title: The origin of regional failure in oral cavity squamous cell carcinoma with pathologically negative neck metastases.
abstract: OBJECTIVE
  Squamous cell carcinoma of the oral cavity (OSCC) is a common malignant tumor worldwide.
  
  
  OBJECTIVE
  To determine if regional failure in patients with OSCC and pathologically negative neck nodes (pN-) is due to an incomplete sampling procedure during surgery.
  
  
  METHODS
  We retrospectively reviewed the medical records of 2258 patients from 11 cancer centers worldwide who underwent neck dissection for OSCC (1990-2011) and who were pN-. Of those, 345 had clinical evidence of nodal metastases (cN+) on radiologic workup. The neck specimens were available for reanalysis in 193 patients. Survival rates were calculated using the Kaplan-Meier graphs and analyzed by multivariable analysis.
  
  
  METHODS
  Five-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS).
  
  
  RESULTS
  Resectioning and analysis of the neck dissection specimens in the cN+/pN- subgroup revealed false-negative results in 29 (15%) of 193 patients. The negative predictive value of the initial pathologic examination was 85%. The 5-year OS and DSS in the cN-/pN- group were 77.6% and 87.2%, respectively. The 5-year OS and DSS of the cN+/pN- group were 62.6% and 78.5%, respectively (P < .001). In multivariable analysis, cN+ classification was significantly associated with poor OS (hazard ratio [HR], 1.7; 95% CI, 1.1-3.8; P = .03) and poor DSS (HR, 1.46; 95% CI, 1.1-4.1; P = .04). A cN+ classification was associated with lower DFS (66.3% vs 76.2%; P = .05) and lower regional recurrence-free survival (68.6% vs 78.8%; P = .02) but not with local (P = .20) or distant recurrence (P = .80).
  
  
  CONCLUSIONS
  Pathologic staging underestimates the incidence of nodal metastases in cN+ disease. After correction for pathologically missed nodal metastases, radiologic evidence of neck nodes is an independent predictor of outcome, suggesting that traditional sampling during surgery might miss metastases, and this fact might explain the origin of treatment failure in these patients.
authors: Laboratory for Applied Cancer Research, Clinical Research Institute at Rambam, Haifa, Israel2Department of Otolaryngology-Head and Neck Surgery, Rambam Medical Center, Rappaport School of Medicine, the Technion, Israel Institute of Technology, Haifa, Isra.
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: A.C. Camargo Cancer Center, São Paulo, Brazil.
authors: Luiz Paulo
authors: LP
authors: Kowalski
authors: A.C. Camargo Cancer Center, São Paulo, Brazil.
authors: Hugo F
authors: HF
authors: Kohler
authors: Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia7Australian School of Advanced Medicine, Macquarie University, Sydney, Australia.
authors: Ardalan
authors: A
authors: Ebrahimi
authors: Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia.
authors: Jonathan R
authors: JR
authors: Clark
authors: Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil.
authors: Claudio Roberto
authors: CR
authors: Cernea
authors: Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil.
authors: Jose S
authors: JS
authors: Brandao
authors: Department of Oral and Cranio-Maxillo and Facial Plastic Surgery, University of Cologne, Germany.
authors: Matthias
authors: M
authors: Kreppel
authors: Department of Oral and Cranio-Maxillo and Facial Plastic Surgery, University of Cologne, Germany.
authors: Joachim E
authors: JE
authors: Zöller
authors: Department of Pathology, Tel Aviv Medical Center, Tel Aviv, Israel.
authors: Leonor
authors: L
authors: Leider-Trejo
authors: Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Israel.
authors: Gideon
authors: G
authors: Bachar
authors: Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Israel.
authors: Thomas
authors: T
authors: Shpitzer
authors: Department of Otorhinolaryngology, University of Brescia, Brescia, Italy.
authors: Andrea Villaret
authors: AV
authors: Bolzoni
authors: University of Auckland, Auckland, New Zeeland.
authors: Raj P
authors: RP
authors: Patel
authors: Southern Illinois University School of Medicine, Springfield.
authors: Sashikanth
authors: S
authors: Jonnalagadda
authors: Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, New York.
authors: Thomas Kevin
authors: TK
authors: Robbins
authors: Southern Illinois University School of Medicine, Springfield.
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: Laboratory for Applied Cancer Research, Clinical Research Institute at Rambam, Haifa, Israel2Department of Otolaryngology-Head and Neck Surgery, Rambam Medical Center, Rappaport School of Medicine, the Technion, Israel Institute of Technology, Haifa, Isra.
authors: Ziv
authors: Z
authors: Gil
mesh_terms: D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000401:mortality* / Q000556:secondary* / Q000628:therapy; D005188:False Negative Reactions; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000628:therapy; D037981:Neck Dissection; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis / Q000453:epidemiology*; D009367:Neoplasm Staging; D012189:Retrospective Studies; D016019:Survival Analysis; D015996:Survival Rate; D017211:Treatment Failure