RESUMEN
Wilms tumor has been selected as an index tumor by the WHO Global Initiative for Childhood Cancer with the aim to improve cure rates worldwide. Nevertheless, there is a scarcity of published data on outcomes beyond those of the major cooperative groups. Therefore, we conducted a retrospective analysis including all patients with Wilms tumor treated at our referral center in Uruguay between 1995 and 2020. Treatment consisted of North American (NA) strategies in 23 cases (1995-2004), followed by the SIOP strategy in 35 cases thereafter. Staging included: I-II = 28, III = 7, IV = 14, and V = 9. There were no major surgical or medical complications; however, a delay in the administration of local radiotherapy was observed (median of 21 days after surgery). There were no cases of toxicity- or surgery-related deaths or treatment abandonment. Five-year probability of overall survival was 0.72 and 0.92 for the NA and SIOP groups, respectively. We conclude that outcomes were better for the SIOP strategy with no unexpected toxicities and high treatment compliance in both strategies. Timely implementation of radiotherapy was challenging.
Asunto(s)
Tumor de Wilms , Humanos , Tumor de Wilms/terapia , Tumor de Wilms/mortalidad , Uruguay , Masculino , Femenino , Estudios Retrospectivos , Preescolar , Lactante , Neoplasias Renales/terapia , Neoplasias Renales/mortalidad , Niño , Tasa de Supervivencia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéuticoRESUMEN
OBJECTIVE: The aim of the study was to create two consensus nomograms for predicting Overall Survival (OS) and Cancer-Specific Survival (CSS) in adults with papillary Renal Cell Carcinoma (pRCC). METHODS: Using the Surveillance, Epidemiology, and End Results databases, a retrospective analysis of 1,074 adults with pRCC from 2004 to 2015 was performed. These patients were then randomly divided into two independent cohorts with a ratio of 7:3 (training cohort: 752; validation cohort: 322). In a retrospective analysis of 752 patients from the training cohort, independent prognostic variables affecting OS and CSS were found. R software was used to create prognostic nomograms based on the findings of Cox regression analysis. The performance of the nomograms was assessed using the Concordance Index (C-index), the Area Under Curve (AUC), a calibration curve, and Decision Curve Analysis (DCA). Data from the 107 postoperative pRCC patients at the Affiliated Hospital of Xuzhou Medical University were used for external validation of the nomogram. RESULTS: For OS and CSS, the C-indices and AUCs of the training cohort and the validation cohort indicated that the model had excellent discrimination. The DCA demonstrated that the model was clinically applicable, and the calibration curves in the internal and external validations showed that the model's accuracy was high. CONCLUSION: The authors developed and validated a prognostic nomogram that accurately predicted the 3-, 5-, and 8-year OS and CSS of adults with pRCC. Clinicians can use this knowledge to direct the clinical management and counseling of patients with pRCC.
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Carcinoma de Células Renales , Neoplasias Renales , Nomogramas , Humanos , Masculino , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/cirugía , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Pronóstico , Adulto , Anciano , Reproducibilidad de los Resultados , Estadificación de Neoplasias , Programa de VERFRESUMEN
Natural Killer (NK) cells play a key role in cancer immunosurveillance. However, NK cells from cancer patients display an altered phenotype and impaired effector functions. In addition, evidence of a regulatory role for NK cells is emerging in diverse models of viral infection, transplantation, and autoimmunity. Here, we analyzed clear cell renal cell carcinoma (ccRCC) datasets from The Cancer Genome Atlas (TCGA) and observed that a higher expression of NK cell signature genes is associated with reduced survival. Analysis of fresh tumor samples from ccRCC patients unraveled the presence of a high frequency of tumor-infiltrating PD-L1+ NK cells, suggesting that these NK cells might exhibit immunoregulatory functions. In vitro, PD-L1 expression was induced on NK cells from healthy donors (HD) upon direct tumor cell recognition through NKG2D and was further up-regulated by monocyte-derived IL-18. Moreover, in vitro generated PD-L1hi NK cells displayed an activated phenotype and enhanced effector functions compared to PD-L1- NK cells, but simultaneously, they directly inhibited CD8+ T cell proliferation in a PD-L1-dependent manner. Our results suggest that tumors might drive the development of PD-L1-expressing NK cells that acquire immunoregulatory functions in humans. Hence, rational manipulation of these regulatory cells emerges as a possibility that may lead to improved anti-tumor immunity in cancer patients.
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Antígeno B7-H1/biosíntesis , Linfocitos T CD8-positivos/citología , Carcinoma de Células Renales/inmunología , Neoplasias Renales/inmunología , Células Asesinas Naturales/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/mortalidad , Línea Celular Tumoral , Proliferación Celular , Células Cultivadas , Conjuntos de Datos como Asunto , Supervivencia sin Enfermedad , Expresión Génica , Humanos , Interferón gamma/farmacología , Interleucina-18/farmacología , Células K562 , Estimación de Kaplan-Meier , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Monitorización Inmunológica , Monocitos/metabolismo , Proteínas Recombinantes/farmacología , Regulación hacia ArribaRESUMEN
Clear cell renal cell carcinoma (ccRCC) has been considered a metabolic disease, with loss of von Hippel-Lindau (VHL) gene and consequent overexpression of hypoxia-inducible factor 1 alpha (HIF-1α), which is central for tumor development and progression. Among other effects, HIF-1α is involved in the metabolic reprogramming of cancer cells towards the Warburg effect involved in tumor cell proliferation, migration and survival. In this context, several proteins are expressed by cancer cells, including glucose and lactate transporters as well as different pH regulators. Among them, monocarboxylate transporters (MCTs) can be highlighted. Our aim is to comprehensively analyze the immunoexpression of MCT1, MCT2, MCT4, CD147, CD44, HIF-1α, GLUT1 and CAIX in ccRCC surgical specimens correlating with classical prognostic factors and survival of patients with long follow-up. Surgical specimens from 207 patients with ccRCC who underwent radical or partial nephrectomy were used to build a tissue microarray. Immunostaining was categorized into absent/weak or moderate/strong and related to all classic ccRCC prognostic parameters. Kaplan-Meier curves were generated to assess overall and cancer-specific survival, and multivariate analysis was performed to identify independent prognostic factors of survival. Multivariate analysis showed that MCT1 together with tumor size and TNM staging, were independently related to cancer-specific survival. MCT1, CD147, CD44 and GLUT1 expression were significantly associated with poor prognostic factors. We show that MCT1 is an independent prognostic factor for cancer-specific survival in ccRCC justifying the use of new target therapies already being tested in clinical trials.
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Biomarcadores de Tumor , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/mortalidad , Proteínas de Ciclo Celular/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/genética , Neoplasias Renales/mortalidad , Proteínas Oncogénicas/genética , Anciano , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/terapia , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Receptores de Hialuranos/metabolismo , Inmunohistoquímica , Neoplasias Renales/diagnóstico , Neoplasias Renales/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , PronósticoRESUMEN
BACKGROUND AND PURPOSE: Renal cell carcinoma (RCC) has traditionally been considered radioresistant with a limited role for conventional fractionation as a local approach. Nevertheless, since the appearance of stereotactic body radiation therapy (SBRT), radiotherapy (RT) has been increasingly employed in the management of metastatic RCC (mRCC). The aim of this study was to evaluate the role of SBRT for synchronous and metachronous oligo metastatic RCC patients in terms of local control, delay of systemic treatment, overall survival and toxicity. PATIENTS AND METHODS: A Monocentric single institution retrospective data collection was performed. Inclusion criteria were: (1) oligo-recurrent or oligo-progressive disease (less than 5 metastases) in mRCC patients after radical/partial nephrectomy or during systemic therapy, (2) metastasectomy or other metastasis-directed, rather than SBRT not feasible, (3) any contraindication to receive systemic therapy (such as comorbidities), (4) all the histologies were included, (5) available signed informed consent form for treatment. Tumor response and toxicity were evaluated using the response evaluation criteria in solid tumors and the Common Terminology Criteria for Adverse Events version 4.03, respectively. Progression-free survival in-field and out-field (in-field and out-field PFS) and overall survival (OS) were calculated via the Kaplan-Meier method. The drug treatment-free interval was calculated from the start of SBRT to the beginning of any systemic therapy. RESULTS: From 2010 to December 2018, 61 patients with extracranial and intracranial metastatic RCC underwent SBRT on 83 lesions. Intracranial and extracranial lesions were included. Forty-five (74%) patients were treated for a solitary metastatic lesion. Median RT dose was 25 Gy (range 10-52) in 5-10 fractions. With a median follow-up of 2.3 years (range 0-7.15), 1-year in-field PFS was 70%, 2-year in-field PFS was 55%. One year out-field PFS was 39% and 1-year OS was 78%. Concomitant systemic therapy was employed for only 11 (18%) patients, for the others 50 (82%) the drug treatment-free rate was 70% and 50% at 1 and 2 years, respectively. No > G1 acute and late toxicities were reported. CONCLUSION: The pattern of failure was pre-dominantly out-of-field, even if the population was negatively selected and the used RT dose could be considered palliative. Therefore, SBRT appears to be a well-tolerated, feasible and safe approach in oligo metastatic RCC patients with an excellent in-field PFS. SBRT might play a role in the management of selected RCC patients allowing for a delay systemic therapy begin (one out of two patients were free from new systemic therapy at 2 years after SBRT). Further research on SBRT dose escalation is warranted.
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Carcinoma de Células Renales/radioterapia , Neoplasias Renales/radioterapia , Radiocirugia/métodos , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/cirugía , Progresión de la Enfermedad , Fraccionamiento de la Dosis de Radiación , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Nefrectomía , Supervivencia sin Progresión , Estudios RetrospectivosRESUMEN
OBJECTIVE: To test for an association between surgical delay and overall survival (OS) for patients with T2 renal masses. Many health care systems are balancing resources to manage the current COVID-19 pandemic, which may result in surgical delay for patients with large renal masses. METHODS: Using Cox proportional hazard models, we analyzed data from the National Cancer Database for patients undergoing extirpative surgery for clinical T2N0M0 renal masses between 2004 and 2015. Study outcomes were to assess for an association between surgical delay with OS and pathologic stage. RESULTS: We identified 11,848 patients who underwent extirpative surgery for clinical T2 renal masses. Compared with patients undergoing surgery within 2 months of diagnosis, we found worse OS for patients with a surgical delay of 3-4 months (hazard ratio [HR] 1.12, 95% confidence interval [CI] 1.00-1.25) or 5-6 months (HR 1.51, 95% CI 1.19-1.91). Considering only healthy patients with Charlson Comorbidity Index = 0, worse OS was associated with surgical delay of 5-6 months (HR 1.68, 95% CI 1.21-2.34, P= .002) but not 3-4 months (HR 1.08, 95% CI 0.93-1.26, P = 309). Pathologic stage (pT or pN) was not associated with surgical delay. CONCLUSION: Prolonged surgical delay (5-6 months) for patients with T2 renal tumors appears to have a negative impact on OS while shorter surgical delay (3-4 months) was not associated with worse OS in healthy patients. The data presented in this study may help patients and providers to weigh the risk of surgical delay versus the risk of iatrogenic SARS-CoV-2 exposure during resurgent waves of the COVID-19 pandemic.
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COVID-19/prevención & control , Toma de Decisiones Clínicas , Neoplasias Renales/mortalidad , Nefrectomía/estadística & datos numéricos , Tiempo de Tratamiento/estadística & datos numéricos , Anciano , COVID-19/epidemiología , COVID-19/transmisión , Control de Enfermedades Transmisibles/normas , Bases de Datos Factuales/estadística & datos numéricos , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/patología , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Mortalidad/tendencias , Estadificación de Neoplasias , Nefrectomía/normas , Nefrectomía/tendencias , Pandemias/prevención & control , Modelos de Riesgos Proporcionales , Puerto Rico/epidemiología , Estudios Retrospectivos , SARS-CoV-2/patogenicidad , Factores de Tiempo , Tiempo de Tratamiento/tendencias , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Recent studies have observed an association between immune-related adverse events (irAE) and favorable clinical outcomes in the setting of cancer treatment with immune checkpoint inhibitors (ICI). However, results have been variable and inconclusive. Therefore, we have conducted a pan-cancer meta-analysis evaluating the relationship between irAEs and clinical outcomes. MATERIALS AND METHODS: The search included studies published in PubMed, Embase, and Web of Science from conception to 12.28.2019 as well as abstracts published in the ASCO and ESMO meetings from 2015 to 2019. Studies were included if ICI was used in advanced or metastatic cancer settings and excluded if data contained only combination therapy regimens or contained anti-CTLA-4. Raw data for overall response rate (ORR), hazard ratios (HR), number of patients (n), and p values for overall survival (OS) and progression-free survival (PFS) were extracted. Pooled sensitivity (SN), specificity (SP), positive (PPV) and negative predictive values (NPV), and odds ratios (ORs) were calculated using the 2 × 2 table and logit transformed proportions; and summary receiver operating curve (sROC) was generated using the bivariate approach for ORR. Pooled HRs were calculated using the means weighted by inverse of the variance for OS and PFS. Heterogeneity was assumed and random effects model was used throughout the analyses. RESULTS: Final analysis included 32 studies, among which ORR data were available in 15 studies, OS in 17, and PFS in 16. 17 studies evaluated non-small cell lung cancer (NSCLC), two studies melanoma, one study gastric cancer, three studies renal cell carcinoma (RCC), seven studies various cancer types, two studies urothelial carcinoma, and one study head and neck cancer (HNSCC). With respect to ORR, pooled SN, SP, PPV and NPV, and OR were 0.522 [0.423-0.619], 0.810 [0.771-0.844], 0.516 [0.413-0.618], 0.819 [0.764-0.864], and 4.59 [3.24-6.50], respectively. The area under the curve (AUC) derived from the sROC was 0.773. HR for OS and PFS were 0.47 [95% CI 0.37-0.60] and 0.46 [95% CI 0.37-0.56], respectively. Between-study publication bias was present for ORR, OS, and PFS; however, results remained significant after trim-fill analysis. CONCLUSION: irAEs predict OR, OS, and PFS across different types of cancer and may represent useful biomarkers in the clinical setting.
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Inhibidores de Puntos de Control Inmunológico/efectos adversos , Neoplasias/terapia , Área Bajo la Curva , Antígeno B7-H1/antagonistas & inhibidores , Sesgo , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/terapia , Carcinoma de Células Transicionales/inmunología , Carcinoma de Células Transicionales/mortalidad , Carcinoma de Células Transicionales/terapia , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/mortalidad , Neoplasias de Cabeza y Cuello/terapia , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Neoplasias Renales/inmunología , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Complejo de Antígeno L1 de Leucocito/inmunología , Neoplasias Pulmonares/inmunología , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Melanoma/inmunología , Melanoma/mortalidad , Melanoma/terapia , Neoplasias/inmunología , Neoplasias/mortalidad , Supervivencia sin Progresión , Sensibilidad y Especificidad , Carcinoma de Células Escamosas de Cabeza y Cuello/inmunología , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Neoplasias Gástricas/inmunología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/terapia , Resultado del TratamientoRESUMEN
BACKGROUND: To evaluate demographic, clinical and pathological characteristics of small renal masses (SRM) (≤ 4 cm) in a Latin-American population provided by LARCG (Latin-American Renal Cancer Group) and analyze predictors of survival, recurrence and metastasis. METHODS: A multi-institutional retrospective cohort study of 1523 patients submitted to surgical treatment for non-metastatic SRM from 1979 to 2016. Comparisons between radical (RN) or partial nephrectomy (PN) and young or elderly patients were performed. Kaplan-Meier curves and log-rank tests estimated 10-year overall survival. Predictors of local recurrence or metastasis were analyzed by a multivariable logistic regression model. RESULTS: PN and RN were performed in 897 (66%) and 461 (34%) patients. A proportional increase of PN cases from 48.5% (1979-2009) to 75% (after 2009) was evidenced. Stratifying by age, elderly patients (≥ 65 years) had better 10-year OS rates when submitted to PN (83.5%), than RN (54.5%), p = 0.044. This disparity was not evidenced in younger patients. On multivariable model, bilaterality, extracapsular extension and ASA (American Society of Anesthesiologists) classification ≥3 were predictors of local recurrence. We did not identify significant predictors for distant metastasis in our series. CONCLUSIONS: PN is performed in Latin-America in a similar proportion to developed areas and it has been increasing in the last years. Even in elderly individuals, if good functional status, sufficiently fit to surgery, and favorable tumor characteristics, they should be encouraged to perform PN. Intending to an earlier diagnosis of recurrence or distant metastasis, SRM cases with unfavorable characteristics should have a more rigorous follow-up routine.
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Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/mortalidad , Neoplasias Renales/diagnóstico , Neoplasias Renales/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Anciano , Carcinoma de Células Renales/secundario , Carcinoma de Células Renales/cirugía , Estudios de Cohortes , Bases de Datos Factuales , Femenino , Humanos , Neoplasias Renales/patología , Neoplasias Renales/cirugía , América Latina , Masculino , Persona de Mediana Edad , Nefrectomía/métodos , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
BACKGROUND: Clear cell renal cell carcinoma (ccRCC), the most aggressive renal cancer, is characterized by early lymph node metastases and bad prognosis. Most therapies targeting advanced or metastatic ccRCC are based, as first-line treatment, on the administration of the vascular endothelial growth factor (VEGF) neutralizing antibody termed Bevacizumab. Despite proven benefits, the expected results were not obtained for the majority of patients. The possibility that an intricate interplay between angiogenesis and immune-checkpoints might exist lead us to evaluate tumor angiogenesis, by means of VEGF expression together with the immune checkpoint HLA-G/ILT4. METHODS: Tumor specimens were obtained from patients from two separate cohorts: One from "Evita Pueblo" Hospital from Berazategui, (Buenos Aires, Argentina) and the second includes patients surgically operated at the Urology Department of Saint-Louis Hospital (Paris, France) with a confirmed ccRCC diagnosis. Immunohistochemistry was performed with specific antibodies directed against HLA-G, VEGF-A, VEGF-C, D240, CD34, ILT4 and Ca-IX. In addition, gene expression levels were measured in a cell line derived from a ccRCC patient by semi-quantitative RT-PCR. RESULTS: Our results show that the highly vascularized tumors of ccRCC patients express high levels of VEGF and the immune-checkpoint HLA-G. In addition, ILT4, one of the HLA-G receptors, was detected on macrophages surrounding tumor cells, suggesting the generation of an immune-tolerant microenvironment that might favor tumorigenesis. Notably, RT-qPCR analysis provided the first evidence on the transcriptional relationship between HLA-G/ILT4 and the VEGF family. Namely, in the presence of HLA-G or ILT4, the levels of VEGF-A are diminished whereas those of VEGF-C are increased. CONCLUSIONS: In an effort to find new therapeutic molecules and fight against metastasis dissemination associated with the poor survival rates of ccRCC patients, these findings provide the rationale for co-targeting angiogenesis and the immune checkpoint HLA-G.
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Carcinoma de Células Renales/genética , Antígenos HLA-G/metabolismo , Neoplasias Renales/genética , Glicoproteínas de Membrana/metabolismo , Neovascularización Patológica/genética , Receptores Inmunológicos/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Adulto , Anciano , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/terapia , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/inmunología , Humanos , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Riñón/irrigación sanguínea , Riñón/patología , Riñón/cirugía , Neoplasias Renales/inmunología , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Masculino , Glicoproteínas de Membrana/antagonistas & inhibidores , Persona de Mediana Edad , Neovascularización Patológica/tratamiento farmacológico , Neovascularización Patológica/patología , Nefrectomía , Receptores Inmunológicos/antagonistas & inhibidores , Estudios Retrospectivos , Tasa de Supervivencia , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidoresRESUMEN
PURPOSE: To present a preliminary clinical experience and a dosimetric comparison of kidney-sparing volumetric modulated arc therapy (VMAT) with three-dimensional conformal radiotherapy (3D-CRT) for whole abdominal irradiation (WAI), in the setting of Wilms tumor (WT) treatment. MATERIALS AND METHODS: From a total of 20 consecutive WT cases treated with adjuvant irradiation, seven were submitted to WAI with VMAT. Renal function and survival rates were evaluated, and, for comparison purposes, similar VMAT and 3D-CRT treatment plans were performed for WAI patients, and differences were dosimetrically evaluated regarding doses to the remaining kidney and other organs at risk and the planning target volume (PTV). RESULTS: After a median follow-up time of 40.8 months (35.3-52.2), no acute significant intestinal toxicity was observed, and median creatinine clearance was 110.1 and 103.3 mL/min/1.73 m², respectively, before treatment and at last follow-up for WAI patients (P = 0.128). For comparative plans, maximum and median doses were lower for the remaining kidney with VMAT than with 3D-CRT. VMAT was associated with better PTV coverage as compared with 3D-CRT, with superior results for all the evaluated parameters (D95, D2, V100%, V98%, V95%; P = 0.018). CONCLUSION: The use of VMAT technique is associated with lower radiation doses to the remaining kidney and better coverage to the PTV than 3D-CRT technique for WAI, with preliminary clinical experience showing a favorable toxicity profile. Long-term results from prospective studies might prove the ability of VMAT to spare renal function in the setting of WT treatment.
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Neoplasias Renales/radioterapia , Riñón , Tratamientos Conservadores del Órgano , Radioterapia de Intensidad Modulada , Tumor de Wilms/radioterapia , Abdomen , Adolescente , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Lactante , Neoplasias Renales/mortalidad , Masculino , Órganos en Riesgo , Tasa de Supervivencia , Tumor de Wilms/mortalidadRESUMEN
El Tumor de Wilms (TW) es el tumor renal más frecuente entre los 1 y 5 años de edad. La evidencia existente respecto de aspectos clínicos, terapéuticos y de supervivencia (SV) del TW es escasa. El objetivo de este estudio fue determinar diferencias en la SV actuarial global (SVAG) y SV libre de enfermedad (SVLE) a 5 años en pacientes con TW tratados con quimioterapia neoadyuvante (QTNA) y cirugía inicial (CI). Serie de casos. Se incluyeron pacientes con TW de 11 meses y 13 años de edad, tratados en el Instituto del Cáncer SOLCA, Cuenca (1994-2019). Las variables resultado fueron SVAG y SVLE a 5 años. Otras variables de interés fueron: localización, estadio, histología, seguimiento y remisión completa (RC). Una vez concluidos sus tratamientos, los pacientes fueron sometidos a un seguimiento clínico. Se utilizó estadística descriptiva (medidas de tendencia central y dispersión) y analítica (Chi2, exacto de Fisher y corrección por continuidad). Se realizaron análisis de SV con curvas de Kaplan Meier y log-rank. Se reclutaron 36 pacientes (52,8 % hombres), con una mediana de edad de 44 meses; 55,5 % de ellos tuvieron histología favorable. La localización y estadio más frecuente fue riñón izquierdo (55,5 %) y I (33,3 %) respectivamente. El 58,3 % fueron sometidos a CI y el 41,7 % QTNA. Luego de aplicados los tratamientos 21 pacientes (58,3 %), alcanzaron RC. La SVAG y SVLE general a 5 años fue 72,0 % y 69,0 % respectivamente. Al comparar los subgrupos con QTNA y CI; se verificaron SVAG y SVLE a 5 años de 60,0 % y 81,0 % (p=0,118); y de 66,7 % y 71,4 % (p=0,536) respectivamente. La SVAG y SVLE verificadas son similares a las reportadas en otros estudios. No se evidenciaron diferencias de éstas con los tratamientos QTNA y CI.
Wilms tumor (WT) is the most common pediatric kidney tumor between 1 and 5 years of age. The existing evidence regarding clinical, therapeutic and survival (SV) aspects of TW is scarce. The aim of this study was to determine differences in 5-year overall survival (OS) and 5-year disease-free survival (DFS), in patients treated by WT with neoadjuvant chemotherapy (NACT) and initial surgery (IS). Case series. Patients with TW between 11 months and 13 years of age, treated at SOLCA Cancer Institute, Cuenca, Ecuador (1994-2019) were included. The outcome variables were OS and DFS. Once their treatments were completed, patients were followed clinically. Descriptive (measures of central tendency and dispersion) and analytical (Chi2, Fisher's exact and continuity correction) statistics were applied. SV analysis with Kaplan Meier curves and log-rank were performed. 36 patients (52.8 % men), with a median age of 44 months; 55.5 % of which had favorable histology were recruited. The most frequent location and stage was left kidney (55.5 %) and I (33.3 %) respectively. 58.3 % underwent IC and 41.7 % QTNA. After treatments, 21 patients (58.3 %) achieved complete remission. General OS and DFS were 72.0 % and 69.0 % respectively. When comparing subgroups with QTNA and CI. When comparing the subgroups with QTNA and CI, OS and DFS of 60.0 % and 81.0 % were verified (p=0.118); and of 66.7 % and 71.4 % (p=0.536) respectively. General OS and DFS observed are similar to those reported in other studies. No differences were evidenced with QTNA and CI treatments.
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Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Tumor de Wilms/mortalidad , Tumor de Wilms/terapia , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Inducción de Remisión , Análisis de Supervivencia , Estudios de Seguimiento , Quimioterapia Adyuvante , Terapia Combinada , Tumor de Wilms/cirugía , Tumor de Wilms/tratamiento farmacológico , Supervivencia sin Enfermedad , Neoplasias Renales/cirugía , Neoplasias Renales/tratamiento farmacológicoRESUMEN
PURPOSE: To examine the possible prognostic factors in patients with type 1 and type 2 papillary renal cell carcinoma (pRCC) after surgical management and to identify the independent predictive factors of the prognosis. METHODS: From 2010 to 2017, 1405 patients underwent surgery for renal cell carcinoma, of whom 114 had type 1 or type 2 pRCC and follow-up data were available for 88 patients. Clinicopathological and prognostic parameters were compared between type 1 and type 2 pRCC. Possible prognostic factors were retrospectively analyzed by univariate and multivariate analyses with Cox regression. RESULTS: The study included 63 males and 25 females with a mean age of 54.27 ± 12.91. 53 patients were diagnosed by regular physical examination and others presented with hematuria or lumbago. 53 (60.2%) underwent radical nephrectomy and 35 (39.8%) underwent nephron sparing surgery. After a mean follow-up of 46.08 ± 22.65 months, 16 patients died of pRCC metastasis and the 5-year disease-specific survival was 79.3%. The comparison of the 39 (44.3%) type 1 and 49 (55.7%) type 2 pRCCs revealed that type 2 pRCC had significantly higher grade and worse prognosis. Univariate analysis showed that symptomatic diagnosis, type, grade, and tumor stage were prognostic factors. Multivariate analysis identified that type and tumor stage were independent factors of the prognosis. CONCLUSIONS: Pathological type and tumor stage could serve as independent factors for the prognosis of patients with pRCC.
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Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Adulto , Anciano , Carcinoma de Células Renales/clasificación , Carcinoma de Células Renales/cirugía , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Renales/clasificación , Neoplasias Renales/cirugía , Masculino , Persona de Mediana Edad , Análisis Multivariante , Nefrectomía , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
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.
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Biomarcadores de Tumor/genética , Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Recurrencia Local de Neoplasia/epidemiología , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/antagonistas & inhibidores , Carcinoma de Células Renales/irrigación sanguínea , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/terapia , Quimioterapia Adyuvante/métodos , Análisis Mutacional de ADN , Supervivencia sin Enfermedad , Genómica , Humanos , Inmunoterapia/métodos , Riñón/patología , Riñón/cirugía , Neoplasias Renales/irrigación sanguínea , Neoplasias Renales/mortalidad , Neoplasias Renales/terapia , Terapia Molecular Dirigida/métodos , Mutación , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/prevención & control , Nefrectomía , Pronóstico , Medición de Riesgo/métodos , Sirolimus/farmacología , Sirolimus/uso terapéuticoRESUMEN
INTRODUCTION: Pazopanib is approved in Latin America as first targeted therapy for patients with metastatic renal cell carcinoma (mRCC). METHODS: A retrospective chart review of adult patients with mRCC who initiated pazopanib as first targeted therapy between January 2011 and March 2016 was conducted among oncology care centers in Argentina, Brazil, Chile, Colombia, and Mexico. Patient characteristics, treatment patterns, overall survival (OS), progression-free survival (PFS), and adverse events were summarized. RESULTS: A total of 156 charts of patients with mRCC receiving first-line pazopanib were reviewed (29, 54, 27, 28, and 18 patients from Argentina, Brazil, Chile, Colombia, and Mexico, respectively). The mean age at initial mRCC diagnosis was 61.6 years, 73.7% were male, and 51.3% were Hispanic. The median dose of pazopanib was 800 mg and the median time from initial mRCC diagnosis to pazopanib start was 2.2 months. The median time on treatment was 10.0 months. At the time of data extraction, 16.7% of patients remained on pazopanib, with clinical progression listed as the main reason for discontinuation. Subsequent therapy was received by 25.6% of patients; the most common were everolimus (9.6%) and axitinib (5.8%). Overall, median PFS and OS were 10.8 and 16.9 months, respectively, and varied across countries. The most common all-grade adverse events were diarrhea (44.9%), asthenia/fatigue (43.6%), and nausea (28.8%). CONCLUSIONS: Pazopanib was used for first-line mRCC treatment in a clinically diverse patient population across Latin America. Real-world PFS and tolerability were similar to clinical studies of pazopanib. FUNDING: Novartis Pharmaceuticals Corporation, Inc.
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Carcinoma de Células Renales/tratamiento farmacológico , Neoplasias Renales/tratamiento farmacológico , Pirimidinas/uso terapéutico , Sulfonamidas/uso terapéutico , Anciano , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Progresión de la Enfermedad , Everolimus/uso terapéutico , Femenino , Humanos , Indazoles , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , América Latina , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Pautas de la Práctica en Medicina , Supervivencia sin Progresión , Pirimidinas/administración & dosificación , Pirimidinas/efectos adversos , Estudios Retrospectivos , Sulfonamidas/administración & dosificación , Sulfonamidas/efectos adversos , Tiempo de TratamientoRESUMEN
INTRODUCTION AND OBJECTIVES: The objective of this study is to evaluate overall survival (OS), cancer-specific survival (CSS), relapse-free survival, local and distant (LRFS and DRFS, respectively) rates in patients with pT3a renal cell carcinoma (RCC) considering the perirenal and/or sinus fat infiltration (FI) as prognostic factors. MATERIALS AND METHODS: Retrospective cohort of patients with pT3a RCC who underwent radical or partial nephrectomy. The data were extracted from the LARCG (Latin American Renal Cancer Group) database. The demographic, clinical, pathological and surgical variables were evaluated. FI was divided into 4 groups (vein, perirenal, sinus and both fats infiltration). The Kaplan Meier and Cox regression curves were performed. RESULTS: 293 patients were included in the study. The mean age was 61.4 years. The median follow-up was 21 months (r: 1-194). CSS, RFS, LRFS and DRFS estimated at 3 years in the group of both fats' infiltration were 53.1, 45.1, 58.7 and 51.6 months, respectively, and always statistically lower than the rest (PË0.005). In the multivariate analysis, the infiltration of both fats significantly increased specific mortality, overall and local relapse with respect to vein infiltration (HR: 4.5, 2.42 and 8.08, respectively). The Fuhrman grade and renal pelvis infiltration were independent predictors of CSS and RFS. CONCLUSIONS: Infiltration of both fats increases the risk of overall and local relapse in pT3a RCC. In the same way, it is associated with a lower cancer-specific survival and should be considered as a factor of poor prognosis.
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Tejido Adiposo/patología , Carcinoma de Células Renales/mortalidad , Carcinoma de Células Renales/patología , Neoplasias Renales/mortalidad , Neoplasias Renales/patología , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
ABSTRACT Purpose: Radical treatment in elderly patients with renal tumor remains debatable due to uncertainties regarding the risk of surgical complications, risk of end-stage renal disease (ESRD) and survival benefit. The aim of the study was to assess outcomes of radical treatment for renal cancer in elderly patients. Materials and Methods: This retrospective analysis enrolled 507 consecutive patients treated with partial or radical nephrectomy due to renal mass. Patients with upfront metastatic disease (n=46) and patients lost to follow-up (n=110) were excluded from the analysis. Surgical, functional (screen for ESRD development) and survival outcomes were analyzed in patients aged >75 years in comparison to younger individuals. Results: The analyzed group included 55 elderly patients and 296 younger controls. Within the cohort a total of 148 and 203 patients underwent radical and partial nephrectomies respectively. The rate of surgical complications, including grade ≥3 Clavien- Dindo complications, did not differ between groups (3.6% vs. 4.4%, p=0.63). Median length of hospital stay was equal in both groups (7 days). During a follow-up (median 51.9 months, no difference between groups), ESRD occurred in 3.4% of controls and was not reported in elderly group (p=0.37). Younger patients demonstrated a statistically significant advantage in both overall survival and cancer-specific survival over elderly patients (OS 94.6% vs. 87% p=0.036, CSS 97.3% vs. 89.1% p=0.0008). Conclusions: Surgical treatment in elderly patients with renal tumor is as safe as in younger individuals and does not increase the risk of ESRD. However, cancer specific survival among these patients remains shorter than in younger patients.
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Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Nefrectomía/métodos , Complicaciones Posoperatorias , Carcinoma de Células Renales/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Estadísticas no Paramétricas , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Persona de Mediana Edad , Nefrectomía/efectos adversos , Nefrectomía/mortalidadRESUMEN
Renal cell carcinoma (RCC) is the major cause of death among patients with von Hippel-Lindau (VHL) disease. Resistance to therapies targeting tumor angiogenesis opens the question about the underlying mechanisms. Previously we have described that RWDD3 or RSUME (RWD domain-containing protein SUMO Enhancer) sumoylates and binds VHL protein and negatively regulates HIF degradation, leading to xenograft RCC tumor growth in mice. In this study, we performed a bioinformatics analysis in a ccRCC dataset showing an association of RSUME levels with VHL mutations and tumor progression, and we demonstrate the molecular mechanism by which RSUME regulates the pathologic angiogenic phenotype of VHL missense mutations. We report that VHL mutants fail to downregulate RSUME protein levels accounting for the increased RSUME expression found in RCC tumors. Furthermore, we prove that targeting RSUME in RCC cell line clones carrying missense VHL mutants results in decreased early tumor angiogenesis. The mechanism we describe is that RSUME sumoylates VHL mutants and beyond its sumoylation capacity, interacts with Type 2 VHL mutants, reduces HIF-2α-VHL mutants binding, and negatively regulates the assembly of the Type 2 VHL, Elongins and Cullins (ECV) complex. Altogether these results show RSUME involvement in VHL mutants deregulation that leads to the angiogenic phenotype of RCC tumors.
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Carcinoma de Células Renales/genética , Neoplasias Renales/genética , Factores de Transcripción/metabolismo , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Enfermedad de von Hippel-Lindau/genética , Animales , Células COS , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/mortalidad , Línea Celular Tumoral , Chlorocebus aethiops , Medios de Cultivo Condicionados , Elonguina/genética , Elonguina/metabolismo , Regulación Neoplásica de la Expresión Génica , Células Endoteliales de la Vena Umbilical Humana , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/mortalidad , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Mutación Missense , Neovascularización Patológica/genética , Neovascularización Patológica/metabolismo , Sumoilación , Factores de Transcripción/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismo , Enfermedad de von Hippel-Lindau/complicaciones , Enfermedad de von Hippel-Lindau/metabolismoRESUMEN
PURPOSE: Radical treatment in elderly patients with renal tumor remains debatable due to uncertainties regarding the risk of surgical complications, risk of end-stage renal disease (ESRD) and survival benefit. The aim of the study was to assess outcomes of radical treatment for renal cancer in elderly patients. MATERIALS AND METHODS: This retrospective analysis enrolled 507 consecutive patients treated with partial or radical nephrectomy due to renal mass. Patients with upfront metastatic disease (n=46) and patients lost to follow-up (n=110) were excluded from the analysis. Surgical, functional (screen for ESRD development) and survival outcomes were analyzed in patients aged >75 years in comparison to younger individuals. RESULTS: The analyzed group included 55 elderly patients and 296 younger controls. Within the cohort a total of 148 and 203 patients underwent radical and partial nephrectomies respectively. The rate of surgical complications, including grade >3 Clavien- Dindo complications, did not differ between groups (3.6% vs. 4.4%, p=0.63). Median length of hospital stay was equal in both groups (7 days). During a follow-up (median 51.9 months, no difference between groups), ESRD occurred in 3.4% of controls and was not reported in elderly group (p=0.37). Younger patients demonstrated a statistically significant advantage in both overall survival and cancer-specific survival over elderly patients (OS 94.6% vs. 87% p=0.036, CSS 97.3% vs. 89.1% p=0.0008). CONCLUSIONS: Surgical treatment in elderly patients with renal tumor is as safe as in younger individuals and does not increase the risk of ESRD. However, cancer specific survival among these patients remains shorter than in younger patients.
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Carcinoma de Células Renales/cirugía , Neoplasias Renales/cirugía , Nefrectomía/métodos , Anciano , Anciano de 80 o más Años , Carcinoma de Células Renales/mortalidad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Renales/mortalidad , Masculino , Persona de Mediana Edad , Nefrectomía/efectos adversos , Nefrectomía/mortalidad , Complicaciones Posoperatorias , Estudios Retrospectivos , Factores de Riesgo , Estadísticas no Paramétricas , Resultado del TratamientoRESUMEN
AIM: To investigate the role of the transcription factor YY1 in Wilms tumor (WT). PATIENTS & METHODS: We measured YY1 expression using tissue microarray from patients with pediatric renal tumors, mainly WT and evaluated correlations with the predicted clinical evolution. YY1 expression was measured using immunohistochemical and protein expression was determined by digital pathology. RESULTS & CONCLUSION: YY1 significantly increased in WT patients. In addition, an increase in YY1 expression had a greater risk of adverse outcomes in WT patients with favorable histology. YY1 expression was higher in the blastemal component of tumors, and high nuclear expression positively correlated with metastasis. YY1 may be considered as a metastasis risk factor in WT.
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Expresión Génica , Neoplasias Renales/genética , Neoplasias Renales/patología , Factor de Transcripción YY1/genética , Niño , Preescolar , Femenino , Humanos , Inmunohistoquímica , Lactante , Neoplasias Renales/mortalidad , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Factores de Riesgo , Tumor de WilmsRESUMEN
ABSTRACT Purpose: In this study we aimed to review urological soft tissue sarcomas of genitourinary tract that were diagnosed in our institution and their prognostic factors for survival. Materials and Methods: The clinical and pathological records of 31 patients who had diagnosis of soft tissue sarcomas primarily originating from the genitourinary tract between 2005-2011 were reviewed. Results: The most common site was kidney (17 cases, 54.8%), and most common diagnosis was leiomyosarcoma (11 cases, 35.4%). A total of 24 patients (77.4%) had surgical excision. The surgical margins were positive in 7 patients who presented with local recurrence after primary resection. Twelve patients developed metastatic disease. During follow-up (range 9-70 month), 26 of the 31 patients (88.9%) were alive. Significant survival differences were found according to histological type (p: 0.001), with lower survival rates for malignant fibrous histiocytoma. The tumor size, the presence of metastasis at the time of diagnosis and tumor localization were not statistically significant for overall survival. Conclusions: In our series, prostate sarcomas, paratesticular rhabdomyosarcoma and malignant fibrous histiocytoma had poor prognosis, especially in patients presenting with metastatic disease.