title: Soft tissue metastasis in p16-positive oropharynx carcinoma: Prevalence and association with distant metastasis.
abstract: BACKGROUND
  Ungraded extracapsular spread (ECS) has been found non-prognostic in p16-positive, surgically-treated oropharynx squamous cell carcinoma (OPSCC). However, soft tissue metastasis (STM), the highest ECS grade, is reported prognostic. Our study's objective is to explore STM relative to distant metastasis (DM), the most frequent recurrence site in surgically-treated p16-positive OPSCC.
  
  
  METHODS
  Primary p16-positive OPSCC patients undergoing transoral surgery (TOS) and neck dissections were identified from a prospectively-assembled database. DM and regional recurrence (RR) rates, and DM-free survival (DMFS) were compared in pN+patients without STM (group I) and with STM (group II).
  
  
  RESULTS
  Of 222 patients, 202 had pN+disease: 147 (73%) in group I and 55 (27%) in group II. The DM rate was 6.7% (n=15/222) overall. The DM rates were 4% (n=6/147) vs. 16.4% (n=9/55), RR rates were 2% (n=3) vs. 5% (n=3), and 5-year DMFS rates were 94.8% vs. 82.4%, in groups I and II respectively. STM was significantly associated with poorer DMFS (HR=4.6, 95% CI: 1.65, 13.03, p=0.004), an observation driven by its effect in the T3-T4 and not the T1-T2 subset. Amongst patients receiving adjuvant therapy, STM's association with poorer DMFS was lost in multivariable analysis; high T-classification, however, remained significant (HR=5.16, 95% CI: 1.43, 18.52, p=0.012). Five-year DMFS for STM patients was 82.2% in chemoradiation (37% T3-T4) vs. 85.6% in radiation (35% T3-T4) group.
  
  
  CONCLUSIONS
  STM was significantly associated with DM and DMFS, but only in the T3-T4, not T1-T2 subset; no significant association was seen with RR. In patients receiving adjuvant therapy, only high T-classification was associated with DMFS, not STM. Chemoradiation used as adjuvant therapy was not associated with better DMFS in STM patients for any T-classification.
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Parul
authors.initials: P
authors.lastname: Sinha
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: James S
authors.initials: JS
authors.lastname: Lewis
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA; Clinical Outcomes Research, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Dorina
authors.initials: D
authors.lastname: Kallogjeri
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Nussenbaum
authors.affiliation: Otolaryngology-Head and Neck Surgery, Washington University School of Medicine, St. Louis, MO, USA. Electronic address: haugheyb@ent.wustl.edu.
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 / Q000453:epidemiology* / Q000556:secondary* / Q000628:therapy; D005260:Female; D019942:Genes, p16; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009959:Oropharyngeal Neoplasms / Q000473:pathology* / Q000628:therapy; D015995:Prevalence; D011379:Prognosis; D011446:Prospective Studies; D012307:Risk Factors; D012983:Soft Tissue Neoplasms / Q000453:epidemiology* / Q000556:secondary*
keywords: Adjuvant chemotherapy; Adjuvant radiotherapy; Distant metastasis; Extracapsular spread; Human papillomavirus; Oropharynx cancer; Soft tissue metastasis; p16-positive