title: Extracapsular spread and adjuvant therapy in human papillomavirus-related, p16-positive oropharyngeal carcinoma.
abstract: BACKGROUND
  Extracapsular spread (ECS) is commonly used to justify adjuvant chemotherapy in patients with head and neck cancer. The role of ECS as a prognosticator and adjuvant therapy determinant in surgically resected, human papillomavirus-related oropharyngeal squamous cell carcinoma (OPSCC), however, has never been determined.
  
  
  METHODS
  Of 210 oropharynx patients in a prospective transoral laser microsurgery database, 152 patients who had p16-positive primary OPSCC and pathologically positive necks were eligible for the study. ECS was measured from routine reporting (ECS(report)) and by using a novel histologic grading system (ECS(graded)). Proportional hazards models and matched analyses were used to compare the impact of ECS and adjuvant therapy on disease-free survival (DFS). Patients with and without graded ECS were matched for T-stage, surgical margins, and adjuvant therapy.
  
  
  RESULTS
  At a median follow-up of 43 months, the presence of ECS was not associated with poorer DFS in multivariate analyses (ECS(report): hazard ratio [HR], 3.42; 95% confidence interval [CI], 0.45-25.88; P = .23; ECS(graded): HR, 2.54; 95% CI, 0.88-7.34; P = .09). T-stage and high-grade ECS, ie soft tissue metastasis (STM(graded)) were prognostic. Overall and in the presence of ECS or even STM, adjuvant CRT was not associated with better DFS over radiotherapy alone (HR, 0.25; 95% CI, 0.06-1.13; P = .07). In addition, matched analyses demonstrated no significant reduction in DFS for the presence of ECS versus the absence of ECS or reduced DFS for the administration of adjuvant radiotherapy alone versus CRT in ECS-positive patients.
  
  
  CONCLUSIONS
  Routinely reported ECS was not prognostic in this study. Adjuvant CRT versus radiotherapy alone produced no improvement in DFS for ECS-positive patients. The authors propose that de-escalated adjuvant therapy should be considered for patients with p16-positive OPSCC who undergo surgery and that routinely reported ECS should not be used to justify adjuvant chemotherapy.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Parul
authors.initials: P
authors.lastname: Sinha
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.forename: Jay F
authors.initials: JF
authors.lastname: Piccirillo
authors.forename: Dorina
authors.initials: D
authors.lastname: Kallogjeri
authors.forename: Bruce H
authors.initials: BH
authors.lastname: Haughey
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology; D003131:Combined Modality Therapy; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis*; D009959:Oropharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy* / Q000821:virology; D027383:Papillomaviridae / Q000302:isolation & purification* / Q000378:metabolism; D011379:Prognosis
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; D009363:Neoplasm Proteins