Early, precise, and safe clinical evaluation of the pharmacodynamic effects of novel agents in the intact human tumor microenvironment.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit). Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4-96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure. Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment. Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

Otolaryngology Resident Education and Perceptions of e-cigarettes.

OBJECTIVE: To date, there are no reports of otolaryngology residents' knowledge and confidence in discussing e-cigarette use. The purpose of this study was to evaluate otolaryngology resident e-cigarette knowledge and confidence in counseling patients on e-cigarette use. STUDY DESIGN: Cross-sectional national survey. SETTING: Accreditation Council for Graduate Medical Education otolaryngology residents in the United States. METHODS: US otolaryngology residents were distributed surveys electronically in September 2020. RESULTS: A total of 150 participants replied for a response rate of 8.88%. The majority, 93.10% have not received formal education on e-cigarettes during their residency training. The most common resource of e-cigarette information overall was social media (78.46%). Within academia, the most common resources of e-cigarette education were patient interactions (63.16%) and colleagues (54.74%). Patients commonly inquire residents about e-cigarettes for smoking cessation (85.07%) and their long-term health effects (83.58%). Almost 67% of residents rarely or never ask patients about e-cigarette use. Only 4.35% of residents are not confident discussing traditional cigarette use, while 58.70% are not confident discussing e-cigarettes. CONCLUSION: Otolaryngology residents have not received formal education in e-cigarettes and are not confident discussing e-cigarettes with their patients. This highlights the need for e-cigarette education during otolaryngology residency to improve patient e-cigarette counseling.

E-cigarette use and tobacco harm reduction: Pilot survey study evaluating perspectives of head and neck surgeons.

BACKGROUND: Electronic cigarettes (EC) are popular devices that aerosolize a nicotine and have been controversially considered tool for smoking cessation and tobacco harm reduction (THR). The purpose of this pilot study was to identify head and neck cancer (HNC) surgeons' attitudes/perspectives of EC and smoking cessation counseling. METHODS: Cross-sectional survey administered to American Head and Neck Society (AHNS) members. RESULTS: Response rate was 136 members (15.1%) with the majority 102 (75.00%) having unfavorable attitude toward EC for smoking cessation. Fifty-eight respondents (42.7%) were familiar with THR. Those familiar with THR 37 (63.79%) routinely inquire about EC use. Compared between THR familiarity, 22 (37.93%) believed the benefits of EC for smoking cessation outweighed the potential risks. CONCLUSIONS: HNC specialists have an unfavorable attitude toward EC. Those familiar with THR were more likely to inquire about EC use. They were also less likely to have a definitive opinion on the benefits of quitting combustible cigarettes.

Molecular Classification of Lymph Node Metastases Subtypes Predict for Survival in Head and Neck Cancer.

PURPOSE: In advanced stage head and neck squamous cell cancers (HNSCC), approximately half of the patients with lymph node metastases (LNM) are not cured. Given the heterogeneous outcomes in these patients, we profiled the expression patterns of LNMs to identify the biological factors associated with patient outcomes.Experimental Design: We performed mRNAseq and miRNAseq on 72 LNMs and 29 matched primary tumors from 34 patients with HNSCC. Clustering identified molecular subtypes in LNMs and in primary tumors. Prediction Analysis of Microarrays algorithm identified a 73-gene classifier that distinguished LNM subtypes. Gene-set enrichment analysis identified pathways upregulated in LNM subtypes. RESULTS: Integrative clustering identified three distinct LNM subtypes: (i) an immune subtype (Group 1), (ii) an invasive subtype (Group 2), and (iii) a metabolic/proliferative subtype (Group 3). Group 2 subtype was associated with significantly worse locoregional control and survival. LNM-specific subtypes were not observed in matched primary tumor specimens. In HNSCCs, breast cancers, and melanomas, a 73-gene classifier identified similar Group 2 LNM subtypes that were associated with worse disease control and survival only when applied to lymph node sites, but not when applied to other primary tumors or metastatic sites. Similarly, previously proposed prognostic classifiers better distinguished patients with worse outcomes when applied to the transcriptional profiles of LNMs, but not the profiles of primary tumors. CONCLUSIONS: The transcriptional profiles of LNMs better predict outcomes than transcriptional profiles of primary tumors. The LNMs display site-specific subtypes associated with worse disease control and survival across multiple cancer types.

Survival outcomes for postoperative chemoradiation in intermediate-risk oral tongue cancers.

BACKGROUND: The survival outcomes for surgery + postoperative radiotherapy (S+RT) or surgery + postoperative chemoradiation (S+CRT) was compared in patients having oral tongue cancers with intermediate-risk pathological features. METHODS: Using the National Cancer Database (NCDB), overall survival (OS) for S+RT or S+CRT was estimated using the Kaplan-Meier methods and Cox proportional hazard models in the entire population (n = 2803) and in a propensity-matched cohort (n = 1136). RESULTS: The 3-year OS was 73.3% for S+CRT versus 66.7% for S+RT (P = .02). The S+CRT improved the 3-year OS for patients with 2 or more involved metastatic lymph nodes (≥2 MLNs; P = .01) but not for patients with <2 MLNs (P = .73). Undergoing S+CRT improved the 3-year OS for patients with pathologic T classification (pT) pT3-pT4 disease (P = .01) but not for patients with pT1-pT2 disease (P = .18). CONCLUSION: Undergoing S+CRT was associated with improved survival for patients with tongue cancers with ≥2 MLNs and/or pT3-pT4 suggesting that specific intermediate-risk pathological features benefit from treatment intensification.

Differences in Survival With Surgery and Postoperative Radiotherapy Compared With Definitive Chemoradiotherapy for Oral Cavity Cancer: A National Cancer Database Analysis.

Importance: Because locally advanced oral cavity squamous cell carcinoma (OCSCC) is often treated with surgery followed by postoperative radiotherapy (S+PORT), the effectiveness of organ preservation with concurrent chemoradiotherapy (CRT) remains unclear. Objective: To compare the differences in survival between patients with locally advanced OCSCC treated with S+PORT or CRT. Design, Setting, and Participants: Using the National Cancer Database, this study compared 6900 patients with stage III to IVA OCSCC treated with S+PORT and CRT from 2004 through 2012 at academic and community-based cancer clinics. Comparisons were made using Kaplan-Meier methods and Cox proportional hazards regression models using the entire cohort and a propensity score-matched cohort of 2286 patients. Main Outcomes and Measures: Overall survival (OS). Results: Of the 6900 study patients, 4809 received S+PORT (3080 male [64.0%] and 1792 [36.0%] female) and 2091 received CRT (1453 male [69.5%] and 638 [30.5%] female). Median follow-up for the entire group was 23.0 months overall but was shorter for patients receiving CRT (17.3-month) vs S+PORT (25.6 months). Patients receiving CRT were more likely to be older than 60 years, treated before 2007, live within 10 miles of the treating facility, treated at nonacademic centers, have more comorbidities, have T3 to T4a tumors, and have N2a to N2c nodal disease. Propensity score matching identified cohorts of patients with similar clinical variables. S+PORT was associated with improved survival among all patients (3-year OS: 53.9% for S+PORT vs 37.8% for CRT; difference = 16.1%; 95% CI, 13.6%-18.6%) and in the propensity score-matched cohort (3-year OS: 51.8% for S+PORT vs 39.3% for CRT; difference = 11.9%; 95% CI, 7.8%-16.0%). S+PORT was associated with improved survival among patients with T3 to T4a tumors (3-year OS: 49.7% for S+PORT vs 36.0% for CRT; difference = 16.1%; 95% CI, 13.6%-18.6%) but was not associated with improved survival among patients with T1 to T2 tumors (3-year OS: 59.1% for S+PORT vs 53.5% for CRT; difference = 5.6%; 95% CI, -3.1% to 14.3%). Conclusions and Relevance: Compared with CRT, S+PORT was associated with improved survival for locally advanced OCSCCs, especially in T3 to T4a disease. These data support the use of surgery as the initial treatment modality for operable OCSCCs.

Predictors and outcomes for chronic tracheostomy after chemoradiation for advanced laryngohypopharyngeal cancer.

OBJECTIVES/HYPOTHESIS: After concurrent chemoradiation for head and neck squamous cell cancer, patients with laryngeal incompetence may not recover function. We assessed variables predicting tracheostomy dependence as a measure of poor laryngeal function after chemoradiation. STUDY DESIGN: Retrospective METHODS: Analysis of 109 patients treated with chemoradiation for locoregionally advanced laryngohypopharyngeal squamous cell cancers between 1992 and 2013. Median follow-up was 17.0 and 17.2 months for tracheostomy and nontracheostomy dependent patients, respectively. RESULTS: For all patients, multivariate analysis demonstrated persistent tracheostomy was associated with pretreatment tracheostomy, subglottic extension, three-dimensional conformal radiotherapy (3DCRT) and postradiotherapy lymphadenectomy. When analyzed by primary site, tracheostomy dependence was associated with pretreatment tracheostomy, subglottic extension, and 3DCRT in larynx primaries, and with pretreatment tracheostomy and feeding tube dependency in hypopharynx primaries. Tracheostomy dependence did not impact local control, progression-free survival or overall survival on univariate analysis. CONCLUSION: After curative chemoradiation, long-term tracheostomy was associated with pretreatment tracheostomy, subglottic extension, postradiotherapy lymphadenectomy, and 3DCRT but did not impact outcomes. These factors may inform treatment decision making regarding organ preservation approaches for locally advanced laryngeal and hypopharyngeal cancers. LEVEL OF EVIDENCE: 4.

Effect of postradiotherapy neck dissection on nonregional disease sites.

IMPORTANCE: After chemoradiation for head and neck cancer, more than 90% of patients who achieve a complete clinical response on imaging have their disease regionally controlled without postradiotherapy neck dissections (PRNDs). Because several groups have reported that lymph node involvement also predicts failure at both the primary and distant sites, the extent to which PRND affects nonregional sites of disease remains unclear. OBJECTIVE: To evaluate how PRND affects local control (LC) and distant control in patients who achieve a complete clinical response. DESIGN, SETTING, AND PARTICIPANTS: We retrospectively reviewed 287 patients (74 of whom underwent PRND) from the University of Illinois at Chicago Medical Center who were treated for stage III/IV disease with definitive chemoradiation from January 1, 1990, through December 31, 2012. INTERVENTIONS: Chemoradiation followed by lymph node dissection or observation. MAIN OUTCOMES AND MEASURES: End points evaluated included LC, regional control, freedom from distant metastasis, progression-free survival (PFS), and overall survival using first-failure analysis. RESULTS: Patients with advanced nodal disease (stage N2b or greater; n = 176) had improved PFS (74.6% vs 39.1%; P < .001), whereas patients with lesser nodal disease had similar PFS. For patients with advanced nodal disease, PRND improved 2-year LC (85.5% vs 53.5%; P < .001), locoregional control with PRND (78.9% vs 45.7%; P < .001), freedom from distant metastasis (79.5% vs 67.5%; P = .03), and overall survival (84.5% vs 61.7%; P = .004) but not regional control (96.9% vs 90.1%; P = .21). The benefit in LC (87.4% vs 66.2%; P = .02) and PFS (80.7% vs 53.4%; P = .01) persisted for those with negative posttreatment imaging results who underwent PRND. On univariate analysis, PRND, alcohol use, nodal stage, and chemoradiation significantly affected 2-year LC and/or PFS. On multivariate analysis, PRND remained strongly prognostic for 2-year LC (hazard ratio, 0.22; 95% CI, 0.07-0.54; P < .001) and PFS (hazard ratio, 0.42; 95% CI, 0.23-0.74; P = .002). CONCLUSIONS AND RELEVANCE: Postradiotherapy neck dissection improved control of nonregional sites of disease in patients with advanced nodal disease who achieved a complete response after chemoradiation. Thus, PRND may affect the control of nonnodal sites through possible mechanisms, such as clearance of incompetent lymphatics and prevention of reseeding of the primary and distant sites.

Racial parities in outcomes after radiotherapy for head and neck cancer.

BACKGROUND: Although black patients experience worse outcomes after treatment for squamous cell carcinoma of the head and neck (HNSCC), these conclusions were based on populations in which blacks comprised a minority of patients. The objective of the current study was to determine the impact of race on outcomes in patients with HNSCC who received radiotherapy at an institution in which blacks comprised the majority of patients. METHODS: In this retrospective cohort study, the authors reviewed 366 black patients and 236 white patients who had nonmetastatic HNSCC for which they received radiotherapy between 1990 and 2012. The primary study outcome measures were locoregional control, freedom from distant metastasis, progression-free survival, and overall survival. RESULTS: The median follow-up was 18.3 months for all patients. The 2-year locoregional control rate was 71.9% for black patients compared with 64.2% for white patients (hazard ratio, 0.72; P=.03). There was no difference between blacks and whites regarding 2-year freedom from distant metastasis, progression-free survival, or overall survival. Among the patients who had stage III through IVB disease, blacks and whites had similar outcomes. On multivariate analysis, race was not statistically significant for locoregional control, freedom from distant metastasis, progression-free survival, or overall survival. Despite these similar outcomes, black patients had worse socioeconomic factors and increased comorbidities but had similar treatment compliance compared with white patients. CONCLUSIONS: With more adverse prognostic factors, black patients experienced oncologic outcomes similar to the outcomes of white patients after receiving radiotherapy for HNSCC. The current data suggest that centers that treat large percentages of minority patients who receive radiotherapy for HNSCCs may overcome existing health care disparities through improved treatment compliance.

Case report: Metastatic breast cancer presenting as a hypopharyngeal mass.

Although carcinoma of the breast has a propensity toward distant metastasis, metastasis to the head and neck is uncommon. Most patients with metastasis to the head and neck region present with cervical lymphadenopathy; however, spread to the upper aerodigestive tract has been described previously. We present a case of a patient found to have a pedunculated mass in her right piriform sinus. When she swallowed, the mass would completely prolapse into the esophagus and cause symptoms. Subsequent workup revealed widespread metastatic disease, for which the patient was treated with chemoradiotherapy. Microlaryngoscopy with excision of the mass was performed for palliation of her dysphagia, and a diagnosis of metastatic breast carcinoma was obtained. The patient healed well from the excision and went on to be treated for the metastatic breast cancer. To our knowledge, our report represents the first case of metastatic breast carcinoma presenting as severe dysphagia.

The efficacy of preoperative screening and the treatment of methicillin-resistant Staphylococcus aureus in an otolaryngology surgical practice.

OBJECTIVE: To examine the efficacy of preoperative Staphylococcus aureus screening on postoperative methicillin-resistant S aureus (MRSA) infection rates in otolaryngology. STUDY DESIGN: Chart review. SUBJECTS AND METHODS: Postoperative MRSA infection rates in unscreened patients during a 1-year period were compared with infection rates in patients after preoperative S aureus screening was initiated. Colonized patients were treated with mupirocin and chlorhexidine preoperatively. RESULTS: Records of 420 patients were reviewed. In the 241 patients without screening, nine patients had S aureus infections, and there were two (0.8%) postoperative MRSA surgical-site infections. Of 179 patients after screening was initiated, 24 patients (13.4%) were colonized with S aureus and underwent preoperative treatment. There were no MRSA infections in the postoperative period. CONCLUSION: Early results show the potential benefit of preoperative S aureus screening in MRSA infection rate reduction. Although larger studies are needed, screening and treatment of MRSA colonized patients preoperatively may reduce infectious complications in otolaryngology.

Changes in surgical anatomy following thyroidectomy.

Thyroid reoperation is known to carry a higher risk for complications because of the increased challenge of identifying tissue planes, presence of adherent strap muscles, and generalized scarring of the thyroid bed. Consideration of postsurgical changes in the anatomy of important landmarks, such as the recurrent and superior laryngeal nerves, brachiocephalic artery, and parathyroid glands, is crucial during preoperative planning for thyroid reoperations. This article provides a review of these key changes in surgical anatomy and the implications of the anatomic changes after thyroidectomy.

Continuous intraoperative facial nerve monitoring in predicting postoperative injury during parotidectomy.

OBJECTIVES/HYPOTHESIS: To assess whether the use of continuous intraoperative facial nerve monitoring correlates to postoperative facial nerve injury during parotidectomy. STUDY DESIGN: A retrospective analysis. METHODS: Forty-five consecutive parotidectomies were performed using an electromyograph (EMG)-based intraoperative facial nerve monitor. Of those, 37 had complete data for analysis. Intraoperative findings and final interpretation of the EMGs were analyzed by a senior neurologist and neurophysiologist. All patients were analyzed, including those with preoperative weakness and facial nerve sacrifice. RESULTS: The overall incidence of facial paralysis (House-Brackmann scale > 1) was 43% for temporary and 22% for permanent deficits. This includes an 11% incidence of preoperative weakness and 14% with intraoperative sacrifice. An abnormal EMG occurred in only 16% of cases and was not significantly associated with permanent or temporary facial nerve paralysis (chi, P < 1.0; Fisher's exact P < .68). Of the eight patients with permanent paralysis, only two had abnormalities on the facial nerve monitor. Also, only one of five patients with intraoperative sacrifice of the facial nerve had an abnormal EMG. Factors significantly associated with the incidence of facial paralysis include malignancy, advanced age, extent of parotidectomy, and dissection beyond the parotid gland (chi and Fisher's, P < .05). CONCLUSIONS: The results suggest that abnormalities on the intraoperative continuous facial nerve monitor during parotidectomy do not predict facial nerve injury. The incidence of permanent and temporary facial nerve paralysis compare favorably with the literature given that this study includes patients with revision surgery, intraoperative sacrifice, and preoperative paralysis. Standard of care implications will be discussed.

Neck dissection in the combined-modality therapy of patients with locoregionally advanced head and neck cancer.

PURPOSE: The purpose of this study was to evaluate the role of neck lymph node (ND) in the combined dissection modality therapy for locoregionally advanced head and neck. METHODS: We identified patients with N2-N3 head and neck cancers who were enrolled in three consecutive multicenter phase II studies of concurrent chemoradiotherapy utilizing 5-fluorouracil and hydroxyurea on an alternate-week schedule with radiotherapy twice daily plus either cisplatin (C-FHX) or paclitaxel (T-FHX). Patients with unknown primary tumors, nasopharyngeal or paranasal sinus primaries, nonsquamous histology, progression or death during therapy, or incomplete therapy were excluded. RESULTS: A total of 131 patients were analyzed. Seventy-nine percent had N2 stage. ND was performed in 92 patients (70%), either prior to enrollment (n = 31) or after chemoradiotherapy (n = 61). With a median follow-up of 4.6 years, the 5-year locoregional and neck progression-free survival (PFS) rates were higher in patients with ND versus patients without ND: 88% versus 74% (p =.02) and 99% versus 82% (p =.0007). respectively; there was also a trend toward improved overall survival (OS) with ND, but PFS and distant PFS were comparable. In the subset of patients with N3 disease, ND was associated not only with better locoregional control but also with improved distant PFS. However, in patients with clinical complete response (n = 92), no significant differences in PFS (68% vs 75% at 5 years, p =.53) or any other survival parameters with or without ND were observed. CONCLUSIONS: ND improves neck control and is required for patients with clinically residual disease or N3 neck cancer but has no significant impact on the outcome of patients with N2 stage disease who are rendered clinically disease-free with intensive concurrent chemoradiotherapy.

Intratumoral cisplatin/epinephrine gel in advanced head and neck cancer: a multicenter, randomized, double-blind, phase III study in North America.

BACKGROUND: The objective was to evaluate the efficacy and safety of a novel intratumoral cisplatin/epinephrine injectable gel (CDDP/epi gel) for local control and palliation of tumor-related symptoms in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: Eighty-seven patients were randomly assigned to either CDDP/epi or placebo gel in this phase III, double-blind study. Tumors were < or =20 cm(3); most recurrences (88%) were in a previously irradiated field. The most symptomatic or threatening tumor was designated as the target tumor. DOSE: 0.25 mL CDDP/epi gel/cm(3) tumor volume. TREATMENTS: < or =6 weekly intratumoral injections in an 8-week period. PRIMARY OUTCOMES: target tumor response and symptom relief. RESULTS: During the blinded phase, 34% (21 of 62) of patients achieved an objective response (CR or PR) in the target tumor treated with CDDP/epi gel vs 0% (0 of 24) treated with placebo gel (p <.001). Responses occurred within a median of four treatments (range, 2-6) and were durable (median, 95 days; range, 34-168+ days). More patients treated with CDDP/epi gel achieved palliative benefit than did those treated with placebo gel (37% vs 12%, p =.036). Most frequent side effects were local pain and local cutaneous reactions, which resolved over 3-12 weeks. Renal and hematologic toxicities were rare. CONCLUSIONS: This phase III trial showed that CDDP/epi gel significantly reduces tumor burden, palliates tumor-related symptoms, and is an effective local treatment for recurrent tumors.

The role of intratumoral therapy with cisplatin/epinephrine injectable gel in the management of advanced squamous cell carcinoma of the head and neck.

OBJECTIVE: To determine the safety and efficacy of targeted antitumor therapy with cisplatin/epinephrine injectable gel in patients with advanced squamous cell carcinoma of the head and neck. DESIGN: Two prospective, double-blind, placebo-controlled phase III trials of identical design. Crossover from blinded to open-label phase was permitted for patients with disease progression. SETTING: Tertiary referral centers in North America and Europe. PATIENTS: One hundred seventy-nine intensively pretreated patients with recurrent or refractory squamous cell carcinoma of the head and neck. INTERVENTION: Cisplatin/epinephrine injectable or placebo gel was administered by direct intratumoral injection; up to 6 weekly treatments. Dose was 0.25 mL of active or placebo gel per cubic centimeter of tumor up to 10 mL total. Patient benefit after local tumor control of the most symptomatic tumor was assessed by patients and physicians using the Treatment Goals Questionnaire. MAIN OUTCOME MEASURES: Local tumor response and patient benefit attributable to improvements in tumor-related symptoms. RESULTS: Combined results for the 178 patients with evaluable data in the 2 trials confirmed objective tumor responses in 35 (29%) of 119 patients, including 23 (19%) complete responses achieved with cisplatin/epinephrine gel, vs 1 (2%) of 59 for placebo (P<.001). Tumor response and patient benefit were significantly correlated (P=.006): 47% (17/36) of patients with target tumor responses achieved a rigorously defined benefit based on a prospectively selected treatment goal vs 15% (22/142) of nonresponders. CONCLUSION: Cisplatin/epinephrine injectable gel reduces tumor burden, ameliorates tumor symptoms, and provides a new therapeutic option for treating patients with squamous cell carcinoma of the head and neck.

Telemedicine in otolaryngology.

BACKGROUND: Telemedicine (TM) is the use of advanced information and communication technology to provide health care services. TM in general, and specifically in the field of otolaryngology, has become a reality. Because of the improvements in telecommunications and computer technology, TM applications are becoming more common in both hospitals and private practice. These applications are altering the manner in which otolaryngology is practiced both at the primary care and the specialist level. This study reviews and summarizes the use of TM specifically in otolaryngology, and discusses some of its advantages, barriers, and future. MATERIAL AND METHODS: A review of the current literature pertaining to the use of TM applications in otolaryngology-head and neck surgery was performed. RESULTS: TM applications are being developed and used worldwide in the many fields of otolaryngology. As telecommunication and audio-visual technologies advance, these applications become more exacting and cost effective. CONCLUSION: We encourage the otolaryngologist to understand the technical, legal, ethical, and financial impact of TM on managed care in otolaryngology and to make use of the potential opportunities of TM in otolaryngology-head and neck surgery.