Moran Amit1, Tzu Chen Yen2, Chun Ta Liao2, Pankaj Chaturvedi3, Jai Prakash Agarwal3, Luiz Paulo Kowalski4, Hugo F Kohler4, Ardalan Ebrahimi5, Jonathan R Clark6, Claudio Roberto Cernea7, Jose S Brandao7, Matthias Kreppel8, Joachim E Zöller8, Leonor Leider-Trejo9, Gideon Bachar10, Thomas Shpitzer10, Andrea Villaret Bolzoni11, Raj P Patel12, Sashikanth Jonnalagadda13, Thomas Kevin Robbins14, Jatin P Shah13, Snehal G Patel14, Ziv Gil1. 1. 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. 2. Chang Gung Memorial Hospital, Taoyuan, Taiwan. 3. Tata Memorial Hospital, Mumbai, India. 4. A.C. Camargo Cancer Center, São Paulo, Brazil. 5. Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia7Australian School of Advanced Medicine, Macquarie University, Sydney, Australia. 6. Sydney Head and Neck Cancer Institute, Royal Prince Alfred Hospital, Sydney, Australia. 7. Department of Head and Neck Surgery, University of São Paulo Medical School, São Paulo, Brazil. 8. Department of Oral and Cranio-Maxillo and Facial Plastic Surgery, University of Cologne, Germany. 9. Department of Pathology, Tel Aviv Medical Center, Tel Aviv, Israel. 10. Department of Otolaryngology-Head and Neck Surgery, Rabin Medical Center, Petach Tikva, Israel. 11. Department of Otorhinolaryngology, University of Brescia, Brescia, Italy. 12. University of Auckland, Auckland, New Zeeland. 13. Southern Illinois University School of Medicine, Springfield. 14. Head and Neck Surgery Service, Memorial Sloan Kettering Cancer Center, New York, New York.
Abstract
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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.
IMPORTANCE: 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. DESIGN, SETTING, AND PARTICIPANTS: 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. MAIN OUTCOMES AND MEASURES: 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 AND RELEVANCE: 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: Eran Fridman; Shorook Na'ara; Jaiprakash Agarwal; Moran Amit; Gideon Bachar; Andrea Bolzoni Villaret; Jose Brandao; Claudio R Cernea; Pankaj Chaturvedi; Jonathan Clark; Ardalan Ebrahimi; Dan M Fliss; Sashikanth Jonnalagadda; Hugo F Kohler; Luiz P Kowalski; Matthias Kreppel; Chun-Ta Liao; Snehal G Patel; Rajan S Patel; K Thomas Robbins; Jatin P Shah; Thomas Shpitzer; Tzu-Chen Yen; Joachim E Zöller; Ziv Gil Journal: Cancer Date: 2018-05-14 Impact factor: 6.860