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Asian Journal of Urology, 2017, 4(4): 230-238    doi: 10.1016/j.ajur.2017.04.002
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A novel preoperative inflammatory marker prognostic score in patients with localized
R. Sekar Rishia,Patil Dattatrayaa,Baum Yorama,Pearl Jeffreya,Bausum Annaa,A. Bilen Mehmetb,Kucuk Omerbc,B. Harris Waynebcd,C. Carthon Bradleybc,Alemozaffar Mehrdadac,P. Filson Christopherabd,G. Pattaras Johna,T. Nieh Petera,Ogan Kennetha,A. Master Virajac*()
a Department of Urology, Emory University School of Medicine, Atlanta, GA, USA
b Department of Hematology and Medical Oncology, Emory University School of Medicine, Atlanta, GA, USA
c Winship Cancer Institute of Emory University, Emory University School of Medicine, Atlanta, GA, USA
d The Atlanta VA Medical Center, Emory University School of Medicine, Atlanta, GA, USA
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Abstract: 

Objective: Several inflammatory markers have been studied as potential biomarkers in renal cell carcinoma (RCC), however few reports have analyzed their prognostic value in aggregate and in non-clear cell histologies. We hypothesize that a combination of specific inflammatory markers into an RCC Inflammatory Score (RISK) could serve as a rigorous prognostic indicator of overall survival (OS) in patients with clear cell and non-clear cell RCC.Methods: Combination of preoperative C-reactive protein (CRP), albumin, erythrocyte sedimentation rate (ESR), corrected calcium, and aspartate transaminase to alanine transaminase (AST/ALT) ratio was used to develop RISK. RISK was developed using grid-search methodology, receiver-operating-characteristic (ROC) analysis, and sensitivity-specificity trade-off analysis. Prognostic value of RISK was analyzed using the Kaplan-Meier method and Cox proportional regression models. Predictive accuracy was compared with RISK to Size, Size, Grade, and Necrosis (SSIGN) score, University of California-LOS Angeles (UCLA) Integrated Staging System (UISS), and Leibovich Prognosis Score (LPS).Results: Among 391 RCC patients treated with nephrectomy, area under the curve (AUC) for RISK was 0.783, which was comparable to SSIGN (AUC 0.776, p = 0.82) and UISS (AUC 0.809, p = 0.317). Among patients with localized disease, AUC for RISK and LPS was 0.742 and 0.706, respectively (p= 0.456). On multivariate analysis, we observed a step-wise statistically significant inverse relationship between increasing RISK group and OS (all p < 0.001).Conclusion: RISK is an independent and significant predictor of OS for patients treated with nephrectomy for clear cell and non-clear cell RCC, with accuracy comparable to other histopathological prognostic tools.
Key words:  Renal cell carcinoma    Inflammation    Prognosis    Biomarker
               出版日期:  2017-10-01      发布日期:  2017-10-26      整期出版日期:  2017-10-01
引用本文:    
. [J]. Asian Journal of Urology, 2017, 4(4): 230-238.
R. Sekar Rishi,Patil Dattatraya,Baum Yoram,Pearl Jeffrey,Bausum Anna,A. Bilen Mehmet,Kucuk Omer,B. Harris Wayne,C. Carthon Bradley,Alemozaffar Mehrdad,P. Filson Christopher,G. Pattaras John,T. Nieh Peter,Ogan Kenneth,A. Master Viraj. A novel preoperative inflammatory marker prognostic score in patients with localized. Asian Journal of Urology, 2017, 4(4): 230-238.
链接本文:  
http://www.ajurology.com/CN/10.1016/j.ajur.2017.04.002  或          http://www.ajurology.com/CN/Y2017/V4/I4/230
  
Laboratory valueCollection time before surgeryaAssay method and kit information
Albumin (g/dL)Within 21 daysBeckman Coulter Synchron System
C-reactive protein (mg/L)Within 14 daysBeckman Coulter Synchron System
Erythrocyte sedimentation rate (mm/h)Within 30 daysALCOR Scientific iSED Automated Sedimentation Rate Analyzer
AST (U/L)Within 7 daysBeckman Coulter Synchron System
ALT (U/L)Within 7 daysBeckman Coulter Synchron System
Calcium (mg/dL)Within 30 daysBeckman Coulter Synchron System
  
ParameterBiomarker Score
012
Albumin (g/dL)>3.52.5–3.5<2.5
CRP (mg/L)<1010–25>25
ESR (mm/h)
 Male<2222–45>45
 Female<2929–55>55
AST/ALT ratio
 Male<1.101.1–1.54>1.54
 Female<1.231.23–1.54>1.54
Corrected calcium (mg/dL)<9.79.7–10.1>10.1
  
FeatureOverallcohort*(n=391)Clearcellsub-cohort*(n=280)
Primarytumor(1997Tstage)a
 T1207(55.95)146(54.48)
 T238(10.27)23(8.58)
 T3114(30.81)94(35.07)
 T411(2.97)5(1.87)
Regionallymphnodes(Nstage)a
 N0328(84.10)234(83.47)
 N157(14.62)45(16.17)
 N25(1.28)1(0.36)
Distantmetastases(Mstage)a
 M0314(80.51)216(77.14)
 M176(19.49)64(22.86)
Tumorsize(cm)
 Mean±SD6.1±4.16.1±4
 Median(min–max)5.1(0.4–23.0)5.3(0.5–23.0)
Nucleargradea
 110(2.66)8(2.88)
 2149(39.62)115(41.37)
 3162(43.09)111(39.93)
 455(14.63)44(15.82)
Necrosisa
 No174(57.24)133(59.37)
 Yes130(42.76)91(40.63)
  
CovariateUnivariableMultivariable
HR (95%CI)p-valueHR (95%CI)p-value
Age1.04 (1.02–1.06)<0.0011.04 (1.01–1.07)0.010
BMI0.94 (0.90–0.98)0.0030.97 (0.93–1.02)0.209
Sex (ref: female)1.08 (0.64–1.82)0.767
Race (ref: non-African-American)1.21 (0.64–2.26)0.556
Pre-op ECOG performance status (ref: 0)3.35 (2.05–5.49)<0.0012.25 (1.31–3.86)0.003
2009 T stage
 pT22.20 (0.85–5.68)0.1020.49 (0.15–1.58)0.229
 pT36.39 (3.50–11.68)<0.0010.88 (0.35–2.21)0.783
 pT410.96 (3.58–33.59)<0.0011.54 (0.36–6.60)0.564
2009 N stage (ref: N0)5.51 (3.33–9.12)<0.0011.82 (0.89–3.72)0.103
2009 M stage (ref: M0)6.01 (3.65–9.89)<0.0011.31 (0.61–2.80)0.483
FNG (ref: G1–G2)3.64 (1.90–6.97)<0.0010.97 (0.39–2.41)0.951
Tumor dimensions (ref: <5 cm)4.31 (2.29–8.12)<0.0012.63 (1.09–6.34)0.031
RISK (ref: baseline)
 Low risk1.35 (0.37–4.92)0.6450.72 (0.18–2.85)0.643
 Intermediate risk8.64 (2.57–29.02)<0.0013.29 (0.83–13.06)0.090
 High risk18.41 (5.60–60.58)<0.0014.80 (1.23–18.74)0.024
C-reactive protein (ref: <10 mg/L)
 10–25 mg/L3.27 (1.45–7.34)0.004
 >25 mg/L9.01 (5.05–16.07)<0.001
Albumin (ref: > 3.5 mg/dL)
 2.5–3.5 mg/dL4.44 (2.61–7.53)<0.001
 <2.5 mg/dL6.15 (2.64–14.32)<0.001
ESR (ref: 0–22 (male)/0–29 (female) mm/h)
 22–45 (male)/29–55 (female) mm/h2.94 (1.29–6.70)0.01
 ≥45 (male)/≥55 (female) mm/h10.08 (5.02–20.24)<0.001
AST/ALT ratio (ref: 1.1 (male)/1.23 (female))
 1.1–1.54 (male)/1.23–1.54 (female)1.08 (0.59–1.97)0.803
 >1.542.65 (1.46–4.84)0.001
Calcium (ref: <9.7 mg/dL)
 9.7–10.11 mg/dL2.12 (1.02–4.39)0.044
 >10.11 mg/dL6.94 (3.58–13.42)<0.001
  
CovariateUnivariableMultivariable
HR (95%CI)p-valueHR (95%CI)p-value
Age1.03 (1.00–1.05)0.0351.02 (0.98–1.05)0.346
BMI0.94 (0.9–0.98)0.0040.97 (0.92–1.01)0.132
Sex (ref: female)1.15 (0.65–2.02)0.631
Race (ref: non-African-American)2.85 (1.46–5.56)0.001
Pre-op ECOG performance status (ref: 0)2.84 (1.66–4.86)<0.0012.15 (1.19–3.90)0.012
2009 T stage
 pT21.82 (0.59–5.59)0.2950.32 (0.08–1.22)0.094
 pT35.85 (3.07–11.12)<0.0010.74 (0.28–1.99)0.554
 pT45.56 (0.72–43.12)0.1010.68 (0.07–6.23)0.735
2009 N stage (ref: N0)5.18 (2.99–8.97)<0.0011.89 (0.87–4.11)
2009 M stage (ref: M0)5.24 (3.05–9.02)<0.0011.13 (0.50–2.55)
FNG (ref: G1–G2)3.47 (1.79–6.73)<0.0010.83 (0.30–2.25)0.710
Tumor dimensions (ref: <5 cm)4.88 (2.37–10.03)<0.0012.95 (1.15–7.55)0.024
RISK (ref: baseline)
 Low risk1.31 (0.34–5.07)0.6960.74 (0.17–3.26)0.886
 Intermediate risk9.55 (2.83–32.25)<0.0015.36 (1.23–23.46)0.026
 High risk16.44 (4.92–54.93)<0.0015.52 (1.29–23.55)0.021
C-reactive protein (ref: <10 mg/L)
 10–25 mg/L3.96 (1.71–9.18)0.001
 >25 mg/L7.62 (4.03–14.41)<0.001
Albumin (ref: > 3.5 mg/dL)
 2.5–3.5 mg/dL4.33 (2.44–7.68)<0.001
 <2.5 mg/dL4.62 (1.73–12.33)0.002
ESR (ref: 0–22 (male)/0–29 (female) mm/h)
 22–45 (male)/29–55 (female) mm/h2.84 (1.15–6.98)0.023
 ≥45 (male)/≥55 (female) mm/h8.72 (4.16–18.25)<0.001
AST/ALT ratio (ref: 1.1 (male)/1.23 (female))
 1.1–1.54 (male)/1.23–1.54 (female)1.41 (0.76–2.62)0.276
 >1.542.67 (1.32–5.39)0.006
Calcium (ref: <9.7 mg/dL)
 9.7–10.11 mg/dL2.43 (1.09–5.42)0.029
 >10.11 mg/dL6.90 (3.35–14.21)<0.001
  
  
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