Jatin P. Shah

Primary Tumor Staging for Oral Cancer and a Proposed Modification Incorporating Depth of Invasion: An International Multicenter Retrospective Study

IMPORTANCE 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. DESIGN, SETTING, AND PARTICIPANTS 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. MAIN OUTCOMES AND MEASURES 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 AND RELEVANCE 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.

The origin of regional failure in oral cavity squamous cell carcinoma with pathologically negative neck metastases.

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.

Cervical Lymph Nodes and Unknown Primary Tumors of the Head and Neck

Risk Assessment Models The AJCC recently established guidelines that will be used to evaluate published statistical prediction models for the purpose of granting endorsement for clinical use. Although this is a monumental step toward the goal of precision medicine, this work was published only very recently. Therefore, the existing models that have been published or may be in clinical use have not yet been evaluated for this cancer site by the Precision Medicine Core of the AJCC. In the future, the statistical prediction models for this cancer site will be evaluated, and those that meet all AJCC criteria will be endorsed.