Comparison of margins and survival between transoral robotic surgery (TORS) and non-robotic endoscopic surgery for oropharyngeal cancer.

OBJECTIVE: To evaluate the impact of transoral robotic surgery (TORS) and non-robotic transoral endoscopic surgery on margin positivity, rates of adjuvant therapy and survival in early stage oropharyngeal squamous cell carcinoma. STUDY DESIGN: Retrospective cohort review. SUBJECTS AND METHODS: The National Cancer Database was queried to form a cohort of patients with T1-T2 N0-N1 MO oropharyngeal squamous cell carcinoma who underwent TORS or Non-robotic endoscopic surgery from 2010 to 2015. Demographics, disease characteristics and rate of positive margin and adjuvant therapy were summarized. A binary logistic regression and a cox-proportional hazard model were performed to evaluate patient demographic, disease, and treatment factors that could predict margin positivity and survival respectively. RESULTS: 1026 patients received TORS treatment while 734 patients received non-robotic endoscopic primary surgery. Non-robotic surgery was more likely to have residual tumor (31.6 % of all cases) compared to TORS procedures (13.6 % of TORS cases); p < .0001. Non-robotic surgery more frequently had non-evaluable margins at 8.1 % compared to only 1.4 % of TORS cases (p < .0001). Non-robotic cases had a significantly higher proportion of patients receiving adjuvant radiotherapy and systemic therapy compared to TORS (66.4 % vs 51.3 % for radiotherapy; p < .0001 and 33.4 % vs 22.2 % for chemotherapy; p < .0001). There was no difference in mortality between the two modalities (non-robotic vs TORS, HR 1.357, 95 % CI 0.937-1.967). CONCLUSION: TORS and non-robotic surgery may have a similar impact on survival in early-stage OPSCC, but non-robotic surgery was found to have a higher likelihood of positive margins and a higher rate of adjuvant chemoradiation therapy.

Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and Neck Cancer.

PURPOSE: Primary or acquired resistance to cetuximab, an antiepidermal growth factor receptor monoclonal antibody (mAb), minimizes its utility in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Aberrant hepatocyte growth factor/cMet pathway activation is an established resistance mechanism. Dual pathway targeting may overcome resistance. PATIENTS AND METHODS: This multicenter, randomized, noncomparative phase II study evaluated ficlatuzumab, an antihepatocyte growth factor mAb, with or without cetuximab in recurrent/metastatic HNSCC. The primary end point was median progression-free survival (PFS); an arm met significance criteria if the lower bound of the 90% CI excluded the historical control of 2 months. Key eligibility criteria were HNSCC with known human papillomavirus (HPV) status, cetuximab resistance (progression within 6 months of exposure in the definitive or recurrent/metastatic setting), and resistance to platinum and anti-PD-1 mAb. Secondary end points included objective response rate (ORR), toxicity, and the association of HPV status and cMet overexpression with efficacy. Continuous Bayesian futility monitoring was used. RESULTS: From 2018 to 2020, 60 patients were randomly assigned and 58 were treated. Twenty-seven versus 33 patients were allocated to monotherapy versus combination. Arms were balanced for major prognostic factors. The monotherapy arm closed early for futility. The combination arm met prespecified significance criteria with a median PFS of 3.7 months (lower bound 90% CI, 2.3 months; P = .04); the ORR was 6 of 32 (19%), including two complete and four partial responses. Exploratory analyses were limited to the combination arm: the median PFS was 2.3 versus 4.1 months (P = .03) and the ORR was 0 of 16 (0%) versus 6 of 16 (38%; P = .02) in the HPV-positive versus HPV-negative subgroups, respectively. cMet overexpression was associated with reduced hazard of progression in HPV-negative but not HPV-positive disease (P interaction = .02). CONCLUSION: The ficlatuzumab-cetuximab arm met significance criteria for PFS and warrants phase III development. HPV-negative HNSCC merits consideration as a selection criterion.

The impact of socioeconomic and geographic factors on access to transoral robotic/endoscopic surgery for early stage oropharyngeal malignancy.

OBJECTIVE: To evaluate the role of social and geographic factors on the likelihood of receiving transoral robotic surgery (TORS) or non-robotic transoral endoscopic surgery treatment in early stage oropharyngeal squamous cell carcinoma (OPSCC). MATERIALS AND METHODS: The National Cancer Database was queried to form a cohort of patients with T1-T2 N0-N1 M0 OPSCC (AJCC v.7) who underwent treatment from 2010 to 2016. Demographics, tumor characteristics, treatment type, social, and geographic factors were all collected. Univariate analysis and multivariate logistic regression were then performed. RESULTS: Among 9267 identified patients, 1774 (19.1%) received transoral robotic surgery (TORS), 1191 (12.9%) received transoral endoscopic surgery, and 6302 (68%) received radiation therapy. We found that lower cancer stage, lower comorbidity burden and HPV- positive status predicted a statistically significant increased likelihood of receiving surgery. Patients who reside in suburban or small urban areas (>1 million population), were low-to- middle income, or rely on Medicaid were less likely to receive surgery. Patients that reside in Medicaid-expansion states were more likely to receive TORS (p > .0001). Patients that reside in states that expanded Medicaid January 2014 and after were more likely to receive non-robotic transoral endoscopic surgery (p > .0001). CONCLUSIONS: Poorer baseline health, lower socioeconomic status and residence in small urban areas may act as barriers to accessing minimally invasive transoral surgery while residence in a Medicaid-expansion state may improve access. Barriers to accessing robotic surgery may be greater than accessing non-robotic surgery.

Association of Perioperative Complications with Vitamin D Levels in Major Head and Neck Surgery.

OBJECTIVES/HYPOTHESIS: To investigate the association of vitamin D level and perioperative complications in patients undergoing major head and neck surgery. STUDY DESIGN: Retrospective Cohort Study. METHODS: A retrospective chart review was performed for all patients undergoing reconstructive head and neck surgery between December 2017 and December 2019. Data regarding patient demographics, serum 25-hydroxyvitamin D (calcidiol) level, hospital course, prior radiation, and fistula formation were collected. Patients were categorized by serum calcidiol level as deficient (<20 ng/mL) or sufficient (≧20 ng/mL) and outcomes were compared between groups. RESULTS: Fifty-seven patients were included in the analysis. Average age at time of surgery was 62.6 ± 10.6 years. Patients with vitamin D levels <20 ng/mL were considered deficient and ≧20 ng/mL were considered sufficient. Individuals in the deficient group (n = 29) had a mean serum calcidiol level of 13.95 ± 3.95 ng/mL, whereas those in the sufficient group (n = 28) had a mean calcidiol level of 28.53 ± 5.73 ng/mL. The rate of fistula was 41.4% in the deficient group, whereas patients in the sufficient group had a rate of fistula of 14.3% (P = .038). On multivariate analysis, higher serum calcidiol level above 20 ng/mL was associated with a lower likelihood of developing fistulae with an odds ratio 0.830 (95% confidence interval: 0.718-0.960, P = .012). CONCLUSION: Vitamin D deficiency may play a role in development of fistula after major head and neck surgery. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:578-583, 2022.

Impact of Close Margins in Head and Neck Mucosal Squamous Cell Carcinoma: A Systematic Review.

OBJECTIVES/HYPOTHESIS: The aim of the study is to investigate whether close surgical margins impact oncologic outcomes compared to clear or involved surgical margins. We hypothesize that close surgical margins portend worse outcomes compared with clear margins, but improved outcomes compared with involved margins. STUDY DESIGN: Systematic review. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-analysis statement standards, a systematic search was conducted for studies that reported oncologic outcomes following excision of primary mucosal head and neck squamous cell carcinoma (HNSCC). A meta-analysis was then performed, comparing local recurrence (LR), locoregional recurrence (LRR), and overall survival (OS) in patients with clear, close, and involved margins. RESULTS: Twenty-six studies met the inclusion criteria, totaling 8,435 patients. About 96% of our included cases involved the oral cavity, 2% involved the oropharynx, and 2% other. Also, 68% of cases were T1/T2 and 32% were T3/T4. On meta-analysis, clear margins were associated with lower incidence of 5-year LR relative risk (RR) 0.50, 95% confidence interval [CI] 0.38-0.65) and higher 5-year OS (RR 1.22, 1.11-1.35), when compared with close margins. Involved margins had higher incidence of 5-year LR (RR 1.75, 1.16-2.64), higher incidence of LRR at last follow-up (RR 1.66, 1.37-2.00), and no difference in 5-year OS (RR 0.82, 0.60-1.11), when compared with close margins. CONCLUSIONS: There is a stepwise improvement in oncologic outcomes as surgical margin categorically improves from involved to close to clear. Patients with close margins therefore may benefit from adjuvant therapy. Further research is required to investigate whether these findings are seen in non-oral cavity cases because they were underrepresented in this analysis. Laryngoscope, 132:307-321, 2022.

Unilateral Cysticercosis of the Parotid Gland: Case Report, Diagnosis, and Clinical Management.

Cysticercosis is a systemic parasitic infection caused by the establishment of the larval form of the parasitic cestode, Taenia solium. Cysticercosis is acquired via the fecal-oral route and is prevalent in low- and middle-income countries (LMICs). Patients typically manifest with skeletal muscle, subcutaneous, or central nervous system involvement. Though there are reports of oral mucosa involvement, solitary involvement of the parotid gland is rare. This is a rare case of a 57-year-old man diagnosed with parotid cysticercosis by imaging and FNA. He was successfully treated by anthelminthic therapy and needle aspiration. The patient has been seen back several times. The cyst is not palpable, and he is satisfied. Parotid cysticercosis should be considered in the differential of a parotid mass in patients who have traveled to endemic regions. Though prior reports have indicated the importance of surgical excision, this patient was treated medically.

Mucosa-Associated Lymphoid Tissue Lymphoma of the Larynx.

BACKGROUND: Mucosa-associated lymphoid tissue (MALT) lymphomas are a subtype of non-Hodgkin lymphoma stemming from marginal zone B-cells. In this case report, we present two patients with an extremely rare localization of MALT lymphoma to the larynx. METHODS: Case 1 is of a 78-year-old male presenting with a six-month history of progressive hoarseness with a past medical history significant for marginal zone lymphoma of the right orbit. Diagnosis was confirmed with a biopsy for extranodal marginal zone B-cell lymphoma of MALT type. An FDG-PET scan was done but did not show any sign of FDG avid malignancy, including at the primary site. Case 2 is a 60-year-old female presenting with one year of worsening throat discomfort, intermittent cough, and dyspnea with exertion. Pathology confirmed a diagnosis of extranodal marginal zone B-cell lymphoma of MALT type. RESULTS: Case 1 was treated with low-dose radiation at 4 Gy delivered over two fractions of 2 Gy each. Upon completion of radiation treatment, he reported a resolution of his hoarseness and normalization of his voice. A four-month follow-up in May 2018 with flexible nasolaryngoscopy revealed a normal exam with fully mobile vocal folds bilaterally and no evidence of left false vocal fold submucosal mass. At seven months following treatment, the patient died unexpectedly of unknown causes. Case 2 was treated with radiation at 30 Gy in 15 fractions over the course of one month. Following completion of radiation therapy, she had improvement of her sore throat, nausea, dysphagia, dysgeusia, and dry mouth. At 21-month follow-up, she had no evidence of disease. CONCLUSION: This case report demonstrates that MALT lymphoma can present with much more benign and subtle symptoms. This highlights the importance of clinicians to keep broad differentials and consider MALT lymphomas in the setting of laryngeal masses.

Neoadjuvant chemotherapy improves survival compared with concurrent chemoradiation alone in nasopharyngeal carcinoma patients with N3 disease.

BACKGROUND: Neoadjuvant chemotherapy (NAC) trials in endemic regions of nasopharyngeal carcinoma (NPC) found improved survival, but studies are lacking in nonendemic regions. We assessed whether adding NAC to concurrent chemoradiation (CRT) improves overall survival (OS), especially in high-risk nonendemic patients. METHODS: Definitively treated NPC patients (n = 5424) from the National Cancer Database were analyzed for predictors of NAC and NAC effects on OS with multivariate Cox proportional hazards analysis (multivariate analysis [MVA]). Propensity score matched (1:2) survival analysis of NAC (n = 968) and CRT alone (n = 1914) was also performed. Effects on OS were stratified by risk group. RESULTS: On MVA, NAC-improved OS among the total cohort (hazard ratio [HR] 0.89, P = .049), particularly among stratified keratinizing histology (HR 0.82, P = .015) and N3 disease (HR 0.73, P = .046). Among propensity matched patients, NAC improved OS in patients with N3 disease (n = 336; HR 0.71, P = .046). CONCLUSIONS: NAC may improve OS among nonendemic NPC patients at higher risk of distant micrometastases, particularly N3 disease and those with unfavorable histology.

The expanding role of scapular free-flaps.

PURPOSE OF REVIEW: The review evaluates the expanding role of scapular free flaps and its application in various complex head and neck defects. RECENT FINDINGS: The recent literature published focuses on the use of three-dimensional modeling for maxillectomy defects, expanded uses in both the megaflap, the various application of the scapular tip flap, and the feasibility of osseointegrated implants. SUMMARY: The subscapular system of flaps remains a versatile option in head and neck reconstruction. It continues to be one of the best options for large defects requiring generous soft tissue, muscle, and bone. Three-dimensional modeling is currently being applied to complex maxillary defects resulting in increased accuracy and efficiency of reconstruction. Expanded uses have also adopted the latissimus dorsi muscle in conjunction with the scapular bony flap to be used in large defects with resulting decreased fistula rates. Finally, there is sufficient evidence that supports the use of dental implantation into the scapula bone with successful retention rates.

Oral sensory dysfunction following radiotherapy.

OBJECTIVES/HYPOTHESIS: To assess differences in oral tactile sensation between subjects who have undergone radiation therapy (XRT) compared to healthy controls. STUDY DESIGN: Cross-sectional cohort comparison. METHODS: Thirty-four subjects with a history of XRT were compared with 23 healthy controls. There was no difference in age (P = .23), but there were slightly more males in the XRT cohort (P = .03). The mean (standard deviation) time after XRT completion was 3.84 (4.84) years. Fifty-six percent of the XRT cohort received chemotherapy. Using our previously validated methodology to measure oral tactile sensory threshold quantitatively with Cheung-Bearelly monofilaments, sensory thresholds of four subsites (anterior tongue, buccal mucosa, posterior tongue, soft palate) were compared for the two cohorts. RESULTS: Site-by-site comparisons showed higher forces were required for stimulus detection at all four subsites among subjects in the XRT cohort compared to healthy controls. Mean force in grams for XRT versus control cohorts were: anterior tongue, 0.39 (1.0) versus 0.02 (0.01); buccal mucosa, 0.42 (0.95) versus 0.06 (0.05); posterior tongue, 0.76 (1.46) versus 0.10 (0.07); and soft palate, 0.86 (1.47) versus 0.08 (0.05) (P < .001 for all comparisons). Combining all four subsites into a single metric to assess an overall level of oral tactile dysfunction, the XRT cohort had reduced sensation by 18.7 dB (P < .001). CONCLUSIONS: After radiation therapy, the oral cavity and oropharynx exhibit global tactile sensory dysfunction, manifested by increased tactile forces required for stimulus detection. The magnitude of sensory impairment is 18.7 dB. LEVEL OF EVIDENCE: 3b. Laryngoscope, 127:2282-2286, 2017.

Sensory Topography of Oral Structures.

Importance: Sensory function in the oral cavity and oropharynx is integral to effective deglutition and speech production. The main hurdle to evaluation of tactile consequences of upper aerodigestive tract diseases and treatments is access to a reliable clinical tool. We propose a rapid and reliable procedure to determine tactile thresholds using buckling monofilaments to advance care. Objective: To develop novel sensory testing monofilaments and map tactile thresholds of oral cavity and oropharyngeal structures. Design, Setting, and Participants: A prospective cross-sectional study of 37 healthy adults (12 men, 25 women), specifically without a medical history of head and neck surgery, radiation, or chemotherapy, was carried out in an academic tertiary medical center to capture normative data on tactile sensory function in oral structures. Interventions: Cheung-Bearelly monofilaments were constructed by securing nylon monofilament sutures (2-0 through 9-0) in the lumen of 5-French ureteral catheters, exposing 20 mm for tapping action. Main Outcomes and Measures: Buckling force consistency was evaluated for 3 lots of each suture size. Sensory thresholds of 4 oral cavity and 2 oropharyngeal subsites in healthy participants (n = 37) were determined by classical signal detection methodology (d-prime ≥1). In 21 participants, test-retest reliability of sensory thresholds was evaluated. Separately in 16 participants, sensory thresholds determined by a modified staircase method were cross-validated with those obtained by classical signal detection. Results: Buckling forces of successive suture sizes were distinct (P < .001), consistent (Cronbach α, 0.99), and logarithmically related (r = 0.99, P < .001). Test-retest reliability of sensory threshold determination was high (Cronbach α, >0.7). The lower lip, anterior tongue, and buccal mucosa were more sensitive than the soft palate, posterior tongue, and posterior pharyngeal wall (P < .001). Threshold determination by classical signal detection and modified staircase methods were highly correlated (r = 0.93, P < .001). Growth of perceptual intensity was logarithmically proportional to stimulus strength (P < .01). Conclusions and Relevance: Topography of normal oral cavity and oropharyngeal tactile sensation is organized in accordance to decreasing sensitivity along the anteroposterior trajectory and growth of perceptual intensity at all subsites is log-linear. Cheung-Bearelly monofilaments are accessible, disposable, and consistent esthesiometers. This novel clinical tool is deployable for quantitative sensory function assessment of oral cavity and oropharyngeal structures.

Transoral robotic-assisted surgical excision of a retropharyngeal parathyroid adenoma: a case report.

BACKGROUND: Transoral robotic surgery has been used with increasing frequency for oropharyngeal malignancies. We present the first known case of a transoral robotic-assisted parathyroidectomy. METHODS/RESULTS: A 77-year-old woman with primary hyperparathyroidism was suspected of having a parathyroid adenoma. After several nonlocalizing single photon emission CT/CT sestamibi scans, a neck ultrasound revealed a suspicious low level 6 nodule. Surgical excision of this nodule proved to be a reactive lymph node. She then had a dynamic parathyroid protocol MRI and CT, which revealed a small retropharyngeal adenoma candidate. A transoral robotic-assisted surgical approach was utilized to bluntly dissect the retropharyngeal space just above the arytenoids to excise the nodule. After excision, the intraoperative parathyroid hormone (PTH) normalized and surgical pathology confirmed parathyroid adenoma. CONCLUSION: Transoral robotic-assisted surgery is a novel technique that can be utilized for resection of a parathyroid adenoma in the retropharyngeal space.

Predictors of Salivary Fistulas in Patients Undergoing Salvage Total Laryngectomy.

Background. Salivary fistula is a common complication after salvage total laryngectomy. Previous studies have not considered the number of layers of pharyngeal closure and have not classified fistulas according to severity. Our objective was to analyze our institutional experience with salvage total laryngectomy, categorize salivary fistulas based on severity, and study the effect of various pharyngeal closure techniques on fistula incidence. Methods. Retrospective analysis of 48 patients who underwent salvage total laryngectomy, comparing pharyngeal closure technique and use of a pectoralis major flap with regard to salivary fistula rate. Fistulas were categorized into major and minor fistulas based on whether operative intervention was required. Results. The major fistula rate was 18.8% (9/48) and the minor fistula rate was 29.2% (14/48). The overall (major plus minor) fistula rate was 47.9%. The overall fistula and major fistula rates decreased with increasing the number of closure layers and with use of a pectoralis major flap; however, these correlations did not reach statistical significance. Other than age, there were no clinicopathologic variables associated with salivary fistulas. Conclusion. For salvage total laryngectomies, increasing the number of closure layers or use of a pectoralis major flap may reduce the risk of salivary fistula.

Outcomes in head and neck oncologic surgery at academic medical centers in the United States.

OBJECTIVES/HYPOTHESIS: To evaluate the impact of case volume and other variables on outcomes after head and neck oncologic surgery was performed at academic medical centers in the United States. STUDY DESIGN: Cross Sectional Ecological Study. METHODS: The University HealthSystems Consortium (UHC) database was analyzed for discharge data on all patients who underwent surgery for head and neck cancers (excluding thyroid and skin cancer) at full- member academic medical centers between quarter 4 of 2006 and quarter 4 of 2009. Multivariate and linear regression analyses and chi-square tests were applied to evaluate significant associations between hospital surgical volume and other independent variables, and to evaluate the risk of mortality, mortality index, complications, length of stay (LOS), LOS index, cost, and cost index. RESULTS: Of 22,357 surgical cases, 11,573 met our inclusion criteria. The only outcome that was statistically significant based on volume was a lower complication rate in high volume hospitals (P = 0.0486) as compared to low volume hospitals. All Payer Refined-Diagnosis Related Group defined major severity of illness was the only independent variable significantly associated with higher complication rates, observed LOS, and observed cost (P <0.0001, P = 0.0139, and P = 0.0092, respectively). Management of male patients and black patients resulted in a lower cost index (P = 0.0472) and a higher complication rate (P = 0.0297), respectively. Patients with private insurance had lower complication rates, observed LOS, and observed cost (P = 0.0401, P = 0.0001, and P = 0.0187, respectively). CONCLUSIONS: After controlling for other factors, academic medical centers with a higher cumulative case volume have lower rates of complications.