共查询到20条相似文献，搜索用时 31 毫秒
1.
Daniel M. Tennenbaum Brandon J. Manley Emily Zabor Maria F. Becerra Maria I. Carlo Jozefina Casuscelli Almedina Redzematovic Nabeela Khan Maria E. Arcila Martin H. Voss Darren R. Feldman Robert J. Motzer Nicole E. Benfante Jonathan A. Coleman Paul Russo James J. Hsieh Abraham Ari Hakimi 《Urologic oncology》2017,35(8):532.e7-532.e13
Purpose
To establish prognostic genomic biomarkers for patients with metastatic clear cell renal cell carcinoma (ccRCC).Materials and methods
We identified 60 patients who presented with metastatic ccRCC at our institution between 2001 and 2015 and had genomic sequencing on their primary tumor. We pooled these patients with 107 other patients with the same inclusion criteria from three well-known public databases. Five commonly mutated genes were chosen for analysis: VHL, PBRM1, BAP1, SETD2, and KDM5C. Overall survival (OS) was estimated using the Kaplan-Meier method and the log-rank test was used for comparisons between groups.Results
Median OS in the cohort was 2.5 years. Higher Fuhrman grade was associated with decreased median OS (P<0.001). Mutations in SETD2 (P = 0.027) and KDM5C (P = 0.019) were associated with reduced risk of death (hazard ratio [HR] = 0.58 [95% CI: 0.35–0.94] and HR = 0.43 [95% CI: 0.22–0.85], respectively). BAP1 mutations (P = 0.008) were associated with increased risk of death (HR = 1.81 [95% CI: 1.16–2.83]). There were significantly more female patients with a BAP1 mutation than females in the overall cohort (P = 0.001).Conclusions
Mutations in BAP1 negatively affected OS, whereas SETD2 and KDM5C mutations were associated with prolonged OS in our pooled cohort of 167 patients with metastatic ccRCC. Our results expand upon efforts at understanding genomic biomarkers in localized disease. Those efforts set the stage for our novel investigation examining associations of select recurrent somatic mutations in stage IV patients with ccRCC. 相似文献2.
Solène-Florence Kammerer-Jacquet Angelique Brunot Karim Bensalah Boris Campillo-Gimenez Mathilde Lefort Sahar Bayat Alain Ravaud Frantz Dupuis Mokrane Yacoub Gregory Verhoest Benoit Peyronnet Romain Mathieu Alexandra Lespagnol Jean Mosser Julien Edeline Brigitte Laguerre Jean-Christophe Bernhard Nathalie Rioux-Leclercq 《Urologic oncology》2017,35(10):603.e7-603.e14
Introduction
The selection of patients with metastatic clear cell renal cell carcinoma (ccRCC) who may benefit from targeted tyrosine kinase inhibitors has been a challenge, even more so now with the advent of new therapies. Hilar fat infiltration (HFI) is a validated prognostic factor in nonmetastatic ccRCC (TNM 2009 staging system) but has never been studied in metastatic patients. We aimed to assess its phenotype and prognostic effect in patients with metastatic ccRCC treated with first-line sunitinib.Materials and methods
In a multicentric study, we retrospectively included 90 patients and studied the corresponding ccRCC at the pathological, immunohistochemical, and molecular levels. Patient and tumor characteristics were compared using univariate and multivariate analysis. All the features were then studied by Cox models for prognostic effect.Results
HFI was found in 42 patients (46.7%), who had worse prognosis (Heng criteria) (P = 0.003), liver metastases (P = 0.036), and progressive diseases at first radiological evaluation (P = 0.024). The corresponding ccRCC was associated with poor pathological prognostic factors that are well known in nonmetastatic ccRCC. For these patients, median progression-free survival was 4 months vs. 13 months (P = 0.02), and median overall survival was 14 months vs. 29 months (P = 0.006). In a multivariate Cox model integrating all the variables, only poor prognosis, according to the Heng criteria and HFI, remained independently associated with both progression-free survival and overall survival.Conclusion
HFI was demonstrated for the first time to be an independent poor prognostic factor. Its potential role in predicting resistance to antiangiogenic therapy warrants further investigation. 相似文献3.
Daniel J. Serie Richard W. Joseph John C. Cheville Thai H. Ho Mansi Parasramka Tracy Hilton R. Houston Thompson Bradley C. Leibovich Alexander S. Parker Jeanette E. Eckel-Passow 《European urology》2017,71(6):979-985
Background
Intratumor molecular heterogeneity has been reported for primary clear cell renal cell carcinoma (ccRCC) tumors; however, heterogeneity in metastatic ccRCC tumors has not been explored.Objective
To evaluate intra- and intertumor molecular heterogeneity in resected metastatic ccRCC tumors.Design, setting, and participants
We identified 111 patients who had tissue available from their primary tumor and at least one metastasis. ClearCode34 genes were analyzed for all tumors.Outcome measurements and statistical analysis
Primary and metastatic tumors were classified as clear cell type A (ccA) or B (ccB) subtypes. Logistic and Cox regression were used to evaluate associations with pathologic features and survival.Results and limitations
Intratumor heterogeneity of ccA/ccB subtypes was observed in 22% (95% confidence interval [CI] 3–60%) of metastatic tumors. Subtype differed across longitudinal metastatic tumors from the same patient in 23% (95% CI 10–42%) of patients and across patient-matched primary and metastatic tumors in 43% (95% CI 32–55%) of patients. Association of subtype with survival was validated in primary ccRCC tumors. The ccA/ccB subtype in metastatic tumors was significantly associated with metastatic tumor location, metastatic tumor grade, and presence of tumor necrosis. A limitation of this study is that we only analyzed patients who had both a nephrectomy and metastasectomy.Conclusions
Approximately one quarter of metastatic tumors displayed intratumor heterogeneity; a similar rate of heterogeneity was observed across longitudinal metastatic tumors. Thus, for biomarker studies it is likely adequate to analyze a single sample per metastatic tumor provided that pathologic review is incorporated into the study design. Subtypes across patient-matched primary and metastatic tumors differed 43% of the time, suggesting that the primary tumor is not a good surrogate for the metastatic tumor.Patient summary
Primary and secondary/metastatic cancers of the kidney differed in nearly one half of ccRCC patients. The pattern of this relationship may affect tumor growth and the most suitable treatment. 相似文献4.
5.
Giuseppe Lucarelli Monica Rutigliano Matteo Ferro Andrea Giglio Angelica Intini Francesco Triggiano Silvano Palazzo Margherita Gigante Giuseppe Castellano Elena Ranieri Carlo Buonerba Daniela Terracciano Francesca Sanguedolce Anna Napoli Eugenio Maiorano Franco Morelli Pasquale Ditonno Michele Battaglia 《Urologic oncology》2017,35(7):461.e15-461.e27
Objective
To investigate the expression of the kynurenine (KYN) pathway components and the prognostic role of the KYN-to-tryptophan ratio (KTR) in a cohort of patients with clear cell renal cell carcinoma (ccRCC).Materials and methods
The expression of KYN pathway components was investigated by tissue microarray-based immunohistochemistry, indirect immunofluorescence, and confocal microscopy analysis in 100 ccRCC cases and 30 normal renal samples. The role of this pathway in sustaining cancer cell proliferation, migration, and chemoresistance was evaluated. In addition, tryptophan and KYN concentrations and their ratio were measured in serum of 195 patients with ccRCC using a sandwich enzyme-linked immunosorbent assay. The role of KTR as a prognostic factor for ccRCC cancer-specific survival (CSS) and progression-free survival (PFS) was assessed.Results
Tissue microarray-based immunohistochemistry and indirect immunofluorescence staining showed an increased signal for KYN pathway components in ccRCC. Kaplan-Meier curves showed significant differences in CSS and PFS among groups of patients with high vs. low KTR. In particular, patients with high KTR values had a 5-year survival rate of 76.9% as compared with 92.3% for subjects with low levels (P ?<?0.0001). Similar findings were observed for PFS (72.8% vs. 96.8% at 5 y). At multivariate analysis, KTR was an independent adverse prognostic factor for CSS (hazard ratio? =?1.24, P? = ?0.001), and PFS (hazard ratio? =? 1.14, P? =? 0.001).Conclusions
The involvement of the KYN pathway enzymes and catabolites in ccRCC occurs via both immune and nonimmune mechanisms. Our data suggest that KTR could serve as a marker of ccRCC aggressiveness and as a prognostic factor for CSS and PFS. 相似文献6.
Yuan Chang Lin Zhou Le Xu Qiang Fu Yuanfeng Yang Zongming Lin Jiejie Xu 《Urologic oncology》2017,35(12):675.e17-675.e24
Purpose
Accumulating evidence indicates that CXC chemokine receptor 6 (CXCR6) has a crucial role in cancer development and progression, however, its role in clear cell renal cell carcinoma (ccRCC) remains obscure. The aim of this study is to investigate the prognostic value of CXCR6 expression in patients with ccRCC following surgery.Materials and methods
This study retrospectively included 239 patients with ccRCC who underwent nephrectomy and had paraffin tissue available at a single center. CXCR6 expression in tumor tissue was evaluated by immunohistochemistry and its associations with overall survival (OS) and recurrence-free survival (RFS) were investigated.Results
A total of 47.3% tumors were considered as high expression of CXCR6, which was significantly associated with the male sex (P = 0.003) and high Fuhrman grade (P<0.001). A high expression of CXCR6 indicated a reduced OS (P<0.001) and RFS (P = 0.007). Multivariate analysis demonstrated that CXCR6 expression was an independent prognostic factor of OS (hazard ratio = 2.604; 95% CI: 1.338–5.068; P = 0.005) and RFS (hazard ratio = 1.957; 95% CI: 1.065–3.595; P = 0.031). Subgroup analysis found that CXCR6 expression could differentiate survival risks among patients with high-risk disease. Moreover, a nomogram integrating CXCR6 expression and traditional clinical and pathologic features was established and predicted postsurgical recurrence-risk well at 3- and 5-year.Conclusions
The expression of CXCR6 in tumor tissue may serve as a potential prognostic biomarker to refine clinical prognosis prediction combined with traditional clinical and pathological analysis for patients with ccRCC after surgery. 相似文献7.
8.
Fan Zhang Xin Ma Huizi Li Gang Guo Pengfei Li Hongzhao Li Liangyou Gu Xintao Li Luyao Chen Xu Zhang 《Urologic oncology》2017,35(6):392-400
Objectives
To investigate the predictive and prognostic values of the logistic regression model based on the serum amino acid levels.Materials and methods
The study enrolled 42 patients with clear cell renal cell carcinoma (ccRCC) and 66 matched healthy people admitted to PLA General Hospital from April 2015 to June 2015. Serum samples from the 2 groups were analyzed by isobaric tags for relative and absolute quantitation-liquid chromatography-tandem mass spectrometry (iTRAQ-LC-MS/MS) method. Variables of the 2 groups were compared by Student’s t-test or chi-square test. The prediction model was constructed by logistic regression analysis. Oncological outcomes were evaluated by Kaplan-Meier survival analysis and Cox regression analysis.Results
Pathological diagnosis confirmed that all patients had ccRCC. No significant differences were found in the distribution of age, sex, or body mass index between patients with ccRCC and matched healthy people. A total of 32 amino acids were quantitatively analyzed, and serum levels of 23 amino acids were significantly different between the 2 groups. A predictive logistic regression model containing histidine, glutamine, 1-methyl histidine, and norvaline was constructed. Receiver operating characteristic (ROC) curves for all patients with ccRCC and controls, patients with T1 ccRCC and controls, patients with Fuhrman grade 1 to 2 ccRCC and controls, patients with T2 ccRCC and controls, and patients with Fuhrman grade 3 ccRCC and controls were drawn based on the model. The area under the curve values of the 5 receiver operating characteristic curves were 0.878, 0.885, 0.890, 0.830, and 0.788, respectively. Patients with higher model scores (>2) had significantly poorer progression-free survival (PFS) than patients with lower model scores (≤2). Multivariable Cox regression analysis showed that logistic regression model score was an independent predictor of PFS.Conclusion
Serum amino acid levels are a potential predictive biomarker for distinguishing patients with ccRCC, especially early T-stage and low Fuhrman grade patients, from healthy people. Serum amino acid levels can also be used in the prognostic evaluation of patients with ccRCC. 相似文献9.
Vesna M. Coric Tatjana P. Simic Tatjana D. Pekmezovic Gordana M. Basta-Jovanovic Ana R. Savic-Radojevic Sanja M. Radojevic-Skodric Marija G. Matic Sonja R. Suvakov Dejan P. Dragicevic Tanja M. Radic Zoran M. Dzamic Marija S. Pljesa-Ercegovac 《Urologic oncology》2017,35(6):409-417
Purpose
Owing to dual functionality of cytosolic glutathione S-transferases (GSTs), they might affect both the development and the progression of renal cell carcinoma (RCC). However, the data on the prognostic value of GST polymorphism in patients with RCC are scarce. Hence, we evaluated the effect of GST gene variants on both the risk of RCC development and the postoperative prognosis in patients with clear cell RCC (ccRCC).Methods
GST genotypes were determined in 305 patients with RCC and 326 matched controls, whereas the overall survival was evaluated in patients with ccRCC only. The presence of GSTM1:ASK1 protein-protein interaction in ccRCC tissue samples was analyzed by methods of immunoprecipitation and immunoblot.Results
We noted an increased risk of RCC development in carriers of GSTM1-null and GSTP1-variant genotype (P<0.05). On the contrary, survival analysis indicated shorter overall survival for patients with ccRCC with GSTM1-active genotype (P = 0.026). Furthermore, patients with ccRCC with GSTM1-active genotype had significantly higher hazard ratio (P<0.05), in analyzed regression models, compared with the carriers of GSTM1-null genotype. Finally, the presence of GSTM1:ASK1 protein-protein interaction was found in all RCC tissue samples studied.Conclusions
Carriers of GSTM1-null and GSTP1-variant genotypes are in increased risk of RCC development. On the contrary, GSTM1-null genotype is associated with favorable postoperative prognosis in ccRCC. The possible molecular mechanism underlying the role of GSTM1 protein in RCC progression might be the presence of GSTM1:ASK1 protein-protein interaction. Hence, determination of GSTM1-genotype might serve as a valuable indicator in both RCC risk assessment and postoperative prognosis. 相似文献10.
Objective
To analyze the expression pattern of immune checkpoint–associated molecules in tumor tissues to determine the prognostic significance of these molecules in patients with metastatic renal cell carcinoma (mRCC) treated with tyrosine kinase inhibitors (TKIs).Methods
Radical nephrectomy specimens were obtained from 62 patients treated with TKIs as first-line systemic therapy for mRCC. The proportions of programmed death-1 (PD-1)-positive tumor infiltrating lymphocytes (TILs) as well as those of tumor cells positive for PD-ligand 1 (PD-L1) and PD-L2 were analyzed by immunohistochemical staining.Results
Overall, 12 patients (19.3%) were revealed to be positive for PD-1-positive TILs, whereas positive expression of PD-L1 and PD-L2 were detected in 12 (19.3%) and 10 (16.1%) patients, respectively. Patients with positivePDL-L1 expression had significantly unfavorable progression-free survival (PFS) compared with those without positive PD-L1 expression, despite the remaining 2 molecules having no significant effect on PFS. Additionally, overall survival in patients positive for PD-1, PD-L1, or PD-L2 expression was significantly poorer than that in those without expression of each immune checkpoint–associated molecule. Multivariate analyses of several parameters identified the following independent prognosticators after the introduction of TKIs: PD-L1 expression status for PFS and lymph node metastasis, Memorial Sloan-Kettering Cancer Center classification and expression statuses of PD-1-positive TILs, and PD-L1 for overall survival.Conclusions
Positive expression of immune checkpoint–associated molecules in tumor tissues could be useful prognosticators in patients with mRCC receiving TKIs as first-line systemic therapy. 相似文献11.
Introduction
The role of percutaneous biopsy to characterize large, locally advanced and metastatic primary renal tumors has not been well described. The goal of this article is to describe the potential advantages of biopsy for preoperative evaluation of patients with large renal tumors and advanced disease.Methods
Literature was reviewed for percutaneous biopsy and for locally advanced and metastatic renal tumors.Results
Multiple studies have confirmed that percutaneous biopsy is safe, and the cost is minimal relative to the cost of surgical operation. Biopsy of large masses should obtain multiple core samples from several sites with tumors to decrease error from sampling heterogeneous tumors.Conclusions
Potential advantages of biopsy for large renal masses include identification of patients for retroperitoneal lymph node dissection who may have occult lymph node metastasis. In patients with metastatic renal cell carcinoma, biopsy characterizes tumors for patients who may not benefit from cytoreductive surgical operation. The role of biopsy is likely to expand in the future with the development of advanced molecular tools for risk stratification. 相似文献12.
Ning Liu Daoguang Huang Xiangming Cheng Yankun Chong Wei Wang Weidong Gan Hongqian Guo 《Urologic oncology》2017,35(8):530.e1-530.e6
Objectives
To compare the clinical outcomes of percutaneous radiofrequency ablation (PRFA) and partial nephrectomy (PN) in patients with clear cell renal cell carcinoma (ccRCC) and non–clear cell RCC (nccRCC) of the most common subtypes.Materials and methods
A retrospective study was conducted to review the records of all the patients who underwent PRFA or PN between February 2005 and April 2014 at our institution. Patients with histologic confirmation of ccRCC, papillary RCC, and chromophobe RCC were included. The Mann-Whitney U test was applied to compare PRFA to PN in the ccRCC and nccRCC groups. The Kaplan-Meier method was used to generate the survival curves that were compared to the log-rank test.Results
A total of 264 patients meeting the selection criteria were included in this study. The tumor size ranged from 0.9 to 7.0 cm. The median follow-up period was 78 months (range: 8–132 mo). Although PRFA provided comparable 10-year overall survival rates and 10-year disease-free survival (DFS) rates to PN both in ccRCC ≤4 cm and nccRCC, the 10-year DFS for patients treated with PRFA was lower than that of PN in ccRCC >4 cm. The DFS survival curve between the 2 operations and 2 subtypes was statistically significant in patients with tumor size >4 cm. Limitations include retrospective review and selection bias.Conclusions
Patients with T1b ccRCC treated with PRFA have less favorable outcomes than those with PN whereas PRFA provides comparable oncologic outcomes to PN in patients with T1b nccRCC. It is necessary to take RCC subtypes into consideration when choosing a surgical approach to treat T1b RCC between PFRA and PN. 相似文献13.
Tian C. Zhou Alexander I. Sankin Steven A. Porcelli David S. Perlin Mark P. Schoenberg Xingxing Zang 《Urologic oncology》2017,35(1):14-20
Purpose
Recent observations have focused attention on the means that human tumors employ to evade host defense systems critical to immune surveillance. The concepts of immunotherapy are familiar to urologists because of the use of bacillus Calmette-Guérin in bladder cancer. Research demonstrating the importance of checkpoint inhibitors in suppressing immune responses against tumors has heightened interest in immunotherapy at a time when there is a need for alternatives to bacillus Calmette-Guérin. We review the literature on the application of immunotherapeutic agents targeting a key checkpoint pathway, programmed death 1 (PD-1) and its ligand (PD-L1), in the field of bladder cancer.Materials and methods
A comprehensive literature review was performed using Medline/Pubmed and Embase.Results
The PD-1/PD-L1 pathway may be manipulated by cancer cells to subvert the immune system. PD-1/PD-L1 blockade has been tested in clinical trials for various malignancies including metastatic urothelial carcinoma, with significant response rates and limited side effects. PD-L1 expression has also been proposed as a prognostic marker for bladder cancer with mixed results.Conclusions
PD-1 is one of several key receptors mediating immune escape, and agents targeting its ligand PD-L1 have already been successfully applied to patients with metastatic urothelial cancer. More research is needed to standardize criteria for PD-L1 positivity, explore its use as a biomarker, and optimize its use in the treatment for bladder cancer. 相似文献14.
Chenzhang Ou Li Liu Jiajun Wang Siyuan Dai Yang Qu Ying Xiong Wei Xi Jiejie Xu Jianming Guo 《Urologic oncology》2017,35(10):607.e1-607.e8
Purpose
Sialic acid-binding immunoglobulin-like lectins (siglecs) family has important functions in tumor progression. The purpose of our study is to figure out the correlation between the expression level of Siglec-8 and prognosis of patients with clear cell renal cell carcinoma (ccRCC), and then to predict the overall survival (OS) via a novel nomogram.Materials and methods
A group of patients (n = 267) histologically diagnosed with ccRCC from Zhongshan Hospital were included into our study. Immunohistochemistry of Siglec-8 was performed in the tissue microarray, and the staining intensity was divided into high/low according to the median value of the H-score grading. Survival analyses including Kaplan-Meier analyses and Cox regression analyses were performed to evaluate the association between Siglec-8 expression and the survival of patients in different risk groups. Stage, size, grade, and necrosis score and University of California Los Angeles Integrated Staging System score were used in the risk stratification. A nomogram incorporating Siglec-8 and several other clinical parameters was plotted for predicting the 5-year and 8-year OS.Results
Siglec-8 was observed dominantly on the membrane of tumor cells. The enhanced expression level of Siglec-8 had significant correlation with adverse overall and disease-free survival of patients (P<0.0001 and P = 0.0186, respectively). The association was more significant in patients with lower risk. Cox regression analyses defined Siglec-8 as an independent prognostic factor of OS (P<0.001 for univariate analysis, P = 0.003 for multivariate analysis). The new nomogram integrating Siglec-8 with several traditional prognostic factors proved to be more accurate than conventional prognostic system using tumor node metastasis stage only (Harrell c-index: 0.801, 95% CI: 0.755–0.847 vs. 0.717, 95% CI: 0.662–0.772).Conclusion
Our study has found that the elevated expression level of Siglec-8 was correlated with poor prognosis of patients with ccRCC. Siglec-8, incorporation with other clinical parameters, could perform better in prediction of patients? OS. 相似文献15.
Yohei Sekino Naohide Oue Yoshinori Shigematsu Akira Ishikawa Naoya Sakamoto Kazuhiro Sentani Jun Teishima Akio Matsubara Wataru Yasui 《Urologic oncology》2017,35(1):31.e13-31.e20
Objectives
Prostate cancer (PCa) is a common malignancy worldwide. Docetaxel has been an important treatment option for patients with metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients with CRPC treated with docetaxel eventually become refractory. In the present study, we analyzed the expression and distribution of kinesin family member C1 (KIFC1) in human PCa by immunohistochemistry and examined the effect of inhibiting KIFC1 expression on docetaxel resistance.Methods
Expression of KIFC1 was determined using immunohistochemistry. RNA interference was used to inhibit KIFC1 expression in PCa cell lines. To examine cell viability, we performed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays.Conclusions
These results indicate that KIFC1 plays an important role in PCa progression. Immunohistochemical analysis of KIFC1 would facilitate identification of patients with poor prognoses after radical prostatectomy, as well as patients with poor therapeutic outcomes after docetaxel-based chemotherapy. 相似文献16.
Romain Boissier Jennifer Campagna Nicolas Branger Gilles Karsenty Eric Lechevallier 《Urologic oncology》2017,35(4):135-141
Background
The neutrophil-lymphocyte ratio (NLR) is a biological marker of inflammation with a significant prognostic value in the field of oncology.Aim
In this review, we discuss the prognostic value of the NLR in renal cell carcinoma (RCC).Material and Method
We conducted a literature review of the PubMed database in August 2016. Initial research identified 31 publications. Following full-text screening, 15 studies were finally included: 7 studies concerning metastatic or locally advanced renal cancer, 6 studies dealing with localized renal cancer, 2 articles evaluating the NLR in renal cancer whatever the status of the disease (metastatic or localized).Results
For localized RCC, an NLR o 3 was predictive of a reduced risk of recurrence (hazard ratio ¼ 1.63 [1.15, 2.29]). The prognostic value of the NLR was stronger for metastatic or locally advanced RCC. An NLR o 3 predicted increased overall survival (hazard ratio ¼ 1.55 [1.36, 1.76]), progression-free survivals (hazard ratio ¼ 3.19 [2.23, 4.57]), and a response to systemic treatment.Conclusion
In current practice, the NLR is a simple and inexpensive prognostic factor with potential improvement in the prognostic performance of nomograms used in renal oncology. 相似文献17.
Alp Tuna Beksac David J. Paulucci Kyle A. Blum Shalini Singh Yadav John P. Sfakianos Ketan K. Badani 《Urologic oncology》2017,35(8):507-515
Introduction
In recent years, molecular characterization of renal cell carcinoma has facilitated the identification of driver genes, specific molecular pathways, and characterization of the tumor microenvironment, which has led to a better understanding of the disease. This comprehension has revolutionized the treatment for patients with metastatic disease, but despite these advancements many patients will develop resistance leading to treatment failure. A primary cause of this resistance and subsequent treatment failure is tumor heterogeneity. We reviewed the literature on the mechanisms of tumor heterogeneity and its clinical implications.Methods
A comprehensive literature search was performed using the MEDLINE/PubMed Index.Results
Intertumor and intratumor heterogeneity is possibly a reason for treatment failure and development of resistance. Specifically, the genetic profile of a renal tumor differs spatially within a tumor as well as among patients. Genomic mutations can change temporally with resistant subclones becoming dominant over time.Conclusions
Accounting for intratumor and intertumor heterogeneity with better sampling of cancer tissue is needed. This will hopefully lead to improved identification of driver mutations and actionable targets. Only then, we can move past the one-size-fits-all approach toward personalized treatment based on each individual?s molecular profile. 相似文献18.
Johan Abrahamsson Kristina Aaltonen Helgi Engilbertsson Fredrik Liedberg Oliver Patschan Lisa Rydén Gottfrid Sjödahl Sigurdur Gudjonsson 《Urologic oncology》2017,35(10):606.e9-606.e16
Background
There are currently no methods in clinical use that can detect early systemic dissemination of urothelial tumor cells.Objective
To evaluate measurement of circulating tumor cells (CTCs) as a biomarker for disseminated disease in patients with advanced bladder cancer.Design, setting, and participants
Between March 2013 and October 2015, 88 patients were prospectively included in the study: 78 were scheduled for radical cystectomy (RC) ± perioperative chemotherapy and 10 treated with palliative chemotherapy. The CellSearch CTC test was further assessed in this context by investigating expression of epithelial cell adhesion molecule (EpCAM) in primary tumors obtained at cystectomy from an independent cohort of 409 patients.Outcome measurements and statistical analysis
Presence of CTCs was tested for association with tumor stage, lymph node metastases, metastatic disease on [18 F]-fluorodeoxyglucose-positron emission tomography (FDG-PET), and cancer-specific and progression-free survival.Results
CTCs were detected in 17/88 patients (19%). In 61 patients who underwent FDG-PET-computed tomography (CT), a statistically significant association with presence of CTCs was found for radiological metastatic disease but not for normal PET-CT results (12/35 [34%] vs. 2/26 [8%], P = 0.014). After a median follow-up time of 16.5 months (95% CI: 9.6–21.4), presence of CTCs was associated with an increased risk of progression among patients treated with RC with or without perioperative chemotherapy (n = 75, P = 0.049). A multivariate analysis adjusted for clinical tumor stage, clinical lymph node status, and age showed that CTCs were an independent marker of progression (n = 75; hazard ratio = 2.78; 95% CI: 1.005–7.69; P = 0.049) but not of cancer-specific death (P = 0.596). In 409 cystectomised patients, more than 392 (96%) of the bladder tumors expressed EpCAM.Conclusions
CTCs were present in 19% of patients with advanced urothelial tumors and were associated with metastatic disease on FDG-PET-CT and with increased risk of disease progression after RC. A significant portion of urothelial cancer cells do express EpCAM and can thus be identified using EpCAM-antigen–based CTC detection methods. 相似文献19.
Kenji Omae Shingo Fukuma Tatsuyoshi Ikenoue Tsunenori Kondo Toshio Takagi Hiroki Ishihara Kazunari Tanabe Shunichi Fukuhara 《Urologic oncology》2017,35(9):540.e7-540.e12
Objectives
To assess the effect of blood type on survival outcomes and adverse events (AEs) in patients treated with tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC).Materials and methods
Patients who received TKIs as first-line therapy for mRCC between 2008 and 2015 at our hospital were included in the study (n = 136). Patients were divided into 2 groups based on their blood type as O and non-O. Survival outcomes and AEs were compared according to blood type. Cox regression models were used for univariate and multivariate survival analyses.Results
Of the 136 patients, 34 (25%) and 102 (75%) had O and non-O blood types, respectively. Blood type O was associated with an increased number of disease sites. There were no differences between the 2 groups with respect to other baseline characteristics. The progression-free survival in patients with O and non-O blood types was 12.1 and 11.6 months, respectively; the overall survival was 34.4 and 24.8 months, respectively. On univariate and multivariate analyses, the ABO blood type was not a significant prognostic factor for progression-free survival or overall survival. Furthermore, the incidences of serious AEs were similar in the 2 blood groups.Conclusions
ABO blood type was not associated with survival outcomes or incidences of serious AEs in mRCC patients treated with TKIs. However, blood type O may be associated with an increased number of disease sites. 相似文献20.
Anica Högner Hans Krause Burkhard Jandrig Mumtaz Kasim Tom Florian Fuller Martin Schostak Andreas Erbersdobler Andreas Patzak Ergin Kilic 《Urologic oncology》2018,36(3):94.e1-94.e14