Impact of Nodal Metastases in HPV-Negative Oropharyngeal Cancer.

BACKGROUND: The updated American Joint Committee on Cancer (AJCC) 8th Edition staging manual restructured nodal classification and staging by placing less prognostic emphasis on nodal metastases for human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC). However, there was no change for HPV-negative OPSCC. The purpose of our study is to examine the impact of nodal metastases on survival in HPV-negative OPSCC. METHODS: HPV-negative OPSCC was queried from the National Cancer Database (NCDB) and Surveillance, Epidemiology and End Results program (SEER) databases. Univariable and multivariable models were utilized to determine the impact of nodal status on overall survival. These patients were reclassified according to AJCC 8 HPV-positive criteria (TNM8+) and risk stratification was quantified with C-statistic. RESULTS: There were 11,147 cases of HPV-negative OPSCC in the NCDB and 3,613 cases in SEER that were included in the nodal classification analysis. Unlike nonoropharyngeal malignancies, increased nodal stage is not clearly associated with survival for patients with OPSCC independent of HPV status. When the TNM8+ was applied to HPV-negative patients, there was improved concordance in the NCDB cohort, 0.561 (plus minus) 0.004 to 0.624 (plus minus) 0.004 (difference +0.063) and the SEER cohort, 0.561 (plus minus) 0.008 to 0.625 (plus minus) 0.008 (difference +0.065). CONCLUSIONS: We demonstrated a reduced impact of nodal metastasis on OPSCC survival, independent of HPV status and specific to OPSCC. IMPACT: We demonstrate, for the first time that when nodal staging is deemphasized as a part of overall staging, we see improved concordance and risk stratification for HPV-negative OPSCC. The exact mechanism of this differential impact remains unknown but offers a novel area of study.

A Consideration for Surgical Management in Select T4b Oral Cavity Squamous Cell Carcinoma.

OBJECTIVES: The role of surgery for conventionally "unresectable" (cT4b) oral cavity squamous cell carcinoma is unclear. We analyzed factors associated with overall survival in cT4b relative to cT4a oral cavity squamous cell carcinoma. METHODS: We identified 6830 cT4a and 522 cT4b oral cavity squamous cell carcinoma chemoradiation or surgery + adjuvant therapy patients in the National Cancer Data Base from 2004 to 2016. The main outcome was overall survival. Statistical analysis was performed using chi-squared tests, univariable and multivariable regression analysis. RESULTS: The cT4b group had a higher rate of positive margins (30.4% vs 21.3%, P = .009) and downstaging (41.2% vs 13.1%; P < .001) compared to cT4a, while only 1.7% were upstaged. cT4b surgery + chemoradiation patients had similar survival to cT4a surgery + radiation (HR 0.93; 95% CI, 0.70-1.25) and cT4a surgery + chemoradiation patients (HR, 0.92; 95% CI, 0.69-1.23), while cT4b surgery + radiation patients had worse OS (HR, 1.55; 95% CI, 1.05-1.47). CONCLUSIONS: Clinical T4b staging is a poor predictor of pathologic staging given a high rate of downstaging on final pathology. Surgical resection with adjuvant chemoradiation is an option in select cT4b oral cavity squamous cell carcinoma patients.

Lymph node metastases in pediatric medullary thyroid carcinoma.

BACKGROUND: Unlike medullary thyroid carcinoma in adults, the vast majority of pediatric medullary thyroid carcinoma is hereditary. Pediatric medullary thyroid carcinoma is known to have different genetic alterations driving tumorigenesis, but it is not known if pediatric medullary thyroid carcinoma has different clinicopathologic features. This study aims to identify which pediatric medullary thyroid carcinoma patients might warrant elective neck dissection. METHODS: We selected all patients ages 0 to 19 diagnosed with clinically evident medullary thyroid carcinoma in the National Cancer Database between 2004 to 2016. Clinicopathologic factors, treatments, and outcomes were analyzed and compared between this cohort and adults (ages ≥20) with medullary thyroid carcinoma. RESULTS: One hundred twenty-five pediatric medullary thyroid carcinoma (median age: 13) and 5,086 adult medullary thyroid carcinoma (median age: 57) patients were identified. Pediatric patients had smaller tumors (median diameter: 1.2 cm vs 2.0 cm; P < .001), lower rates of nodal metastases (n = 31, 36.9% vs 1,689, 50.4%; P = .02) but double the incidence of multifocal tumors (n = 70, 59.3%, vs 1,412, 29.9%; P < .001) compared with adults. Multifocal tumors conferred a significantly increased risk of nodal metastases in adult medullary thyroid carcinoma (64.4% vs 43.2%; P < .001) but not pediatric medullary thyroid carcinoma (37.7% vs 35.7%; P = .85). Nodal metastases were more frequent among older children (0-5 years: 0.0%, 6-12: 40.7%, 13-19: 41.7%; P = .04). However, rates of occult nodal metastases were similar between older children (6-19 years: n = 12, 21.4%) and adults (557, 25.8% P = .56). CONCLUSION: Pediatric medullary thyroid carcinoma has lower rates of lymph node metastases compared with adults. The risk of nodal disease was low among the youngest children, but older children ages 6 to 19 were at considerable risk for occult metastases. These findings could guide clinicians in selecting pediatric patients considered for elective lymph node dissection.

Survival of oral tongue squamous cell carcinoma in young adults.

BACKGROUND: Small cohort studies have suggested oral tongue squamous cell carcinoma (OTSCC) could be associated with worse prognosis in individuals younger than 40. METHODS: We compared the survival of all OTSCC cases in the National Cancer Database under 40 years old with those older than 40, excluding patients over 70. Cox regression and propensity score matched (PSM) survival analyses were performed. RESULTS: A total of 22 930 OTSCC patients were identified. The under 40 group consisted of 2566 (9.9%) cases; 20664 were 40 to 70 (90.1%). Most were male (13 713, 59.8%), stage I-II (12 754, 72.4%), and treated by surgery alone (13 973, 63.2%). Survival in patients under 40 was higher (79.6% vs 69.5%, P < .001). In PSM analysis (n = 2928) controlling for all 10 significant factors in multivariate regression, patients under 40 had a 9% higher 5-year survival (77.1% vs 68.2%, P < .001). CONCLUSION: Contrary to the prior reports, younger patients with OTSCC did not have worse survival in the National Cancer Database.