Predicting tumor-specific survival in patients with spinal metastatic renal cell carcinoma: which scoring system is most accurate?

2020 ◽  
Vol 33 (4) ◽  
pp. 529-539
Author(s):  
Elie Massaad ◽  
Muhamed Hadzipasic ◽  
Christopher Alvarez-Breckenridge ◽  
Ali Kiapour ◽  
Nida Fatima ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Regression Analysis ◽  
Cell Carcinoma ◽  
Spine Surgery ◽  
Renal Cell ◽  
Scoring System ◽  
Performance Status ◽  
Area Under The Curve ◽  
Scoring Systems ◽  
Metastatic Rcc

OBJECTIVEAlthough several prognostic scores for spinal metastatic disease have been developed in the past 2 decades, the applicability and validity of these models to specific cancer types are not yet clear. Most of the data used for model formation are from small population sets and have not been updated or externally validated to assess their performance. Developing predictive models is clinically relevant as prognostic assessment is crucial to optimal decision-making, particularly the decision for or against spine surgery. In this study, the authors investigated the performance of various spinal metastatic disease risk models in predicting prognosis for spine surgery to treat metastatic renal cell carcinoma (RCC).METHODSData of patients who underwent surgery for RCC metastatic to the spine at 2 tertiary centers between 2010 and 2019 were retrospectively retrieved. The authors determined the prognostic value associated with the following scoring systems: the Tomita score, original and revised Tokuhashi scores, original and modified Bauer scores, Katagiri score, the Skeletal Oncology Research Group (SORG) classic algorithm and nomogram, and the New England Spinal Metastasis Score (NESMS). Regression analysis of patient variables in association with 1-year survival after surgery was assessed using Cox proportional hazard models. Calibration and time-dependent discrimination analysis were tested to quantify the accuracy of each scoring system at 3 months, 6 months, and 1 year.RESULTSA total of 86 metastatic RCC patients were included (median age 64 years [range 29–84 years]; 63 males [73.26%]). The 1-year survival rate was 72%. The 1-year survival group had a good performance status (Karnofsky Performance Scale [KPS] score 80%–100%) and an albumin level > 3.5 g/dL (p < 0.05). Multivariable-adjusted Cox regression analysis showed that poor performance status (KPS score < 70%), neurological deficit (Frankel grade A–D), and hypoalbuminemia (< 3.5 g/dL) were associated with a higher risk of death before 1 year (p < 0.05). The SORG nomogram, SORG classic, original Tokuhashi, and original Bauer demonstrated fair performance (0.7 < area under the curve < 0.8). The NESMS differentiates survival among the prognostic categories with the highest accuracy (area under the curve > 0.8).CONCLUSIONSThe present study shows that the most cited and commonly used scoring systems have a fair performance predicting survival for patients undergoing spine surgery for metastatic RCC. The NESMS had the best performance at predicting 1-year survival after surgery.

The effectiveness of systemic therapies after surgery for metastatic renal cell carcinoma to the spine: a propensity analysis controlling for sarcopenia, frailty, and nutrition

2021 ◽  
pp. 1-10
Author(s):  
Elie Massaad ◽  
Philip J. Saylor ◽  
Muhamed Hadzipasic ◽  
Ali Kiapour ◽  
Kevin Oh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Spine Surgery ◽  
Treatment Effect ◽  
Renal Cell ◽  
Performance Status ◽  
Eastern Cooperative Oncology Group ◽  
Spinal Metastases ◽  
Metastatic Rcc ◽  
Systemic Therapies

OBJECTIVE The effectiveness of starting systemic therapies after surgery for spinal metastases from renal cell carcinoma (RCC) has not been evaluated in randomized controlled trials. Agents that target tyrosine kinases, mammalian target of rapamycin signaling, and immune checkpoints are now commonly used. Variables like sarcopenia, nutritional status, and frailty may impact recovery from spine surgery and are considered when evaluating a patient’s candidacy for such treatments. A better understanding of the significance of these variables may help improve patient selection for available treatment options after surgery. The authors used comparative effectiveness methods to study the treatment effect of postoperative systemic therapies (PSTs) on survival. METHODS Univariable and multivariable Cox regression analyses were performed to determine factors associated with overall survival (OS) in a retrospective cohort of adult patients who underwent spine surgery for metastatic RCC between 2010 and 2019. Propensity score–matched (PSM) analysis and inverse probability weighting (IPW) were performed to determine the treatment effect of PST on OS. To address confounding and minimize bias in estimations, PSM and IPW were adjusted for covariates, including age, sex, frailty, sarcopenia, nutrition, visceral metastases, International Metastatic RCC Database Consortium (IMDC) risk score, and performance status. RESULTS In total, 88 patients (73.9% male; median age 62 years, range 29–84 years) were identified; 49 patients (55.7%) had an intermediate IMDC risk, and 29 (33.0%) had a poor IMDC risk. The median follow-up was 17 months (range 1–104 months) during which 57 patients (64.7%) died. Poor IMDC risk (HR 3.2 [95% CI 1.08–9.3]), baseline performance status (Eastern Cooperative Oncology Group score 3 or 4; HR 2.7 [95% CI 1.5–4.7]), and nutrition (prognostic nutritional index [PNI] first tertile, PNI < 40.74; HR 2.69 [95% CI 1.42–5.1]) were associated with worse OS. Sarcopenia and frailty were not significantly associated with poor survival. PST was associated with prolonged OS, demonstrated by similar effects from multivariable Cox analysis (HR 0.55 [95% CI 0.30–1.00]), PSM (HR 0.53 [95% CI 0.29–0.93]), IPW (HR 0.47 [95% CI 0.24–0.94]), and comparable confidence intervals. The median survival for those receiving PST was 28 (95% CI 19–43) months versus 12 (95% CI 4–37) months for those who only had surgery (log-rank p = 0.027). CONCLUSIONS This comparative analysis demonstrated that PST is associated with improved survival in specific cohorts with metastatic spinal RCC after adjusting for frailty, sarcopenia, and malnutrition. The marked differences in survival should be taken into consideration when planning for surgery.

Clinical features of metastatic renal cell carcinoma patients with intrinsic resistance to sunitinib: A Korean multicenter study.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 462-462
Author(s):  
Jung Hoon Kim ◽  
Young-Woong Won ◽  
Seung Tae Kim ◽  
Se Hoon Park ◽  
Soonil Lee ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Features ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Performance Status ◽  
Intrinsic Resistance ◽  
Distant Metastatic Disease ◽  
Resistant Disease ◽  
Metastatic Rcc

462 Background: In a subset of patients with metastatic renal cell carcinoma (RCC), primary resistance to first VEGF targeted therapy is not fully understood, and the optimal treatment approach for these patients is still controversial. This study was aimed to characterize the primary sunitinib resistant patients and associated predicting factors. Methods: A total of 134 patients with recurrent or metastatic RCC, who were initially treated with sunitinib, consecutively selected from 4 centers in Korea, between January 2008 and March 2013. Patients in whom progressive disease (PD) was the best response during treatment with sunitinib were included in the primary sunitinib resistant group. Results: Among 134 patients, 33 (25%) patients primary resistant to sunitinib with a median age of 59 years (range, 28-78) were identified. Most patients had clear cell histology (94%) and good ECOG performance status (0, 1) (82%). According to MSKCC risk, 25% of patients were at favorable risk, 72% at intermediate risk, and 3% at poor risk. Univariate analysis revealed that poor performance status (ECOG≥2), elevated LDH, neutrophilia, and higher number of distant metastatic disease (≥3) and bone or hepatic metastasis were significant factors associated with intrinsic resistant disease. Neutrophilia (OR=7.4, p=0.015) and more than three distant metastatic disease (OR=3.6, p=0.031) were independently significant risk factors of predicting intrinsic resistant disease on multivariate analysis. There was statistically significant difference with regard to overall survival (median, 11.7 vs. 31.1 month; p=0.001) and progression free survival (median, 2.4 vs. 12.5 month; p<0.0001) between the patients with and without intrinsic resistance. Conclusions: Intrinsic resistance to sunitinib treatment is associated with a dismal prognosis in metastatic RCC patients. Along with above predicting clinical features, more understanding of the underlying mechanism and molecular biomarkers for detecting the intrinsic resistant disease are needed.

scholarly journals The Fib-PNI-MLR Score, an Integrative Model of Coagulation Cascades, Nutrition Status, and Systemic Inflammatory Response, Predicts Urological Outcomes After Surgery in Patients With Non-Metastatic Renal Cell Carcinoma

2021 ◽  
Vol 10 ◽  
Author(s):  
Xiaomin Gao ◽  
Yue Pan ◽  
Lina Zhou ◽  
Yeping Li ◽  
Binwei Lin ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Area Under The Curve ◽  
Prognostic Nutritional Index ◽  
Integrative Model ◽  
Nutrition Status ◽  
Cancer Specific Survival ◽  
Fuhrman Grade ◽  
Metastatic Rcc

Cancer-associated inflammation, activation of coagulation cascades, and malnutrition are closely related to the prognosis of patients with malignancy, including renal cell carcinoma (RCC). This study aimed to investigate the prognostic value of a combination of preoperative plasma fibrinogen, prognostic nutritional index, and monocyte-to-lymphocyte ratio (Fib-PNI-MLR) in patients with non-metastatic RCC undergoing nephrectomy. We retrospectively collected medical data from 829 of the 1,019 cases of RCC. The optimal cutoff values of fibrinogen (≥3.54 vs. &lt;3.54, mg/dl), PNI (&lt;47.03 vs. ≥47.03), and MLR (≥0.29 vs. &lt;0.29) were defined using receiver operating characteristic (ROC) analysis and the Fib-PNI-MLR score (range, 0–3) was determined as the sum of points (0 or 1) assigned to each indicator. As a result, Fib-PNI-MLR was an independent risk factor for overall survival (OS), cancer-specific survival (CSS), and metastatic-free survival (MFS) (all P &lt; 0.05). The concordance-index and area under the curve (AUC) were larger for the Fib-PNI-MLR score than that for other clinical parameters. Subgroup analysis (Fuhrman grade G1+G2 and Fuhrman grade G3+G4; pathologic T1, T2, and T3–4 stage) revealed the significant association of a higher Fib-PNI-MLR score with poor urological outcomes (all P &lt; 0.05). Data indicated that patients with higher Fib-PNI-MLR might benefit from partial nephrectomy. The Fib-PNI-MLR score might serve as a promising prognostic factor in patients with non-metastatic RCC.

scholarly journals Novel risk scoring system for metastatic renal cell carcinoma patients treated with cabozantinib

2021 ◽  
pp. 100393
Author(s):  
Dylan J. Martini ◽  
Meredith R. Kline ◽  
Yuan Liu ◽  
Julie M. Shabto ◽  
Bradley C. Carthon ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Metastatic Renal Cell Carcinoma ◽  
Renal Cell ◽  
Scoring System ◽  
Risk Scoring ◽  
Risk Scoring System

Randomized clinical trials and real life studies: Comparison of baseline characteristics of patients in oral target therapies for renal cell carcinoma

2021 ◽  
pp. 107815522110055
Author(s):  
Ruggero Lasala ◽  
Fiorenzo Santoleri ◽  
Alessia Romagnoli ◽  
Felice Musicco ◽  
Paolo Abrate ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Clinical Trials ◽  
Performance Status ◽  
Relevant Literature ◽  
Real Life ◽  
Ecog Performance Status ◽  
Target Therapies ◽  
Baseline Characteristics

Introduction Pivotal Randomized Controlled Trials (RCTs) constitute scientific evidence in support of therapeutic choices when a drug is authorized in the market. In RCTs, patients are selected in a rigorous manner, in order to avoid bias that may influence efficacy assessments. Therefore, patients who take the drug in Real Life Studies (RLSs) are not the same as those participating in RCTs, which, in turn, leads to low data transferability from RCTs to RLS. The objective of this study was to evaluate the differences between RCTs and RLS, in terms of patient baseline characteristics. Materials and Methods Our study includes all oral target therapies for RCC (Renal Cell Carcinoma) marketed in Europe before March 31, 2019. For each treatment, we considered both RCTs and RLSs, the former gathered from Summary of Product Characteristics published on the European Medicine Agency (EMA) website, and the latter yielded by our search in relevant literature. For each drug considered, we then compared the baseline characteristics of patients included in the RCT samples with those of the samples included in the RLSs using the Chi-squared and Mann-Whitney tests. Results We considered six medicines, for a total of 9 pivotal RCTs and 31 RLSs. RCTs reported the same type of patient baseline characteristics, whereas RLSs are more varied in reporting. Some patient baseline characteristics (metastases, previous treatments, etc.) were significantly different between RCTs and RLs. Other characteristics, such as ECOG Performance Status, brain metastases, and comorbidities, liver and kidney failure, are comprised in exclusion criteria of RCTs, though are included in RLS. Discussion and Conclusion: While evaluating equal treatments for the same indications, RCTs and RLSs do not always assess patients with the same characteristics. It would be necessary to produce evidence from RLSs so as to have an idea of treatment effectiveness in patients groups that are not eligible or underrepresented in RCTs.

scholarly journals Prognostic Value of Plasma hPG80 (Circulating Progastrin) in Metastatic Renal Cell Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 375
Author(s):  
Manish Kohli ◽  
Winston Tan ◽  
Bérengère Vire ◽  
Pierre Liaud ◽  
Mélina Blairvacq ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Prognostic Value ◽  
Risk Model ◽  
Predictive Accuracy ◽  
Area Under The Curve ◽  
Risk Groups ◽  
Prognostic Impact ◽  
Significant Difference

Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18–25 year old controls and 50–80 year old controls, respectively. mRCC patients with high hPG80 levels (>4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<4.5 pM) (12 versus 31.2 months, respectively; p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels > 4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.

scholarly journals Immune-Related Meningoencephalitis following Nivolumab in Metastatic Renal Cell Carcinoma

2021 ◽  
pp. 1051-1058
Author(s):  
Lisa B.E. Shields ◽  
Mohammad S. Alsorogi ◽  
Nataliya Mar ◽  
Arash Rezazadeh Kalebasty
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Checkpoint Inhibitors ◽  
Rare Complication ◽  
Psoas Muscle ◽  
High Dose ◽  
Lower Extremity Weakness ◽  
Left Psoas Muscle ◽  
Metastatic Rcc

While immunotherapy with nivolumab is promising for patients with renal cell carcinoma (RCC), overactivation of the immune system can lead to serious side effects. Immune-related meningoencephalitis without a viral or microbial etiology is a rare complication that may occur in patients treated with checkpoint inhibitors (CPI). Herein, we report a 66-year-old man who underwent a partial nephrectomy which revealed a papillary RCC with clear cell component. Three years later, an abdomen and pelvic CT revealed metastatic lesions in the left psoas muscle and in the left 12th rib. The patient was treated with pazopanib which was discontinued after 2 weeks due to significant hepatic and renal toxicity. He subsequently started sunitinib. Two months later, a chest, abdomen, and pelvic CT demonstrated progressive metastatic RCC in the retroperitoneal mass of the left psoas muscle and paraspinal musculature as well as a left renal mass. The patient was treated with 7 cycles of the CPI nivolumab. He was subsequently hospitalized for 3 weeks after experiencing bilateral lower extremity weakness, lethargy, several falls, hyperthermia, confusion, and gait abnormalities. A CSF analysis demonstrated a lymphocyte pleocytosis with elevated protein and no bacterial or viral growth. The patient was treated with high-dose steroids after which his symptoms resolved. Chest, abdomen, and pelvic CT scans over the next 3 years revealed no evidence of metastatic disease, reflecting a progression-free survival of 40 months. We highlight the unique case of a patient with metastatic RCC who experienced immune-related meningoencephalitis following immunotherapy with nivolumab. Medical oncologists should be alert to the potential development of immune-related encephalitis in patients treated with nivolumab and should promptly diagnose and treat this concerning condition. The excellent oncologic outcome of this case emphasizes the need for continued aggressive measures for management of CNS toxicity resulting from CPI therapy.

Diagnostic ability of four cell-free miRNA signatures pre- and post-nephrectomy concordantly found in the tumor and blood from patients with renal cell carcinoma.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16577-e16577
Author(s):  
Matias Bustos ◽  
Rebecca Gross ◽  
Rebeka Dejenie ◽  
Ryu Suyeon ◽  
Negin Rahimzadeh ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Tumor Cells ◽  
Renal Cell ◽  
Incidental Finding ◽  
Area Under The Curve ◽  
Roc Curves ◽  
Diagnostic Ability ◽  
Paired Samples ◽  
Tumor Tissues

e16577 Background: Renal cell carcinoma (RCC) has shown an increase in incidence based on continued incidental finding of these tumors by imaging. There is a need for reliable biomarkers like MicroRNAs (miRNA) that are released by the tumor cells and can be detected in assays using blood or urine samples. The first aim of the present pilot study is to determine the diagnostic ability of cell-free miRNA (cfmiR) biomarkers released by RCC tumor cells in urine and plasma samples. The secondary aim was to determine cfmiRs utility in monitoring RCC before and after radical or partial nephrectomy. Methods: We profiled tumor tissues (n = 11), pre-operative (pre-P n = 18; pre-U n = 17) and post-operative (post-P n = 18; post-U n = 17) plasma and urine paired samples from 18 RCC patients with a median follow-up of 18.4 months. As a control, we utilized plasma (n = 73) and urine (n = 16) samples taken from normal healthy donors (NHD). All specimens (n = 170) were processed and analyzed using HTG EdgeSeq miRNA whole transcriptome assay. All of the samples were normalized and DESeq2. Only miRNAs with a FC < -1.5 or > 1.5, FDR < 0.05, normalized counts > 30 were considered Results: We assessed urine, plasma, and tissue for 2083 miRNAs. The pre-U profiles from patients with RCC and NHD were compared to find differentially expressed (DE) cfmiRs. We found 182 cfmiRs DE in pre-U RCC, of which 106 were upregulated and 76 were downregulated. Similarly, we found 830 cfmiRs DE in the pre-P from RCC compared to NHD, of which 192 were upregulated and 638 were downregulated. We then searched for the top 100 miRNAs most frequently detected and identified in the tumor and in pre-P and pre-U samples. Forty miRNAs were consistently found and highly detected in all of the specimens. Of those 40 miRNAs, 33 cfmiRs were found DE in pre-P and 9 cfmiRs significantly decreased in post-P samples after surgery to the level values observed in the plasma from NHD. In the pre-P and pre-U samples from RCC patients, let-7a-5p, let-7b-5p, miR-23b-3p, and miR-30d-5p were found to be consistently upregulated compared to their respective controls. By using receiving operating characteristic (ROC) curves we assessed the area under the curve (AUC) of all the four cfmiRs in detecting RCC patients. The values of AUC for the four cfmiRs detected in pre-P ranged from 76.2-81% [sensitivity, 61.1-83.3%; specificity, 74-86.3%] and in pre-U samples ranged from 76.1-82.4% [sensitivity, 64.7-70.6%; specificity, 100%]. We observed that the four cfmiRs significantly decreased in the post-U samples from RCC patients after surgery to the level values observed in urine from NHD. Conclusions: Our results propose a four cfmiR signature as a potential diagnostic/monitoring urine biomarker that is also detectable in the plasma and tumor tissues from RRC. Further studies to validate these cfmiRNAs as biomarkers for RCC in blood and urine are ongoing.

scholarly journals Individual approach in choosing second-line targeted therapy for metastatic renal cell carcinoma

2018 ◽  
Vol 14 (2) ◽  
pp. 68-78 ◽  
Author(s):  
B. Ya. Alekseev ◽  
I. M. Shevchuk ◽  
A. D. Kaprin
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
Surgical Treatment ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Optimal Dosage ◽  
Second Line ◽  
Newly Diagnosed ◽  
Disease Prognosis ◽  
Metastatic Rcc

Renal cell carcinoma (RCC) is one of the most common genitourinary malignancies worldwide. Approximately 25–30 % of newly diagnosed patients have metastatic RCC (mRCC), whereas in 20–30 % of cases, dissemination occurs after radical surgical treatment. The development of targeted and immunooncological agents in recent years significantly increased survival in patients with mRCC. However, clinicians faced a problem of choosing an optimal therapeutic regimen to achieve maximum effectiveness of the treatment. This article discusses the choice of second-line drugs for mRCC, advantages of axitinib and its optimal dosage, and efficacy of sunitinib depending on the disease prognosis.

Interleukin-4 Promoter Polymorphisms: A Genetic Prognostic Factor for Survival in Metastatic Renal Cell Carcinoma

2007 ◽  
Vol 25 (7) ◽  
pp. 845-851 ◽  
Author(s):  
Thomas Kleinrath ◽  
Christoph Gassner ◽  
Peter Lackner ◽  
Martin Thurnher ◽  
Reinhold Ramoner
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Cox Regression ◽  
Clinical Course ◽  
Prognostic Significance ◽  
Interleukin 4 ◽  
Promoter Polymorphisms ◽  
Cox Regression Analysis ◽  
Metastatic Rcc

Purpose Renal cell carcinoma (RCC) is considered a cytokine-responsive tumor. The clinical course of a patient may thus be influenced by the patient's capacity to produce distinct cytokines. Therefore, cytokine gene polymorphisms in RCC patients were analyzed to determine haplotype combinations with prognostic significance. Patients and Methods A selection of 21 single nucleotide polymorphisms within the promoter regions of 13 cytokine genes were analyzed in a cross-sectional single-center study of 80 metastatic RCC patients. Univariate and multivariate analyses and the Cox forward-stepwise regression model were chosen to assess genetic risk factors. Results Multivariate Cox regression analysis confirmed by a bootstrap technique identified the heterozygous IL4 genotype −589T−33T/−589C−33C as an independent prognostic risk factor (risk ratio, 3.1; P < .01; 95% CI, 1.4 to 6.9; adjusted for age, sex, and nuclear grading) in metastatic RCC patients. IL4 haplotype −589T−33T and −589C−33C were found with a frequency of 0.069 and 0.925, respectively, which represents a two-fold decrease of IL4 haplotype −589T−33T (P < .01) and an increase of IL4 haplotype −589C−33C frequency (P < .05) in metastatic RCC compared with other white reference study populations. The median overall survival was decreased 3.5-fold (P < .05) in heterozygote patients carrying IL4 haplotype −589T−33T and −589C−33C (3.78 months) compared with patients homozygote for IL4 haplotype −589C−33C (13.44 months). In addition, a linkage disequilibrium between the IL4 gene and the KIF3A gene was detected. Conclusion Our findings indicate that IL4 promoter variants influence prognosis in patients with metastatic RCC and suggest that genetically determined interleukin-4 (IL-4) production affects the clinical course of the disease possibly through regulation of immune surveillance.

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