title: The role of parotid gland irradiation in the development of severe hyposalivation (xerostomia) after intensity-modulated radiation therapy for head and neck cancer: Temporal patterns, risk factors, and testing the QUANTEC guidelines.
abstract: BACKGROUND
  The aims of this study were to investigate temporal patterns and potential risk factors for severe hyposalivation (xerostomia) after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC), and to test the two QUANTEC (Quantitative Analysis of Normal Tissue Effects in the Clinic) guidelines.
  
  
  METHODS
  Sixty-three patients treated at the Memorial Sloan Kettering Cancer Center between 2006 and 2015, who had a minimum of three stimulated whole mouth saliva flow measurements (WMSFM) at a median follow-up time of 11 (range: 3-24) months were included. Xerostomia was defined as WMSFM ≤25% compared to relative pre-radiotherapy. Patients were stratified into three follow-up groups: 1: <6 months; 2: 6-11 months; and 3: 12-24 months. Potential risk factors were investigated (Mann-Whitney U test), and relative risks (RRs) assessed for the two QUANTEC guidelines.
  
  
  RESULTS
  The incidence of xerostomia was 27%, 14% and 17% at follow-up time points 1, 2 and 3, respectively. At <6 months, the mean dose to the contralateral and the ipsilateral parotid glands (Dmeancontra, Dmeanipsi) was higher among patients with xerostomia (Dmeancontra: 25 Gy vs. 15 Gy; Dmeanipsi: 44 Gy vs. 25 Gy). Patients with xerostomia had higher pre-RT WMSFM (3.5 g vs. 2.4 g), and had been treated more frequently with additional chemotherapy (93% vs. 63%; all 4 variables: p < 0.05). At 6-11 months, Dmeancontraamong patients with xerostomia was higher compared to patients without (26 Gy vs. 20 Gy). The RR as specified by the one- and two-gland QUANTEC guideline was 2.3 and 1.4 for patients with <6 months follow-up time, and 2.0 and 1.2 for patients with longer follow-up (6-11 + 6-24 months).
  
  
  CONCLUSIONS
  Xerostomia following IMRT peaks within six months post-radiotherapy and fades with time. Limiting the mean dose to both parotid glands (ipsilateral <25 Gy, contralateral <25 Gy) and reducing the use of chemotherapy will likely decrease the rate of xerostomia. Both QUANTEC guidelines are effective in preventing xerostomia.
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Adepitan A
authors.initials: AA
authors.lastname: Owosho
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Thor
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Jung Hun
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Riaz
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: C Jillian
authors.initials: CJ
authors.lastname: Tsai
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Haley
authors.initials: H
authors.lastname: Rosenberg
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Spyridon
authors.initials: S
authors.lastname: Varthis
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Sae Hee K
authors.initials: SH
authors.lastname: Yom
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Huryn
authors.affiliation: Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Lee
authors.affiliation: Department of Medical Physics, Memorial Sloan Kettering Cancer Center, NY, New York, USA.
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
authors.affiliation: Department of Surgery, Memorial Sloan Kettering Cancer Center, NY, New York, USA. Electronic address: estiloc@mskcc.org.
authors.forename: Cherry L
authors.initials: CL
authors.lastname: Estilo
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010306:Parotid Gland / Q000528:radiation effects*; D017410:Practice Guidelines as Topic; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013997:Time Factors; D014987:Xerostomia / Q000209:etiology*
keywords: Head and neck cancer; IMRT; QUANTEC; Severe hyposalivation; Xerostomia