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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.

Background: Survival outcomes are generally better for human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) than other forms of head and neck cancer. However, less is known about oncologic outcomes, late adverse events, and gastrostomy tube dependence associated with salvage surgery after the failure of definitive chemoradiation in patients with HPV+ OPSCC., Methods: A secondary analysis of the Radiation Therapy Oncology Group 1016 randomized trial, which compared radiotherapy plus cetuximab to radiotherapy plus cisplatin in patients with HPV+ OPSCC, was performed. The oncologic and adverse event outcomes for patients who underwent salvage surgery were examined., Results: Among the 805 patients who were assigned to treatment and were eligible for analysis, 198 developed treatment failure. Salvage surgery was required for 61 patients (7.6%), with 33 patients undergoing salvage surgery after locoregional failure (LRF) and 28 patients undergoing salvage neck dissection within the 20 weeks after treatment. Patients with LRF who underwent salvage surgery experienced improved overall survival in comparison with patients with LRF who did not undergo surgery (45% vs. 17% at 5 years after treatment; hazard ratio, 0.41; 95% confidence interval [CI], 0.23-0.74). Surgical salvage after LRF was associated with similar frequencies of late grade 3/4 dysphagia in comparison with LRF without surgery (24% [95% CI, 13%-41%] vs. 20% [95% CI, 12%-32%]; p = .64) and with similar gastrostomy tube dependence at 2 years (29% [95% CI, 15%-49%] vs. 13% [95% CI, 5%-28%]; p = .12)., Conclusions: Salvage surgery in patients with HPV+ OPSCC is associated with favorable survival and adverse event outcomes., (© 2022 American Cancer Society.)

Background: Initial primary head and neck cancer (IPHNC) is associated with second primary lung cancer (SPLC). We studied this association in a population with a high proportion of African American (AA) patients., Methods: Patients with IPHNC and SPLC treated between 2000 and 2017 were reviewed for demographic, disease, and treatment-related characteristics and compared to age-and-stage-matched controls without SPLC. Logistic and Cox regression models were used to analyze the relationship of these characteristics with the development of SPLC and overall survival (OS)., Results: Eighty-seven patients and controls were compared respectively. AA race was associated with a significantly higher risk of developing SPLC (OR 2.92, 95% CI 1.35-6.66). After correcting for immortal time bias, patients with SPLC had a significantly lower OS when compared with controls (HR 0.248, 95% CI 0.170-0.362)., Conclusions: We show that AA race is associated with an increased risk of SPLC after IPHNC; reasons of this increased risk warrant further investigation., (© 2022 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objectives/hypothesis: To evaluate the incidence of head and neck cancers (HNC) in high-risk current and/or former smokers with screening low-dose computed tomography (LDCT) chest versus chest x-ray (CXR)., Study Design: Second analysis of randomized clinical trial., Methods: We performed a secondary analysis examining the incidence of HNC in the National Lung Screening Trial. This was a randomized trial comparing LDCT versus CXR screening for lung cancer detection in high-risk individuals (30 pack-year smokers who currently smoke or quit within the last 15 years, aged 55-74). We compared the incidence of HNC in participants screened with LDCT versus CXR. We performed subgroup analyses in participants with mucosal HNC (oral cavity, oropharynx, larynx, hypopharynx, nasal/sinus cavity, or nasopharynx) or nonmucosal HNC (thyroid or salivary gland) and examined survival in the two screening arms., Results: This trial enrolled 53,452 participants with a median follow-up of 6.2 years after randomization. The incidence of HNC was 111.8 cases per 100,000 person-years in the LDCT group versus 87.1 cases per 100,000 person-years in the CXR group (rate ratio 1.30, 95% confidence interval [CI] 1.05-1.61). There were 11.7 deaths from HNC per 100,000 person-years in the LDCT group and 12.9 deaths per 100,000 person-years in the CXR group (hazard ratio 0.80, 95% CI 0.42-1.52)., Conclusions: Participants screened with LDCT had a modestly higher incidence of HNC. As uptake and adherence of lung cancer screening guidelines improve, clinicians should recognize that incidental findings from screening may lead to increased detection of HNC., Level of Evidence: 3 Laryngoscope, 132:1609-1614, 2022., (© 2022 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: In head and neck cancer survivors, lung cancer screening may aid in detecting a second primary lung cancer or metastatic head and neck cancer earlier in the course of disease, which may improve treatment outcomes. However, no randomized data exist to assess the value of lung cancer screening in this population., Objective: To evaluate the incidence of second primary lung cancer in survivors of head and neck cancer survivors with screening low-dose computed tomography (CT) vs chest radiography (CXR)., Design, Setting and Participants: For this ad hoc secondary analysis of a randomized clinical trial, head and neck cancer survivors were identified from the National Lung Screening Trial, which enrolled participants from August 2002 to April 2004. This randomized clinical trial compared screening using low-dose CT chest vs CXR in patients aged 55 to 74 years with at least a 30 pack-year history of cigarette smoking and who were current smokers or had quit within the past 15 years and who were at high risk for lung cancer. The incidences of second primary lung cancer and second primary head and neck cancer were compared with screening using low-dose CT vs CXR. Data were analyzed from December 1, 2020, to June 30, 2021., Interventions: Screening low-dose CT of the chest vs CXR., Main Outcomes and Measures: The primary outcome was the incidence of a second primary lung cancer., Results: Among 53 452 enrolled participants, we identified 171 survivors of head and neck cancer, of whom 82 were screened with low-dose CT of the chest and 89 with CXR. Participants' mean (SD) age was 61 (5) years, and 132 were men (77.2%). The incidence of lung cancer was higher among head and neck cancer survivors compared with participants without head and neck cancer (2080 per 100 000 person-years [2.1%] vs 609 per 100 000 person-years [0.6%]; adjusted rate ratio, 2.54; 95% CI, 1.63-3.95). In head and neck cancer survivors, the incidence of second primary lung cancer was 2610 cases per 100 000 person-years in the low-dose CT group vs 1594 cases per 100 000 person-years in the CXR group (rate ratio, 1.55; 95% CI, 0.59-3.63). In head and neck cancer survivors, overall survival was 7.07 years with low-dose CT vs 6.66 years with CXR (log-rank P = .48)., Conclusions and Relevance: The results of this ad hoc secondary analysis of a randomized clinical trial suggest that head and neck cancer survivors are at especially high risk for a second primary lung cancer. These findings underscore the importance of low-dose CT screening in head and neck cancer survivors with significant cigarette smoking history who are fit to undergo treatment with curative intent.

Background: The standardization of quality measures has been key in advancing the aims of the National Quality Forum established to improve health outcomes., Methods: The National Cancer Database was used to identify eligible patients. Two quality metrics were evaluated including time to treatment initiation (TTI) and chemotherapy in locoregionally head and neck squamous cell carcinoma (HNSCC)., Results: TTI was significantly associated with mortality reflected by a hazard ratio (HR) of 1.13 for 60-90 days of TTI (95% CI 1.08-1.17), 1.19 for >90 days of TTI (95% CI 1.13-1.26). Patients with locoregionally advanced HNSCC had an 87% adherence to chemotherapy, which correlated with reduced mortality (HR 0.57; 95% CI 0.55-0.59). Patients treated at high quality centers had a 9% increase in survival (HR 0.91; 95% CI 0.88-0.93)., Conclusion: We identified that both TTI and chemotherapy for locoregionally advanced HNSCC meet criteria for valid quality metrics potentially suitable for national adoption., (© 2021 Wiley Periodicals LLC.)

Objectives/hypothesis: To assess the causative factors that contribute to racial disparities in head and neck squamous cell carcinoma (HNSCC) and establish the role of hospital factors in racial disparities., Study Design: Retrospective database analysis., Methods: Patients with surgically treated HNSCC were identified using the National Cancer Database (2004-2014). Logistic and proportional-hazard regression models were used to characterize the factors that contribute to racial disparities. Differences in quality of care received were compared among black and white patients using previously validated metrics., Results: We identified 69,186 eligible patients. Black patients had a 48% higher mortality than white patients (HR 1.48; 95% confidence interval [CI], 1.41-1.54). Black patients had a lower mean quality score (67.6%; 95% CI, 66.8%-69.4%) compared with white patients (71.2%: 95% CI, 71.0%-71.4%) for five quality metrics. After adjusting for differences in patient, oncologic, and hospital factors we were able to explain 60% of the excess mortality for black patients. Oncologic factors at presentation accounted for 57.7% of observed mortality differences, whereas hospital characteristics and quality of care accounted for 11.5%. After adjusting for these factors, black patients still had a 19% higher mortality (HR 1.19; 95% CI, 1.14-1.24)., Conclusions: Oncologic factors at presentation are a major contributor to racial disparities in outcomes for HNSCC. Hospital factors, such as quality, volume, and safety-net status, constitute a minor factor in the mortality difference. Resolving existing disparities will require detecting head and neck cancer at an earlier stage and improving the quality of care for black patients., Level of Evidence: 3. Laryngoscope, 131:1053-1059, 2021., (© 2020 American Laryngological, Rhinological and Otological Society Inc, "The Triological Society" and American Laryngological Association (ALA).)

Three randomized phase III trials have now conclusively proven that exposure to a PD-1 inhibitor prolongs survival in recurrent/metastatic (R/M) HNSCC, and it is clear that such agents should be used in the management of all patients who do not have contraindications to their use. Two of these phase III randomized trials showed that the anti-PD1 antibodies nivolumab and pembrolizumab were superior to investigators' choice chemotherapy in second-line platinum-refractory R/M HNSCC. Recently, a third phase III randomized trial, KEYNOTE-048, showed that pembrolizumab with chemotherapy was superior to the EXTREME regimen (cis- or carboplatin, 5-fluorouracil (5-FU) and cetuximab) in all patients, and pembrolizumab monotherapy was superior in patients whose tumors express PD-L1 in first-line R/M HNSCC. Pembrolizumab is now approved as monotherapy in PD-L1 expressing disease (combined positive score ≥1) or in combination with chemotherapy for all patients with R/M HNSCC. Thus, PD-L1 biomarker testing will be routinely used in R/M HNSCC, and this employs a scoring system that incorporates immune cell staining, referred to as the combined positive score (CPS). Additionally, for the 85% of patients with PD-L1 CPS ≥1, clinical judgment will guide the choice of pembrolizumab monotherapy or pembrolizumab plus chemotherapy, until more detailed clinical data are forthcoming to better inform this decision. In this article we discuss the clinical trials leading to these therapeutic advances and we will review initial results from clinical trials in previously untreated, locally advanced disease, and those using novel combinations of checkpoint inhibitors, co-stimulatory agonists, and therapeutic vaccines., (Copyright © 2019. Published by Elsevier Ltd.)

Head and neck cancers are a heterogeneous collection of malignancies of the upper aerodigestive tract, salivary glands and thyroid. In this Review, we primarily focus on the changing therapeutic landscape of head and neck squamous cell carcinomas (HNSCCs) that can arise in the oral cavity, oropharynx, hypopharynx and larynx. We highlight developments in surgical and non-surgical therapies (mainly involving the combination of radiotherapy and chemotherapy), outlining how these treatments are being used in the current era of widespread testing for the presence of human papillomavirus infection in patients with HNSCC. Finally, we describe the clinical trials that led to the approval of the first immunotherapeutic agents for HNSCC, and discuss the development of strategies to decrease the toxicity of different treatment modalities.

Objectives: Pain is common among patients with cancer, stemming from both malignancy and side effects of treatment. The extent to which pain persists after treatment has received little attention. We examined the prevalence, predictors, and impact on quality of life (QOL) caused by pain among survivors of head and neck cancer., Study Design: Cohort study., Setting: Tertiary head and neck cancer survivorship clinic., Subjects and Methods: We identified survivors of head and neck cancer ≥1 year after diagnosis and examined the prevalence and risk factors for development of pain. Pain and QOL were assessed with multiple QOL instruments. Ordinal regression modeling examined predictors of pain in survivors., Results: We identified 175 patients at a median of 6.6 years after diagnosis. Among survivors, 45.1% reported pain, and 11.5% reported severe pain. Among patients with current pain, 46% reported low overall QOL versus only 12% of those without pain ( P < .001). On multivariable analysis after adjustment for age, sex, and stage of disease, pain was associated with trimodality treatment (odds ratio [OR], 3.55; 95% CI, 1.06-12.77). Multivariable analysis of QOL issues revealed that pain was associated with major depression (OR, 3.91; 95% CI, 1.68-9.11), anxiety (OR, 4.22; 95% CI, 2.28-7.81), poor recreation (OR, 3.31; 95% CI, 1.70-6.48), and low overall QOL (OR, 2.20; 95% CI, 1.12-4.34)., Conclusions: Years after head and neck cancer treatment, pain remains a significant problem and is associated with worse QOL. Future efforts should focus on preventing pain from treatment and comprehensive management.

Background: The National Quality Forum has endorsed quality-improvement measures for multiple cancer types that are being developed into actionable tools to improve cancer care. No nationally endorsed quality metrics currently exist for head and neck cancer., Methods: The authors identified patients with surgically treated, invasive, head and neck squamous cell carcinoma in the National Cancer Data Base from 2004 to 2014 and compared the rate of adherence to 5 different quality metrics and whether compliance with these quality metrics impacted overall survival. The metrics examined included negative surgical margins, neck dissection lymph node (LN) yield ≥ 18, appropriate adjuvant radiation, appropriate adjuvant chemoradiation, adjuvant therapy within 6 weeks, as well as overall quality., Results: In total, 76,853 eligible patients were identified. There was substantial variability in patient-level adherence, which was 80% for negative surgical margins, 73.1% for neck dissection LN yield, 69% for adjuvant radiation, 42.6% for adjuvant chemoradiation, and 44.5% for adjuvant therapy within 6 weeks. Risk-adjusted Cox proportional-hazard models indicated that all metrics were associated with a reduced risk of death: negative margins (hazard ratio [HR] 0.73; 95% confidence interval [CI], 0.71-0.76), LN yield ≥ 18 (HR, 0.93; 95% CI, 0.89-0.96), adjuvant radiation (HR, 0.67; 95% CI, 0.64-0.70), adjuvant chemoradiation (HR, 0.84; 95% CI, 0.79-0.88), and adjuvant therapy ≤6 weeks (HR, 0.92; 95% CI, 0.89-0.96). Patients who received high-quality care had a 19% reduced adjusted hazard of mortality (HR, 0.81; 95% CI, 0.79-0.83)., Conclusions: Five head and neck cancer quality metrics were identified that have substantial variability in adherence and meaningfully impact overall survival. These metrics are appropriate candidates for national adoption. Cancer 2017;123:4372-81. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Objectives/hypothesis: Head and neck cancer patients have multiple risk factors for liver disease. However, little is known about the incidence of liver disease or the safety of surgery in these patients., Study Design: We conducted a retrospective cohort study using the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2013., Methods: We identified patients undergoing head and neck surgery and excluded them if preoperative laboratory data were missing. Patients were classified as having liver disease if their preoperative aspartate aminotransferase-to-platelet ratio index was ≥ 0.7, and as having advanced liver disease if their Model for End-Stage Liver Disease-Sodium score was ≥ 10. We compared the rate of postoperative complications using multivariable logistic regression., Results: Among 19,138 eligible patients, the incidence of any degree of liver disease was 6.8% for aerodigestive tract surgery and 3.3% for controls. The 30-day mortality rate after major head and neck surgery, which included composite resection; free tissue transfer; and total laryngectomy with advanced, mild, and no liver disease, was 14.6%, 3.0%, and 0.9%, respectively (P < 0.001). For nonmajor surgery, the mortality rate was 3.0%, 0.3%, and 0.3%, respectively (P < 0.001). On multivariable analysis, patients with advanced liver disease experienced a six-fold higher rate of 30-day mortality (odds ratio 6.1; 95% confidence interval, 2.9-12.8)., Conclusion: There is a high risk to detect liver disease in patients undergoing head and neck surgery of the aerodigestive tract. Those with advanced liver disease are at high risk for perioperative mortality, and this risk should be judiciously considered in medical/surgical decision making and postoperative care., Level of Evidence: 2c. Laryngoscope, 127:102-109, 2017., (© 2016 The American Laryngological, Rhinological and Otological Society, Inc.)

Importance: Airway management during microvascular reconstruction of the upper aerodigestive tract is of utmost importance; however, there is considerable debate about optimal management of the airway., Objective: To examine if free tissue transfer to the upper aerodigestive tract without tracheotomy was associated with an increased rate of airway complications or death., Design, Setting, and Participants: Cohort study of 861 patients undergoing microvascular reconstruction to sites in the oral cavity, oropharynx (excluding the base of tongue), and nasal and/or sinus cavity using data from the American College of Surgeons National Surgical Quality Improvement Program from 2005 to 2013. We compared the rate of airway-specific complications of patients who underwent simultaneous tracheotomy vs those who did not undergo tracheotomy., Exposure: Tracheotomy., Main Outcomes and Measures: The 30-day rate of airway-specific complications, including unplanned intubation, prolonged mechanical ventilation, or death., Results: Among the 861 patients included in this study (mean age 61 years and 63.3% male), 551 underwent tracheotomy and 310 did not undergo tracheotomy. The rate of tracheotomy based on anatomic site was 66.1% for oral cavity (n = 728), 40.5% for nasal/sinus cavity (n = 85), and 70.3% for oropharynx (n = 48). The difference in the overall rate of airway complications between patients in the no-tracheotomy (10.3%) and tracheotomy (8.3%) groups was 2.0% (95% CI, 1.9%-6.4%). There were no significant differences in the rate of airway complications in the no-tracheotomy and tracheotomy groups for death (0.3% vs 0.7%, respectively; difference, 0.3%; 95% CI, -2.0% to 3.2%), unplanned intubation (3.2% vs 2.9%, respectively; difference, 0.3%; 95% CI, -2.0% to 3.2%) or for prolonged mechanical ventilation (8.1% vs 7.3%; difference, 0.8%; 95% CI, -2.7% to 4.8%). On multivariate analysis tracheotomy was not associated with the primary outcome (odds ratio [OR], 0.8; 95% CI, 0.5-1.3); however, preoperative bleeding disorder (OR, 9.0; 95% CI, 3.3-24.4), preoperative dyspnea (OR, 2.9; 95% CI, 1.5-5.5), and resection of the floor of mouth (OR, 2.1; 95% CI, 1.1-3.9) were associated with airway complications or death., Conclusions and Relevance: Free tissue transfer to the upper aerodigestive tract is frequently performed without tracheotomy, and this is not associated with a significantly increased rate of airway complications. Routine tracheotomy may be safely avoided in a subset of patients undergoing microvascular reconstruction of the upper aerodigestive tract.

Objective: In recent decades, there has been a reduction in the length of postoperative hospital stay, with a corresponding increase in discharge to postacute care. Discharge to postacute care facilities represents a meaningful patient-centered outcome; however, little has been published about this outcome after head and neck surgery., Study Design: Retrospective review of national database., Setting: American College of Surgeons National Surgical Quality Improvement Program from 2011 to 2013., Subjects and Methods: We compared the rate of discharge to home versus postacute care facilities in patients admitted after head and neck surgery and used multivariable logistic regression to identify predictors of discharge to postacute care., Results: The overall rate of discharge to postacute care facilities after head and neck surgery (n = 15,890) was 15.7% after major surgery (including laryngectomy, composite resection, and free tissue transfer), 4.4% after moderate surgery (including regional tissue transfer, oropharyngeal or oral cavity resection, and neck dissection), and 1.1% after minor head and neck surgery (including endocrine or salivary gland surgery). On multivariable analysis, significant preoperative predictors of discharge to postacute care were advanced age, functional status, major or moderate surgical procedures, tracheostomy, advanced American Society of Anesthesiologists class, low body mass index, and dyspnea., Conclusion: Our study indicates that patients undergoing major or moderate head and neck surgery, patients with reduced functional status, and patients with advanced comorbidities are at substantial risk of discharge to postacute care. The possibility of discharge to postacute care should be discussed with high-risk patients., (© American Academy of Otolaryngology—Head and Neck Surgery Foundation 2016.)

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. [ABSTRACT FROM AUTHOR]