title: Confounding factors associated with oral mucositis assessment in patients receiving chemoradiotherapy for head and neck cancer.
abstract: The aim of this study was to identify patient-centered, mucositis-associated adverse impact factors and events that might confound physician-assessed oral mucositis (OM) in head and neck cancer (HNC) patients receiving chemoradiotherapy.
  
  
  
  This was a post hoc analysis of a previously conducted randomized trial to determine the efficacy of 5% phenylbutyrate mouthwash in preventing chemoradiotherapy-induced OM. This analysis identified patient-centered symptomatic, observable, and measurable factors that may confound physician scoring of the severity of OM during chemoradiotherapy. Confounding factors were then combined with physician-rated OM scores according to World Health Organization (WHO) and OM Assessment Scale (OMAS) criteria to investigate the therapeutic implications of OM treatment.
  
  
  
  The original analysis found no significant differences between experimental and placebo groups with respect to the cumulative incidence of physician-recorded severe OM (WHO ≥3 or OMAS ≥2), patient-reported adverse events, and opioid use. However, patients in the experimental arm had relatively lower rates of OM-associated adverse clinical issues including unplanned short radiation breaks, skipping of chemotherapy, nausea/vomiting, late loss of body weight, and early opioid use, all of which could potentially interfere with physician-assessed OM scoring. When WHO OM grade (functional impact and pain), OMAS ulceration size (organic impact), and prolonged radiation treatment time (cancer treatment impact) were combined, there were significantly fewer interruptions of chemoradiotherapy treatment in symptomatic OM patients in the experimental compared to the placebo group. The benefits conferred by reducing the amount of chemoradiotherapy-related, OM-associated adverse impacts in the experimental group were reflected by better 5-year locoregional recurrence-free survival.
  
  
  
  This exploratory study raises questions as to whether the severity reflected by physician-rated OM scores is in concordance with OM-induced adverse impacts on HNC patients. Further investigations are warranted to identify patient-related and cancer-associated symptom burdens that may affect tolerance, compliance, and outcome of chemoradiotherapy and confound the evaluation of therapeutic effects on chemoradiotherapy-induced OM.
authors.affiliation: Department of Radiation Oncology, Koo Foundation Sun Yat-Sen Cancer Center, No. 125 Lih-Der Road, Pei-Tou District, Taipei, 112, Taiwan. ylchung@kfsyscc.org.
authors.forename: Yih-Lin
authors.initials: YL
authors.lastname: Chung
authors.affiliation: Sunny Pharmtech Inc., New Taipei City, Taiwan.
authors.forename: Newman N M
authors.initials: NNM
authors.lastname: Pui
mesh_terms: D000328:Adult; D000368:Aged; D059248:Chemoradiotherapy / Q000009:adverse effects* / Q000379:methods; D005260:Female; D006258:Head and Neck Neoplasms / Q000150:complications* / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D013280:Stomatitis / Q000209:etiology*
keywords: Chemoradiotherapy; Confounding factors; Head and neck cancer; Oral mucositis assessment; Survival