Management of Comorbidities in Diabetics With Renal Cell Carcinoma

2013 ◽  
Vol 27 (1) ◽  
pp. 31-39 ◽  
Author(s):  
Jonathan L. Rabey ◽  
Jingjing Yin ◽  
Tammy M. Kublas ◽  
Terry Mashtare ◽  
Alice C. Ceacareanu

Objectives: This study evaluated whether particular diabetes mellitus (DM), hyperlipidemia, or hypertension pharmacotherapy was associated with improved renal cell carcinoma (RCC) outcomes in diabetics with emergent RCC. Methods: All DM cases newly diagnosed with RCC at Roswell Park Cancer Institute (January 01, 2003-December 31, 2010) were included (n = 95). Baseline demographic information, clinical history, and cancer outcomes were documented after chart review. Fisher’s test was used for the analysis of categorical outcomes across different treatment groups. Univariate and multivariate analyses for the comparisons of the overall survival and progression-free survival across treatment groups were assessed using Kaplan-Meier log-rank test and Cox proportional hazards models. Results: We found that DM pharmacotherapy users, which may represent a more advanced disease as compared to those controlled by diet alone, displayed significantly greater mortality ( P = .01). Additionally, we found that cholesterol-lowering pharmacotherapy use was associated with decreased RCC mortality (hazard ratio = 0.54, P = .06). Individuals receiving combined hypertension regimens had a lower chance to present with baseline metastasis; however, hypertension pharmacotherapy use added no survival benefit. Conclusion: Reinforcing guidelines compliance for hyperlipidemia management in patients with DM may provide a considerable cancer benefit if diagnosed with RCC. Studies evaluating the need for cholesterol-lowering pharmacotherapy in guidelines-noncompliant DM cases upon RCC diagnosis are currently needed.

2017 ◽  
Vol 10 (1) ◽  
pp. 3-10 ◽  
Author(s):  
Reza Mehrazin ◽  
Essel Dulaimi ◽  
Robert G. Uzzo ◽  
Karthik Devarjan ◽  
Jianming Pei ◽  
...  

Background: The proto-oncogene c-MYC, located on chromosome 8q, can be upregulated through gain of 8q, causing alteration in biology of renal cell carcinoma (RCC). The aim of this study was to evaluate the prevalence of c-MYC through chromosome 8q gain and to correlate findings with cancer-specific mortality (CSM), and overall survival (OS). Methods: Cytogenetic analysis by conventional or Chromosomal Genomic Microarray Analysis (CMA) was performed on 414 renal tumors. Nonclear and nonpapillary RCC were excluded. Impact of gain in chromosome 8q status on CSM, OS, and its correlation with clinicopathological variables were evaluated. CSM and OS were assessed using log-rank test and the Cox proportional hazards model. Results: A total of 297 RCC tumors with cytogenetic analysis were included. Gain of 8q was detected in 18 (6.1%) tumors (9 clear cell and 9 papillary RCC), using conventional method ( n = 11) or CMA ( n = 7). Gain of 8q was associated with higher T stage ( p < 0.001), grade ( p < 0.001), nodal involvement ( p = 0.005), and distant metastasis ( p < 0.001). No association between gain of 8q and age ( p = 0.23), sex ( p = 0.46), and Charlson comorbidity index (CCI, p = 0.59) were seen. Gain of 8q was associated with an 8.38-fold [95% confidence interval (CI), 3.83–18.34, p < 0.001] and 3.31-fold (95% CI, 1.56–7.04, p = 0.001) increase in CSM and decrease in OS, respectively, at a median follow up of 56 months. Conclusion: Chromosome 8q harbors the proto-oncogene c-MYC, which can be upregulated by gain of 8q. Our findings suggest that gain of 8q, can predict aggressive tumor phenotype and inferior survival in RCC.


PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242429
Author(s):  
Shian-Ying Sung ◽  
Trang Thi Huynh Le ◽  
Jin- Hua Chen ◽  
Teng-Fu Hsieh ◽  
Chia-Ling Hsieh

Elevated Renal cell carcinoma (RCC) risk has been associated with the use of several antihypertensive medications but has not yet been elucidated in the populations prescribed alpha-1 blockers that are commonly used in the treatment of hypertension and lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS-BPH). The aim of the present study was to investigate the association between alpha-1 blocker use and the risk of developing RCC using a nationwide population-based database in Taiwan. Patients who were treated with alpha-1 blockers for at least 28 days were identified through the Taiwan National Health Insurance Research Database from 2000 to 2010. The unexposed participants were matched with the exposed cases according to age, sex, and index year at a ratio of 3:1. Cox proportional hazards regression, stratified by sex and comorbidities and adjusted for age, was performed to estimate hazard ratios (HRs) for the risk of subsequent RCC. Among 2,232,092 subjects, patients who received alpha-1 blocker treatment had a higher risk of RCC than the unexposed group. Taking into account hypertension and BPH, the adjusted HR was significantly higher in male alpha-1 blocker users who had no BPH and either the presence (HR: 1.63, 95% confidence interval [CI] = 1.22–2.18) or absence (HR: 2.31, 95% CI = 1.40–3.81) of hypertension than in men not receiving these drugs. Taken together, male alpha-1 blocker users who had no comorbidity of BPH exhibited an increased risk for developing RCC independent of hypertension. Further study is warranted to elucidate the underlying mechanisms of this association.


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 341-341
Author(s):  
Matthew D Tucker ◽  
Katy Beckermann ◽  
Kristin Kathleen Ancell ◽  
Kerry Schaffer ◽  
Renee McAlister ◽  
...  

341 Background: Neutrophilia is known to be associated with worse prognosis in metastatic renal cell carcinoma (mRCC); however, less is known about the role of eosinophils in the response to immunotherapy (IO). We investigated the association of the baseline neutrophil to eosinophil ratio (NER) with outcomes to IO-based combination treatment in mRCC. Methods: Patients with mRCC treated with ipilimumab plus nivolumab, pembrolizumab plus axitinib, or avelumab plus axitinib at the Vanderbilt-Ingram Cancer Center were retrospectively identified. Patients on >10mg prednisone and patients with prior IO were excluded. Baseline NER (at time of first IO) and association with progression free survival (PFS), overall survival (OS), and objective response rate (ORR) were investigated. Data cutoff was 9/1/2020. Analysis for PFS and OS was performed using the log-rank test and Mantel-Haenszel method, and analysis of the odds ratio for ORR was performed using Fischer’s exact test. Results: Sixty-one patients were identified: 89% clear cell histology, 74% prior nephrectomy, 69% IMDC intermediate risk, and 72% treatment-naïve. Patients with baseline NER < median (N=31) had improved clinical outcomes compared to patients with baseline NER > median (N=30) (Table). Improvement in PFS by NER was maintained when stratified by anti-PD-1/CTLA-4 and anti-PD(L)-1/VEGF (p= 0.0062 and p= 0.049); however, differences in OS and ORR were no longer significant. The median baseline NER among patients with partial response (PR) was significantly lower at 22.7 (95% CI 18.9-31.1) vs. 51.6 (95% CI 39.5-93.1) among those with progressive disease (PD) (p= 0.0054). For comparison, the median neutrophil to lymphocyte ratio was not significantly different between PR (2.60) and PD (3.84, p= 0.056). Conclusions: Patients with a low baseline NER treated with IO-based combinations had improved clinical outcomes compared to patients with a high baseline NER. Additional investigation of this parameter in larger cohorts is warranted. [Table: see text]


2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 701-702
Author(s):  
Samuel Miller ◽  
Lauren Wilson ◽  
Melissa Greiner ◽  
Jessica Pritchard ◽  
Tian Zhang ◽  
...  

Abstract Renal dysfunction is a driver of dementia. It is also associated with renal cell carcinoma, possibly the result of the tumor itself or from cancer treatment. This study evaluates metastatic renal cell carcinoma (mRCC) as a risk factor for developing mild cognitive impairment or dementia (MCI/D) as well as the impact of RCC-directed therapies on the development of MCI/D. We identified all patients diagnosed with mRCC in SEER-Medicare from 2007-2015. The main outcome was incident MCI/D within one year of mRCC diagnosis or cohort entry. Exclusion criteria included age &lt;65 at mRCC diagnosis and diagnosis of MCI/D within preceding year of mRCC diagnosis. Patients with mRCC (n=2,533) were matched to non-cancer controls (n=7,027) on age, sex, race, comorbidities and year. Cox proportional hazards regression showed that having mRCC (HR 8.52, 95% MCI/D 6.49-11.18, p&lt;0.001) and being older (HR 1.05 for 1-year age increase, 95% MCI/D 1.03-1.07, p&lt;0.001) were predictive of developing MCI/D. A second Cox proportional hazards regression of only patients with mRCC revealed that neither those initiating treatment with oral anticancer agents (OAAs) nor those who underwent nephrectomy were more likely to develop MCI/D. Black patients had a higher risk of dementia compared to white patients (HR 1.92, 95% MCI/D 1.02-3.59, p=0.047). In conclusion, patients with mRCC were more likely to develop MCI/D than those without mRCC. The medical and surgical therapies evaluated were not associated with increased incidence of MCI/D. The increased incidence of MCI/D in older adults with mRCC may be the result of the pathology itself.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 595-595
Author(s):  
Ridwan Alam ◽  
Hiten Patel ◽  
Phillip M. Pierorazio

595 Background: Quality of life (QOL) in cancer patients has gained increasing attention and may provide prognostic value above and beyond traditional demographic and disease parameters. We evaluate the utility of self-reported QOL to predict mortality in patients with renal cell carcinoma (RCC). Methods: The Medicare Health Outcomes Survey was linked to SEER data to identify patients who completed a QOL questionnaire after the diagnosis of RCC from 1998-2014. Mental component summary (MCS) and physical component summary (PCS) scores were classified as high (≥50) or low ( < 50) based on a population mean score of 50 points. Patients were classified into four groups: 1) high MCS, high PCS; 2) high MCS, low PCS; 3) low MCS, high PCS; and 4) low MCS, low PCS. Multivariable Cox proportional hazards regression evaluated associations between QOL and all-cause mortality (ACM). The Harrell’s concordance statistic (C-index) estimated predictive accuracy. Fine and Gray competing risks models adjusted for stage, demographics, and comorbidities evaluated RCC-specific and non-RCC-specific mortality. Results: A total of 1494 patients with a median age of 73.4 years (IQR 68.8-79.3) at survey completion were included. Median follow-up was 5.6 years (IQR 4.0-8.3). There were 747 deaths, of which 139 were due to RCC. Models showed that each additional MCS and PCS point reduced the hazard of ACM by 1.3% (95% CI 0.981-0.993, P< 0.001) and 2.2% (95% CI 0.972-0.985, P< 0.001), respectively. The C-index was 72.1%. In the competing risks model, the subdistribution hazard ratio (SHR) of RCC mortality in Groups 2, 3, and 4 were 2.71 (95% CI 1.18-6.22, P= 0.02), 4.55 (95% CI 1.57-13.18, P= 0.005), and 3.11 (95% CI 1.35-7.16, P= 0.008), respectively, compared to Group 1. The SHR for non-RCC mortality were 1.50 (95% CI 1.16-1.94, P= 0.002), 1.03 (95% CI 0.59-1.78, P= 0.9), and 1.83 (95% CI 1.41-2.38, P< 0.001), respectively, relative to Group 1. Conclusions: Self-reported QOL metrics can be used to predict ACM in RCC patients with good accuracy; lower PCS and MCS scores led to higher rates of ACM, even after accounting for differences in disease, demographics, and comorbidity. Furthermore, non-RCC mortality was associated more with low physical health rather than low mental health.


2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 4551-4551
Author(s):  
Kevin Zarrabi ◽  
Elizabeth A. Handorf ◽  
Benjamin Miron ◽  
Matthew R. Zibelman ◽  
Fern Anari ◽  
...  

4551 Background: Front-line treatment for patients (pts) with metastatic clear cell renal cell carcinoma (mRCC) has undergone rapid advances in the last five years. This evolution has led to uncertainty about the optimal first line combination regimen. Herein, we compare real-world outcomes in pts treated with either axitinib/pembrolizumab (A/P) or ipilimumab/nivolumab (I/N) reported by International Metastatic RCC Database Consortium (IMDC) score. Methods: The nationwide Flatiron Health electronic health records-derived database was used to select pts diagnosed with mRCC and treated with front-line A/P or I/N from 2018-2020. The primary endpoints were overall-survival (OS) and real-world progression free survival (rwPFS). The survival analyses were adjusted using propensity score-based Inverse Probability of Treatment weighting, providing balance on age, gender, insurance, race, IMDC, practice type, and nephrectomy. Survival was assessed from beginning of therapy, and survival by treatment groups was compared using weighted and unweighted Kaplan-Meier curves with log-rank tests and weighted Cox proportional hazards regressions. Disease characteristics between the treatment groups were compared using chi-square and T-tests. Results: 821 pts received frontline A/P (n=259) or I/N (n= 562). Demographics and clinical parameters were similar between the two cohorts. Median age was 66 years, 73% were male, and 54.9% had a nephrectomy. 459 pts had all IMDC criteria factors available, 242 pts had missing factors but enough to define as intermediate/poor risk, 120 pts had unknown IMDC risk. Adjusted median OS was not statistically different: mOS for A/P was not reached (NR) while I/N was 22 mo (95% CI, 19.8-NR; p=0.40). Twelve-month survival was 68.5% for A/P treated pts and 65.8% for I/N treated pts (P=0.41). Twelve-month rwPFS was 41.4% for A/P treated pts and 39.7% for I/N treated pts (P=0.14). No statistical difference in survival was seen within IMDC risk strata (see table). Conclusions: In this retrospective, real-world study of pts treated with front-line A/P or I/N, 12-month survival was not statistically different irrespective of IMDC risk. Longer follow-up will be necessary to discern any significant differences.[Table: see text]


2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 283-283
Author(s):  
Arnav Srivastava ◽  
Hiren V. Patel ◽  
Sinae Kim ◽  
Brian Shinder ◽  
Joshua Sterling ◽  
...  

283 Background: During COVID-19, many operating rooms were reserved exclusively for emergent cases. As a result, many elective surgeries for renal cell carcinoma (RCC) were deferred, with an unknown impact on outcomes. Since surveillance is commonplace for small renal masses, we focused on larger, organ-confined, RCCs. Our primary endpoint was pT3a upstaging and our secondary endpoint was overall survival (OS). Methods: We retrospectively abstracted cT1b-cT2bN0M0 RCC patients from the National Cancer Database (NCDB), stratifying them by clinical stage and time from diagnosis to surgery. We selected only those patients who underwent surgery. Patients were grouped by having surgery within <1 month, 1-3 months, or >3 months after diagnosis. Logistic regression models measured pT3a upstaging risk. Kaplan Meier curves and Cox proportional hazards models assessed OS. Results: 29,746 patients underwent partial or radical nephrectomy. Delaying surgery >3 months after diagnosis did not confer pT3a upstaging risk among cT1b (OR=0.90; 95%CI: 0.77–1.05, p = 0.170), cT2a (OR=0.90; 95%CI: 0.69–1.19, p=0.454), or cT2b (OR=0.96; 95%CI:0.62–1.51, p=0.873) masses (Table). In all clinical stage strata, non-clear cell RCCs were significantly less likely to be upstaged (p<0.001). A sensitivity analysis, performed for delays of <1, 1-3, 3-6, and >6 months, also showed no increase in upstaging risk. Conclusions: Delaying surgery up to, and even beyond, 3 months does not significantly increase risk of tumor progression in clinically localized RCC. However, if deciding to delay surgery due to COVID-19, tumor histology, growth kinetics, patient comorbidities, and hospital capacity/resources, should be considered. [Table: see text]


2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5091-5091
Author(s):  
T. Klatte ◽  
M. Remzi ◽  
J. W. Said ◽  
A. Haitel ◽  
F. F. Kabbinavar ◽  
...  

5091 Background: Whereas multiple nomograms have been developed to assess outcomes of patients with clear cell renal cell carcinoma, a model to assess prognosis of papillary renal cell carcinoma (PRCC) has not yet been developed. After data collection and slide review of a large cohort of patients, the aim of this study was to develop and to internally validate a nomogram for prediction of disease-specific survival for PRCC. Methods: Out of 2,687 patients who underwent surgery for a renal tumor between 1989 and 2008 at two institutions, 258 (10%) were found to have PRCC. H&E slides were reviewed by one uro-pathologist at each institution for papillary sub-type, tumor grade, microvascular invasion, sarcomatoid features, collecting system invasion and presence and extent of tumor necrosis. A nomogram was constructed as a graphical representation of significant variables of disease-specific survival in multivariate Cox proportional hazards regression analysis. The discrimination and calibration of the nomogram were assessed, both utilizing bootstrapping to obtain relatively unbiased estimates. Results: After a median follow-up of 35 months, 49 PRCC-related deaths (19%) had occurred. In univariate analysis, incidental detection, T, N, M stage, grade, microvascular invasion, collecting system invasion, papillary sub-type, sarcomatoid features, and necrosis were all associated with prognosis. Multivariate Cox proportional hazards analysis, however, identified incidental detection, T stage, M stage, microvascular invasion, and necrosis, but not papillary sub-type as independent prognostic factors of disease-specific survival. These variables formed the basis of the nomogram that predicted 5-year disease-specific survival probability. The nomogram predicted well, with a bootstrapped corrected concordance index of 0.93, and showed good calibration. Conclusions: A highly accurate tool utilizing basic clinical and pathological information for predicting disease-specific survival was developed specifically for PRCC. This tool should be helpful for identification of the subset of PRCC patients with aggressive clinical behavior, and may contribute to the ability to individualize postoperative surveillance and therapy. No significant financial relationships to disclose.


BMC Cancer ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Wenliang Ma ◽  
Jun Yang ◽  
Ning Liu ◽  
Xiaohong Pu ◽  
Feng Qu ◽  
...  

Abstract Background Tumor micro-angiogenesis and lymphangiogenesis are effective prognostic predictors in many solid malignancies. However, its role on Xp11.2 translocation RCC has not been fully elucidated. Herein, we purposed to explore the correlation between quantitative parameters of tumor-related micro-angiogenesis or lymphangiogenesis and the prognosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 translocation RCC). Methods Tissue samples were obtained from 34 Xp11.2 translocation RCC and 77 clear cell renal cell carcinoma (ccRCC) between January 2007 and December 2018. Micro-angiogenesis was detected using CD34 antibody and quantified with microvessel density (MVD) and microvessel area (MVA), while the lymphangiogenesis in RCC was immunostained with D2–40 antibody and assessed using lymphatic vessel density (LVD) and lymphatic vessel area (LVA). The Kaplan-Meier method of survival analysis was used to estimate prognosis, and both univariate and multivariate analysis was performing using the Cox proportional hazards. Results The MVD and MVA of Xp11.2 translocation RCC in two detected areas (intratumoral and peritumoral area) were not significantly different from that of ccRCC (all P > 0.05). Notably, D2–40-positive lymphatic vessels of Xp11.2 translocation RCC were highly detected in the peritumoral area compared to the intratumoral area. Interestingly, the peritumoral LVD and LVA of Xp11.2 translocation RCC were higher than that of ccRCC (all P < 0.05). Furthermore, both intratumoral MVD or MVA and peritumoral LVD or LVA were significantly associated with pT stage, pN stage, cM stage, AJCC stage, and WHO/ISUP grade (all P < 0.05). Univariate analysis of Cancer-specific survival (CSS) revealed that CSS was substantially longer in patients with low intratumoral MVD or MVA than in patients with high intratumoral MVD or MVA (P = 0.005 and P = 0.001, respectively). Lastly, the Cox proportional hazards model in CSS demonstrated that both intratumoral MVD or MVA and peritumoral LVD or LVA were not independent prognostic parameters (all P > 0.05). Conclusions This study outlines that Xp11.2 translocation RCC is a highly vascularized solid RCC, characterized by rich lymph vessels in the peritumoral area. Quantitative parameters of micro-angiogenesis and lymphangiogenesis could not be considered as novel prognostic factors for patients with xp11.2 translocation RCC.


2020 ◽  
Author(s):  
Yon-Bo Chen ◽  
Liang Gao ◽  
Liang-You Tang ◽  
Yu-Chang Tian ◽  
Guan-Qiang Tian ◽  
...  

Abstract Background: This study aimed to construct the competing endogenous RNA (ceRNA) network in chromophobe renal cell carcinoma (ChRCC). Methods: Clinical and RNA sequence profiles of patients with ChRCC, including messenger RNAs (mRNAs), microRNAs (miRNAs), and long noncoding RNAs (lncRNAs), were obtained from The Cancer Genome Atlas (TCGA) database. “EdgeR” and “clusterProfiler” packages were utilized to obtain the expression matrices of differential RNAs (DERNAs) and to conduct gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Weighted gene co-expression network analysis (WGCNA) was performed to screen the highly related RNAs, and miRcode, StarBase, miRTarBase, miRDB, and TargetScan datasets were used to predict the connections between them. Univariate and multivariate Cox proportional hazards regressions were performed in turn to elucidate prognosis-related mRNAs in order to construct the ceRNA regulatory network. Results: A total of 1628 DElncRNAs, 104 DEmiRNAs, and 2619 DEmRNAs were identified. WGCNA showed significant correlation in 1534 DElncRNAs, 98 DEmiRNAs, and 2543 DEmRNAs, which were related to ChRCC. Fourteen DEmiRNAs, 113 DElncRNAs, and 43 DEmRNAs were screened. Nine mRNAs (ALPL, ARHGAP29, CADM2, KIT, KLRD1, MYBL1, PSD3, SFRP1, SLC7A11) significantly contributed to the overall survival (OS) of patients with ChRCC (P < 0.05). Furthermore, two mRNAs (CADM2, SFRP1) appeared to be independent risk factors for ChRCC. Conclusion: The findings revealed the molecular mechanism of ChRCC and potential therapeutic targets for the disease.


Sign in / Sign up

Export Citation Format

Share Document