The prognostic value of extranodal extension in human papillomavirus-associated oropharyngeal squamous cell carcinoma.

Extranodal (or extracapsular) extension (ENE) is an adverse prognostic factor in patients with head and neck cancers who undergo primary surgery. However, the significance of ENE in human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) is not well established, and single-institution studies have not established that ENE predicts inferior outcome. The authors investigated the prognostic value of ENE in HPV-positive patients who underwent primary surgery and whether adjuvant chemoradiation improved overall survival (OS) compared with radiation alone in ENE-positive patients. Patients who underwent primary surgery for pathologic T1 (pT1) through pT4 tumors, pathologic N1 (pN1) through pN3 lymph node status, HPV-positive OPSCC were identified in the National Cancer Data Base from 2010 through 2012. Features associated with ENE were analyzed. Univariable and multivariable Cox regression analyses identified predictors of OS. The effect of adjuvant treatment on OS in ENE-positive cohort was also evaluated. In total, 1043 patients met inclusion criteria, among whom 43.5% were ENE-positive. Of the ENE-positive patients who had treatment details available, 72% received concurrent chemoradiotherapy, 16% received radiotherapy, and 12% received no adjuvant treatment. After a median follow-up of 28.4 months, ENE was associated with worse 3-year OS (89.3% vs 93.6%; P = .01). On multivariable analysis that included involved lymph nodes, only ENE, lymphovascular invasion, pT3/pT4 tumors, and Charlson-Deyo score were associated with worse OS. Among ENE-positive patients, there was no difference in 3-year OS between those who received adjuvant concurrent chemoradiotherapy versus radiotherapy alone (89.6% vs 89.3%, respectively; P = .55). Propensity score-matched comparison revealed similar results. ENE is associated with inferior OS in patients with HPV-positive OPSCC. However, OS was not better with adjuvant chemoradiotherapy compared with radiotherapy alone in ENE-positive patients. The current findings support the need for prospective studies of adjuvant chemoradiation in HPV-positive patients with ENE. Cancer 2017;123:2762-72. © 2017 American Cancer Society.

An Y ，Park HS ，Kelly JR ，Stahl JM ，Yarbrough WG ，Burtness BA ，Contessa JN ，Decker RH ，Koshy M ，Husain ZA ... -  《-》

Extranodal extension is a strong prognosticator in HPV-positive oropharyngeal squamous cell carcinoma.

To comprehensively examine the prognostic significance of extranodal extension (ENE) in human papillomavirus-positive oropharyngeal squamous cell carcinoma (HPV-positive OPSCC). Retrospective cohort of cases diagnosed with HPV-positive OPSCC from 2010 to 2015 in the National Cancer Database. Inclusion of all OPSCC HPV-positive cases with appropriate International Classification of Diseases-0-3 codes that received surgery with a neck dissection. Univariate and multivariable analyses were conducted. Hazard ratios (HR) for the independent effects of ENE and N stage on overall survival were estimated by Cox proportional hazards regression. Cases that were ENE-negative had the highest 5-year survival (92.6%; 95% confidence interval [CI]: 90.5%-94.7%). ENE-positive cases had the lowest 5-year survival (84.0%; 95% CI: 80.7%-87.4%). After adjusting for confounding variables, ENE-positivity was associated with almost twice the hazard of death (HR = 1.90; 95% CI: 1.35-2.67) compared to ENE-negative cases. Nodal (N) category 1, ENE-positive status was associated with an increased risk of death (HR = 1.88; 95% CI: 1.26-2.80) compared with N1, ENE-negative status. Compared to N1/ENE-negative cases, N2/ENE-positive cases had the poorest survival (HR: 2.93; 95% CI: 1.94-4.43). Both microscopic and macroscopic ENE were associated with worse outcomes compared to node-positive/ENE-negative status. The implementation of the American Joint Committee on Cancer 8th edition staging system provides a much-improved framework to develop and discuss treatment plans for HPV-positive OPSCC. We feel that careful consideration should be given to the importance of ENE in patients with HPV-positive OPSCC. 4 Laryngoscope, 130:939-945, 2020.

Bauer E ，Mazul A ，Chernock R ，Rich J ，Jackson RS ，Paniello R ，Pipkorn P ，Oppelt P ，Gay H ，Daly M ，El-Mofty S ，Thorstad W ，Adkins D ，Zevallos J ... -  《-》

Prognostic Value of Radiologic Extranodal Extension in Human Papillomavirus-Related Oropharyngeal Squamous Cell Carcinoma.

To determine whether radiologic extranodal extension (ENE) appearing on pretreatment CT and MRI could predict the prognosis in patients with human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC). The study population was obtained from a historical cohort diagnosed with HPV-related OPSCC. A total of 134 OPSCC patients who had a metastatic lymph node on pretreatment CT or MRI were included, and radiologic ENE was evaluated by two experienced head and neck radiologists. Kaplan-Meier and multivariate Cox regression analyses were performed to evaluate the impact of radiologic ENE on progression-free survival (PFS). The diagnostic performance of CT and MRI for the diagnosis of ENE was also evaluated in patients who underwent neck dissection. Seventy patients (52.2%) showed radiologic ENE-positive findings. Although patients showing radiologic ENE had a worse 3-year PFS (83.7% vs. 95.3%, p = 0.023), the association between radiologic ENE and PFS was not statistically significant on multivariate analysis (p = 0.141; hazard ratio, 2.68; 95% confidence interval, 0.72-9.97). CT or MRI had a sensitivity of 62%, specificity of 77.8%, and accuracy of 71.9% for predicting pathologic ENE. Radiologic ENE on CT or MRI did not predict poor PFS in patients with HPV-related OPSCC, although there was a trend towards worse PFS. Further studies are warranted to determine whether radiologic ENE is a useful imaging biomarker to risk-stratify patients with HPV-related OPSCC.

Lee B ，Choi YJ ，Kim SO ，Lee YS ，Hong JY ，Baek JH ，Lee JH ... -  《-》

Risk of Pathologic Extranodal Extension and Other Adverse Features After Transoral Robotic Surgery in Patients With HPV-Positive Oropharynx Cancer.

Zebolsky AL ，George E ，Gulati A ，Wai KC ，Carpenter P ，Van Zante A ，Ha PK ，Heaton CM ，Ryan WR ... -  《-》

Predictors of Mortality in HPV-Associated Oropharynx Carcinoma Treated With Surgery Alone.

Survival outcomes for human papillomavirus-associated oropharynx squamous cell carcinoma (HPV + OPSCC) treated with surgery alone are unclear. To increase understanding, we assessed overall survival (OS) outcomes using the national cancer database (NCDB). We conducted a retrospective analysis of OS of 736 NCDB HPV + OPSCC patients who underwent surgery alone from 2010 to 2014 using univariate and multivariate analyses and the Kaplan-Meir method. Multivariable analysis found the following independent risk factors for death: American Joint Commission on Cancer (AJCC) 8th edition pathologic stage(p)N2 versus pN0 disease (hazard ratio [HR], 5.5; P = 0.000006), macroscopic extranodal extension (ENE) versus non-ENE (HR, 4.9; P < 0.02), a positive lymph nodes (LN) percentage of ≥10% (HR, 4.2; P = 0.0002), and five or more positive LNs (HR, 4.9; P = 0.00004). Three-year OS was significantly worse for AJCC 8th edition pN2 versus pN0 but not for 7th edition pN2 versus pN0 disease. Five-year OS was significantly worse for positive versus negative surgical margins, AJCC 8th edition stage II versus I, and either microscopic or macroscopic ENE versus non-ENE positive LNs. For 523 (71%) AJCC 8th edition stage I patients and for 283 (38%) patients who were pT1-T2, with negative margins, pN0-N1, with ≤4 pathologic LNs, without ENE, and with >20 LNs removed during neck dissection, the 3-year OS rates were 93% and 95%, respectively, and the 5-year OS rates were 91% and 95%, respectively. In the context of the lack of detail and possible inaccuracies found in the NCDB, surgery alone for AJCC 8th edition stage I HPV + OPSCC, particularly pT1-T2, pN0-N1 with ≤4 pathologic LNs, without ENE, and with negative surgical margins has a high OS. 4 Laryngoscope, 130:E423-E435, 2020.

Han M ，Stanford-Moore GB ，Larson AR ，Schoppy DW ，Cognetti DM ，Joshi AS ，Houlton JJ ，Ryan WR ... -  《-》