title: Internal and external generalizability of temporal dose-response relationships for xerostomia following IMRT for head and neck cancer.
abstract: To study internal and external generalizability of temporal dose-response relationships for xerostomia after intensity-modulated radiotherapy (IMRT) for head and neck cancer, and to investigate potential amendments of the QUANTEC guidelines.
  
  
  
  Objective xerostomia was assessed in 121 patients (nCohort1=55; nCohort2=66) treated to 70Gy@2Gy in 2006-2015. Univariate and multivariate analyses (UVA, MVA with 1000 bootstrap populations) were conducted in Cohort1, and generalizability of the best-performing MVA model was investigated in Cohort2 (performance: AUC, p-values, and Hosmer-Lemeshow p-values (pHL)). Ultimately and for clinical guidance, minimum mean dose thresholds to the contralateral and the ipsilateral parotid glands (Dmeancontra, Dmeanipsi) were estimated from the generated dose-response curves.
  
  
  
  The observed xerostomia rate was 38%/47% (3months) and 19%/23% (11-12months) in Cohort1/Cohort2. Risk of xerostomia at 3months increased for higher Dmeancontraand Dmeanipsi(Cohort1: 0.17·Dmeancontra+0.11·Dmeanipsi-8.13; AUC=0.90±0.05; p=0.0002±0.002; pHL=0.22±0.23; Cohort2: AUC=0.81; p<0.0001; pHL=0.27). The identified minimum Dmeancontrathresholds were lower than in the QUANTEC guidelines (Cohort1/Cohort2: Dmeancontra=12/19Gy; Dmeancontra, Dmeanipsi=16, 25/20, 26Gy).
  
  
  
  Increased Dmeancontraand Dmeanipsiexplain short-term xerostomia following IMRT. Our results also suggest decreasing Dmeancontrato below 20Gy, while keeping Dmeanipsito around 25Gy. Long-term xerostomia was less frequent, and no dose-response relationship was established for this follow-up time.
authors.affiliation: Dept. of Medical Physics, Memorial Sloan Kettering Cancer Center, USA. Electronic address: thorm@mskcc.org.
authors.forename: Maria
authors.initials: M
authors.lastname: Thor
authors.affiliation: Dept. of Surgery, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Adepitan A
authors.initials: AA
authors.lastname: Owosho
authors.affiliation: Dept. of Physics and Astronomy, University of British Columbia, Vancouver, Canada; Dept. of Medical Physics, British Columbia Cancer Agency-Vancouver Centre, Vancouver, Canada.
authors.forename: Haley D
authors.initials: HD
authors.lastname: Clark
authors.affiliation: Dept. of Medical Physics, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Jung Hun
authors.initials: JH
authors.lastname: Oh
authors.affiliation: Dept. of Radiation Oncology, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Nadeem
authors.initials: N
authors.lastname: Riaz
authors.affiliation: Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, Canada.
authors.forename: Allan
authors.initials: A
authors.lastname: Hovan
authors.affiliation: Dept. of Radiation Oncology, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Jillian
authors.initials: J
authors.lastname: Tsai
authors.affiliation: Dept. of Medical Physics, British Columbia Cancer Agency-Vancouver Centre, Vancouver, Canada.
authors.forename: Steven D
authors.initials: SD
authors.lastname: Thomas
authors.affiliation: Dept. of Surgery, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Sae Hee K
authors.initials: SHK
authors.lastname: Yom
authors.affiliation: Radiation Oncology, British Columbia Cancer Agency-Vancouver Centre, Vancouver, Canada.
authors.forename: Jonn S
authors.initials: JS
authors.lastname: Wu
authors.affiliation: Dept. of Surgery, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Huryn
authors.affiliation: Dept. of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, USA.
authors.forename: Vitali
authors.initials: V
authors.lastname: Moiseenko
authors.affiliation: Dept. of Radiation Oncology, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Lee
authors.affiliation: Dept. of Surgery, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Cherry L
authors.initials: CL
authors.lastname: Estilo
authors.affiliation: Dept. of Medical Physics, Memorial Sloan Kettering Cancer Center, USA.
authors.forename: Joseph O
authors.initials: JO
authors.lastname: Deasy
mesh_terms: D000328:Adult; D000368:Aged; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010306:Parotid Gland / Q000528:radiation effects; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D012189:Retrospective Studies; D014987:Xerostomia / Q000209:etiology*
keywords: Dose response; Head and neck; IMRT; QUANTEC; Radiotherapy; Xerostomia