title: Dexamethasone exerts profound immunologic interference on treatment efficacy for recurrent glioblastoma.
abstract: BACKGROUND
  Patients with recurrent glioblastoma have a poor outcome. Data from the phase III registration trial comparing tumour-treating alternating electric fields (TTFields) vs chemotherapy provided a unique opportunity to study dexamethasone effects on patient outcome unencumbered by the confounding immune and myeloablative side effects of chemotherapy.
  
  
  METHODS
  Using an unsupervised binary partitioning algorithm, we segregated both cohorts of the trial based on the dexamethasone dose that yielded the greatest statistical difference in overall survival (OS). The results were validated in a separate cohort treated in a single institution with TTFields and their T lymphocytes were correlated with OS.
  
  
  RESULTS
  Patients who used dexamethasone doses >4.1 mg per day had a significant reduction in OS when compared with those who used ⩽4.1 mg per day, 4.8 vs 11.0 months respectively (χ(2)=34.6, P<0.0001) in the TTField-treated cohort and 6.0 vs 8.9 months respectively (χ(2)=10.0, P<0.0015) in the chemotherapy-treated cohort. In a single institution validation cohort treated with TTFields, the median OS of patients who used dexamethasone >4.1 mg per day was 3.2 months compared with those who used ⩽4.1 mg per day was 8.7 months (χ(2)=11.1, P=0.0009). There was a significant correlation between OS and T-lymphocyte counts.
  
  
  CONCLUSIONS
  Dexamethasone exerted profound effects on both TTFields and chemotherapy efficacy resulting in lower patient OS. Therefore, global immunosuppression by dexamethasone likely interferes with immune functions that are necessary for the treatment of glioblastoma.
authors.affiliation: Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: E T
authors.initials: ET
authors.lastname: Wong
authors.affiliation: Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: E
authors.initials: E
authors.lastname: Lok
authors.affiliation: Division of Biostatistics, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
authors.forename: S
authors.initials: S
authors.lastname: Gautam
authors.affiliation: Brain Tumor Center and Neuro-Oncology Unit, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Swanson
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004599:Electric Stimulation Therapy; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000276:immunology / Q000401:mortality; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome
chemical_list: D003907:Dexamethasone