title: Effects of definitive chemoradiation on circulating immunologic angiogenic cytokines in head and neck cancer patients.
abstract: BACKGROUND
  Preclinical studies suggest a synergistic effect between radiation, immunotherapy and anti-angiogenic therapy, although the mechanisms are unclear. Angiogenic cytokines are known to affect the immune system, and their levels may be associated with response to immunotherapy. Here, we assess changes in circulating VEGF, as well as angiogenic cytokines angiopoietin-1 and -2 (Ang1, Ang2), and placental growth factor (PLGF) that occur during definitive chemo-radiotherapy in HNSCC patients.
  
  
  METHODS
  We prospectively collected blood samples from patients receiving definitive radiation with or without chemotherapy. Serum Ang1, Ang2, VEGF, and PLGF were measured via cytokine assays.
  
  
  RESULTS
  The majority of patients had advanced stage, node positive HPV-associated oropharyngeal cancer, and received radiation to a median dose of 70 Gy with concurrent cisplatin. Over the course of treatment, serum VEGF and Ang1 levels decreased in 20/24 (84 %, p < 0.0001) and 21/24 (88 %, p < 0.0001) patients, respectively, and Ang2 and PLGF levels increased in 20/24 (83 %, p < 0.0001) patients.
  
  
  CONCLUSIONS
  We find significant changes in angiogenic cytokines in the majority of HNSCC patients over the course of chemoradiation. Decreases in VEGF caused by radiation may represent one mechanism of potential synergy with immunotherapy. Increases in Ang2 and PLGF are interesting given their link to tumor associated angiogenesis and poor prognosis. Additional studies are needed to explore synergies between anti-angiogenic treatments, immunotherapy, and chemoradiation in HNSCC.
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, 450 Brookline Ave, DA L2-57, Boston, MA 02114 USA ; Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA USA.
authors.forename: Vishwajith
authors.initials: V
authors.lastname: Sridharan
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, 450 Brookline Ave, DA L2-57, Boston, MA 02114 USA.
authors.forename: Danielle N
authors.initials: DN
authors.lastname: Margalit
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, 450 Brookline Ave, DA L2-57, Boston, MA 02114 USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Lynch
authors.affiliation: Center for Immuno-oncology, Dana-Farber Cancer Institute, Boston, MA USA.
authors.forename: Mariano
authors.initials: M
authors.lastname: Severgnini
authors.affiliation: Center for Immuno-oncology, Dana-Farber Cancer Institute, Boston, MA USA ; Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA USA.
authors.forename: F Stephen
authors.initials: FS
authors.lastname: Hodi
authors.affiliation: Department of Medical Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, Boston, MA USA.
authors.forename: Robert I
authors.initials: RI
authors.lastname: Haddad
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, 450 Brookline Ave, DA L2-57, Boston, MA 02114 USA.
authors.forename: Roy B
authors.initials: RB
authors.lastname: Tishler
authors.affiliation: Department of Radiation Oncology, Brigham and Women's Hospital/Dana-Farber Cancer Center, 450 Brookline Ave, DA L2-57, Boston, MA 02114 USA.
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Schoenfeld
keywords: Angiogenesis; Angiopoietins; Cytokines; Head and neck cancer; PLGF; Radiation; VEGF