TP53 mutations in head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) arising in the mucosal linings of the upper aerodigestive tract are highly heterogeneous, aggressive, and multifactorial tumors affecting more than half a million patients worldwide each year. Classical etiological factors for HNSCC include alcohol, tobacco, and human papillomavirus (HPV) infection. Current treatment options for HNSCCs encompass surgery, radiotherapy, chemotherapy, or combinatorial remedies. Comprehensive integrative genomic analysis of HNSCC has identified mutations in TP53 gene as the most frequent of all somatic genomic alterations. TP53 mutations are associated with either loss of wild-type p53 function or gain of functions that promote invasion, metastasis, genomic instability, and cancer cell proliferation. Interestingly, disruptive TP53 mutations in tumor DNA are associated with aggressiveness and reduced survival after surgical treatment of HNSCC. This review summarizes the current evidence and impact of TP53 mutations in HNSCC.

Patient Burden with Current Surveillance Paradigm and Factors Associated with Interest in Altered Surveillance for Early Stage HPV-Related Oropharyngeal Cancer.

INTRODUCTION: Optimal surveillance paradigms for survivors of early stage human papillomavirus (HPV)-related oropharyngeal cancer are not well defined. This study aimed to characterize patient interest in and factors associated with an altered surveillance paradigm. MATERIALS AND METHODS: We surveyed patients with Stage I or II HPV-related oropharyngeal cancer treated at a tertiary care institution from 2016 to 2019. Primary outcomes were descriptive assessment of patient knowledge, interest in altered surveillance, burdens of in-person appointments, and priorities for surveillance visits. Ordinal regression was used to identify correlates of interest in altered surveillance. RESULTS: Sixty-seven patients completed surveys from February to April 2020 at a median of 21 months since completing definitive treatment. A majority (61%) of patients were interested in a surveillance approach that decreased in-person clinic visits. Patients who self-identified as medical maximizers, had higher worry of cancer recurrence, or were in long-term relationships were less likely to be interested. Patients reported significant burdens associated with surveillance visits, including driving distance, time off work, and nonmedical costs. Patients were most concerned with discussing cancer recurrence (76%), physical quality of life (70%), mortality (61%), and mental quality of life (52%) with their providers at follow-up visits. CONCLUSION: Patients with early stage HPV-related oropharyngeal cancers are interested in altered surveillance approaches, experience significant burdens related to surveillance visits, and have concerns that are not well addressed with current surveillance approaches, including physical and mental quality of life. Optimized surveillance approaches should incorporate patient priorities and minimize associated burdens. IMPLICATIONS FOR PRACTICE: The number of patients with HPV-related oropharyngeal cancers is increasing, and numerous clinical trials are investigating novel approaches to treating these good-prognosis patients. There has been limited work assessing optimal surveillance paradigms in these patients. Patients experience significant appointment-related burdens and have concerns such as physical and mental quality of life. Additionally, patients with early stage HPV-related oropharyngeal cancers express interest in altered surveillance approaches that decrease in-person clinic visits. Optimization of surveillance paradigms to promote broader survivorship care in clinical practice is needed.

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.

"My Research Is Their Business, but I'm Not Their Business": Patient and Clinician Perspectives on Commercialization of Precision Oncology Data.

BACKGROUND: Genetic sequencing and precision oncology have supported clinical breakthroughs but depend upon access to vast arrays of research specimens and data. One way for academic medical centers to fund such infrastructure and research is "commercialization" of access to specimens and data to industry. Here we explore patient and clinician perspectives regarding cancer specimen and data commercialization with the goal of improving such processes in the future. MATERIALS AND METHODS: This qualitative analysis was embedded within a prospective precision oncology sequencing study of adults with head and neck cancer. Via semistructured dyadic interviews with patients with cancer and their doctors, we assessed understanding and concerns regarding potential commercialization, opinions regarding investment of profits, and perspectives regarding the return of information directly to participants from industry. RESULTS: Several patient- and clinician-participants did not understand that the consent form already permitted commercialization of patient genetic data and expressed concerns regarding who would profit from the data, how profits would be used, and privacy and access. Patients were generally more comfortable with commercialization than clinicians. Many patients and clinicians were comfortable with investing profits back into research, but clinicians were more interested in investment in head and neck cancer research specifically. Patients generally supported potential return-of-results from a private entity, but their clinicians were more skeptical. CONCLUSION: Our results illustrate the limitations of mandatory disclosures in the informed consent process. The voices of both patients and their doctors are critical to mitigate violations of privacy and a degradation of trust as stakeholders negotiate the terms of academic and commercial engagement. IMPLICATIONS FOR PRACTICE: Further education is needed regarding how and why specimens and data in precision oncology research may be commercialized for both patients and providers alike. This process will require increased transparency, comprehension, and engagement of involved stakeholders.

Predictors of survival in patients undergoing oropharyngeal surgery for cancer recurrence after radiation therapy.

PURPOSE: The incidence of oropharyngeal squamous cell carcinoma continues to rise with the majority of patients receiving definitive or adjunctive radiation. For patients with locoregional recurrence after radiation, optimal treatment involves salvage surgery. The aim of this study is to identify factors that predict survival to ultimately improve patient selection for salvage surgery. METHODS: Retrospective cohort study at an NCI-designated cancer center. We analyzed patients with a history of head and neck radiation who presented with persistent/recurrent or second primary disease requiring salvage oropharyngeal resection from 1998-2017 (n = 120). Patients were stratified into three classes based on time to recurrence and presence of laryngopharyngeal dysfunction. Primary outcomes were 5-year overall survival (OS) and disease specific survival (DSS). RESULTS: Median OS was 27 months (median follow-up 20 months). Five-year OS was 47% for class I (recurrence > 2 years), 26% for class II (recurrence ≤ 2 years), and 0% for class III (recurrence ≤ 2 years and laryngopharyngeal dysfunction), (p < 0.0001). Five-year DSS showed significant differences between classes (p < 0.0001). On multivariate analysis, class remained predictive of OS (p = 0.04- < 0.001) and DSS (p = 0.04-0.001). Adjuvant radiation after salvage surgery with negative margins showed superior OS (71% vs. 28%, p = 0.01) and DSS (83% vs 37%, p = 0.02) compared to surgery alone and was a significant predictor of improved survival on multivariate analysis (HR 0.1, p = 0.04). CONCLUSION: This study identified a subset of patients with oropharyngeal cancer recurrence within two years of initial treatment and with laryngopharyngeal dysfunction who have poor outcomes for salvage surgery.

Speech and swallowing outcomes after laryngectomy for the dysfunctional irradiated larynx.

PURPOSE: To characterize outcomes of total laryngectomy for the dysfunctional larynx after radiation. METHODS: Retrospective case series of all subjects who underwent total laryngectomy for the irradiated dysfunctional larynx between 2000 and 2018 at an NCI-designated comprehensive cancer center at a single tertiary care academic medical center. Main outcomes included enteral tube feeding dependency, functional tracheoesophageal speech, and number and timing of postoperative pharyngeal dilations. RESULTS: Median time from radiation to laryngectomy was 2.8 years (range 0.5-27 years). Functional outcomes were analyzed for the 32 patients with 1-year follow-up. Preoperatively, 81% required at least partial enteral tube feeding, as compared to 34% 1-year postoperatively (p = 0.0003). At 1 year, 81% had achieved functional tracheoesophageal speech, which was associated with cricopharyngeal myotomy (p = 0.04, HR 0.04, 95% CI 0.002-0.949). There were 34% of subjects who required at least one pharyngeal dilation for stricture by 1 year postoperatively. Over half (60%) of the cohort were dilated over the study period. CONCLUSIONS: Laryngectomy for the dysfunctional larynx improves speech and swallowing outcomes in many patients. Cricopharyngeal myotomy is associated with improved postoperative voice. While the need for enteral feeding is decreased, persistent postoperative swallowing dysfunction is common. Careful patient selection and education regarding functional expectations are paramount.

Analysis of tumor-infiltrating CD103 resident memory T-cell content in recurrent laryngeal squamous cell carcinoma.

BACKGROUND: Recurrent laryngeal squamous cell carcinomas (LSCCs) are associated with poor outcomes, without reliable biomarkers to identify patients who may benefit from adjuvant therapies. Given the emergence of tumor-infiltrating lymphocytes (TIL) as a biomarker in head and neck squamous cell carcinoma, we generated predictive models to understand the utility of CD4+, CD8+ and/or CD103+ TIL status in patients with advanced LSCC. METHODS: Tissue microarrays were constructed from salvage laryngectomy specimens of 183 patients with recurrent/persistent LSCC and independently stained for CD4+, CD8+, and CD103+ TIL content. Cox proportional hazards regression analysis was employed to assess combinations of CD4+, CD8+, and CD103+ TIL levels for prediction of overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) in patients with recurrent/persistent LSCC. RESULTS: High tumor CD103+ TIL content was associated with significantly improved OS, DSS, and DFS and was a stronger predictor of survival in recurrent/persistent LSCC than either high CD8+ or CD4+ TIL content. On multivariate analysis, an "immune-rich" phenotype, in which tumors were enriched for both CD103+ and CD4+ TILs, conferred a survival benefit (OS hazard ratio: 0.28, p = 0.0014; DSS hazard ratio: 0.09, p = 0.0015; DFS hazard ratio: 0.18, p = 0.0018) in recurrent/persistent LSCC. CONCLUSIONS: An immune profile driven by CD103+ TIL content, alone and in combination with CD4+ TIL content, is a prognostic biomarker of survival in patients with recurrent/persistent LSCC. Predictive models described herein may thus prove valuable in prognostic stratification and lead to personalized treatment paradigms for this patient population.

Elective Paratracheal Lymph Node Dissection in Salvage Laryngectomy.

BACKGROUND: Indications for and efficacy of paratracheal nodal dissection (PTND) in patients undergoing laryngectomy (salvage) for persistent or recurrent laryngeal squamous cell carcinoma are not well-defined. METHODS: A retrospective cohort study was performed for patients undergoing salvage laryngectomy with clinically and radiographically negative neck disease between 1998 and 2015 (n = 210). Univariate and multivariate Cox regression analyses were performed. RESULTS: PTND was performed on 77/210 patients (36%). The PTND cohort had a greater proportion of advanced T classification (rT3/rT4) tumors (78%) than subjects without PTND (55%; p = 0.001). There was a 14% rate of occult nodal metastases in the paratracheal basin; of these, 55% did not have pathologic lateral neck disease. Multivariate analysis controlling for tumor site, tumor stage, and pathologic lateral neck disease demonstrated that PTND was associated with improved overall survival [OS] (p = 0.03; hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.38-0.96), disease-free survival [DFS] (p = 0.03; HR 0.55, 95% CI 0.31-0.96), and distant DFS survival (p = 0.01; HR 0.29, 95% CI 0.11-0.77). The rate of hypocalcemia did not differ between subjects who underwent bilateral PTND, unilateral PTND, or no PTND (p = 0.19 at discharge, p = 0.17 at last follow-up). CONCLUSIONS: PTND at the time of salvage laryngectomy was more common in patients with rT3/rT4 tumors and was associated with improved OS and DFS, with no effect on hypocalcemia. In patients undergoing PTND, the finding of occult paratracheal metastases was often independent of lateral neck metastases.

Hypothyroidism and Wound Healing After Salvage Laryngectomy.

BACKGROUND: Patients undergoing salvage laryngectomy are predisposed to radiation-induced hypothyroidism and impaired wound healing secondary to the tissue effects of prior treatment. The impact of hypothyroidism on postoperative wound healing is not established. METHODS: A single-institution retrospective case series was performed. The inclusion criteria specified preoperatively euthyroid adults who underwent salvage laryngectomy with concurrent neck dissection between 1997 and 2015 for persistent or recurrent laryngeal squamous cell carcinoma after radiation or chemoradiation therapy (n = 182). The principal explanatory variable was postoperative hypothyroidism, defined as thyroid-stimulating hormone (TSH) higher than 5.5 mIU/L. The primary end points of the study were pharyngocutaneous fistulas and wounds requiring reoperation. Multivariate analysis was performed. RESULTS: The fistula rate was 47% among hypothyroid patients versus 23% among euthyroid patients. In the multivariate analysis, the patients who experienced hypothyroidism in the postoperative period had a 3.6-fold greater risk of fistula [95% confidence interval (CI) 1.8-7.1; p = 0.0002]. The hypothyroid patients had an 11.4-fold greater risk for a required reoperation (24.4 vs 5.4%) than the euthyroid patients (95% CI 2.6-49.9; p = 0.001). The risk for fistula (p = 0.003) and reoperation (p = 0.001) increased with increasing TSH. This corresponds to an approximate 12.5% incremental increase in the absolute risk for fistula and a 10% increase in the absolute risk for reoperation with each doubling of the TSH. CONCLUSION: Postoperative hypothyroidism independently predicts postoperative wound-healing complications. The association of hypothyroidism with fistula formation may yield opportunities to modulate wound healing with thyroid supplementation or to provide a biomarker of wound progression.

Management of the facial nerve in parotid cancer: preservation or resection and reconstruction.

PURPOSE: Management of the facial nerve is instrumental in the surgical treatment of parotid cancer. METHODS: A literature search was conducted using PubMed and ScienceDirect database. A total of 195 articles were finally included into the analysis, based on relevance, scientific evidence and actuality. RESULTS: In the majority of cases the facial nerve is not involved by tumor. In these cases, identification and preservation of the nerve, in addition to complete tumor removal, are essential for successful surgery. When the nerve is infiltrated by tumor, the affected portion of the nerve must be resected as part of radical parotidectomy. Primary nerve reconstruction or other reanimation techniques give the best long-term functional and cosmetic results. A comprehensive diagnostic evaluation with current imaging and electrophysiological studies will provide the surgeon with the best knowledge of the relationship of the facial nerve to the tumor. Several standardized methods are helpful in finding, dissecting and preserving the nerve during parotid cancer surgery. When radical parotidectomy is indicated, the initial diagnostic work-up can assist in defining the need for adjuvant postoperative therapy and facial reanimation. The aim of rehabilitation is to restore tone, symmetry, and movement to the paralyzed face. CONCLUSIONS: The surgical management of facial paralysis has undergone many improvements in recent years. This review gives an overview of recent advances in the diagnostic work-up, surgical techniques and any necessary rehabilitation of the facial nerve in parotid cancer surgery.

The natural history of thin melanoma and the utility of sentinel lymph node biopsy.

BACKGROUND AND OBJECTIVES: Current literature may overestimate the risk of nodal metastasis from thin melanoma due to reporting of data only from lesions treated with SLNB. Our objective was to define the natural history of thin melanoma, assessing the likelihood of nodal disease, in order to guide selection for SLNB. METHODS: Retrospective review. The primary outcome was the rate of nodal disease. Clinicopathologic factors were evaluated to find associations with nodal disease. RESULTS: Five hundred and twelve lesions, follow up available for 488 (median: 48 months). Lesions treated with WLE/SLNB compared to WLE alone were more likely to have high-risk features. The rate of nodal disease was higher in the WLE/SLNB group (24 positive SLNB, five false-negative SLNB with nodal recurrence: 10.2%) compared to WLE alone (four nodal recurrences: 2.0%). Univariate analysis showed age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm2 , and ulceration were associated with nodal disease. Multivariate analysis confirmed the association of age ≤45 and ulceration. CONCLUSIONS: SLNB for melanoma 0.75-0.99 mm should be considered in patients age ≤45, Breslow depth ≥0.85 mm, mitotic rate >1 mm2 , and/or with ulceration. Thin melanoma <0.85 mm without high-risk features may be treated with WLE alone.

Does Quitting Smoking Make a Difference Among Newly Diagnosed Head and Neck Cancer Patients?

INTRODUCTION: To determine if smoking after a cancer diagnosis makes a difference in mortality among newly diagnosed head and neck cancer patients. METHODS: Longitudinal data were collected from newly diagnosed head and neck cancer patients with a median follow-up time of 1627 days (N = 590). Mortality was censored at 8 years or September 1, 2011, whichever came first. Based on smoking status, all patients were categorized into four groups: continuing smokers, quitters, former smokers, or never-smokers. A broad range of covariates were included in the analyses. Kaplan-Meier curves, bivariate and multivariate Cox proportional hazards models were constructed. RESULTS: Eight-year overall mortality and cancer-specific mortality were 40.5% (239/590) and 25.4% (150/590), respectively. Smoking status after a cancer diagnosis predicted overall mortality and cancer-specific mortality. Compared to never-smokers, continuing smokers had the highest hazard ratio (HR) of dying from all causes (HR = 2.71, 95% confidence interval [CI] = 1.48-4.98). Those who smoked at diagnosis, but quit and did not relapse-quitters-had an improved hazard ratio of dying (HR = 2.38, 95% CI = 1.29-4.36) and former smokers at diagnosis with no relapse after diagnosis-former smokers-had the lowest hazard ratio of dying from all causes (HR = 1.68, 95% CI = 1.12-2.56). Similarly, quitters had a slightly higher hazard ratio of dying from cancer-specific reasons (HR = 2.38, 95% CI = 1.13-5.01) than never-smokers, which was similar to current smokers (HR = 2.07, 95% CI = 0.96-4.47), followed by former smokers (HR = 1.70, 95% CI = 1.00-2.89). CONCLUSIONS: Compared to never-smokers, continuing smokers have the highest HR of overall mortality followed by quitters and former smokers, which indicates that smoking cessation, even after a cancer diagnosis, may improve overall mortality among newly diagnosed head and neck cancer patients. Health care providers should consider incorporating smoking cessation interventions into standard cancer treatment to improve survival among this population. IMPLICATIONS: Using prospective observational longitudinal data from 590 head and neck cancer patients, this study showed that continuing smokers have the highest overall mortality relative to never-smokers, which indicates that smoking cessation, even after a cancer diagnosis, may have beneficial effects on long-term overall mortality. Health care providers should consider incorporating smoking cessation interventions into standard cancer treatment to improve survival among this population.

Management of locally advanced HPV-related oropharyngeal squamous cell carcinoma: where are we?

HPV-related (HPV+) oropharyngeal cancer (OPC) has a better prognosis compared to HPV unrelated (HPV-) OPC. This review summarizes and discusses several of the controversies regarding the management of HPV+ OPC, including the mechanism of its treatment sensitivity, modern surgical techniques, chemotherapy regimens, and treatment de-intensification protocols. We also discuss and reconsider potential adverse prognostic factors such as tumor EGFR expression, tumor hypoxia, and patient smoking history, as well as the significance of retropharyngeal adenopathy. Finally, we discuss elective nodal treatment of uninvolved lymph node stations. While this review does not exhaust all controversies related to the management of HPV+ OPC, it aims to highlight some of the most clinically relevant ones.

NDN and CD1A are novel prognostic methylation markers in patients with head and neck squamous carcinomas.

BACKGROUND: HPV-associated HNSCCs have a distinct etiologic mechanism and better prognosis than those with non-HPV associated HNSCCs. However, even within the each group, there is heterogeneity in survival time. Here, we test the hypothesis that specific candidate gene methylation markers (CCNA1, NDN, CD1A, DCC, p16, GADD45A) are associated with tumor recurrence and survival, in a well-characterized, prospective, cohort of 346 HNSCC patients. METHODS: Kaplan-Meier curves were used to estimate survival time distributions. Multivariable Cox Proportional Hazards models were used to test associations between each methylation marker and OST/RPFT after adjusting for known or identified prognostic factors. Stratified Cox models included an interaction term between HPV and methylation marker to test for differences in the associations of the biomarker with OST or RPFT across HPV status. RESULTS: Methylation markers were differentially associated with patient characteristics. DNA hypermethylation of NDN and CD1A was found to be significantly associated with overall survival time (OST) in all HNSCC patients (NDN hazard ratio (HR): 2.35, 95% CI: 1.40-3.94; CD1A HR: 1.31, 95% CI: 1.01-1.71). Stratification by HPV status revealed hypermethylation of CD1A was associated with better OST and recurrence/persistence-free time (RPFT) (OST HR: 3.34, 95% CI: 1.88-5.93; RPFT HR: 2.06, 95% CI: 1.21-3.49), while hypomethylation of CCNA1 was associated with increased RPFT in HPV (+) patients only (HR: 0.31, 95% CI: 0.13-0.74). CONCLUSIONS: This study is the first to describe novel epigenetic alterations associated with survival in an unselected, prospectively collected, consecutive cohort of patients with HNSCC. DNA hypermethylation of NDN and CD1A was found to be significantly associated with increased overall survival time in all HNSCC patients. However, stratification by the important prognostic factor of HPV status revealed the immune marker, CD1A, and the cell cycle regulator, CCNA1 to be associated with prognosis in HPV (+) patients, specifically. Here, we identified novel methylation markers and specific, epigenetic molecular differences associated with HPV status, which warrant further investigation.

NCCN Guidelines implementation in the multidisciplinary Merkel Cell Carcinoma Program at the University of Michigan.

Merkel cell carcinoma (MCC) is a rare malignancy of the skin, and prospective randomized clinical studies on management and treatment are very limited. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for MCC provide up-to-date, best evidence-based, and consensus-driven management pathways with the purpose of providing best care and outcomes. Multidisciplinary management with consensus treatment recommendations to individualize patient care within the framework of these guidelines is optimal. The University of Michigan multidisciplinary MCC program uses NCCN Guidelines in the management and treatment of its patients. This article discusses 4 patient presentations to highlight the implementation of the NCCN Guidelines for MCC at the University of Michigan.

UM-SCC-103: a unique tongue cancer cell line that recapitulates the tumorigenic stem cell population of the primary tumor.

OBJECTIVE: A new head and neck cancer cell line was developed from a highly aggressive HNSCC of the oral cavity diagnosed in a 26-year-old pregnant woman. METHODS: Cells from the primary tumor were passaged in culture and genotyped as a unique cell line. The resultant cell line was assessed for its ability to replicate the primary tumor. RESULTS: The primary tumor and cell line contained 19.03% and 19.62% CD44(high) cells, respectively. CD44(high) cancer stem cells from UM-SCC-103 formed tumors after flank injections in mice that reconstituted the heterogeneity of the primary tumor. CD44 staining and histology in the primary tumor and tumors grown in vivo from the cell line were similar. CD44(high) cells from the primary tumor resulted in lung colony formation in 2 out of 2 tail vein injections in mice, whereas CD44(low) cells did not. Similarly, CD44(high) cells from UM-SCC-103 formed lung tumors in 2 out of 4 mice, whereas CD44(low) cells did not. CONCLUSION: The similarity in marker expression and tumorigenic behavior between the primary tumor and the resulting cell line strongly suggests that the cell line resembles the primary tumor that it was derived from and provides an important new research tool for the study of head and neck carcinomas in young patients.

The role of sentinel lymph node biopsy for thin cutaneous melanomas of the head and neck.

From 18% to 35% of cutaneous melanomas are located in the head and neck, and nearly 70% are thin (Breslow thickness ≤ 1 mm). Sentinel lymph node biopsy (SLNB) has an established role in staging of intermediate-thickness melanomas, however its use in thin melanomas remains controversial. In this article, we review the literature regarding risk factors for occult nodal metastasis in thin cutaneous melanoma of the head and neck (CMHN). Based on the current literature, we recommend SLNB for all lesions with Breslow thickness ≥ 0.75 mm, particularly when accompanied by adverse features including mitotic rate ≥ 1 per mm(2), ulceration, and extensive regression. SLNB should also be strongly considered in younger patients (e.g. < 40 years old), especially in the presence of additional adverse features. All patients who do not proceed with sentinel lymph node biopsy must be carefully followed to monitor for regional relapse.

Prospective head and neck cancer research: a four-decade bibliometric perspective.

BACKGROUND: It is unknown whether changes in study sponsorship have affected the proportion of prospective research on surgery, radiotherapy, and pharmacotherapy for head and neck squamous cell carcinoma (HNSCC) being published over time. PATIENTS AND METHODS: We examined prospective studies from PubMed, Ovid MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials from 1980, 1985, 1990, 1995, 2000, 2005, and 2010. Chi-squared tests were used to identify significant associations between sponsorship and authorship, treatments within study protocols, and presentation of results, whereas time-based trends were analyzed using the Cochran-Armitage test. RESULTS: Among 309 articles, industry (70, 22.7%) and the U.S. government (65, 21%) were the most common sponsors. There was a significant increase in the proportion of industry-sponsored research (p for trend = .013) and a decline in U.S. government-sponsored research (p for trend = .001) over time. The inclusion of surgery in treatment protocols declined over the past four decades (p for trend = .003). Protocols incorporating pharmacotherapy were more likely to have industry support than those without pharmacotherapy (p = .001), whereas protocols with radiotherapy (p = .003) or surgery (p = .002) were less likely to have industry support. CONCLUSION: Industry is the predominant sponsor of prospective HNSCC research, with an emphasis on pharmacotherapy.

Clinicopathologic features of primary Merkel cell carcinoma: a detailed descriptive analysis of a large contemporary cohort.

BACKGROUND: Little uniformity exists in the clinical and histologic variables reported with primary Merkel cell carcinoma (MCC). OBJECTIVE: To provide a rigorous descriptive analysis of a contemporary cohort and promote the prospective collection of detailed data on MCC for future outcome studies. METHODS AND MATERIALS: A detailed descriptive analysis was performed for clinical and histologic features of 147 patients with 150 primary MCC tumors in a prospectively collected database from 2006 to 2010. RESULTS: The majority (73.5%) of patients were at American Joint Committee on Cancer clinical stage I or II at presentation, 20.4% at stage III, and 6.1% at stage IV. Detailed descriptive clinical and histologic findings are presented. CONCLUSION: Clinical and histologic profiling of primary MCC in the literature is variable and limited. Systematic prospective collection of MCC data is needed for future outcome studies and the ability to compare and share data from multiple sources for this relatively rare tumor.