title: Predictors of severe long-term toxicity after re-irradiation for head and neck cancer.
abstract: To identify predictive factors of severe long-term toxicity after re-irradiation of recurrent/persistent or second-primary head and neck cancer.
  
  
  
  Outcomes and treatment plans of patients who underwent modern IMRT based re-irradiation to the head and neck from 2008-2015 were reviewed. Co-variables including demographic, clinical and oncologic factors, as well as interval to re-irradiation and re-irradiated planning tumor volume (PTV) were analyzed as predictors of developing severe (CTCAE grade⩾3) long-term toxicity with death as a competing risk.
  
  
  
  A total of 66 patients who met inclusion criteria were eligible for analysis. A median re-irradiation dose of 70Gy was delivered at a median of 37.5months after initial radiotherapy. Re-irradiation followed surgical resection in 25 (38%) patients, and concurrent chemotherapy was delivered to 41 (62%) patients. Median follow-up after re-irradiation was 23months and median overall survival was 22months (predicted 2year overall survival 49%). Of the 60 patients who survived longer than 3months after re-irradiation, 16 (25%) patients experienced severe long-term toxicity, with the majority (12 of 16) being feeding tube -dependent dysphagia. In multivariable analysis, shorter intervals to re-irradiation (<20months) and larger re-irradiated PTVs (>100cm(3)) were independent predictors of developing severe long-term toxicity. Patients with longer disease-free intervals and smaller PTVs had a 94% probability of being free of severe toxicity at two years.
  
  
  
  Selection of patients with longer re-irradiation intervals and requiring smaller re-irradiated PTVs can independently predict avoidance of severe long-term toxicity.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Jae Y
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States; Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Krithika
authors.initials: K
authors.lastname: Suresh
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Nguyen
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Eli
authors.initials: E
authors.lastname: Sapir
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Janell S
authors.initials: JS
authors.lastname: Dow
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: George S
authors.initials: GS
authors.lastname: Arnould
authors.affiliation: Department of Internal Medicine, Hematology/Oncology, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Francis P
authors.initials: FP
authors.lastname: Worden
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Spector
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Mark E
authors.initials: ME
authors.lastname: Prince
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Scott A
authors.initials: SA
authors.lastname: McLean
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Andrew G
authors.initials: AG
authors.lastname: Shuman
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Kelly M
authors.initials: KM
authors.lastname: Malloy
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Keith
authors.initials: K
authors.lastname: Casper
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Carol R
authors.initials: CR
authors.lastname: Bradford
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States; Department of Biostatistics, University of Michigan, Ann Arbor, MI, United States.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Schipper
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI, United States. Electronic address: eisbruch@med.umich.edu.
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D050397:Radiotherapy, Intensity-Modulated / Q000009:adverse effects*; D016019:Survival Analysis
keywords: Dysphagia; Head and neck re-irradiation; Interval to re-irradiation; Re-irradiated volume; Re-irradiation toxicity