title: The role of postoperative chemoradiation for oropharynx carcinoma: a critical appraisal of the published literature and National Comprehensive Cancer Network guidelines.
abstract: The National Comprehensive Cancer Network (NCCN) describes the presence of extracapsular spread and/or positive margins in oropharynx cancer (OPC) as an indication for the addition of chemotherapy to postoperative radiation. The guideline's category 1 consensus is based on what they term high-level evidence. For this study, the authors performed a critical appraisal of the research upon which the NCCN guideline is based and assessed its relevance in the era of human papillomavirus (HPV)/p16-positive OPC. Multiple shortcomings were identified, including patient exclusion after randomization and the use of unplanned subgroup analyses without multivariate adjustment, which undermined internal validity. Indeterminate HPV/p16 status limited external validity. Given the unique biology of HPV/p16-positive tumors and the problems of internal and external validity, the authors concluded that the literature upon which the recommendation for the addition of chemotherapy to adjuvant radiation was based does not generate high-level evidence, and its relevance for the postoperative management of patients with HPV/p16-positive OPC remains unknown.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Parul
authors.initials: P
authors.lastname: Sinha
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri.|Clinical Outcomes Research Office, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Jay F
authors.initials: JF
authors.lastname: Piccirillo
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri.|Clinical Outcomes Research Office, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Dorina
authors.initials: D
authors.lastname: Kallogjeri
authors.affiliation: Department of Mathematics, Washington University in St. Louis, Missouri.
authors.forename: Edward L
authors.initials: EL
authors.lastname: Spitznagel
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, Missouri.
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Haughey
mesh_terms: D059186:Chemoradiotherapy, Adjuvant; D018572:Disease-Free Survival; D017408:Guidelines as Topic; D006801:Humans; D009959:Oropharyngeal Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy* / Q000601:surgery; D017410:Practice Guidelines as Topic; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic
keywords: National Comprehensive Cancer Network guideline; adjuvant chemoradiation; critical appraisal; extracapsular spread; human papillomavirus; oropharynx cancer; positive margins