title: Prognostic significance of neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in patients treated with selective internal radiation therapy.
abstract: BACKGROUND
  Elevated neutrophil-to-lymphocyte (NLR) and platelet-to-lymphocyte ratios (PLR) may represent markers of a suboptimal host immune response to cancer and have been shown to correlate with prognosis in multiple tumor types across different treatment modalities, including radiation therapy. Limited data suggest that NLR may predict for survival and disease control in patients receiving selective internal radiation therapy (SIRT). The correlation between clinical outcomes and change in NLR and PLR after SIRT has not been evaluated.
  
  
  METHODS
  We retrospectively reviewed 339 consecutive patients with primary (n=37) or metastatic (n=79) liver cancer treated with SIRT from 2006 to 2014. Complete blood counts with differential were available for 116 patients both before and after (median, 29 and 20 days, respectively) SIRT. Survival and progression were calculated from date of initial SIRT. Patient and tumor characteristics evaluated for ability to predict overall survival (OS) and progression free survival (PFS) included pre- and post-treatment neutrophil, platelet, and lymphocyte counts (LCs), as well as NLR, PLR, and relative change in NLR and PLR. Cutoff values were determined for variables that were significant on multivariate analysis (MVA) for OS and/or PFS.
  
  
  RESULTS
  Median follow-up of surviving patients was 12 months. Median OS was 8 months from SIRT and 20 months from date of liver metastasis diagnosis. Significant factors on univariate analysis (UVA) for both lower OS and PFS included higher post-treatment neutrophil count (NC), higher post-treatment NLR, higher liver tumor volume, higher percentage liver tumor burden, and worse Eastern Cooperative Oncology Group (ECOG) performance status. Significant factors on MVA for lower OS and PFS were ECOG performance status ≥2, higher liver tumor volume, higher pretreatment PLR, and increase in PLR after SIRT. Post-treatment increase in PLR >3-fold was the most predictive early marker for increased risk of death when compared with those whose PLR did not increase or increased <3-fold. Pretreatment PLR >78 was the most predictive serum marker associated with improved OS prior to therapy.
  
  
  CONCLUSIONS
  This is the largest study to evaluate the association between NLR and PLR with clinical outcomes in patients receiving SIRT, with results that confirm that pre- and/or post-treatment NLR and/or PLR are predictive of clinical outcomes. The largest increase in risk of death as well as local and extrahepatic disease progression was related to change in PLR, a datum not well reported in the literature. The impact of SIRT on blood count changes and the underlying implications of these ratios should be further characterized in a prospective study.
authors.affiliation: 1 Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA ; 2 University of Pennsylvania School of Nursing, Philadelphia, PA, USA ; 3 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Nicole
authors.initials: N
authors.lastname: D'Emic
authors.affiliation: 1 Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA ; 2 University of Pennsylvania School of Nursing, Philadelphia, PA, USA ; 3 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Alexander
authors.initials: A
authors.lastname: Engelman
authors.affiliation: 1 Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA ; 2 University of Pennsylvania School of Nursing, Philadelphia, PA, USA ; 3 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Molitoris
authors.affiliation: 1 Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA ; 2 University of Pennsylvania School of Nursing, Philadelphia, PA, USA ; 3 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Hanlon
authors.affiliation: 1 Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA ; 2 University of Pennsylvania School of Nursing, Philadelphia, PA, USA ; 3 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Navesh K
authors.initials: NK
authors.lastname: Sharma
authors.affiliation: 1 Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA ; 2 University of Pennsylvania School of Nursing, Philadelphia, PA, USA ; 3 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Fred M
authors.initials: FM
authors.lastname: Moeslein
authors.affiliation: 1 Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD, USA ; 2 University of Pennsylvania School of Nursing, Philadelphia, PA, USA ; 3 Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Chuong
keywords: Selective internal radiation therapy (SIRT); liver cancer; radioembolization; selective internal radiation-sphere (SIR-sphere)