ampla , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imunoterapia/métodos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Polimorfismo de Nucleotídeo Único , Fator de Transcrição STAT3/imunologia , Linfócitos T Citotóxicos , Fatores de Transcrição/imunologia
5.
Cancer Radiother ; 25(6-7): 565-569, 2021 Oct.
Artigo em Francês | MEDLINE | ID: mdl-34391648

RESUMO

Immunotherapy occupies a growing place in urologic oncology, mainly for kidney and bladder cancers. On the basis of encouraging preclinical work, the combination of immunotherapy with radiotherapy aims to increase the tumor response, including in metastatic tumors, which raises many hopes, which this article reviews.


Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/terapia , Neoplasias da Próstata/terapia , Radioterapia/métodos , Neoplasias da Bexiga Urinária/terapia , Terapia Combinada/métodos , Humanos , Imunomodulação , Neoplasias Renais/imunologia , Masculino , Neoplasias da Próstata/imunologia , Neoplasias da Bexiga Urinária/imunologia
7.
Front Immunol ; 12: 646085, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211459

RESUMO

There is little evidence around Camrelizumab combined with cytoreductive nephrectomy (CN) and radiotherapy (RT) as a treatment option for metastatic renal cell carcinoma (mRCC). The influence of CN on immune responses and the abscopal effect are not well understood. In this paper, we report a case of anti-programmed cell death-1 (PD-1) treated with combined RT once CN reduced the primary tumor burden (TB). This patient also encountered an increased response to targeted radiotherapy after immune resistance. We also observed a macrophage-to-lymphocyte ratio (MLR) peak, which may be correlated with subsequent pseudoprogression after thoracic radiotherapy. Consequently, even with the disease, this patient has remained stable. This peculiar instance suggests there is a need to investigate the underlying mechanisms of CN in promoting the abscopal effect during immunotherapy when combined with RT. It also suggests that there is a need for further investigation into the role of RT in overcoming immune resistance, and the value of MLR in predicting pseudoprogression. We hypothesize that a heavy tumor burden might suppress the abscopal effect, thereby ensuring that CN promotes it. However, radiotherapy may overcome immune resistance during oligoprogression.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Carcinoma de Células Renais/terapia , Procedimentos Cirúrgicos de Citorredução/métodos , Neoplasias Renais/terapia , Nefrectomia/métodos , Idoso , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Terapia Combinada , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Teste de Cultura Mista de Linfócitos , Masculino , Metástase Neoplásica , Dosagem Radioterapêutica , Receptores de Antígenos de Linfócitos T alfa-beta/fisiologia , Macrófagos Associados a Tumor/imunologia
8.
J Immunother Cancer ; 9(7)2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34272309

RESUMO

The clinical and immunologic implications of the SARS-CoV-2 pandemic for patients with cancer receiving systemic anticancer therapy have introduced a multitude of clinical challenges and academic controversies. This review summarizes the current evidence, discussion points, and recommendations regarding the use of immune checkpoint inhibitors (ICIs) in patients with cancer during the SARS-CoV-2 pandemic, with a focus on patients with melanoma and renal cell carcinoma (RCC). More specifically, we summarize the theoretical concepts and available objective data regarding the relationships between ICIs and the antiviral immune response, along with recommended clinical approaches to the management of melanoma and RCC patient cohorts receiving ICIs throughout the course of the COVID-19 pandemic. Additional insights regarding the use of ICIs in the setting of current and upcoming COVID-19 vaccines and broader implications toward future pandemics are also discussed.


Assuntos
COVID-19/imunologia , Carcinoma de Células Renais/imunologia , Inibidores de Checkpoint Imunológico/imunologia , Neoplasias Renais/imunologia , Melanoma/imunologia , SARS-CoV-2/imunologia , COVID-19/tratamento farmacológico , COVID-19/epidemiologia , Vacinas contra COVID-19/imunologia , Vacinas contra COVID-19/uso terapêutico , Carcinoma de Células Renais/terapia , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Imunoterapia/métodos , Neoplasias Renais/terapia , Melanoma/terapia , Pandemias/prevenção & controle , SARS-CoV-2/efeitos dos fármacos
9.
Cancer Sci ; 112(9): 3469-3483, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34157192

RESUMO

Renal carcinoma shows a high risk of invasion and metastasis without effective treatment. Herein, we developed a chitosan (CS) nanoparticle-mediated DNA vaccine containing an activated factor L-Myc and a tumor-specific antigen CAIX for renal carcinoma treatment. The subcutaneous tumor models were intramuscularly immunized with CS-pL-Myc/pCAIX or control vaccine, respectively. Compared with single immunization group, the tumor growth was significantly suppressed in CS-pL-Myc/pCAIX co-immunization group. The increased proportion and mature of CD11c+ DCs, CD8+ CD11c+ DCs and CD103+ CD11c+ DCs were observed in the splenocytes from CS-pL-Myc/pCAIX co-immunized mice. Furthermore, the enhanced antigen-specific CD8+ T lymphocyte proliferation, cytotoxic T lymphocyte (CTL) responses, and multi-functional CD8+ T cell induction were detected in CS-pL-Myc/pCAIX co-immunization group compared with CS-pCAIX immunization group. Of note, the depletion of CD8 T cells resulted in the reduction of CD8+ T cells or CD8+ CD11c+ DCs and the loss of anti-tumor efficacy induced by CS-pL-Myc/pCAIX vaccine, suggesting the therapeutic efficacy of the vaccine was required for CD8+ DCs and CD103+ DCs mediated CD8+ T cells responses. Likewise, CS-pL-Myc/pCAIX co-immunization also significantly inhibited the lung metastasis of renal carcinoma models accompanied with the increased induction of multi-functional CD8+ T cell responses. Therefore, these results indicated that CS-pL-Myc/pCAIX vaccine could effectively induce CD8+ DCs and CD103+ DCs mediated tumor-specific multi-functional CD8+ T cell responses and exert the anti-tumor efficacy. This vaccine strategy offers a potential and promising approach for solid or metastatic tumor treatment.


Assuntos
Antígenos CD/metabolismo , Antígenos de Neoplasias/administração & dosagem , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/imunologia , Anidrase Carbônica IX/administração & dosagem , Carcinoma de Células Renais/terapia , Quitosana/química , Células Dendríticas/imunologia , Sistemas de Liberação de Medicamentos/métodos , Imunidade , Imunização/métodos , Cadeias alfa de Integrinas/metabolismo , Neoplasias Renais/terapia , Nanopartículas/química , Proteínas Proto-Oncogênicas c-myc/administração & dosagem , Vacinas de DNA/administração & dosagem , Animais , Antígenos de Neoplasias/genética , Anidrase Carbônica IX/genética , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Modelos Animais de Doenças , Feminino , Células HEK293 , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia , Camundongos , Camundongos Endogâmicos BALB C , Proteínas Proto-Oncogênicas c-myc/genética , Resultado do Tratamento , Vacinas de DNA/imunologia
10.
J Urol ; 206(2): 209-218, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34115531

RESUMO

PURPOSE: This AUA Guideline focuses on active surveillance (AS) and follow-up after intervention for adult patients with clinically-localized renal masses suspicious for cancer, including solid enhancing tumors and Bosniak 3/4 complex cystic lesions. MATERIALS AND METHODS: In January 2021, the Renal Mass and Localized Renal Cancer guideline underwent additional amendment based on a current literature-search. This literature search retrieved additional studies published between July 2016 to October 2020 using the same Key Questions and search criteria from the Renal Mass and Localized Renal Cancer guideline. When sufficient evidence existed, the body of evidence was assigned strength-rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: AS with potential delayed intervention should be considered for patients with solid, enhancing renal masses <2cm or Bosniak 3-4 lesions that are predominantly-cystic. Shared decision-making about AS should consider risks of intervention/competing mortality versus the potential oncologic benefits of intervention. Recommendations for renal mass biopsy and considerations for periodic clinical/imaging-based surveillance are discussed. After intervention, risk-based surveillance protocols are defined incorporating clinical/laboratory evaluation and abdominal/chest imaging designed to detect local/systemic recurrences and possible treatment-related sequelae, such as progressive renal-insufficiency. CONCLUSION: AS is a potential management strategy for some patients with clinically-localized renal masses that requires careful risk-assessment, shared decision-making and periodic-reassessment. Follow-up after intervention is designed to identify local/systemic recurrences and potential treatment-related sequelae. A risk-based approach should be prioritized with selective use of laboratory/imaging resources.


Assuntos
Continuidade da Assistência ao Paciente , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Tomada de Decisão Clínica , Humanos , Medição de Risco , Conduta Expectante
11.
J Urol ; 206(2): 199-208, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34115547

RESUMO

PURPOSE: This AUA Guideline focuses on evaluation/counseling/management of adult patients with clinically-localized renal masses suspicious for cancer, including solid-enhancing tumors and Bosniak 3/4 complex-cystic lesions. MATERIALS/METHODS: The Renal Mass and Localized Renal Cancer guideline underwent an update literature review which resulted in the 2021 amendment. When sufficient evidence existed, the body of evidence was assigned a strength rating of A (high), B (moderate), or C (low) for support of Strong, Moderate, or Conditional Recommendations. In the absence of sufficient evidence, additional information is provided as Clinical Principles and Expert Opinions (table 1[Table: see text]). RESULTS: Great progress has been made regarding the evaluation/management of clinically-localized renal masses. These guidelines provide updated, evidence-based recommendations regarding evaluation/counseling including the evolving role of renal-mass-biopsy (RMB). Given great variability of clinical/oncologic/functional characteristics, index patients are not utilized and the panel advocates individualized counseling/management. Options for intervention (partial-nephrectomy (PN), radical-nephrectomy (RN), and thermal-ablation (TA)) are reviewed including recent data about comparative-effectiveness/potential morbidities. Oncologic issues are prioritized while recognizing the importance of functional-outcomes for survivorship. Granular criteria for RN are provided to help reduce overutilization of RN while also avoiding imprudent PN. Priority for PN is recommended for clinical T1a lesions, along with selective utilization of TA, which has good efficacy for tumors≤3.0 cm. Recommendations for genetic-counseling have been revised and considerations for adjuvant-therapies are addressed. Active-surveillance and follow-up after intervention are discussed in an adjunctive article. CONCLUSION: Several factors require consideration during counseling/management of patients with clinically-localized renal masses including general health/comorbidities, oncologic-considerations, functional-consequences, and relative efficacy/potential morbidities of various management-strategies.


Assuntos
Neoplasias Renais/diagnóstico , Neoplasias Renais/terapia , Técnicas de Ablação , Antineoplásicos/uso terapêutico , Aconselhamento , Medicina Baseada em Evidências , Humanos , Neoplasias Renais/patologia , Nefrectomia
13.
Adv Exp Med Biol ; 1311: 117-126, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34014538

RESUMO

According to data from the American Cancer Society, cancer is one of the deadliest health problems globally. Annually, renal cell carcinoma (RCC) causes more than 100,000 deaths worldwide [1-4], posing an urgent need to develop effective treatments to increase patient survival outcomes. New therapies are expected to address a major factor contributing to cancer's resistance to standard therapies: oncogenic heterogeneity. Gene expression can vary tremendously among different types of cancers, different patients of the same tumor type, and even within individual tumors; various metabolic phenotypes can emerge, making singletherapy approaches insufficient. Novel strategies targeting the diverse metabolism of cancers aim to overcome this obstacle. Though some have yielded positive results, it remains a challenge to uncover all of the distinct metabolic profiles of RCC. In the quest to overcome this obstacle, the metabolic oriented research focusing on these cancers has offered freshly new perspectives, which are expected to contribute heavily to the development of new treatments.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Humanos , Neoplasias Renais/genética , Neoplasias Renais/terapia , Fenótipo
14.
Radiol Clin North Am ; 59(4): 631-646, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34053610

RESUMO

Renal masses are commonly encountered on cross-sectional imaging examinations performed for nonrenal indications. Although most can be dismissed as benign cysts, a subset will be either indeterminate or suspicious; in many cases, imaging cannot be used to reliably differentiate between benign and malignant masses. On-going research in defining characteristics of common renal masses on advanced imaging shows promise in offering solutions to this issue. A recent update of the Bosniak classification (used to categorize cystic renal masses) was proposed with the goals of decreasing imaging follow-up in likely benign cystic masses, and therefore avoiding unnecessary surgical resection of such masses.


Assuntos
Diagnóstico por Imagem/métodos , Achados Incidentais , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/terapia , Humanos , Rim/diagnóstico por imagem
16.
Adv Ther ; 38(6): 3373-3388, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34021481

RESUMO

INTRODUCTION: Renal cell carcinoma (RCC), an immunogenic tumor, is the most common form of kidney cancer worldwide. Immune checkpoint inhibitors (ICIs) play an important role in the treatment of metastatic RCC. Programmed death-ligand (PD-L1) has already been proposed as a possible prognosticator for ICIs effectiveness. To elucidate the feasible role of ICIs in neoadjuvant settings, we have assessed the most common PD-L1 expression modalities [tumor proportion score (TPS), combined positivity score (CPS) and inflammatory cell (IC) score] in primary tumors (PTs) and venous tumor thrombi (VTT) in first diagnosed, previously untreated RCC patients with accompanying VTT. METHODS: Between January 1999 and December 2016, 71 patients with a first diagnosed, untreated, locally advanced RCC (aRCC) (≥ pT3a) underwent surgery in Hanover Medical School (MHH). PD-L1 expression was examined separately in PTs and VTT using the CPS, IC score and TPS. We also considered the age at the time of the initial surgery and gender as probable influencing factors. By using a cutoff value of 1 (1%), PD-L1 expression levels in PTs and VTT were assessed to enable the determination of any frequency differences. RESULTS: Positive scores for PTs were shown by 54 (CPS), 53 (IC score) and 34 (TPS) patients, whereas in VTT, positive scores were evaluated for a total of 50 (CPS), 47 (IC-score) and 36 (TPS) patients. No statistically significant differences were obtained between the PD-L1 expression immunoscores for PTs and VTT. The covariates age at the time of the initial surgery and gender could not be statistically proven to influence the differences in PD-L1 expression between the VTT and PTs. CONCLUSION: To the best of our knowledge, this research is the largest study to investigate PD-L1 expression in PTs and VTT in 71 cases. It could have relevance for the future development of neoadjuvant immunotherapy options, particularly in aRCC with VTT.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Antígeno B7-H1 , Carcinoma de Células Renais/terapia , Humanos , Neoplasias Renais/terapia , Ligantes , Estudos Retrospectivos
17.
Int J Mol Sci ; 22(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923219

RESUMO

Renal cell carcinoma (RCC) is a malignant tumor associated with various tumor microenvironments (TMEs). The immune system is activated by the development of cancer and drives T cell anti-tumor response. CD8 T cells are known to improve clinical outcomes and sensitivity to immunotherapy, and play a crucial role against tumors. In contrast, tumor-associated macrophages (TAMs) suppress immunity against malignancy and lead to tumor progression. TAMs are promoted from damaged TMEs and mount proinflammatory responses to pathogens. Initial immunotherapy consists of interferon-α and interleukin-2. However, response to such therapy is unclear in most patients, and it is associated with high levels of toxicity. Immune checkpoint inhibitors (ICIs), which up-regulate immune responses by blocking the programed cell death protein 1 (PD-1) receptor, the ligand of PD-1, or cytotoxic T-lymphocyte-associated protein 4 T cells, have led to a new era of immunotherapy. Furthermore, combination strategies with ICIs have proven effective through several randomized controlled trials. We expect the next generation of immunotherapy to lead to better outcomes based on ongoing trials and inspire new therapeutic strategies.


Assuntos
Carcinoma de Células Renais/terapia , Imunoterapia/métodos , Neoplasias Renais/terapia , Microambiente Tumoral/imunologia , Animais , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/patologia , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/patologia
18.
Medicine (Baltimore) ; 100(14): e25397, 2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33832133

RESUMO

ABSTRACT: Decision-making to stop cancer treatment in patients with advanced cancer is stressful, and it significantly influences subsequent end-of-life palliative treatment. However, little is known about the extent to which the patient's self-decisions influenced the prognostic period. This study focused on the patient's self-decision and investigated the impact of the self-decision to stop cancer treatment on their post-cancer treatment survival period and place of death.We retrospectively analyzed 167 cases of advanced genitourinary cancer patients (kidney cancer: 42; bladder cancer: 68; prostate cancer: 57) treated at the University of Fukui Hospital (UFH), who later died because of cancer. Of these, 100 patients decided to stop cancer treatment by themselves (self-decision group), while the families of the remaining 67 patients (family's decision group) decided to stop treatment on their behalf because the patient's decision-making ability was already impaired. Differences in the post-cancer-treatment survival period and place of death between the 2 groups were examined. The association between place of death and survival period was also analyzed.The median survival period after terminating cancer treatment was approximately 6 times longer in the self-decision group (145.5 days in self-decision group vs 23.0 days in family's decision group, P < .001). Proportions for places of death were as follows: among the self-decision group, 42.0% of patients died at UFH, 45.0% at other medical institutions, and 13.0% at home; among the family's decision group, 62.7% died at UFH, 32.8% at other medical institutions, and 4.5% at home. The proportion of patients who died at UFH was significantly higher among the family's decision group (P = .011). The median survival period was significantly shorter for patients who died at UFH (UFH: 30.0 days; other institutions/home: 161.0 days; P < .001).Significantly longer post-cancer-treatment survival period and higher home death rate were observed among patients whose cancer treatment was terminated based on their self-decision. Our results provide clinical evidence, especially in terms of prognostic period and place of death that support the importance of discussing bad news, such as stopping cancer treatment with patients.


Assuntos
Família/psicologia , Doente Terminal/psicologia , Neoplasias Urogenitais/mortalidade , Neoplasias Urogenitais/terapia , Suspensão de Tratamento/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Atitude Frente a Morte , Estudos de Casos e Controles , Tomada de Decisões/fisiologia , Feminino , Humanos , Japão/epidemiologia , Neoplasias Renais/epidemiologia , Neoplasias Renais/mortalidade , Neoplasias Renais/psicologia , Neoplasias Renais/terapia , Masculino , Pessoa de Meia-Idade , Cuidados Paliativos/ética , Cuidados Paliativos/psicologia , Prognóstico , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/psicologia , Neoplasias da Próstata/terapia , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Assistência Terminal/ética , Assistência Terminal/psicologia , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/psicologia , Neoplasias da Bexiga Urinária/terapia , Neoplasias Urogenitais/patologia , Neoplasias Urogenitais/psicologia
19.
Curr Opin Urol ; 31(4): 409-415, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33882560

RESUMO

PURPOSE OF REVIEW: Artificial intelligence holds tremendous potential for disrupting clinical medicine. Here we review the current role of artificial intelligence in the kidney cancer space. RECENT FINDINGS: Machine learning and deep learning algorithms have been developed using information extracted from radiomic, histopathologic, and genomic datasets of patients with renal masses. SUMMARY: Although artificial intelligence applications in medicine are still in their infancy, they already hold immediate promise to improve accuracy of renal mass characterization, grade, and prognostication. As algorithms become more robust and generalizable, artificial intelligence is poised to significantly disrupt kidney cancer care.


Assuntos
Inteligência Artificial , Neoplasias Renais , Algoritmos , Humanos , Rim , Neoplasias Renais/terapia , Aprendizado de Máquina
20.
Asia Pac J Clin Oncol ; 17 Suppl 3: 27-38, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33860644

RESUMO

BACKGROUND: To establish a set of consensus statements for the management of metastatic renal cell carcinoma, a total of 12 urologists and clinical oncologists from two professional associations in Hong Kong formed an expert consensus panel. METHODS: Through a series of meetings and using the modified Delphi method, the panelists presented recent evidence, discussed clinical experiences, and drafted consensus statements on several areas of focus regarding the management of metastatic renal cell carcinoma. Each statement was eventually voted upon by every panelist based on the practicability of recommendation. RESULTS: A total of 46 consensus statements were ultimately accepted and established by panel voting. CONCLUSIONS: Derived from recent evidence and expert insights, these consensus statements were aimed at providing practical guidance to optimize metastatic renal cell carcinoma management and promote a higher standard of clinical care.


Assuntos
Carcinoma de Células Renais/terapia , Neoplasias Renais/terapia , Urologia/métodos , Consenso , Hong Kong , Humanos , Metástase Neoplásica
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