title: Primary tumor staging for oral cancer and a proposed modification incorporating depth of invasion: an international multicenter retrospective study.
abstract: OBJECTIVE
  The current American Joint Committee on Cancer (AJCC) staging system for oral cancer demonstrates wide prognostic variability within each primary tumor stage and provides suboptimal staging and prognostic information for some patients.
  
  
  OBJECTIVE
  To determine if a modified staging system for oral cancer that integrates depth of invasion (DOI) into the T categories improves prognostic performance compared with the current AJCC T staging.
  
  
  METHODS
  Retrospective analysis of 3149 patients with oral squamous cell carcinoma treated with curative intent at 11 comprehensive cancer centers worldwide between 1990 and 2011 with surgery ± adjuvant therapy, with a median follow-up of 40 months.
  
  
  METHODS
  We assessed the impact of DOI on disease-specific and overall survival in multivariable Cox proportional hazard models and investigated for institutional heterogeneity using 2-stage random effects meta-analyses. Candidate staging systems were developed after identification of optimal DOI cutpoints within each AJCC T category using the Akaike information criterion (AIC) and likelihood ratio tests. Staging systems were evaluated using the Harrel concordance index (C-index), AIC, and visual inspection for stratification into distinct prognostic categories, with internal validation using bootstrapping techniques.
  
  
  RESULTS
  The mean and median DOI were 12.9 mm and 10.0 mm, respectively. On multivariable analysis, DOI was a significantly associated with disease-specific survival (P < .001), demonstrated no institutional prognostic heterogeneity (I² = 6.3%; P = .38), and resulted in improved model fit compared with T category alone (lower AIC, P < .001). Optimal cutpoints of 5 mm in T1 and 10 mm in T2-4 category disease were used to develop a modified T staging system that was preferred to the AJCC system on the basis of lower AIC, visual inspection of Kaplan-Meier curves, and significant improvement in bootstrapped C-index.
  
  
  CONCLUSIONS
  We propose an improved oral cancer T staging system based on incorporation of DOI that should be considered in future versions of the AJCC staging system after external validation.
authors: Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia2Department of Head and Neck Surgery, Liverpool Hospital, Sydney, New South Wales, Australia3Australian School of Advanced Medicine, Macquarie Universit.
authors: Ardalan
authors: A
authors: Ebrahimi
authors: The Laboratory for Applied Cancer Research, Haifa, Israel6Department of Otolaryngology Rambam Medical Center, Rappaport School of Medicine, the Technion, Israel institute of technology, Haifa, Israel.
authors: Ziv
authors: Z
authors: Gil
authors: The Laboratory for Applied Cancer Research, Haifa, Israel6Department of Otolaryngology Rambam Medical Center, Rappaport School of Medicine, the Technion, Israel institute of technology, Haifa, Israel.
authors: Moran
authors: M
authors: Amit
authors: Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors: Tzu-Chen
authors: TC
authors: Yen
authors: Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors: Chun-Ta
authors: CT
authors: Liao
authors: Tata Memorial Hospital, Mumbai, India.
authors: Pankaj
authors: P
authors: Chaturvedi
authors: Tata Memorial Hospital, Mumbai, India.
authors: Jai Prakash
authors: JP
authors: Agarwal
authors: Hospital A. C. Camargo, São Paulo, Brazil.
authors: Luiz P
authors: LP
authors: Kowalski
authors: Department of Oral and Cranio-Maxillo and Facial Plastic Surgery University of Cologne, Cologne, Germany.
authors: Matthias
authors: M
authors: Kreppel
authors: Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil.
authors: Claudio R
authors: CR
authors: Cernea
authors: Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil.
authors: Jose
authors: J
authors: Brandao
authors: Department of Otolaryngology Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Israel.
authors: Gideon
authors: G
authors: Bachar
authors: Ear, Nose, and Throat Department, University of Brescia, Brescia, Italy.
authors: Andrea
authors: A
authors: Bolzoni Villaret
authors: Department of Otolaryngology Head and Neck Surgery, Tel Aviv Medical Center, Tel Aviv, Israel.
authors: Dan
authors: D
authors: Fliss
authors: Department of Otolaryngology Head and Neck Surgery, Tel Aviv Medical Center, Tel Aviv, Israel.
authors: Eran
authors: E
authors: Fridman
authors: Southern Illinois University School of Medicine, Springfield, Illinois.
authors: K Thomas
authors: KT
authors: Robbins
authors: Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Jatin P
authors: JP
authors: Shah
authors: Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Snehal G
authors: SG
authors: Patel
authors: Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, New South Wales, Australia2Department of Head and Neck Surgery, Liverpool Hospital, Sydney, New South Wales, Australia.
authors: Jonathan R
authors: JR
authors: Clark
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging / Q000379:methods*; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015996:Survival Rate; D055815:Young Adult