title: Clinical and Dosimetric Predictors of Acute Severe Lymphopenia During Radiation Therapy and Concurrent Temozolomide for High-Grade Glioma.
abstract: OBJECTIVE
  Acute severe lymphopenia (ASL) frequently develops during radiation therapy (RT) and concurrent temozolomide (TMZ) for high-grade glioma (HGG) and is associated with decreased survival. The current study was designed to identify potential predictors of ASL, with a focus on actionable RT-specific dosimetric parameters.
  
  
  METHODS
  From January 2007 to December 2012, 183 patients with HGG were treated with RT+TMZ and had available data including total lymphocyte count (TLC) and radiation dose-volume histogram parameters. ASL was defined as TLC of <500/μL within the first 3 months from the start of RT. Stepwise logistic regression analysis was used to determine the most important predictors of ASL.
  
  
  RESULTS
  Fifty-three patients (29%) developed ASL. Patients with ASL had significantly worse overall survival than those without (median: 12.5 vs 20.2 months, respectively, P<.001). Stepwise logistic regression analysis identified female sex (odds ratio [OR]: 5.30; 95% confidence interval [CI]: 2.46-11.41), older age (OR: 1.05; 95% CI: 1.02-1.09), lower baseline TLC (OR: 0.92; 95% CI: 0.87-0.98), and higher brain volume receiving 25 Gy (V25Gy) (OR: 1.03; 95% CI: 1.003-1.05) as the most significant predictors for ASL. Brain V25Gy <56% appeared to be the optimal threshold (OR: 2.36; 95% CI: 1.11-5.01), with an ASL rate of 38% versus 20% above and below this threshold, respectively (P=.006).
  
  
  CONCLUSIONS
  Female sex, older age, lower baseline TLC, and higher brain V25Gy are significant predictors of ASL during RT+TMZ therapy for HGG. Maintaining the V25Gy of brain below 56% may reduce the risk of ASL.
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri. Electronic address: jhuang@radonc.wustl.edu.
authors.forename: Jiayi
authors.initials: J
authors.lastname: Huang
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Todd A
authors.initials: TA
authors.lastname: DeWees
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Shahed N
authors.initials: SN
authors.lastname: Badiyan
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Christina K
authors.initials: CK
authors.lastname: Speirs
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Mullen
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Sandra
authors.initials: S
authors.lastname: Fergus
authors.affiliation: Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri.
authors.forename: David D
authors.initials: DD
authors.lastname: Tran
authors.affiliation: Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Gerry
authors.initials: G
authors.lastname: Linette
authors.affiliation: Division of Medical Oncology, Department of Medicine, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Jian L
authors.initials: JL
authors.lastname: Campian
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Michael R
authors.initials: MR
authors.lastname: Chicoine
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Albert H
authors.initials: AH
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Gavin
authors.initials: G
authors.lastname: Dunn
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Joseph R
authors.initials: JR
authors.lastname: Simpson
authors.affiliation: Department of Radiation Oncology, Washington University School of Medicine, St Louis, Missouri.
authors.forename: Clifford G
authors.initials: CG
authors.lastname: Robinson
mesh_terms: D000208:Acute Disease; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000009:adverse effects*; D001921:Brain / Q000528:radiation effects; D001932:Brain Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D017024:Chemotherapy, Adjuvant; D016371:Cranial Irradiation / Q000009:adverse effects* / Q000379:methods; D003606:Dacarbazine / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005910:Glioma / Q000188:drug therapy / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D018655:Lymphocyte Count; D008231:Lymphopenia / Q000209:etiology* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D011879:Radiotherapy Dosage; D012044:Regression Analysis; D012737:Sex Factors; D000077204:Temozolomide; D055815:Young Adult
chemical_list: D018906:Antineoplastic Agents, Alkylating; D003606:Dacarbazine; D000077204:Temozolomide