The Global Experience of Laryngeal Transplantation: Series of Eleven Patients in Three Continents.

BACKGROUND: The loss of laryngeal function affects breathing, swallowing, and voice, thus severely compromises quality of life. Laryngeal transplantation has long been suggested as a solution for selected highly affected patients with complete laryngeal function loss. OBJECTIVE: To obtain insights regarding the advantages, weaknesses, and limitations of this procedure and facilitate future advances, we collected uniform data from all known laryngeal transplants reported internationally. METHODOLOGY: A case series. Patients were enrolled retrospectively by each institutional hospital or clinic. Eleven patients with complete loss of laryngeal function undergoing total laryngeal transplantation between 1998 and 2018 were recruited. RESULTS: After a minimum of 24 months follow-up, three patients had died (27%), and there were two graft explants in survivors, one total and one partial, due to chronic rejection. In the remaining cases, voice was functional in 62.5% and 50% achieved decannulation. Swallowing was initially restricted, but only one patient was gastrostomy-dependent by 6 months and all had normal or near-normal swallowing by the end of year two after transplantation. Median follow-up was 73 months. Functional (voice, swallowing, airway) recovery peaked between 12 and 24 months. CONCLUSIONS: Laryngeal transplantation is a complex procedure with significant morbidity. Significant improvements in quality of life are possible for highly selected individuals with end-stage laryngeal disorders, including laryngeal neoplasia, but further technical and pharmacological developments are required if the technique is to be more widely applicable. An international registry should be created to provide better quality pooled data for analysis of outcomes of any future laryngeal transplants. LEVEL OF EVIDENCE: IV Laryngoscope, 2024.

Functional Laryngectomy and Quality of Life in Survivors of Head and Neck Cancer With Intractable Aspiration.

Importance: Late effects of head and neck cancer (HNC) treatment include profound dysphagia, chronic aspiration, and death. Functional laryngectomy (FL) can improve patient survival and quality of life (QoL); however, removing a failing larynx for a noncancer reason is a difficult decision. Data regarding the ability of FL to improve self-perceptions of voice, swallowing, and QOL in survivors of HNC with intractable aspiration are inconclusive. Objective: To investigate the association of FL with changes in self-reported perceptions of voice, swallowing, oral intake, QoL, and mood in survivors of HNC experiencing profound dysphagia and intractable aspiration. Design, Settings, and Participants: This cohort study was conducted at a single academic institution and included survivors of HNC with profound swallowing dysfunction and intractable aspiration who underwent FL from July 2016 through March 2022. Of the initial 22 patients enrolled, 2 patients (15%) died of aspiration pneumonia before receiving FL. Data analyses were performed from July 2016 through March 2023. Main Outcomes and Measures: Self-reported measures of voice using the VHI (30-item Voice Handicap Index), swallowing using the EAT-10 (10-item Eating Assessment Tool), functional oral intake scale using the FOIS (Functional Oral Intake Scale), and quality of life using the FACT-H&N (Functional Assessment of Cancer Therapy-Head & Neck) were assessed before FL and at 1, 3, and 6 months after FL. Mood states were evaluated using the POMS (Profile of Mood States, second edition), before FL and at 6 months after FL. Results: The study analyses included 20 patients (mean [SD] age, 72.4 (7.0) years; 19 [95%] males and 1 [5%] female) who underwent FL and had complete data across all time points. Among these, 12 patients (60%) had received chemoradiation for oropharyngeal, 7 (35%) for laryngeal, or 1 (5%) for nasopharyngeal cancer. The mean (SD) time from completion of oncologic treatment to FL was 15.5 (5.5) years. Mean (SD) score on the EAT-10 improved from 33.2 (7.4) to 23.1 (10.8) at 1 month; 12.1 (9.1) at 3 months; and 8.3 (7.4) at 6 months, with a large effect size (η2 = 0.72; 95% CI, 0.54-0.80). Mean (SD) score on the FOIS improved from 2.0 (1.5) to 2.9 (1.7) at 1 month; 4.8 (2.5) at 3 months; and 5.2 (1.7) at 6 months, with a large effect size (η2 = 0.6; 95% CI, 0.38-0.71). Improvement in oral intake was achieved in 19 patients (95%), and feeding tubes were removed in 10 of 16 patients (63%) who were feeding tube-dependent; 6 patients (27%) continued to require supplemental tube feedings. Mean (SD) score on the VHI improved from 63.6 (34.0) to 86.9 (33.7) at 1 month; 71.3 (36.1) at 3 months; and 39.7 (26.9) at 6 months, with a large effect size (η2 = 0.42; 95% CI, 0.19-0.56). Seventeen patients (85%) were able to use a tracheoesophageal voice prosthesis for alaryngeal communication. Mean (SD) score on the FACT-H&N improved from 86.2 (17.8) to 93.6 (18.4) at 1 month; 109.0 (18.4) at 3 months; and 121.0 (16.8) at 6 months, with a large effect size (η2 = 0.64; 95% CI, 0.42-0.74). Mean (SD) score on the POMS improved from 58.9 (13.2) at baseline to 44.5 (9.9) at 6 months, with a large effect size (Cohen d = 1.04; 95% CI, 0.48-1.57). None of the patients experienced major complications of FL; 1 patient (5%) had a postoperative pharyngocutaneous fistula. Conclusions and Relevance: The findings of this cohort study indicate that FL was associated with marked improvements in self-perception of voice and swallowing, functional oral intake, QoL, and mood state among survivors of HNC. These findings can serve as a framework for FL counseling among HNC survivors experiencing profound dysphagia and intractable aspiration.

Anatomy-Specific Classification Model Using Label-Free FLIm to Aid Intraoperative Surgical Guidance of Head and Neck Cancer.

Intraoperative identification of head and neck cancer tissue is essential to achieve complete tumor resection and mitigate tumor recurrence. Mesoscopic fluorescence lifetime imaging (FLIm) of intrinsic tissue fluorophores emission has demonstrated the potential to demarcate the extent of the tumor in patients undergoing surgical procedures of the oral cavity and the oropharynx. Here, we report FLIm-based classification methods using standard machine learning models that account for the diverse anatomical and biochemical composition across the head and neck anatomy to improve tumor region identification. Three anatomy-specific binary classification models were developed (i.e., "base of tongue," "palatine tonsil," and "oral tongue"). FLIm data from patients (N = 85) undergoing upper aerodigestive oncologic surgery were used to train and validate the classification models using a leave-one-patient-out cross-validation method. These models were evaluated for two classification tasks: (1) to discriminate between healthy and cancer tissue, and (2) to apply the binary classification model trained on healthy and cancer to discriminate dysplasia through transfer learning. This approach achieved superior classification performance compared to models that are anatomy-agnostic; specifically, a ROC-AUC of 0.94 was for the first task and 0.92 for the second. Furthermore, the model demonstrated detection of dysplasia, highlighting the generalization of the FLIm-based classifier. Current findings demonstrate that a classifier that accounts for tumor location can improve the ability to accurately identify surgical margins and underscore FLIm's potential as a tool for surgical guidance in head and neck cancer patients, including those subjects of robotic surgery.

Using the Patient Health Questionnaire-2 to improve depression screening in head and neck cancer patients.

PURPOSE: The purpose of this study is to examine the use of the Patient Health Questionnaire-2 (PHQ-2) to screen for depression in patients undergoing treatment for head and neck cancer and to evaluate potential patient-specific risk factors that may contribute to depression. MATERIALS AND METHODS: This is a retrospective study at a tertiary-level hospital of outpatient adult patients with head and neck cancer who completed the PHQ-2/9 from 2019 to 2020. Patients were given a PHQ-2 during a surveillance visit. A positive PHQ-2 screen (score ≥ 3) prompted further evaluation with a PHQ-9. Patients were stratified into either low risk (PHQ-2 score < 3) or high risk (PHQ-2 score ≥ 3) for depression. Univariate regression was performed on all variables, and a multivariate logistic regression was performed on statistically significant variables (P < 0.05). RESULTS: In total, 110 patients were included in this study. Fifteen (14 %) patients had a positive PHQ-2 screen with a score ≥ 3 and underwent evaluation with a PHQ-9. The median PHQ-9 score was 15 (6-26). The PHQ-2 ≥ 3 group were significantly younger (59 years vs. 67 years; P = 0.03) and had a greater number of patients with a psychiatric history (33 % vs. 8 %; P < 0.01). CONCLUSIONS: There is a strong association between a PHQ-2 score ≥ 3 and detection of depressive symptoms among patients with head and neck cancer. Younger age and pretreatment mental illness are significant risk factors for developing depression following treatment. Early screening and treatment should be considered for all patients to mitigate the burden of depression and suicide in this patient population. Further research is warranted to investigate utilization of the PHQ-2/9 to detect depression and barriers that exist for timely screening and interventions.

Quality appraisal of clinical practice guidelines for the use of radiofrequency ablation in the treatment of thyroid nodules and cancer.

INTRODUCTION: Radiofrequency ablation (RFA) has gained significant recent global interest in the treatment of benign thyroid nodules and thyroid cancer. It is a relatively new, minimally invasive, thermal ablation technique that is an alternative to surgery. Several clinical practice guidelines (CPGs), consensus statements, and recommendations currently exist for the use of RFA in the treatment of benign thyroid nodules and thyroid cancers. These documents have considerable variability amongst them, and to date, their quality and methodologic rigor have not been appraised. OBJECTIVE: To identify and perform a quality appraisal of clinical practice guidelines for RFA in the treatment of benign thyroid nodules and thyroid cancer using the Appraisal of Guidelines for Research and Evaluation (AGREE II) tool. METHODS: A comprehensive literature search was performed in MEDLINE (via PubMed), EMBASE, and SCOPUS databases from inception to November 1, 2021. Four reviewers independently evaluated each guideline using the AGREE II instrument. Scaled domain scores were generated and the threshold used for satisfactory quality was >60%. Additionally, intraclass correlation coefficients (ICCs) were calculated to determine level of agreement between reviewers. RESULTS: Seven guidelines were selected for final evaluation based on inclusion/exclusion criteria. Two guidelines were classified "high" quality, one "average" quality, and the rest "low" quality. The "Clarity and Presentation" (65.68 ± 26.1) and "Editorial Independence" (61.32 ± 25.8) domains received the highest mean scores, while the "Applicability" (32.14 ± 22.8) and "Rigor of Development" (45.02 ± 29.8) domains received the lowest mean scores. ICC statistical analysis showed high magnitude of agreement between reviewers with a range of (0.722-0.944). CONCLUSION: Reflecting upon our quality appraisal, it is evident that the quality and methodologic rigor of RFA guidelines can be improved upon in the future. Our findings also elucidate the existing variability/discrepancies amongst guidelines in the indications and use of RFA.

Polyamine Metabolites as Biomarkers in Head and Neck Cancer Biofluids.

Background: Novel, non-invasive diagnostic biomarkers that facilitate early intervention in head and neck cancer are urgently needed. Polyamine metabolites have been observed to be elevated in numerous cancer types and correlated with poor prognosis. The aim of this study was to assess the concentration of polyamines in the saliva and urine from head and neck cancer (HNC) patients, compared to healthy controls. Methods: Targeted metabolomic analysis was performed on saliva and urine from 39 HNC patient samples and compared to 89 healthy controls using a quantitative, targeted liquid chromatography mass spectrometry approach. Results: The metabolites N1-acetylspermine (ASP), N8-acetylspermidine (ASD) and N1,N12-diacetylspermine (DAS) were detected at significantly different concentrations in the urine of HNC patients as compared to healthy controls. Only ASP was detected at elevated levels in HNC saliva as compared to healthy controls. Conclusion: These data suggest that assessment of polyamine-based metabolite biomarkers within the saliva and urine warrants further investigation as a potential diagnostic in HNC patients.

Head and neck cancer survivorship consensus statement from the American Head and Neck Society.

OBJECTIVES: To provide a consensus statement describing best practices and evidence regarding head and neck cancer survivorship. METHODS: Key topics regarding head and neck cancer survivorship were identified by the multidisciplinary membership of the American Head and Neck Society Survivorship, Supportive Care & Rehabilitation Service. Guidelines were generated by combining expert opinion and a review of the literature and categorized by level of evidence. RESULTS: Several areas regarding survivorship including dysphonia, dysphagia, fatigue, chronic pain, intimacy, the ability to return to work, financial toxicity, lymphedema, psycho-oncology, physical activity, and substance abuse were identified and discussed. Additionally, the group identified and described the role of key clinicians in survivorship including surgical, medical and radiation oncologists; dentists; primary care physicians; psychotherapists; as well as physical, occupational, speech, and respiratory therapists. CONCLUSION: Head and neck cancer survivorship is complex and requires a multidisciplinary approach centered around patients and their caregivers. As survival related to head and neck cancer treatment improves, addressing post-treatment concerns appropriately is critically important to our patient's quality of life. There continues to be a need to define effective and efficient programs that can coordinate this multidisciplinary effort toward survivorship.

Bereavement Practices Among Head and Neck Cancer Surgeons.

OBJECTIVES: Head and neck cancer surgeons frequently interact with dying patients with advanced disease and their families, but little is known about their bereavement practices after a patient's death. The aim of this study is to elucidate the frequency of common bereavement practices, cited barriers to bereavement, and predictive physician factors that lead to an increase in bereavement practices among head and neck cancer surgeons. METHODS: A 20-item survey was sent to 827 active surgeons of the American Head and Neck Society. Approval was obtained and the survey was distributed through the American Head and Neck Society. Demographics, frequency of common bereavement practices, empathy, and barriers were assessed. Multiple linear regression was performed to determine physician factors associated with more frequent bereavement follow-up. RESULTS: There were 156 respondents (18.9% response rate). Overall, surgeons were more likely to usually/always call (48.5%) or send a letter (42.4%) compared with other practices such as attending funerals (0%), offering family meetings (18.6%), or referring family members to counseling (7.7%). Many barriers were cited as being at least somewhat important: being unaware about a patient's death (67.3%) was the most cited, whereas 51.3% cited a lack of mentorship/training in this area. Scoring higher on empathy questions (P ≤ .001) was associated with more frequent surgeon bereavement follow-up with the family of deceased patients. CONCLUSION: There is substantial practice variation among surgeons suggesting a lack of consensus on their roles in bereavement follow-up. Having higher empathy was predictive of higher engagement. LEVEL OF EVIDENCE: NA Laryngoscope, 132:1971-1975, 2022.

Autologous Muscle-Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer.

OBJECTIVES/HYPOTHESIS: To evaluate the safety and potential efficacy of autologous muscle-derived cells (AMDCs) for the treatment of swallowing impairment following treatment for oropharynx cancer. STUDY DESIGN: Prospective, phase I, open label, clinical trial. METHODS: Oropharynx cancer survivors disease free ≥2 years post chemoradiation were recruited. All patients had swallowing impairment but were not feeding tube dependent (Functional Oral Intake Scale [FOIS] ≥ 5). Muscle tissue (50-250 mg) was harvested from the vastus lateralis and 150 × 106 AMDCs were prepared (Cook MyoSite Inc., Pittsburgh, PA). The cells were injected into four sites throughout the intrinsic tongue musculature. Participants were followed for 24 months. The primary outcome measure was safety. Secondary endpoints included objective measures on swallowing fluoroscopy, oral and pharyngeal pressure, and changes in patient-reported outcomes. RESULTS: Ten individuals were enrolled. 100% (10/10) were male. The mean age of the cohort was 65 (±8.87) years. No serious adverse event occurred. Mean tongue pressure increased significantly from 26.3 (±11.1) to 31.8 (±9.5) kPa (P = .017). The mean penetration-aspiration scale did not significantly change from 5.6 (±2.1) to 6.8 (±1.8), and the mean FOIS did not significantly change from 5.4 (±0.5) to 4.6 (±0.7). The incidence of pneumonia was 30% (3/10) and only 10% (1/10) experienced deterioration in swallowing function throughout 2 years of follow-up. The mean eating assessment tool (EAT-10) did not significantly change from 24.1 (±5.57) to 21.3 (±6.3) (P = .12). CONCLUSION: Results of this phase I clinical trial demonstrate that injection of 150 × 106 AMDCs into the tongue is safe and may improve tongue strength, which is durable at 2 years. A blinded placebo-controlled trial is warranted. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:523-527, 2022.

Influence of Socioeconomic Status on Incident Medical Conditions in Two-Year Survivors of Adolescent or Young Adult Differentiated Thyroid Cancer.

Purpose: We sought to enumerate secondary medical conditions from hospitalization records in adolescent and young adult (AYA) differentiated thyroid cancer (DTC) survivors and identify characteristics of patients with increased likelihood of subsequent medical diagnoses. Methods: Using data from the California Cancer Registry and statewide hospitalization data, we examined incident oncologic, endocrine, pulmonary, hematologic, and cardiovascular diagnoses in 12,312 AYA (aged 15-39) patients diagnosed with DTC in 1996-2012 and surviving >2 years after diagnosis with follow-up through 2014. We calculated the cumulative incidence of each condition accounting for the competing risk of death and used multivariable Cox proportional hazards regression to evaluate sociodemographic and clinical characteristics associated with each incident condition. Results: The 10-year cumulative incidences of multiple medical conditions were particularly high in blacks and Hispanics. Asian/Pacific Islander survivors were most likely to develop subsequent cancers. Men had higher rates of cardiovascular and diabetes diagnoses than women, but lower rates of asthma and cytopenias. Low socioeconomic status and/or public or no insurance were associated with a higher risk of several diagnoses. More extensive disease stage and thyroid surgery increased the risk of calcium and phosphorus metabolism disorders. Neck reoperation associated with the risk of cytopenias, as well as subsequent endocrine, cardiovascular, and respiratory diagnoses. Conclusion: The incidence of medical conditions after thyroid cancer diagnosis and treatment differ among racial/ethnic groups and sexes. Those residing in lower socioeconomic neighborhoods, those with public or no insurance, and those who require further neck surgery have substantially higher burdens of subsequent medical diagnoses.

The Impact of COVID-19 on Head and Neck Cancer Treatment: Before and During the Pandemic.

OBJECTIVES: To describe the impact that the coronavirus disease 2019 (COVID-19) pandemic had on the presentation of patients with head and neck cancer in a single tertiary care center. STUDY DESIGN: Retrospective cohort study. SETTING: Academic institution. METHODS: We performed a retrospective review of patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC) who presented as new patients between September 10, 2019, and September 11, 2020. Patients presenting during the 6 months leading up to the announcement of the pandemic (pre-COVID-19 period) on March 11, 2020, were compared to those presenting during the first 6 months of the pandemic (COVID-19 period). Demographics, time to diagnosis and treatment, and tumor characteristics were analyzed. RESULTS: There were a total of 137 patients analyzed with newly diagnosed malignancies. There were 22% fewer patients evaluated during the COVID-19 timeframe. The groups were similar in demographics, duration of symptoms, time to diagnosis, time to surgery, extent of surgery, and adjuvant therapy. There was a larger proportion of tumors classified as T3/T4 (61.7%) in the COVID-19 period vs the pre-COVID-19 period (40.3%) (P = .024), as well as a larger median tumor size during the COVID-19 period (P = .0002). There were no differences between nodal disease burden (P = .48) and distant metastases (P = .42). CONCLUSION: Despite similar characteristics, time to diagnosis, and surgery, our findings suggest that there was an increase in primary tumor burden in patients with HNSCC during the early COVID-19 pandemic.

Intraoperative Margin Assessment in Oral and Oropharyngeal Cancer Using Label-Free Fluorescence Lifetime Imaging and Machine Learning.

OBJECTIVE: To demonstrate the diagnostic ability of label-free, point-scanning, fiber-based Fluorescence Lifetime Imaging (FLIm) as a means of intraoperative guidance during oral and oropharyngeal cancer removal surgery. METHODS: FLIm point-measurements acquired from 53 patients (n = 67893 pre-resection in vivo, n = 89695 post-resection ex vivo) undergoing oral or oropharyngeal cancer removal surgery were used for analysis. Discrimination of healthy tissue and cancer was investigated using various FLIm-derived parameter sets and classifiers (Support Vector Machine, Random Forests, CNN). Classifier output for the acquired set of point-measurements was visualized through an interpolation-based approach to generate a probabilistic heatmap of cancer within the surgical field. Classifier output for dysplasia at the resection margins was also investigated. RESULTS: Statistically significant change (P 0.01) between healthy and cancer was observed in vivo for the acquired FLIm signal parameters (e.g., average lifetime) linked with metabolic activity. Superior classification was achieved at the tissue region level using the Random Forests method (ROC-AUC: 0.88). Classifier output for dysplasia (% probability of cancer) was observed to lie between that of cancer and healthy tissue, highlighting FLIm's ability to distinguish various conditions. CONCLUSION: The developed approach demonstrates the potential of FLIm for fast, reliable intraoperative margin assessment without the need for contrast agents. SIGNIFICANCE: Fiber-based FLIm has the potential to be used as a diagnostic tool during cancer resection surgery, including Transoral Robotic Surgery (TORS), helping ensure complete resections and improve the survival rate of oral and oropharyngeal cancer patients.

Laryngeal Transplantation.

Laryngeal transplantation offers the hope of replacing voice and laryngeal function in patients with debilitating laryngeal injuries or loss of the larynx from trauma or oncologic reasons. Our group at UC Davis performed a laryngotracheal transplantation, and our experience is reviewed in this chapter. The indications, challenges, and limitations of this procedure are highlighted, and the world's other published cases are reviewed.

Myopericytoma of the Neck Originating From the Middle Scalene: A Case Report.

We report the case of a myopericytoma of the neck. A 23-year-old female noticed a small, nontender mass in her left supraclavicular fossa. The mass grew over a period of 5 months, prompting the patient to seek evaluation. There were no motor or sensory deficits. Imaging suggested a mass originating from the middle scalene muscle. Computed tomography-guided core needle biopsy demonstrated a spindle cell neoplasm with smooth muscle differentiation. Complete surgical excision was performed. Histopathological and immunohistochemical evaluation of the tissue sample suggested myopericytoma. Myopericytoma is an extremely rare tumor of the head and neck. To our knowledge, this is the first reported case of a myopericytoma originating from a scalene muscle.

Preclinical translation of exosomes derived from mesenchymal stem/stromal cells.

Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizontal transfer of various macromolecules previously believed to be cell-autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane-associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there have been more than 200 preclinical studies of exosome-based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC-derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC-derived exosome-based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC-exosomes published to date are promising, several outstanding questions remain to be answered that warrant further preclinical investigation.

Oncologic outcomes after surgery for locally aggressive basal cell carcinoma of the head and neck.

OBJECTIVE: Although basal cell carcinoma (BCC) is the most common skin cancer, locally aggressive BCC of the head and neck is rare and not well studied. STUDY DESIGN: Retrospective review of patients who underwent primary surgical resection of locally aggressive head and neck BCC at a single tertiary academic center. RESULTS: Eighty-seven patients with 98 tumors demonstrated a 5-year Kaplan-Meier estimated recurrence-free survival of 64.5%, overall survival of 83.3%, and disease-specific survival of 98.3%. Intraoperative positive frozen section margin was a strong independent predictor of local recurrence (hazard ratio 6.88, P = 0.038) and was more likely to occur in tumors previously treated with radiation (odds ratio 6.47 = 0.05). CONCLUSION: Locally aggressive BCCs of the head and neck have high rates of local recurrence but low disease-specific mortality when treated with primary surgery and selected use of adjuvant therapy. Intraoperative positive frozen section margin is a strong independent predictor of local recurrence and is more likely in tumors that were previously treated with radiation therapy. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:115-119, 2020.

Immunoregulatory Potential of Exosomes Derived from Cancer Stem Cells.

Head and neck squamous cell carcinomas (HNSCCs) are malignancies that originate in the mucosal lining of the upper aerodigestive tract. Despite advances in therapeutic interventions, survival rates among HNSCC patients have remained static for years. Cancer stem cells (CSCs) are tumor-initiating cells that are highly resistant to treatment, and are hypothesized to contribute to a significant fraction of tumor recurrences. Consequently, further investigations of how CSCs mediate recurrence may provide insights into novel druggable targets. A key element of recurrence involves the tumor's ability to evade immunosurveillance. Recent published reports suggest that CSCs possess immunosuppressive properties, however, the underlying mechanism have yet to be fully elucidated. To date, most groups have focused on the role of CSC-derived secretory proteins, such as cytokines and growth factors. Here, we review the established immunoregulatory role of exosomes derived from mixed tumor cell populations, and propose further study of CSC-derived exosomes may be warranted. Such studies may yield novel insights into new druggable targets, or lay the foundation for future exosome-based diagnostics.

Malnutrition evaluation in head and neck cancer patients: Practice patterns among otolaryngologists and radiation oncologists.

BACKGROUND: Physician practice patterns regarding diagnosis and management of malnutrition in the head and neck cancer patient population are not well studied. METHODS: A 17-question survey was distributed to 1392 members of the American Head and Neck Society (AHNS). The impact of hospital type, fellowship training, experience, and specialty was assessed. RESULTS: Among AHNS members, there were 124 total respondents (9% response rate), including both otolaryngologists and radiation oncologists. Respondents strongly agreed (90%) that malnutrition negatively impacts patient outcomes. The majority (63%) felt comfortable screening for malnutrition, but 13% reported no routine assessment of malnutrition; 57% were unfamiliar with relevant guidelines. Barriers to screening included lack of familiarity with screening tools/guidelines, lack of time, and lack of access to dietitian. CONCLUSION: Although there was a strong consensus among respondents that the identification and management of malnutrition among head and neck cancer patients is critical, familiarity with relevant guidelines was poor.

MET Genomic Alterations in Head and Neck Squamous Cell Carcinoma (HNSCC): Rapid Response to Crizotinib in a Patient with HNSCC with a Novel MET R1004G Mutation.

Identification of effective targeted therapies for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) remains an unmet medical need. A patient with platinum-refractory recurrent oral cavity HNSCC underwent comprehensive genomic profiling (CGP) that identified an activating MET mutation (R1004). The patient was treated with the oral MET tyrosine kinase inhibitor crizotinib with rapid response to treatment.Based on this index case, we determined the frequency of MET alterations in 1,637 HNSCC samples, which had been analyzed with hybrid capture-based CGP performed in the routine course of clinical care. The specimens were sequenced to a median depth of >500× for all coding exons from 182 (version 1, n = 24), 236 (version 2, n = 326), or 315 (version 3, n = 1,287) cancer-related genes, plus select introns from 14 (version 1), 19 (version 2), or 28 (version 3) genes frequently rearranged in cancer. We identified 13 HNSCC cases (0.79%) with MET alterations (4 point mutation events and 9 focal amplification events). MET-mutant or amplified tumors represent a small but potentially actionable molecular subset of HNSCC. KEY POINTS: This case report is believed to be the first reported pan-cancer case of a patient harboring a MET mutation at R1004 demonstrating a clinical response to crizotinib, in addition to the first documented case of head and neck squamous cell carcinoma (HNSCC) with any MET alteration responding to crizotinib.The positive response to MET inhibition in this patient highlights the significance of comprehensive genomic profiling in advanced metastatic HNSCC to identify actionable targetable molecular alterations as current treatment options are limited.

HPV-related oropharyngeal cancer: a review on burden of the disease and opportunities for prevention and early detection.

The incidence of oropharyngeal cancer (OPC) related to infection with human papillomavirus (HPV) is rising, making it now the most common HPV-related malignancy in the United States. These tumors present differently than traditional mucosal head and neck cancers, and those affected often lack classic risk factors such as tobacco and alcohol use. Currently, there are no approved approaches for prevention and early detection of disease, thus leading many patients to present with advanced cancers requiring intense surgical or nonsurgical therapies resulting in significant side effects and cost to the health-care system. In this review, we outline the evolving epidemiology of HPV-related OPC. We also summarize the available evidence corresponding to HPV-related OPC prevention, including efficacy and safety of the HPV vaccine in preventing oral HPV infections. Finally, we describe emerging techniques for identifying and screening those who may be at high risk for developing these tumors.