title: Minimum nodal yield in oral squamous cell carcinoma: defining the standard of care in a multicenter international pooled validation study.
abstract: OBJECTIVE
  There is evidence to suggest that a nodal yield <18 is an independent prognostic factor in patients with clinically node negative (cN0) oral squamous cell carcinoma (SCC) treated with elective neck dissection (END). We sought to evaluate this hypothesis with external validation and to investigate for heterogeneity between institutions.
  
  
  METHODS
  We analyzed pooled individual data from 1,567 patients treated at nine comprehensive cancer centers worldwide between 1970 and 2011. Nodal yield was assessed with Cox proportional hazard models, stratified by study center, and adjusted for age, sex, pathological T and N stage, margin status, extracapsular nodal spread, time period of primary treatment, and adjuvant therapy. Two-stage random-effects meta-analyses were used to investigate for heterogeneity between institutions.
  
  
  RESULTS
  In multivariable analyses of patients undergoing selective neck dissection, nodal yield <18 was associated with reduced overall survival [hazard ratio (HR) 1.69; 95 % confidence interval (CI) 1.22-2.34; p = 0.002] and disease-specific survival (HR 1.88; 95 % CI 1.21-2.91; p = 0.005), and increased risk of locoregional recurrence (HR 1.53; 95 % CI 1.04-2.26; p = 0.032). Despite significant differences between institutions in terms of patient clinicopathological factors, nodal yield, and outcomes, random-effects meta-analysis demonstrated no evidence of heterogeneity between centers in regards to the impact of nodal yield on disease-specific survival (p = 0.663; I (2) statistic = 0).
  
  
  CONCLUSIONS
  Our data confirm that nodal yield is a robust independent prognostic factor in patients undergoing END for cN0 oral SCC, and may be applied irrespective of the underlying patient population and treating institution. A minimum adequate lymphadenectomy in this setting should include at least 18 nodes.
authors.affiliation: Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, NSW, Australia, ebrahimi.ardalan@post.harvard.edu.
authors.forename: Ardalan
authors.initials: A
authors.lastname: Ebrahimi
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Clark
authors.forename: M
authors.initials: M
authors.lastname: Amit
authors.forename: T C
authors.initials: TC
authors.lastname: Yen
authors.forename: Chun-Ta
authors.initials: CT
authors.lastname: Liao
authors.forename: Luis P
authors.initials: LP
authors.lastname: Kowalski
authors.forename: Matthias
authors.initials: M
authors.lastname: Kreppel
authors.forename: Claudio R
authors.initials: CR
authors.lastname: Cernea
authors.forename: Gideon
authors.initials: G
authors.lastname: Bachar
authors.forename: Andrea Bolzoni
authors.initials: AB
authors.lastname: Villaret
authors.forename: Dan
authors.initials: D
authors.lastname: Fliss
authors.forename: Eran
authors.initials: E
authors.lastname: Fridman
authors.forename: K T
authors.initials: KT
authors.lastname: Robbins
authors.forename: Jatin P
authors.initials: JP
authors.lastname: Shah
authors.forename: Snehal G
authors.initials: SG
authors.lastname: Patel
authors.forename: Ziv
authors.initials: Z
authors.lastname: Gil
mesh_terms: D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007390:International Agencies; D008197:Lymph Node Excision / Q000592:standards*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D009367:Neoplasm Staging; D011379:Prognosis; D059039:Standard of Care; D015996:Survival Rate