Early Detection of Lymph Node Metastasis Using Primary Head and Neck Cancer Computed Tomography and Fluorescence Lifetime Imaging.

Objectives: Early detection and accurate diagnosis of lymph node metastasis (LNM) in head and neck cancer (HNC) are crucial for enhancing patient prognosis and survival rates. Current imaging methods have limitations, necessitating new evaluation of new diagnostic techniques. This study investigates the potential of combining pre-operative CT and intra-operative fluorescence lifetime imaging (FLIm) to enhance LNM prediction in HNC using primary tumor signatures. Methods: CT and FLIm data were collected from 46 HNC patients. A total of 42 FLIm features and 924 CT radiomic features were extracted from the primary tumor site and fused. A support vector machine (SVM) model with a radial basis function kernel was trained to predict LNM. Hyperparameter tuning was conducted using 10-fold nested cross-validation. Prediction performance was evaluated using balanced accuracy (bACC) and the area under the ROC curve (AUC). Results: The model, leveraging combined CT and FLIm features, demonstrated improved testing accuracy (bACC: 0.71, AUC: 0.79) over the CT-only (bACC: 0.58, AUC: 0.67) and FLIm-only (bACC: 0.61, AUC: 0.72) models. Feature selection identified that a subset of 10 FLIm and 10 CT features provided optimal predictive capability. Feature contribution analysis identified high-pass and low-pass wavelet-filtered CT images as well as Laguerre coefficients from FLIm as key predictors. Conclusions: Combining CT and FLIm of the primary tumor improves the prediction of HNC LNM compared to either modality alone. Significance: This study underscores the potential of combining pre-operative radiomics with intra-operative FLIm for more accurate LNM prediction in HNC, offering promise to enhance patient outcomes.

Fibula Free Flap Reconstruction of Cervical Spine Defects: A Multi-Institutional Study.

INTRODUCTION: Cervical spine defects result in spinal instability, putting the spinal cord and vertebral arteries at risk of damage and possibly devastating neurological injuries. The fibula free flap can span the spinal defects for stability. There is a paucity of literature on this technique. METHOD: Multi-institutional retrospective case series reviewing patients who underwent cervical spine reconstruction with a fibula free flap. Patient demographic information, comorbidities, characteristics of cervical spine defects, and free flap complications were collected. RESULTS: A total of 1187 fibula free flaps across 10 different institutions were reviewed. Thirteen patients (1.09%) underwent cervical spine reconstruction with a fibula free flap. Average age was 52.3 years old with an age range of 12-79 years. There were six males (46.1%) and seven females (53.8%). The most common defect etiology was infection (n = 6, 46.1%). Most commonly involved cervical spine level of the defect was C5 (n = 10) followed by C6 (n = 9) and C4 (n = 8). The majority of reconstructed defects spanned three or more cervical levels, (n = 9, 69.2%). Facial artery was the most common arterial anastomosis (n = 8). Eight patients (61.5%) required a tracheostomy during their postoperative course. None of the patients had symptomatic or radiographic nonunion. CONCLUSION: This case series demonstrates that a vascularized fibula flap is a potential reconstructive option for cervical spine defects, especially in defects greater than three cervical levels, in the setting of infection, and previously radiated patients. LEVEL OF EVIDENCE: Level 4 Laryngoscope, 2024.

CT predictors of sub-centimeter occult lymph node metastases in oral cavity squamous cell carcinoma: A case-control study.

BACKGROUND: For patients with oral cavity squamous cell carcinoma (OCSCC) without evidence of nodal metastasis (cN0) on pre-operative evaluation, there are no clear guidelines who should undergo elective neck dissection (END) versus clinical surveillance. OBJECTIVE: To identify CT imaging characteristics of sub-centimeter lymph nodes that would help predict the likelihood of nodal metastases on pathology. METHODS: Retrospective review of cN0 OCSCC patients at a tertiary academic medical center was performed. Inclusion criteria included elective neck dissection, pre-operative CT imaging and presence of metastatic disease within lymph nodes. Control group consisted of patients without nodal metastases on pathology. CT features that were evaluated included asymmetric size, disrupted fatty hilum, asymmetric number, presence of cortical nodule, cortical nodule size, and round/oval shape. We evaluated the associations between CT LN features and the presence of metastases using multi-level mixed-effects logistic regression models. Model evaluation was performed using 5-fold cross-validation. The positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS: 26 patients in each study and control groups were included. Three-level mixed-effects logistic regression models indicated round/oval shape (OR = 1.39, p = .01), asymmetric number (OR = 7.20, p = .005), and disrupted fatty hilum (OR = 3.31, p = .04) to be independently predictive in a 3-variable model with sensitivity = 38.0%, specificity = 92.0%, and PPV = 93.8%. CONCLUSIONS: In cN0 OCSCC patients undergoing END, round/oval shape, asymmetric number, and disrupted fatty hilum of lymph nodes on pre-operative CT imaging are novel and highly predictive of occult nodal disease.

Tumor and Nodal Disease Growth Rates in Patients with Oropharyngeal Squamous Cell Carcinoma.

Though specific growth rate (SGR) has potential prognostic value for oropharyngeal squamous cell carcinoma (OPSCC), there is sparse literature defining these rates. Our aims were to establish the SGRs of primary tumors (PTs) and lymph nodes (LNs) in OPSCC and to correlate SGR with oncologic outcome. A pilot study was designed with a retrospective analysis examining 54 patients from the University of California, Davis with OPSCC (diagnosed 2012-2019). Radiation oncology software and pretreatment serial CT scans were used to measure PT and LN volumes to calculate SGR and doubling time (DT). The mean PT-SGR was 1.2 ± 2.2%/day and the mean LN-SGR was 1.6 ± 1.9%/day. There was no statistically significant difference between slow-growing and fast-growing cohorts in terms of age, gender, smoking status, tumor subsite, HPV status (as determined with p16 staining), initial volume, or overall stage. SGR had no impact on 2-year overall survival, disease-free survival, or disease-specific survival. We found the average daily growth rates for OPSCC to be 1.2%/day and 1.6%/day. Our findings suggest PT- and LN-SGR are independent factors, not heavily influenced by known biomarkers and patient characteristics, without a statistical impact on prognosis. This information has value in patient counseling regarding tumor growth and in providing patients worried about fast-growing tumors the appropriate reassurance.

Virtual Tumor Boards for Remote Learning in Head and Neck Surgical Oncology.

Importance: In addition to their patient management value, multidisciplinary tumor boards have been recognized as effective learning tools. However, the value of using a virtual tumor board as a learning tool for head and neck surgical oncology fellows has not been studied. Objective: To describe the structure and content of the American Head and Neck Society (AHNS) Virtual Tumor Board and assess its educational value as perceived by attendees. Design, Setting, and Participants: All sessions of the AHNS Virtual Tumor Board from April 8, 2020, to June 1, 2022, were reviewed. Topics, presenters, participants, and viewership data were collected as of October 15, 2022, from session recordings posted to an online video sharing and social media platform. Additionally, an anonymous, 14-question online survey was designed to elicit feedback from head and neck surgery trainees on virtual tumor board engagement, strengths, and weaknesses. The survey was electronically distributed in June and July 2022 to the 101 fellows enrolled in AHNS-accredited programs between July 1, 2020, and June 30, 2022. Main Outcomes and Measures: The primary aim was to tabulate online viewership of the sessions. The secondary aim was to qualitatively assess the experience of head and neck trainees with the AHNS Virtual Tumor Board using a survey. Results: Forty-two sessions of the virtual tumor board were held between April 8, 2020, and June 1, 2022. Almost all sessions (41 [98%]) were case based. One hundred and sixteen cases were presented, representing 2 to 3 cases per session, by 75 unique faculty members. Each session was viewed a mean of 217 times (range, 64-2216 views). In the 2021 to 2022 academic year, a mean of 60 viewers (range, 30-92 viewers) attended each live session. In all, 29 survey responses were collected from 101 fellows in AHNS-accredited programs (29% response rate). Most respondents felt the format allowed for excellent teaching (18 of 26 respondents [69%]) and discussion (19 of 26 respondents [73%]). Most respondents (22 of 29 respondents [76%]) believed that practicing head and neck surgeons would benefit from the sessions. Conclusions and Relevance: This survey study found that the AHNS Virtual Tumor Board was well-attended and well-reviewed by head and neck surgical oncology trainees. The virtual tumor board format could be used as model of remote learning for other organizations.

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.

Stratification of surgical margin distances by the millimeter on local recurrence in oral cavity cancer: A systematic review and meta-analysis.

There are limited data supporting the commonly suggested 5 mm margin cutoff as the optimum value in defining clear margins in oral cancer. A database search of Pubmed/Medline, Web of Science, and EBSCOhost was performed from inception to June 2022. A random-effects model was chosen for this meta-analysis. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines were followed throughout this study. Seven studies met study criteria (2215 patients). The risk ratio was significantly higher for margins <5 mm when compared to those ≥5 mm (2.09 (95%CI: 1.53-2.86, I2  = 0.47)). Subgroup analysis (I2  = 0.15) of margin distances of 0.0-0.9, 1.0-1.9, 2.0-2.9, 3.0-3.9, and 4.0-4.9 mm calculated risk ratios for local recurrence of 2.96, 2.01, 2.17, 1.8, and 0.98, respectively. Margins between 4.0 and 4.9 mm had similar risk ratios for local recurrence compared to ≥5 mm, while margins <4.0 were significantly higher.

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.

Predictors of Health Care Utilization Following Major Head and Neck Oncologic Surgery in Older Patients.

OBJECTIVE: To identify patient factors in older patients associated with making posttreatment visits in the first year after major head and neck oncologic surgery. STUDY DESIGN: Retrospective cohort study. SETTING: Academic institution. METHODS: Patients aged ≥60 years who underwent a neck dissection with or without a free flap reconstruction were retrospectively analyzed. Data collected included patient demographics, comorbidities, social variables, perioperative course, and clinical visits. RESULTS: Within a 1-year postoperative period, the 181 patients in our cohort had a mean ± SD 6.37 ± 3.6 postoperative clinic visits; 70% attended at least 4 visits. Multivariable regression analysis showed a significant association with distance closer to the hospital (P = .013): for every 10-mile increase in distance, the number of visits decreased by 0.15 (SE = 0.06). Additionally, receiving adjuvant radiation therapy (P = .0096) demonstrated significant associations: when compared with no adjuvant therapy, radiation therapy had on average 1.5 (SE = 0.56) more visits, and chemoradiation had 0.04 (SE = 0.73) more visits. CONCLUSION: Older patients who undergo major head and neck oncology surgery are more likely to attend posttreatment visits in the 1 year following surgery if they are discharged home rather than to a skilled nursing facility, live closer to the hospital, and undergo adjuvant radiation therapy.

Head and Neck Cutaneous Soft-Tissue Sarcoma Demonstrate Sex and Racial/Ethnic Disparities in Incidence and Socioeconomic Disparities in Survival.

BACKGROUND: Cutaneous soft-tissue sarcoma (CSTS) of the head and neck are rare and are known to have aggressive clinical course. The current study utilizes a population-based registry in the U.S. to characterize these malignancies and explore disparities. METHODS: National Cancer Institute's (NCI) Surveillance, Epidemiology and End Result (SEER) database from 2000 to 2018 was queried to report incidence and survival data in 4253 cases in the U.S. RESULTS: Males were 5.37 times more likely and Non-Hispanic-White people (NHW) were 4.62 times more likely than females and Non-Hispanic-Black people (NHB) to develop CSTS of the head and neck. The overall incidence was 0.27 per 100,000 persons in 2018, with a significant increase since 2000. Advanced age and stage, histologic group other than 'fibromatous sarcoma' and lower SES groups were independent factors for worse overall survival. CONCLUSIONS: CSTS of the head and neck demonstrate sex and racial/ethnic disparities in incidence and socioeconomic disparities in overall survival. LEVEL OF EVIDENCE: II.

Distribution of the head and neck surgical oncology workforce in the United States.

BACKGROUND: The recent trends in education and geographic distribution of the head and neck surgery workforce have not been studied extensively. METHODS: We reviewed publicly available sources to locate all fellowship-trained head and neck surgeons and recent graduates. The number of surgeons in each state was compared against head and neck cancer incidence data from the Centers for Disease Control. RESULTS: The number of graduates increased annually by 1 per 100 000 000 people from 2011-2020. The average number of fellowship-trained surgeons per state was 10 (SD: 12). The average number of new head and neck cancer cases per surgeon was 247 (SD: 135). Ten states (20%) had cases >1 SD above the national average/surgeon, while 3 (6%) had cases >1 SD below the national average. CONCLUSION: Head and neck surgeons are located in most states, but not uniformly. Most states have approximately average density of surgeons; however, several states are outliers.

Oropharyngeal reconstruction after transoral robotic surgery.

PURPOSE OF REVIEW: Transoral robotic surgery (TORS) has experienced an evolution in recent years. This technique has proved to be a safe and effective method for extirpation of select oropharyngeal tumors. Advances in technology as well as improved surgeon experience allow for the resection of larger, more complex cancers. Although healing by secondary intention remains the current standard for limited oropharyngeal defects, larger resections demand reconstruction with vascularized tissue to minimize morbidity and optimize functional outcomes. The objective of this review is to evaluate recent literature regarding oropharyngeal reconstruction after TORS. RECENT FINDINGS: A variety of reconstructive options to manage oropharyngeal defects exist. Several reconstructive algorithms have been suggested; however, careful consideration must be used to select the most ideal flap type. Locoregional flaps have shown excellent functional outcomes with limited morbidity. An increase in free flap reconstruction has been demonstrated, particularly among patients with larger TORS defects and following chemoradiation therapy. Despite limited data, robotic-assisted flap inset and microvascular anastomosis has recently shown promise. SUMMARY: Reconstruction and flap selection following TORS should be tailored to the patient and unique oropharyngeal defect. Functional outcomes are promising with low complication rates among these patients.

Total laryngectomy negatively impacts sinonasal and olfactory-specific quality of life.

PURPOSE: The purpose of this study is to characterize deficits in olfactory-specific and sinonasal-specific QoL after total laryngectomy (TL) with validated patient reported outcome measures. METHODS: Thirty patients who had a TL were prospectively enrolled. Patient demographics, as well as scores from the Questionnaire of Olfactory Disorders Negative Statements (QOD-NS) and the Sino-nasal Outcome Test-22 (SNOT-22) were collected. Univariate analysis was performed to assess associations between patient characteristics and QoL scores. RESULTS: The average QOD-NS score was 37.9 ± 11.4 (<38.5 is considered abnormal) and average SNOT-22 score was 32.0 ± 3.8 (>20 indicates a moderate/severe impact on QoL). The abnormal QOD-NS group had a greater percentage of former smokers compared to the normal group (77.8% vs. 58.1%; P = 0.56) and more median days from surgery compared to the normal group (904 vs. 477 days; P = 0.24). CONCLUSIONS: Olfactory dysfunction associated with TL results in blunting of olfactory-specific QoL.

Intraoperative delineation of p16+ oropharyngeal carcinoma of unknown primary origin with fluorescence lifetime imaging: Preliminary report.

BACKGROUND: This study evaluated whether fluorescence lifetime imaging (FLIm), coupled with standard diagnostic workups, could enhance primary lesion detection in patients with p16+ head and neck squamous cell carcinoma of the unknown primary (HNSCCUP). METHODS: FLIm was integrated into transoral robotic surgery to acquire optical data on six HNSCCUP patients' oropharyngeal tissues. An additional 55-patient FLIm dataset, comprising conventional primary tumors, trained a machine learning classifier; the output predicted the presence and location of HNSCCUP for the six patients. Validation was performed using histopathology. RESULTS: Among the six HNSCCUP patients, p16+ occult primary was surgically identified in three patients, whereas three patients ultimately had no identifiable primary site in the oropharynx. FLIm correctly detected HNSCCUP in all three patients (ROC-AUC: 0.90 ± 0.06), and correctly predicted benign oropharyngeal tissue for the remaining three patients. The mean sensitivity was 95% ± 3.5%, and specificity 89% ± 12.7%. CONCLUSIONS: FLIm may be a useful diagnostic adjunct for detecting HNSCCUP.

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.

Qualitative assessment of online information available on accredited head and neck surgery fellowship programs.

BACKGROUND: The present study aims to assess the quality and availability of online information about fellowships accredited by the American Head & Neck Society (AHNS). METHODS: AHNS directory pages and institutional web sites of 50 AHNS-accredited fellowships were identified. Web pages were scored using 20 standardized criteria including general information, application information, alumni, surgical training, research, and quality-of-life. RESULTS: Median scores for AHNS directory pages and institutional web sites were 11 (range: 7-14) and 10 (4-15), respectively. Faculty listings, contact information, program location, number of positions, and breadth of surgical exposure were the most commonly listed criteria. Less common criteria included didactic schedule, protected academic time, previous research projects, year of accreditation, work-life balance, fellow selection criteria, interview information, and salary. CONCLUSIONS: The AHNS directory and institutional web sites are most comprehensive in general program information and details about surgical training. Information about the application process, work-life balance, and research opportunities were less common.

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.

Functional laryngectomy for the dysfunctional larynx: indications and outcomes in setting of prior chemoradiotherapy.

PURPOSE OF REVIEW: To review the recent literature on indications for and functional outcomes following laryngectomy for severe laryngeal dysfunction. RECENT FINDINGS: The use of functional laryngectomy as a definitive treatment for severe laryngeal dysfunction is increasing as more patients with head and neck cancer are treated with definitive chemoradiotherapy. Data are emerging on the efficacy of this technique as measured by aspiration, recurrent pneumonias, enteral tube feeding dependence, and surgical complication rates. Though most patients have marked improvement in aspiration and oral intake, difficulties in swallowing and voicing functions may persist. SUMMARY: Functional laryngectomy is an effective treatment for end-stage laryngeal dysfunction. There is a clear benefit with regard to prevention of aspiration and alleviation of nothing by mouth status. However, qualitative speech and swallowing outcomes are less well studied, though available data suggest that many patients still suffer some degree of continued chronic impairment. More research is needed on these outcomes in order to appropriately counsel patients regarding long-term functional outcomes.

Intraparotid Facial Nerve Schwannoma Mimicking Primary Parotid Neoplasm.

The following report is of a 36-year-old male who presented with a growing mass in the region of the parotid gland. Initial fine needle aspiration biopsy suggested a primary neoplasm of the parotid gland, but subsequent frozen section analysis intraoperatively demonstrated a schwannoma of the facial nerve. An intracapsular enucleation of the schwannoma was performed in order to preserve the fibers of the motor nerve.