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Importance: Clear surgical margins reduce the risk of local recurrence, improve survival, and determine decision-making with regard to adjuvant treatment of squamous cell carcinoma of the head and neck (SCCHN). However, the definitions of clear, close, or positive surgical margins vary in both the literature and in practice., Objective: To examine whether the association between surgical margin distance and survival varies by primary tumor site., Design, Setting, and Participants: This was a secondary analysis of a multi-institutional, multinational randomized clinical trial. The trial enrolled patients from January 22, 2007, to March 29, 2013, with stage II to IVA resected SCCHN with extranodal extension (ENE) or positive margins (<5 mm from invasive tumor to the resected margin). The current analysis included those patients with known ENE and margin status and was conducted from April 29, 2022, to December 19, 2022., Interventions: Patients received adjuvant chemoradiotherapy plus either placebo or lapatinib., Main Outcomes and Measures: Overall survival (OS) was calculated to examine association with surgical margin distance, primary site, and survival, with stratification by ENE status., Results: Among 688 patients enrolled in the trial, 630 patients with known ENE and margin status were included. Exact patient ages were not made available; 523 (83%) patients were male, and 415 (66%) patients were White. Patients with 1 high-risk feature (positive margins or ENE) had significantly better OS vs 2 high-risk features (hazard ratio [HR], 0.65; 95% CI, 0.49-0.87), although most other results were not statistically significant. For example, in the cohort with ENE-negative disease, multivariable adjusted analysis showed nonsignificant improvements with shorter surgical margin distance (1- to 5-mm margins), and no association with OS was found in the cohort with ENE-positive status (either >5 mm margins or 1-5 mm margins). The association between survival and margin distance varied based on primary site, human papillomavirus (HPV) status, and ENE status. For example, HPV-positive status was associated with a significant and clinically meaningful increase in survival (adjusted HR, 0.33; 95% CI, 0.11-0.97). The improvement was greatest, although not significantly so, in patients with ENE- and HPV-negative oropharynx (OP), hypopharynx (HP), and larynx cancer (HR, 0.57; 95% CI, 0.30-1.10). No survival benefit was seen in ENE-negative oral cavity cancer (HR, 0.89; 95% CI, 0.45-1.77), nor was an association observed between margins and OS in HPV-positive OP cancer., Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, the presence of high-risk features (extranodal extension, positive margins, or both) was associated with worse survival; longer survival was observed with greater surgical margin distance among patients with oral cavity tumors and human papillomavirus-negative tumors of the OP, larynx, or HP. No other significant differences were found. These findings support variable interpretation of surgical margin distance based on the primary site and HPV status., Trial Registration: ClinicalTrials.gov Identifier: NCT00424255.

Objectives: To evaluate the impact of oral cancer screening if applied to the United States (US) population or various high-risk populations in the US., Methods: We modeled the effects of applying an oral cancer screening program to the US population assuming a similar mortality reduction as seen in the randomized Kerala trial. We combined data on the incidence of oral cancer in the Surveillance, End Results, and Epidemiology database, data on the relative risk in various high-risk groups from the Prostate, Lung, Cervical, and Ovarian screening trial, and the National Lung Screening Trial and data on the prevalence of cigarette use from the National Health Interview Survey., Results: When extrapolating to the US population we predict the number needed to screen to prevent one oral cancer death (NNS) = 9,845 in all individuals aged 35 + . Screening efficiency would increase if applied to higher-risk populations. If oral cancer screening were applied to male ≥ 60 pack-year current smokers or former smokers who have quit within 15 years aged 50-79 we predict a 4.6% reduction in oral cancer mortality with an NNS = 1,485., Conclusions: Targeted screening of individuals at high risk for oral cancer has the potential to maximize the efficiency of screening and meaningfully impact oral cancer mortality. We suggest a future screening trial in high-risk individuals be considered to clarify the role of oral cancer screening in the US., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: American Society of Clinical Oncology guidelines recommend that the decision to give postoperative radiotherapy (PORT) for pN1 oral cavity squamous cell carcinoma (OCSCC) without other adverse features be based on the adequacy of the neck dissection (<18 or ≥18 nodes)., Methods: We conducted a cohort study of the National Cancer Database examining how PORT affects survival. We stratified analyses by the adequacy of the neck dissection and lymph node (LN) size., Results: Our cohort comprised 1909 patients (898 received PORT). PORT conferred a survival benefit in the overall cohort (adjusted hazard ratio 0.82, 95% CI 0.72-0.94). There was similar benefit in patients receiving inadequate and adequate neck dissections. Patients with >10 mm LN metastasis derived greater benefit compared with patients with smaller metastases., Conclusions: In pN1 OCSCC without other adverse features, the size of the LN metastases may predict benefit from PORT, whereas the adequacy of the neck dissection may not., (© 2019 Wiley Periodicals, Inc.)

Background: This article is about the eighth edition staging guidelines for upstaged patients with oral cavity squamous cell carcinoma (OCSCC) with >10 mm depth to pT3. This upstages some patients from stage I-II to stage III, a point at which patients are traditionally considered for postoperative radiation therapy (PORT). The role of PORT in patients upstaged for >10 mm depth is unknown., Methods: We identified patients with surgically resected stage I-II OCSCC with >10 mm depth who were upstaged to stage III. We used Cox proportional hazard modeling to compare patients who received PORT to those who did not (median follow-up 38.6 months)., Results: We observed that 3.6% of patients with OCSCC were upstaged to stage III for depth >10 mm including 823 eligible patients. On adjusted analyses, PORT was associated with improved overall survival in patients upstaged to stage III (adjusted hazard ratio [aHR] 0.47, 95% confidence interval [CI] 0.30-0.73)., Conclusion: PORT is associated with improved survival for patients with OCSCC upstaged to stage III for >10 mm depth., (© 2019 Wiley Periodicals, Inc.)

Objectives: Sentinel lymph node biopsy (SLNB) has been shown to be an accurate technique for staging the neck in early-stage oral cavity squamous cell carcinoma (OCSCC) and has been incorporated in treatment guidelines as an option instead of elective neck dissection (END). However, utilization of SLNB in the United States remains unclear, and existing prospective studies did not directly compare survival between SLNB and END., Methods: We conducted a retrospective cohort study of patients with stage I to II OCSCC (cT1-2cN0cM0) who underwent staging of the neck in the National Cancer Data Base from 2012 to 2015. We compared the practice patterns and outcomes of patients who underwent SLNB versus END., Results: We identified 8,328 eligible patients with a median follow-up of 35.4 months. SLNB was used for 240 patients, or 2.9% of stage I to II OCSCC. Completion neck dissection was avoided in 63.8% of patients undergoing SLNB. SLNB was associated with reduced perioperative morbidity, with median length of hospital stay of 1.0 days versus 3.0 days after END (P < 0.001). Perioperative 30-day mortality was 0% after SLNB versus 0.7% after END (P = 0.42). Overall 3-year survival was 82.0% after SLNB and 77.5% after END (P = 0.40). After adjustment, overall survival was equivalent between patients who underwent SLNB versus END (adjusted hazard ratio 1.03, confidence interval 0.67-1.59)., Conclusions: SLNB for stage I to II OCSCC is associated with reduced length of hospital stay and equivalent overall survival compared with END. Despite these attributes, SLNB remains rarely used in the United States., Level of Evidence: NA Laryngoscope, 129:162-169, 2019., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)

Objective: For the first time in 30 years, the eighth edition of the American Joint Committee on Cancer (AJCC) Staging Manual offers major changes in the staging of oral cavity cancer. We evaluated the predictive ability of the new staging system for oral cavity cancer to validate these changes and hypothesized that the new system would improve prognostic accuracy., Methods: We conducted a retrospective cohort study of patients with oral cavity squamous cell carcinoma in the National Cancer Data Base from 2009 to 2013 and applied the seventh and eighth edition staging AJCC staging systems to all patients. Stage-specific overall survival was calculated using the Kaplan-Meier method and concordance indices to measure the system's prognostic accuracy., Results: We identified 39,361 patients with a median follow-up of 27.1 months (range 0.1-80.4 months). In the seventh edition, there were 43.0%, 15.0%, 10.6%, and 25.7% of patients with pathologic stage I, II, III, and IV disease, respectively. After restaging based on eighth edition pathological guidelines, 10.0% of patients were upstaged (38.1%, 18.1%, 14.2%, and 25.2%, respectively, with stage I, II, III, and IV disease, respectively). The survival concordance index improved from the seventh to eighth edition for pathological staging (concordance index 0.699 and 0.704, respectively) and for clinical staging (concordance index 0.714 and 0.715, respectively)., Conclusion: We provide validation of the new AJCC staging system for oral cavity cancer. Eighth edition AJCC staging guidelines upstage a substantial number of patients with greater depth of invasion or extranodal extension. This resulted in slightly improved prognostication., Level of Evidence: 2c. Laryngoscope, 128:2351-2360, 2018., (© 2018 The American Laryngological, Rhinological and Otological Society, Inc.)