Development and validation of a novel TNM staging N-classification of oral cavity squamous cell carcinoma.

BACKGROUND: For oral cavity squamous cell carcinoma (OSCC), extent of extranodal extension (ENE) (minor, ≤2 mm; major, >2 mm) is differentially prognostic, whereas limitations exist with the 8th edition of American Joint Committee on Cancer/International Union Against Cancer TNM N-classification (TNM-8-N). METHODS: Resected OSCC patients at four centers were included and extent of ENE was recorded. Thresholds for optimal overall survival (OS) discrimination of lymph node (LN) features were established. After dividing into training and validation sets, two new N-classifications were created using 1) recursive partitioning analysis (RPA), and 2) adjusted hazard ratios (aHRs) and were ranked against TNM-8-N and two published proposals. RESULTS: A total of 1460 patients were included (pN0: 696; pN+: 764). Of the pN+ cases, 135 (18%) had bilateral/contralateral LNs; 126 (17%) and 244 (32%) had minor and major ENE, and two (0.3%) had LN(s) >6 cm without ENE (N3a). LN number (1 and >1 vs. 0: aHRs, 1.92 [95% confidence interval (CI), 1.44-2.55] and 3.21 [95% CI, 2.44-4.22]), size (>3 vs. ≤3 cm: aHR, 1.88 [95% CI, 1.44-2.45]), and ENE extent (major vs. minor: aHR, 1.40 [95% CI, 1.05-1.87]) were associated with OS, whereas presence of contralateral LNs was not (aHR, 1.05 [95% CI, 0.81-1.36]). The aHR proposal provided optimal performance with these changes to TNM-8-N: 1) stratification of ENE extent, 2) elimination of N2c and 6-cm threshold, and 3) stratification of N2b by 3 cm threshold. CONCLUSION: A new N-classification improved staging performance compared to TNM-8-N, by stratifying by ENE extent, eliminating the old N2c category and the 6 cm threshold, and by stratifying multiple nodes by size.

Treatment implications of postoperative chemoradiotherapy for squamous cell carcinoma of the oral cavity with minor and major extranodal extension.

OBJECTIVES: To evaluate adjuvant chemoradiotherapy (CRT) for patients with oral cavity squamous cell carcinoma (OSCC) with minor or major extranodal extension (ENE). MATERIALS AND METHODS: Surgically resected OSCC with pathologically involved lymph node(s) (pN+) between 2006 and 2017. Sections of pN+ were re-reviewed and classified as no, minor (≤2 mm), or major (>2 mm) ENE. Patterns of failure and survival were compared between the groups and stratified by adjuvant treatment. Multivariable (MVA) analysis assessed the value of adjuvant treatment for minor and major ENE. RESULTS: Total of 384 patients, 62 had minor and 114 had major ENE. Adjuvant CRT was delivered in 32(15%), 21(34%), and 45(39%) of patients with no, minor and major ENE, respectively. Patients with minor ENE had similar 5-year loco-regional control (LRC) and distant control (DC) but lower disease-free survival (DFS) (38% vs. 51%, p = 0·02) compared to patients with no ENE, while patients with major ENE had marginally lower LRC (59% vs 74%, p = 0·07), lower DC (58% vs 82%,p = 0·005) and DFS (13% vs. 38%, p=·001) compared to those with minor. On MVA, adjuvant chemotherapy was associated with improved DFS for major ENE (adjusted HR = 0·49; 95% CI 0·29-0·85, p = 0·01) but not for minor ENE after adjusting for age, ECOG status, T-, N-category, margin status, and radiotherapy. CONCLUSIONS: Adjuvant chemoradiotherapy improves outcomes in patients with major ENE, but the benefit is unclear in patients with minor ENE. Future trials should focus on intensification of treatment for patients with major ENE and alternative adjuvant strategies for patients with minor ENE.

Mapping the EORTC QLQ-C30 and QLQ-H&N35, onto EQ-5D-5L and HUI-3 indices in patients with head and neck cancer.

BACKGROUND: We sought to develop mapping functions that use EORTC responses to approximate health utility (HU) scores for patients with head and neck cancer (HNC). METHODS: In total, 209 outpatients with HNC completed the EORTC QLQ-C30 & QLQ-H&N35 (EORTC), EQ-5D-5L and the HUI-3. Results of the EORTC were mapped onto both EQ-5D-5L and HUI-3 scores using ordinary least squares regression and two-part models. RESULTS: The OLS model mapping EORTC onto the EQ-5D-5L performed best (adjusted R2 = .75, 10-fold cross-validation RMSE = 0.064, MAE 0.050). The HUI-3 model mapping onto EORTC through OLS was more limited (adjusted R2 = .5746, 10-fold cross cross-validation RMSE = 0.168, MAE 0.080). The EQ-5D-5L model was able to discriminate between certain clinical indices of disease severity on subgroup analysis. CONCLUSION: The EORTC to EQ-5D-5L mapping algorithm has good predictive validity and may enable researchers to translate EORTC scores into HU scores for head and neck patients with cancer.

Mapping the University of Washington Quality of life questionnaire onto EQ-5D and HUI-3 indices in patients with head and neck cancer.

BACKGROUND: There is no mechanism to predict health utility (HU) values from the University of Washington Quality of Life Questionnaire (UWQoL) scores. We sought to develop a mapping algorithm capable of using UWQoL data to approximate HU scores. METHODS: Outpatients with head and neck cancer completed the UWQoL, EQ-5D, and the Health Utilities Index-Mark 3 (HUI-3). Results of the UWQoL were mapped onto both EQ-5D and HUI-3 scores using ordinary least-squares regression models. Two-part models were explored. The predictive power of the model was assessed using 10-fold cross-validation. RESULTS: A total of 209 patients were recruited. The reduced model converting UWQoL data into EQ-5D scores performed best (adjusted R2 = 0.628, root mean square error = 0.076). Both models demonstrated construct validity by discriminating between clinical indices of disease severity. CONCLUSIONS: The abovementioned algorithms enable researchers to perform health economic evaluations with existing UWQoL data in cases where prospectively collected HU values are not available.