Prognostic significance of time trends in treatment of head and neck squamous cell carcinoma.

PURPOSE: To analyze the impact of demographic, clinical, and management variables on time to treatment initiation (TTI) and overall survival (OS). STUDY DESIGN: Retrospective chart review. MATERIALS AND METHODS: Medical records of patients diagnosed with head and neck cancer from 2018 to 2020 were reviewed. Univariate linear and Cox-regressions identified predictors of TTI and OS. Kaplan Meier (KM) curves assessed the difference in survival by diagnostic year and TTI. RESULTS: 381 patients met eligibility criteria. Median TTI was 35.0 days (IQR: 25.0-49.0). Only 10.8 % of all patients reported any treatment delay, with TTI exceeding 90 days found in 3.7 % of patients. TTI increased with African American race (p = 0.02), ED referrals (p = 0.02), and direct admission status (p = 0.01). When compared to treatment with surgery alone, TTI was shorter in patients undergoing surgery with adjuvant radiation (p = 0.02), adjuvant chemoradiation (p = 0.04), and salvage surgery (p = 0.04). Univariate Cox-regressions found smoking (p = 0.01), direct admission status (p = 0.02), increased duration of symptoms (p = 0.02), placement of PEG tubes (p < 0.01) and tracheostomies (p < 0.01), combination treatment (p < 0.01), and surgery with adjuvant chemoradiation treatment (p = 0.01) to increase mortality risk. Disease characteristics, including tumor size (p < 0.01), presence of nodal disease (p = 0.02), and late-stage disease (p < 0.01), increased mortality risk. TTI and diagnostic year did not impact survival. CONCLUSIONS: Our analysis determined several demographic, referral, and treatment factors impacted TTI. However, increased TTI did not impact survival. Characteristics consistent with advanced disease worsened OS. Despite the pandemic burden, patients diagnosed in 2020 showed no difference in short-term survival compared to prior years.

Impact of intraoperative ischemia time on acute complications of head and neck microvascular free tissue transfer: A systematic review and meta-analysis.

BACKGROUND: To evaluate the relationship between intraoperative ischemia time with acute microvascular free tissue transfer (MFTT) complications in head and neck reconstruction. METHODS: A systematic review using PRISMA guidelines was performed. Inclusion encompassed all available studies published and indexed using PubMed, Medline, and Embase. Meta-analyses were performed using the Cochrane Review Manager tool. Methodological Index for Non-Randomized Studies (MINORS), the Revised Cochrane risk-of-bias tool for randomized trials, and the NIH Study Quality Assessment Tool for non-randomized prospective studies. RESULTS: A total of 430 citations were reviewed. 25 were included in our overall qualitative analysis, and 14 for meta-analysis. When comparing ischemia times for flaps with and without complications, no significant difference was observed (p = 0.98). Additionally, in a separate cohort, no significant effect was realized when correlating ischemia time to overall rates and total complications. CONCLUSION: Ischemia time was not significantly different between those with and without acute flap complications.

Job market in head and neck surgery: A survey and analysis of recent fellowship graduates.

OBJECTIVE: Recent years have seen increase in individuals pursuing postgraduate fellowships in head and neck (HN) surgery. This has presented concerns about insufficient jobs where graduates can apply their scope of specialized training. METHODS: Data was collected in two manners- a survey and a manual online search of American Head and Neck Society (AHNS) fellowship graduates. A 25-question survey was sent in 2021 to approximately 400 HN fellows who graduated between 2010 and 2020. The AHNS list of graduates from the same years were searched online to collect information including gender, graduation year, fellowship training, and current job practice. RESULTS: Of the 78 survey responses, 64.1 % were male and 34.6 % female. 96.2 % reported ablative, 84.6 % microvascular, and 82.1 % TORS training. Mean number of interviews was 4 with most interviewing during the 3rd quarter (January to March). Majority reported being in academic and university-based practices (79.6 %). Online search was done on 393 graduates. Since 2010 the number of graduates almost doubled. There was a statistically significant increase in females by year (p = 0.022). There was a significant decrease (p = 0.022) in graduates with additional fellowship training from that of their AHNS fellowship. There was also a statistically significant increase in graduates being in academic practices (p = 0.022). CONCLUSION: Despite growing numbers, there appears to be more graduates entering an academic practice, although the definition of an academic HN practice may be evolving. These results provide guidance on how to approach the job search in a select market. LEVEL OF EVIDENCE: II.

Stage Migration and Survival Trends in Laryngeal Cancer.

BACKGROUND: During the last two decades, significant advancements in the treatment of laryngeal cancer have occurred. Although survival of head and neck cancer patients has improved over time, the temporal trend of laryngeal cancer survival is an area of controversy. METHODS: From 2004 to 2016, 77,527 patients who had laryngeal cancer treated with curative intent in the United States were identified in the National Cancer Database. Relative and observed survival rates were assessed for temporal trends. Multinomial logistic regression investigated the relationship between American Joint Committee on Cancer (AJCC) stage and increasing calendar year. RESULTS: No significant improvement in 2- or 5-year observed survival (OS) or relative survival (RS) was observed. The 5-year RS ranged from 61.72 to 63.97%, and the 5-year OS ranged from 54.26 to 56.52%. With each increasing year, the proportion of stage 4 disease increased, with risk for stage 4 disease at the time of diagnosis increasing 2.2% annually (adjusted odds ratio [aOR], 1.022; 95% confidence interval [CI], 1.017-1.028; p < 0.001). This increase was driven by a 4.7% yearly increase in N2 disease (aOR, 1.047; 95% CI, 1.041-1.053; p < 0.001), with an annual 1.2% increase in T3 disease (aOR, 1.012; 95% CI, 1.007-1.018; p < 0.001) and a 1.2% increase in T4 disease (aOR, 1.012; 95% CI, 1.005-1.018; p < 0.001). CONCLUSION: Despite advances in the field, laryngeal cancer survival in the United States is not improving over time. This may be due to an increase in the proportion of stage 4 disease, driven primarily by increasing nodal disease. To achieve survival improvement commensurate with scientific and technologic advances, efforts should be made to diagnose and treat laryngeal cancer at earlier stages to prevent further stage migration.

A phase 1 trial of Vorinostat in combination with concurrent chemoradiation therapy in the treatment of advanced staged head and neck squamous cell carcinoma.

Purpose Vorinostat is a potent HDAC inhibitor that sensitizes head and neck squamous cell carcinoma (HNSCC) to cytotoxic therapy while sparing normal epithelium. The primary objective of this Phase I study was to determine the maximally tolerated dose (MTD) and safety of Vorinostat in combination with standard chemoradiation therapy treatment in HNSCC. Patients and Methods Eligible patients had pathologically confirmed Stage III, IVa, IVb HNSCC, that was unresectable or borderline resectable involving the larynx, hypopharynx, nasopharynx, and oropharynx. Vorinostat was administered at the assigned dosage level (100-400 mg, three times weekly) in a standard 3 + 3 dose escalation design. Vorinostat therapy began 1 week prior to initiation of standard, concurrent chemoradiation therapy and continued during the entire course of therapy. Results Twenty six patients met eligibility criteria and completed the entire protocol. The primary tumor sites included tonsil (12), base of tongue (9), posterior pharyngeal wall (1), larynx (4) and hypopharynx (3). Of the 26 patients, 17 were HPV-positive and 9 were HPV-negative. The MTD of Vorinostat was 300 mg administered every other day. Anemia (n = 23/26) and leukopenia (n = 20/26) were the most commonly identified toxicities. The most common Grade3/4 events included leukopenia (n = 11) and lymphopenia (n = 17). No patient had Grade IV mucositis, dermatitis or xerostomia. The median follow time was 33.8 months (range 1.6-82.9 months). Twenty four of 26 (96.2%) patients had a complete response to therapy. Conclusion Vorinostat in combination with concurrent chemoradiation therapy is a safe and highly effective treatment regimen in HNSCC. There was a high rate of complete response to therapy with toxicity rates comparable, if not favorable to existing therapies. Further investigation in Phase II and III trials is strongly recommended.

Differential mutation frequencies in metastatic cutaneous squamous cell carcinomas versus primary tumors.

BACKGROUND: Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but typically is associated with low rates of metastasis and high survival rates. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals die each year of this disease. METHODS: Because it is difficult to predict which cSCCs are more likely to metastasize, and because to the best of the authors' knowledge there are no targeted therapies specifically designated for patients with metastatic cSCC, exome and/or targeted sequencing of 18 metastatic and 10 primary cSCCs was performed to identify mutations that were more frequent in metastatic tumors and might be targeted for therapeutic benefit. The authors compared their results with published sequencing results of an additional 223 primary tumors and 68 metastatic cSCCs. RESULTS: The authors identified genes demonstrating higher mutation frequencies in metastatic cSCC compared with primary tumors, including the chromatin remodeling gene lysine methyltransferase 2D (KMT2D) and the classic skin tumor suppressor tumor protein p53 (TP53), which was found to be mutated in 54% of primary tumors compared with 85% of metastatic tumors (P<.0001). CONCLUSIONS: These studies appear to uncover potential pathways that are important in metastatic cSCC and that broaden understanding of the biology contributing to aggressive tumor behavior. These results may lead to new therapeutic strategies. Cancer 2017;123:1184-1193. © 2016 American Cancer Society.

Genome-wide analysis of HPV integration in human cancers reveals recurrent, focal genomic instability.

Genomic instability is a hallmark of human cancers, including the 5% caused by human papillomavirus (HPV). Here we report a striking association between HPV integration and adjacent host genomic structural variation in human cancer cell lines and primary tumors. Whole-genome sequencing revealed HPV integrants flanking and bridging extensive host genomic amplifications and rearrangements, including deletions, inversions, and chromosomal translocations. We present a model of "looping" by which HPV integrant-mediated DNA replication and recombination may result in viral-host DNA concatemers, frequently disrupting genes involved in oncogenesis and amplifying HPV oncogenes E6 and E7. Our high-resolution results shed new light on a catastrophic process, distinct from chromothripsis and other mutational processes, by which HPV directly promotes genomic instability.

Management of complications and compromised free flaps following major head and neck surgery.

Microvascular free flaps are preferred for most major head and neck reconstruction surgeries because of better functional outcomes, improved esthetics, and generally higher success rates. Numerous studies have investigated measures to prevent flap loss, but few have evaluated the optimal treatment for free flap complications. This study aimed to determine the complication rate after free flap reconstructions and discusses our management strategies. Medical records of 260 consecutive patients who underwent free flap reconstructions for head and neck defects between July 2006 and June 2010 were retrospectively reviewed for patient and surgical characteristics and postoperative complications. The results revealed that microvascular free flaps were extremely reliable, with a 3.5 % incidence of flap failure. There were 78 surgical site complications. The most common complication was neck wound infection, followed by dehiscence, vascular congestion, abscess, flap necrosis, hematoma, osteoradionecrosis, and brisk bleeding. Twenty patients with poor wound healing received hyperbaric oxygen therapy, which was ineffective in three patients who eventually experienced complete flap loss. Eleven patients with vascular congestion underwent medicinal leech therapy, which was effective. Among the 78 patients with complications, 44 required repeat surgery, which was performed for postoperative brisk bleeding in three. Eventually, ten patients experienced partial flap loss and nine experienced complete flap loss, with the latter requiring subsequent pectoralis major flap reconstruction. Microvascular free flap reconstruction represents an essential and reliable technique for head and neck defects and allows surgeons to perform radical resection with satisfactory functional results and acceptable complication rates.

The impact of cancer treatment on the diets and food preferences of patients receiving outpatient treatment.

Patients undergoing cancer treatment experience a multitude of symptoms that can influence their ability to complete treatment as well as their quality of life during and after treatment. This cross-sectional study sought to describe the dietary changes experienced by cancer patients and to identify associations between these changes and common treatment symptoms. A convenience sample of 1199 cancer patients aged 18 yr and older undergoing active treatment were recruited from 7 cancer centers to complete a self-administered paper-and-pencil survey. Descriptive analyses were conducted to estimate prevalence of dietary changes and chi-squared tests were used to examine associations between dietary changes and health outcomes. Approximately 40% of patients reported a decreased appetite since beginning treatment, and 67.2% of patients reported at least 1 chemosensory alteration. Increased taste sensitivities were more common than decreased taste sensitivities, with increased sensitivity to metallic being the most common taste sensitivity (18.6%). Patients also had increased sensitivities to certain smells including cleaning solutions (23.4%), perfume (22.4%), and food cooking (11.4%). Patients reported a wide range of food preferences and aversions. Patients who had less energy or lost weight since beginning treatment were more likely than others to report treatment-related dietary changes.

How often parapharyngeal space is encountered in TORS oropharynx cancer resection.

Early stage oropharyngeal squamous cell carcinoma (OPSCC) may occasionally invade parapharyngeal space (PPS). Tumor invasion of PPS structures such as the carotid artery, internal jugular vein and cranial nerves IX-XII may add significant morbidity. We analyzed 73 patients who underwent transoral robotic surgery (TORS) for OPSCC between 2008 and 2012. Patients were selected based on preoperative evaluation including detailed physical and endoscopic examination, neck CT and/or PET-CT scan. T1, T2 and selected T3 cases were included in this study. None of the patients had obvious PPS extension on preoperative evaluation. All patients had OPSCC in palatine tonsil (60; 82.2 %) and base of tongue (13; 17.8 %). Twenty-seven patients had cT1 (37 %), 39 had cT2 (53.4 %), and 7 had cT3 (9.6 %) disease in clinical and radiologic evaluation. None of the oropharyngeal lesions had obvious radiologic PPS extension prior to operation. During TORS procedure, we encountered PPS in 18 (24.6 %) patients while resecting the deep margin. These parapharynx resections involved external carotid artery in 1, medial pterygoid muscle in 2, and parapharyngeal fat with or without styloid musculature in the remaining 15 patients. Except three cases, we were able to remove the lesions en bloc with negative surgical margins. TORS resection of oropharyngeal cancer extending to PPS appears to be a safe and feasible technique with minimal complications. Significant experience with TORS and further understanding of the endoscopic anatomy of PPS could obviate the morbidity associated with tumor resection in this dense neurovascular region.

Emerging role of nanog in tumorigenesis and cancer stem cells.

Nanog is a transcription factor that is well-established as a key regulator of embryonic stem cell (ESC) maintenance. Recent evidence demonstrates that Nanog is dysregulated and intimately involved in promoting tumorigenesis in part through regulation of the cancer stem cell (CSC) population. Elevated Nanog is associated with poorer outcome in numerous epithelial malignancies. Nanog is enriched in CSCs and ablation of Nanog is sufficient to reduce the CSC pool. Nanog has also been implicated to promote chemoresistance and epithelial-mesenchymal transition (EMT). Insight into the Nanog signaling cascade, upstream regulators and downstream effectors, is beginning to emerge but remains to be fully elucidated. This review highlights the current literature on the emerging role of Nanog in tumorigenesis and CSCs.

Elevated intrinsic cancer stem cell population in human papillomavirus-associated head and neck squamous cell carcinoma.

BACKGROUND: Human papillomavirus 16 (HPV16) is a major risk factor for the development of head and neck squamous cell carcinoma (HNSCC), particularly the development of oropharyngeal squamous cell carcinoma (OPSCC). Cancer stem cells (CSCs) are resistant to conventional therapies, and it is postulated that they are responsible for disease recurrence and/or progression. Because the prognoses of patients with HPV16-positive and HPV-negative HNSCC are distinct, the authors sought to determine whether differences in the number of CSCs could account for this clinical observation. METHODS: CSC populations in HPV16-positive and HPV-negative HNSCC were assessed using a proprietary assay based on expression of the enzyme aldehyde dehydrogenase (ALDH), an in vitro tumorsphere formation assay, and an in vivo limiting cell dilution in nonobese diabetic/severe combined immunodeficiency mice. A high-density tissue microarray was stained with ALDH1, a CSC marker, to determine the association between CSCs and HPV16-positive/HPV-negative OPSCC. RESULTS: HPV16-positive HNSCC had a greater intrinsic CSC pool than HPV-negative HNSCC. Inactivation of p53 has been identified as a major mechanism for the elevated CSC population in HPV16-positive HNSCC. In vivo limiting cell dilution experiments using tumors from patients with HPV16-positive and HPV-negative OPSCC indicated that the CSC frequency was 62.5-fold greater in an HPV16-positive OPSCC tumor than in an HPV-negative OPSCC tumor. Primary tumors from patients with HPV16-positive OPSCC were associated with elevated tumor ALDH1 staining, further extending the association between HPV16 and CSCs. CONCLUSIONS: The current data and the clinical observation that patients with HPV16-positive HNSCC respond more favorably to current treatment paradigms than patients with HPV-negative HNSCC support the suggestion that CSC phenotype is not homogeneous. Therefore, the reliance on the CSC number may be insufficient to accurately assess the potential of a particular tumor for disease recurrence and/or progression.

Does body mass index matter while selecting the flap type for pharyngeal reconstructions?

The aim of our study was to investigate the effect of patient-related factors, such as the body mass index (BMI) and tumor size, in selecting the flap type for the reconstruction of pharyngeal defects. This retrospective review included 182 patients with pharyngeal defect reconstructions with free and pedicled flaps at the Ohio State University from January 2005 to December 2008. We conducted a retrospective comparison of variety of different flap reconstruction techniques. We compared different flap reconstruction with BMI and tumor size without functional outcome such as swallowing and speech data. Although there was no statistically significant correlation (P > 0.05) when comparing the free flaps with pedicled flaps according to the BMI and tumor size, there was an obvious tendency to prefer radial forearm free flap over anterolateral thigh free flap in patients who are overweight and those with obesity with a ratio of 32:3. In the same group of patients, a similar tendency was observed to prefer fibular free flap over iliac crest free flap with a ratio of 14:5, whereas the ratio was becoming 3:5 in favor of iliac crest free flap over fibular free flap in patients with BMI of 24 or lower. Despite the fact that surgeons' experience with a certain flap type is one of the most important factors while determining which flap to reconstruct, BMI might have a significant impact while selecting the free flap types for the reconstruction of pharyngeal defects.

Lipid-based nanoparticle delivery of Pre-miR-107 inhibits the tumorigenicity of head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is the sixth most prevalent cancer worldwide with about 600,000 new cases diagnosed in the last year. Our laboratory showed that miR-107 expression is reduced and functions as a tumor suppressor gene in HNSCC suggesting the potential application of miR-107 as a novel anticancer therapeutic. In this study, we determined the efficiency and efficacy of cationic lipid nanoparticles to deliver pre-miR-107 (NP/pre-miR-107) in HNSCC cells in vitro and in vivo. NP/pre-miR-107 increased delivery of miR-107 into HNSCC cells by greater than 80,000-fold compared to free pre-miR-107. Levels of known miR-107 targets, protein kinase Cε (PKCε), cyclin-dependent kinase 6 (CDK6), and hypoxia-inducible factor 1-ß (HIF1-ß), decreased following NP/pre-miR-107 treatment. Clonogenic survival, cell invasion, and cell migration of HNSCC cells was inhibited with NP/pre-miR-107. Moreover, NP/pre-miR-107 reduced the cancer-initiating cell (CIC) population and dampened the expression of the core embryonic stem cell transcription factors, Nanog, Oct3/4, and Sox2. In a preclinical mouse model of HNSCC, systemic administration of NP/pre-miR-107 significantly retarded tumor growth by 45.2% compared to NP/pre-miR-control (P < 0.005, n = 7). Kaplan-Meier analysis showed a survival advantage for the NP/pre-miR-107 treatment group (P = 0.017). Our results demonstrate that cationic lipid nanoparticles are an effective carrier approach to deliver therapeutic miRs to HNSCC.

Incidence and medical complications of COVID-19 in the total laryngectomy population: A population-based study.

OBJECTIVES: Laryngeal and hypopharyngeal cancers treated with total laryngectomy (TL) may provide a unique avenue for COVID-19 to infect cancer patients. The objective of this investigation was to identify incidence of COVID-19 infection and potential complications in TL patients. MATERIALS AND METHODS: Data was extracted from TriNetX COVID-19 research network from from 2019 to 2021 and ICD-10 codes were utilized to query for laryngeal or hypopharyngeal cancer, and outcomes of interest. Cohorts were propensity score-matched based on demographics and co-morbidities. RESULTS: A query of active patients in TriNetX from January 1, 2019 to December 31, 2021 identified 36,414 patients with laryngeal or hypopharyngeal cancer out of the 50,474,648 active patients in the database. The overall COVID-19 incidence in the non-laryngeal or hypopharyngeal cancer population was 10.8% compared to 18.8% (p < 0.001) in the laryngeal and hypopharyngeal cancer group. Those who underwent TL had a statistically significant increased incidence of acquiring COVID-19 (24.0%) when compared to those without TL (17.7%) (p < 0.001). TL patients with COVID-19 had a higher risk of developing pneumonia RR (risk ratio) 1.80 (1.43, 2.26), death 1.74 (1.41, 2.14), ARDS 2.42 (1.16, 5.05), sepsis 1.77 (1.37, 2.29), shock 2.81 (1.88, 4.18), respiratory failure 2.34 (1.90, 2.88), and malnutrition 2.46 (2.01, 3.01) when matched with those COVID-19 positive cancer patients without TL. CONCLUSIONS: Laryngeal and hypopharyngeal cancer patients had a higher rate of acquiring COVID-19 than patients without these cancers. TL patients have a higher rate of COVID-19 compared to those without TL and may be at a higher risk for sequalae of COVID-19.

Advantages of the scapular system in mandibular reconstruction.

BACKGROUND: Fibula free flaps (FFF) are often considered the first choice for mandibular reconstruction, but scapular system free flaps (SFF) have increased in popularity due to versatility, donor site advantages, and patient factors. METHODS: Retrospective chart review of patients undergoing mandibulectomy with FFF or SFF reconstruction from 2016 to 2021. RESULTS: Hundred and seventy-six patients (FFF n = 145, SFF n = 31) underwent the aforementioned procedures. Mean FFF operative time was 9.47 h versus 9.88 for SFF (p = 0.40). Two-flap reconstructions required 12.65 h versus 10.09 for SFF with soft tissue (p = 0.002). Donor site complications were identified in 65.6% of FFF with skin grafting. CONCLUSIONS: These findings suggest that SFF requires similar operative time and results in reduced donor site morbidity as compared to FFF. Supine, concurrent harvesting of SFF allows for single-flap harvest with significantly shorter operative time. SFF could be considered a primary option for mandible reconstruction for complex defects and in select patients.

Patient-derived three-dimensional culture techniques model tumor heterogeneity in head and neck cancer.

Head and neck squamous cell carcinoma (HNSCC) outcomes remain stagnant, in part due to a poor understanding of HNSCC biology. The importance of tumor heterogeneity as an independent predictor of outcomes and treatment failure in HNSCC has recently come to light. With this understanding, 3D culture systems, including patient derived organoids (PDO) and organotypic culture (OTC), that capture this heterogeneity may allow for modeling and manipulation of critical subpopulations, such as p-EMT, as well as interactions between cancer cells and immune and stromal cells in the microenvironment. Here, we review work that has been done using PDO and OTC models of HNSCC, which demonstrates that these 3D culture models capture in vivo tumor heterogeneity and can be used to model tumor biology and treatment response in a way that faithfully recapitulates in vivo characteristics. As such, in vitro 3D culture models represent an important bridge between 2D monolayer culture and in vivo models such as patient derived xenografts.

High surgical volume is associated with improved survival in head and neck cancer.

OBJECTIVES: Examine the relationship between hospital volume and overall mortality in a surgical cohort of head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS & METHODS: A retrospective review of the NCDB was completed for adults with previously untreated HNSCC diagnosed between 2004 and 2016. Mean annual hospital volume was calculated using the number of head and neck cancer cases treated at a given facility divided by the number of years the facility reported to the NCDB. Facilities were separated into three categories based on their volume percentile, informed by inflection points from a natural cubic spline: Hospital Group 1 (<50%); Hospital Group 2 (50-90%); Hospital Group 3 (90%+). Cox proportional hazard models were used to examine the association between volume percentiles (continuous or categorical) with patient overall survival, adjusting for important patient and facility variables known to impact survival. RESULTS: Risk of death decreased by 2.97% for every 10% increase in facility percentile after adjusting for other risk factors. Patients treated at facilities in Hospital Group 1 had a 23.1% increase in risk of mortality (HR 1.231 [95% CI 1.12-1.35]) relative those at facilities in Hospital Group 3. No significant difference in mortality risk was found between Hospital Group 2 versus Hospital Group 3 (HR 1.031 [95% CI 0.97-1.10]). CONCLUSIONS: Survival of HNSCC patients is significantly improved when treated at facilities >50th percentile in annual hospital volume. This may support the regionalization of care to high volume head and neck centers with comprehensive facilities and supportive services to maximize patient outcomes.

Loss to Follow-up in Head and Neck Cancer: A Systematic Review of Randomized Controlled Trials.

OBJECTIVE: To evaluate the reporting and rates of loss to follow-up (LTFU) in head and neck cancer (HNC) randomized controlled trials based in the United States. DATA SOURCES: Pubmed/MEDLINE, Cochrane, Scopus databases. REVIEW METHODS: A systematic review of titles in Pubmed/MEDLINE, Scopus, and Cochrane Library was performed. Inclusion criteria were US-based randomized controlled trials focused on the diagnosis, treatment, or prevention of HNC. Retrospective analyses and pilot studies were excluded. The mean age, patients randomized, publication details, trial sites, funding, and LTFU data were recorded. Reporting of participants through each stage of the trial was documented. Binary logistic regression was performed to evaluate associations between study characteristics and reporting LTFU. RESULTS: A total of 3255 titles were reviewed. Of these, 128 studies met the inclusion criteria for analysis. A total of 22,016 patients were randomized. The mean age of participants was 58.6 years. Overall, 35 studies (27.3%) reported LTFU, and the mean LTFU rate was 4.37%. With the exception of 2 statistical outliers, study characteristics including publication year, number of trial sites, journal discipline, funding source, and intervention type did not predict the odds of reporting LTFU. Compared to 95% of trials reporting participants at eligibility and 100% reporting randomization, only 47% and 57% reported on withdrawal and details of the analysis, respectively. CONCLUSION: The majority of clinical trials in HNC in the United States do not report LTFU, which inhibits the evaluation of attrition bias that may impact the interpretation of significant findings. Standardized reporting is needed to evaluate the generalizability of trial results to clinical practice.

Immediate resection of positive margins improves local control in oral tongue cancer.

OBJECTIVES: This study investigates the impact of immediate resection of positive margins on local control of oral tongue cancer. MATERIALS AND METHODS: We analyzed 273 consecutive oral tongue cancers resected from 2013 to 2018. Additional resection was performed in cases during the initial operation based on surgeon inspection of the specimen and/or frozen margins. Positive margins were defined as invasive carcinoma/high-grade dysplasia < 1 mm from the inked edge. Patients were grouped as follows: negative margin (Group 1); positive margin with immediate additional tissue resection (Group 2); and positive margin without additional tissue resection (Group 3). RESULTS: Overall, the rate of local recurrence was 7.7 % (21/273), and the rate of positive main specimen margin was 17.9 %. Of these patients, 38.8 % (19/49) underwent immediate additional resection of the presumed positive margin. Group 3 had higher local recurrence rates than Group 1 after adjustment for T-stage (aHR 2.8 [95 % CI 1.0-7.7], p = 0.04). Group 2 had similar rates of local recurrence (aHR 0.45 [95 % CI 0.06-3.6], p = 0.45). Three year local recurrence free survival for Groups 1, 2, and 3 were 91 %, 92 % and 73 %, respectively. Compared to the main specimen margin, sensitivity of intraoperative frozen tumor bed margins was 17.4 %, and specificity was 95 %. CONCLUSION: In patients with positive main specimen margins, anticipation and detection in real-time with immediate additional tissue resection reduced local recurrence to rates similar to those with negative main specimen margins. These findings support the use of technology to provide real-time intraoperative margin data and guide additional resection for improved local control.