title: Association between hemoglobin, calcium, and lactate dehydrogenase variability and mortality among metastatic renal cell carcinoma.
abstract: OBJECTIVE
  There are no robust data on hemoglobin (Hb), lactate dehydrogenase (LDH), and calcium variability for overall survival (OS) in patients with metastatic renal cell carcinoma (mRCC) treated with vascular endothelial growth factor (VEGF)-targeted therapy. We aim to evaluate prognostic implications of Hb, LDH, and calcium variability and establish a novel risk stratification model in RCC patients receiving targeted therapies.
  
  
  METHODS
  We retrospectively studied an unselected cohort of patients with mRCC, who were treated with tyrosine kinase inhibitors. We assessed LDH variability, Ca variability, and Hb variability with various methods using standard deviation and fluctuation across thresholds. Kaplan-Meier and log-rank analyses were employed on OS and multivariate Cox proportional hazard model analyzed clinical parameters for their prognostic relevance.
  
  
  RESULTS
  A total of 59 patients intermediate-risk group according to the Memorial Sloan-Kettering Cancer Center with mRCC who had early progressed after first-line therapy with interferon-α were included in this retrospective single-center study conducted between February 2008 and December 2011. The mean Hb was 12.4 g/dl (min-max 9.1-15.2) throughout the study. Multivariable-adjusted Cox regression showed that patients in the consistently low-Hb group and patients in the low-amplitude and high-amplitude groups had a statistically significant increase in risk compared with patients who were consistently on target (HR 4.1; 95 % CI 1.3-12.9 and HR 2.9; 95 % CI 1.05-8.1 and HR 4.4; 95 % CI 1.7-11.1, respectively). On the other hand, the higher mean LDH (LDH more than 1 >upper limit of normal) was associated with OS. LDH variability and Ca variability were not associated with mortality.
  
  
  CONCLUSIONS
  In patients with mRCC treated with VEGF-targeted therapy, Hb variability and mean LDH level might be associated with OS. This should be investigated prospectively.
authors.affiliation: Division of Medical Oncology, Department of Internal Medicine, Gazi University Faculty of Medicine, 06500, Besevler, Ankara, Turkey, caretta06@hotmail.com.
authors.forename: Bulent
authors.initials: B
authors.lastname: Cetin
authors.forename: Barıs
authors.initials: B
authors.lastname: Afsar
authors.forename: Serpil Muge
authors.initials: SM
authors.lastname: Deger
authors.forename: Ipek Isık
authors.initials: II
authors.lastname: Gonul
authors.forename: Ozge
authors.initials: O
authors.lastname: Gumusay
authors.forename: Ahmet
authors.initials: A
authors.lastname: Ozet
authors.forename: Mustafa
authors.initials: M
authors.lastname: Benekli
authors.forename: Ugur
authors.initials: U
authors.lastname: Coskun
authors.forename: Suleyman
authors.initials: S
authors.lastname: Buyukberber
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002118:Calcium / Q000097:blood*; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy / Q000556:secondary; D018572:Disease-Free Survival; D005260:Female; D006441:Hemoglobin A / Q000378:metabolism*; D006801:Humans; D007191:Indazoles; D007211:Indoles / Q000627:therapeutic use; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy / Q000473:pathology; D007770:L-Lactate Dehydrogenase / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009536:Niacinamide / Q000031:analogs & derivatives / Q000627:therapeutic use; D010671:Phenylurea Compounds / Q000627:therapeutic use; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011743:Pyrimidines / Q000627:therapeutic use; D011758:Pyrroles / Q000627:therapeutic use; D012189:Retrospective Studies; D018570:Risk Assessment; D000077157:Sorafenib; D013449:Sulfonamides / Q000627:therapeutic use; D000077210:Sunitinib; D015996:Survival Rate; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D007191:Indazoles; D007211:Indoles; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D042461:Vascular Endothelial Growth Factor A; D009536:Niacinamide; C516667:pazopanib; D006441:Hemoglobin A; D000077157:Sorafenib; D007770:L-Lactate Dehydrogenase; D002118:Calcium; D000077210:Sunitinib