Improved Survival of Advanced-Stage Anaplastic Thyroid Cancer With Systemic Therapy.

OBJECTIVES: Anaplastic thyroid cancer (ATC) is the most aggressive and fatal thyroid malignancy. Currently, there still exists a paucity of literature studying the relationship between available ATC-targeted therapy, immunotherapy, and survival. We aim to investigate how systemic therapies affect survival outcomes in ATC. METHODS: A single-tertiary-institution chart review of patients diagnosed with advanced-stage ATC, and who underwent surgery as part of their treatment, was performed between 2000 and 2023, with 41 patients included. Demographics, clinical characteristics, and survival data were collected and analyzed via Kaplan-Meier and Cox proportional hazards analyses. RESULTS: 54% of patients were female, and average age was 67.4 years old. The most common mutations identified were BRAF (15 patients), p53 (9 patients), and p63 (2 patients). A total of 18 patients utilized targeted or immunotherapy, with Trametinib and Dabrafenib (9 patients) as the most common agents used. Two-year overall survival was 24%, and 5-year overall survival was 23%, with median survival time of 7.6 months. Kaplan-Meier analysis demonstrated improved survival in patients who received chemotherapy (p = 0.048). Cox proportional hazards analysis demonstrated that patients treated with immunotherapy or targeted therapy had a statistically significant increase in survival compared with patients who did not receive these therapies (p = 0.016). Additionally, females and those with a p63 mutation demonstrated improved survival outcomes (p = 0.010, p = 0.001). CONCLUSIONS: Targeted therapy and immunotherapy use should be strongly considered when treating patients with ATC. Further studies into novel drugs targeting immune checkpoints and combination therapy are needed to better optimize treatment of patients with ATC. LEVEL OF EVIDENCE: 3 Laryngoscope, 2024.

University of Washington Quality of Life subdomain outcomes after treatment of sinonasal malignancy: A prospective, multicenter study.

PURPOSE: Sinonasal malignancies (SNMs) adversely impact patients' quality of life (QOL) and are frequently identified at an advanced stage. Because these tumors are rare, there are few studies that examine the specific QOL areas that are impacted. This knowledge would help improve the care of these patients. METHODS: In this prospective, multi-institutional study, 273 patients with SNMs who underwent definitive treatment with curative intent were evaluated. We used the University of Washington Quality of Life (UWQOL) instrument over 5 years from diagnosis to identify demographic, treatment, and disease-related factors that influence each of the 12 UWQOL subdomains from baseline to 5 -years post-treatment. RESULTS: Multivariate models found endoscopic resection predicted improved pain (vs. nonsurgical treatment CI 2.4, 19.4, p = 0.01) and appearance versus open (CI 27.0, 35.0, p < 0.001) or combined (CI 10.4, 17.1, p < 0.001). Pterygopalatine fossa involvement predicted worse swallow (CI -10.8, -2.4, p = 0.01) and pain (CI -17.0, -4.0, p < 0.001). Neck dissection predicted worse swallow (CI -14.8, -2.8, p < 0.001), taste (CI -31.7, -1.5, p = 0.02), and salivary symptoms (CI -28.4, -8.6, p < 0.001). Maxillary involvement predicted worse chewing (CI 9.8, 33.2; p < 0.001) and speech (CI -21.8, -5.4, p < 0.001) relative to other sites. Advanced T stage predicted worse anxiety (CI -13.0, -2.0, p = 0.03). CONCLUSIONS: Surgical approach, management of cervical disease, tumor extent, and site of involvement impacted variable UWQOL symptom areas. Endoscopic resection predicted better pain, appearance, and chewing compared with open. These results may aid in counseling patients regarding potential QOL expectations in their SNM treatment and recovery course.

Can Calcitonin Levels Guide Prophylactic Neck Dissection in Sporadic Medullary Thyroid Carcinoma?

Medullary thyroid carcinoma (MTC) comprises less than 5% of thyroid cancers but is responsible for over 10% of deaths related to thyroid cancer. Regional lymph node metastasis is common and associated with mortality, thus total thyroidectomy with central compartment lymph node dissection is the standard surgical treatment for MTC. In this best practice submission, we aim to review the existing literature and determine whether calcitonin levels can serve as a reliable method for risk-stratifying MTC without overt lymph node involvement.

Association of Safety-Net Hospital Status With Outcomes Following Head and Neck Cancer Operations.

OBJECTIVE: To assess perioperative and readmission outcomes of patients undergoing head and neck cancer (HNCA) surgery at safety-net hospitals (SNHs) in a modern cohort. STUDY DESIGN: Retrospective cohort study. SETTING: Nationwide Readmissions Database (NRD), 2010 to 2019. METHODS: All elective adult (≥18 years) admissions involving HNCA resection were identified from the NRD. To calculate safety-net burden, the proportion of Medicaid or uninsured patients admitted to each hospital for any indication was tabulated annually, with centers in the highest quartile defined as SNHs. To perform risk adjustment in assessing perioperative and readmission outcomes, multivariable regression models were developed. RESULTS: Of an estimated 133,018 head and neck surgical patients, 26.5% (n = 35,268) received treatment at a SNH. Utilization of SNHs increased over the decade-long study period, with 29.8% of individuals treated at these sites in 2019. After multivariable adjustment, several patient factors were noted to be associated with SNHs, including younger age, lower comorbidity burden, and income within the lowest quartile. Although incidence of adverse events decreased at both SNHs and non-SNHs during the study period, treatment at SNHs remained associated with these events after risk adjustment (adjusted odds ratio: 1.17, 95% confidence interval: 1.08-1.28, P < .001). CONCLUSION: SNHs continue to provide valuable specialty care to underserved populations, often with limited financial resources. Despite promising results from prior decades demonstrating comparable perioperative outcomes, the present study noted increased adverse events following HNCA surgery at these sites. Such findings underscore the need for continued advocacy to secure necessary funding for these centers.

A 22-year single institution review of 119 cases of salivary duct carcinoma.

Objective: Salivary duct carcinoma (SDC) is a rare and aggressive salivary gland malignancy. Herein, we present the largest single-institution review of SDC to date. Methods: This is a retrospective cohort study of all histologically confirmed cases of SDC seen at our institution from January 1, 2002, to August 1, 2022. Patient demographics, treatment, histological characteristics, tumor staging, and outcomes were extracted from the electronic medical record. Kaplan-Meier and Cox regression survival analyses were performed. Results: This study included 119 patients with a mean age of 66.2 years. Most primary tumors arose from the parotid gland (72.3%), and 23.5% were noted to be carcinoma ex-pleomorphic adenoma. 57.1% of patients presented with regional lymph node metastasis, whereas 23.5% presented with distant disease. Kaplan-Meier analysis demonstrated a 62.4% 5-year overall survival (OS) and a 69.0% 5-year disease-specific survival (DSS). Univariate analyses indicated that presence of regional lymph node disease (p<.001), distant metastasis (p<.001), perineural invasion (p = .027), and lymphovascular invasion (p = .018) were predictive of decreased OS and DSS. Trastuzumab administration was not associated with survival in HER-2-positive patients receiving chemotherapy. Multivariate analyses demonstrated that presence of nodal disease (HR 30.337, 95% CI 2.782-330.851, p = .005) and carcinoma ex pleomorphic adenoma (HR 5.54, 95% CI 1.024-29.933, p = .047) were associated with decreased OS. Conclusion: Our patients had more favorable survival rates compared to prior studies, which may be due to lower incidence of nodal disease. Factors associated with worse survival included nodal and distant metastases, perineural invasion, lymphovascular invasion, and tumor size. Level of Evidence: Level 3.

Speech and Swallowing Outcomes of Surgically Managed Cervical Chordoma: A Case Series.

OBJECTIVES: Cervical chordoma is a rare, low-grade primary bone tumor occurring in the axial skeleton. Due to challenges in surgical exposure caused by anatomic location, patients may experience dysfunction in speech and swallowing. The objective of this study was to characterize speech and swallowing outcomes for patients undergoing surgical resection of cervical chordoma. Moreover, we detail in-depth two cases with similar initial presentations to compare prognostic factors and management strategies. METHODS: Eleven patients with histologically confirmed cervical chordoma treated between 1993 and 2020 were included in this retrospective case series. Outcomes measured included overall survival, disease-free survival, need for enteral feeds, as well as results of modified barium swallow study (MBSS) and fiberoptic laryngoscopy. RESULTS: The mean age at diagnosis was 55.9 years. The patient population was 81.8% male. Mean survival after diagnosis was 96 months. Four (36.4%) patients required post-operative MBSS and demonstrated aspiration. All four of these patients presented with tumors in the superior cervical spine and received surgeries utilizing anterior approaches. Of the four, 2 required enteral feeds long-term. Four (36.4%) patients endorsed dysphonia. One patient developed post-operative right vocal fold paresis. The remaining three patients experienced stable dysphonia pre- and post-operatively. Additionally, three (27%) patients required tracheostomy placement, two of which remained in place long-term. CONCLUSIONS: Dysphagia is a common side effect of cervical chordoma resection. It is associated with the use of an anterior approach during resection and with tumors located in the superior cervical spine. Patients with postoperative dysphagia should receive early multidisciplinary swallow rehabilitation. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3706-3712, 2024.

Sensory nerve release of CGRP increases tumor growth in HNSCC by suppressing TILs.

BACKGROUND: Perineural invasion (PNI) and nerve density within the tumor microenvironment (TME) have long been associated with worse outcomes in head and neck squamous cell carcinoma (HNSCC). This prompted an investigation into how nerves within the tumor microenvironment affect the adaptive immune system and tumor growth. METHODS: We used RNA sequencing analysis of human tumor tissue from a recent HNSCC clinical trial, proteomics of human nerves from HNSCC patients, and syngeneic orthotopic murine models of HPV-unrelated HNSCC to investigate how sensory nerves modulate the adaptive immune system. FINDINGS: Calcitonin gene-related peptide (CGRP) directly inhibited CD8 T cell activity in vitro, and blocking sensory nerve function surgically, pharmacologically, or genetically increased CD8 and CD4 T cell activity in vivo. CONCLUSIONS: Our data support sensory nerves playing a role in accelerating tumor growth by directly acting on the adaptive immune system to decrease Th1 CD4 T cells and activated CD8 T cells in the TME. These data support further investigation into the role of sensory nerves in the TME of HNSCC and points toward the possible treatment efficacy of blocking sensory nerve function or specifically inhibiting CGRP release or activity within the TME to improve outcomes. FUNDING: 1R01DE028282-01, 1R01DE028529-01, 1P50CA261605-01 (to S.D.K.), 1R01CA284651-01 (to S.D.K.), and F31 DE029997 (to L.B.D.).

Improving HPV-Related Oropharyngeal Cancer Knowledge and HPV Vaccination Rates via Virtual Workshops.

OBJECTIVE: To validate the efficacy of a virtual, interdisciplinary workshop in improving HPV knowledge, and vaccination practices among primary care and dental trainees. METHODS: A virtual platform was utilized to hold HPV educational workshops with primary care and dental trainees. Online surveys were distributed before and after the 1-h interactive workshop, led by otolaryngology residents. Surveys included the workshop's impact on (a) improving knowledge of HPV-associated oropharyngeal squamous cell carcinoma (OPSCC) and (b) affecting change in HPV vaccination practices. The vaccination rates of trainees were recorded prior to and after workshop attendance. RESULTS: After the workshop, participants demonstrated significantly improved scores related to knowledge of HPV in the head and neck (p = 0.003) and showed an increased comfort level with counseling on HPV vaccination (p = 0.002). Respondents were also more aware that the HPV vaccine is approved to prevent OPSCC (61% vs. 95%, p < 0.05). Ninety-seven percent of respondents stated that the workshop changed their HPV vaccination practices, and 95% of those not fully vaccinated stated they would now be more likely to receive the vaccine themselves. There was a significant increase in the average number of HPV vaccines administered at the studied trainee clinic, from 16.83 vaccines/month to 37.6 vaccines/month (percent increase = 123%) in 5 months following the workshop (p = 0.002). CONCLUSION: The present interactive virtual workshop demonstrates efficacy in improving HPV-related knowledge and vaccination practices among trainees. The virtual nature of the course facilitates knowledge transfer and can be used to foster multi-institutional partnerships regarding medical education and vaccination efforts. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3096-3101, 2024.

Oral Cavity Cancer Surgical and Nodal Management: A Review From the American Head and Neck Society.

Importance: Lymph node metastases from oral cavity cancers are seen frequently, and there is still inconsistency, and occasional controversies, regarding the surgical management of the neck in patients with oral cancer. This review is intended to offer a surgically focused discussion of the current recommendations regarding management of the neck, focusing on the indications and extent of dissection required in patients with oral cavity squamous cell carcinoma while balancing surgical risk and oncologic outcome. Observations: The surgical management of the neck for oral cavity cancer has been robustly studied, as evidenced by substantial existing literature surrounding the topic. Prior published investigations have provided a sound foundation on which data-driven treatment algorithms can generally be recommended. Conclusions: Existing literature suggests that patients with oral cavity cancer should be fully staged preoperatively, and most patients should receive a neck dissection even when clinically N0. Quality standards supported by the literature include separation of each level during specimen handling and lymph node yield of 18 or more nodes. Sentinel lymph node biopsy can be considered in select tumors and within a well-trained multidisciplinary team.

Cutaneous head and neck angiosarcoma: The 30-year UCLA experience.

Background: Cutaneous angiosarcoma is an aggressive tumor commonly found in the head and neck region. There is no consensus regarding the definitive treatment for angiosarcoma. Methods: This was a retrospective chart review that evaluated 64 patients from 1983 to 2019. Demographic and clinical variables were examined for impact on recurrence using the time to recurrence and the overall survival in Kaplan-Meier curves. Results: Average age at diagnosis was 71 (32-95) years, with a 2.8 male: female ratio. Surgery was utilized in 62% of patients, with mean defect size of 11.4 ± 8.1 cm. Recurrence was found in 70% of patients, and mean time to recurrence was 15.3 ± 12.3 months. Decreased recurrence was associated with use of intraoperative frozen section analysis (p = .036) and negative margins (p = .086). Two-year overall survival was 80%, and recurrence free survival was 30%. Conclusions: Negative margins are associated with decreased recurrence, and intraoperative frozen section analysis may be considered to obtain preliminary surgical margins.Level of Evidence: 4.