Effect of preoperative programmed death-1 or programmed death ligand-1 immune check point inhibition on complications after surgery for primary head and neck cancer.

BACKGROUND: There is sparse literature on the effect of preoperative immunotherapy on complications after surgery for primary head and neck squamous cell carcinoma (HNSCC). The objectives are to compare complication rates in patients receiving surgery with and without neoadjuvant immune checkpoint inhibitors (nICI) for primary HNSCC and to evaluate factors associated with increased odds of surgical complications. METHODS: A retrospective review of patients who underwent ablation and free flap reconstruction or transoral robotic surgery (TORS) for primary HNSCC between 2017-2021 was conducted. Complications were compared between patients who underwent surgery with or without nICI before and after propensity score matching. Regression analysis to estimate odds ratios was performed. RESULTS: A total of 463 patients met inclusion criteria. Free flap reconstruction constituted 28.9% of patients and TORS constituted 71.1% of patients. nICI was administered in 83 of 463 (17.9%) patients. There was no statistically significant difference in surgical, medical, or overall complications between patients receiving surgery with or without nICI. In the unmatched cohort, multivariable model identified non-White race, former/current smoking history, free flap surgery, and perineural invasion as factors significantly associated with increased complications. In the matched cohort, multivariable model identified advanced age and free flap surgery as factors significantly associated with increased complications. PLAIN LANGUAGE SUMMARY: It is safe to give immunotherapy before major surgery in patients who have head and neck cancer. Advanced age, non-White race, current/former smoking, free flap surgery, and perineural invasion may be associated with increased the odds of surgical complications.

IL-8 correlates with nonresponse to neoadjuvant nivolumab in HPV positive HNSCC via a potential extracellular vesicle miR-146a mediated mechanism.

Therapy using anti-PD-1 immune checkpoint inhibitors (ICI) has revolutionized the treatment of many cancers including head and neck squamous cell carcinomas (HNSCC), but only a fraction of patients respond. To better understand the molecular mechanisms driving resistance, we performed extensive analysis of plasma and tumor tissues before and after a 4-week neoadjuvant trial in which HNSCC patients were treated with the anti-PD-1 inhibitor, nivolumab. Luminex cytokine analysis of patient plasma demonstrated that HPVpos nonresponders displayed high levels of the proinflammatory chemokine, interleukin-8 (IL-8), which decreased after ICI treatment, but remained higher than responders. miRNAseq analysis of tetraspanin-enriched small extracellular vesicles (sEV) purified from plasma of HPVpos nonresponders demonstrated significantly lower levels of seven miRNAs that target IL-8 including miR-146a. Levels of the pro-survival oncoprotein Dsg2, which has been to down-regulate miR-146a, are elevated with HPVpos tumors displaying higher levels than HPVneg tumors. Dsg2 levels decrease significantly following ICI in responders but not in nonresponders. In cultured HPVpos cells, restoration of miR-146a by forced expression or treatment with miR-146a-loaded sEV, reduced IL-8 level, blocked cell cycle progression, and promoted cell death. These findings identify Dsg2, miR-146a, and IL-8 as potential biomarkers for ICI response and suggest that the Dsg2/miR-146a/IL-8 signaling axis negatively impacts ICI treatment outcomes and could be targeted to improve ICI responsiveness in HPVpos HNSCC patients.

Understanding precancerous lesions of the oral cavity†.

Precancerous lesions provide insight into tumor development as well as prognostication, since distinguishing high-risk from benign disease will stratify clinical management. In a recent issue of The Journal of Pathology, Ghosh et al performed comprehensive genomic characterization of the precancerous lesion leukoplakia, comparing RNA and DNA with peripheral blood, normal mucosa, and squamous cell carcinoma (SCC) of the gingivobuccal region of the oral cavity from the same 28 individuals. The data paint a picture of increasing mutation and early caspase-8 inactivation on the background of inflammation with decreasing immune surveillance in the progression from benign leukoplakia to SCC. This research points to an opportunity for disease intercept at the premalignant niche prior to the development of malignancy. © 2022 The Pathological Society of Great Britain and Ireland.

Functional Swallow-Related Outcomes Following Transoral Robotic Surgery for Base of Tongue Carcinoma.

In an era where the incidence of oropharyngeal cancer is growing steadily, there have been few studies exploring functional outcomes for individuals whose definitive cancer management approach includes transoral robotic surgical (TORS) resection. This study was designed to examine swallow-related outcomes in individuals newly diagnosed with base of tongue cancer whose treatment plan included surgical resection via TORS. The aims of this study were to determine whether TORS resection for early stage BOT SCCA affected: (a) lingual strength, (b) swallow safety and efficiency, (c) oral intake, and (d) swallowing-related quality of life. Nine individuals meeting the inclusion criteria were recruited to participate from March 2017 to April 2018. Each participant was evaluated at four distinct time points: (a) preoperatively, (b) 1 week postoperatively, (c) 1 month postoperatively, and (d) 3 months postoperatively. The following data were collected at each time point: (a) maximum isometric lingual pressure, (b) Penetration-Aspiration Scale score, (c) Yale Pharyngeal Residue Severity Rating Scale scores, (d) Functional Oral Intake Scale score, and (e) EAT-10 score. Data analysis revealed that a significant decline in maximum isometric lingual pressure, EAT-10 scores, and Functional Oral Intake Scale scores occurred between preoperative baseline measurements and 1 week post surgery. All participants in the study demonstrated a return to levels at or near their baseline level of function for maximum isometric lingual pressure, EAT-10 score, and Functional Oral Intake Scale score by 1 or 3 months post surgery. There were no significant changes in swallow safety or efficiency observed at any time point during the study.

Risk factors for gastrostomy tube dependence in transoral robotic surgery patients.

OBJECTIVES: To determine the rate of gastrostomy tube dependence after transoral robotic surgery (TORS), and to determine which patient or surgical factors increase the likelihood of gastrostomy tube dependence. METHODS: Retrospective chart review of all patients who underwent TORS for oropharyngeal squamous cell carcinoma (OPSCC) at a single institution from January 2011 through July 2016. Patients who underwent TORS for recurrent OPSCC were excluded. Primary outcome was gastrostomy tube (g-tube) dependence. Univariable and multivariable logistic regression were performed to identify risk factors for g-tube dependence at 3-months and 1-year. RESULTS: A total of 231 patients underwent TORS during the study period. At 3-month follow-up, 58/226 patients (25.7%) required g-tube. At 1-year and 2-year follow-up, 8/203 (3.9%) and 5/176 (2.8%), remained dependent on g-tube, respectively. Advanced T stage (T3) (OR = 6.07; 95% CI, 1.28-28.9) and discharge from the hospital with enteral access (OR = 7.50; 95% CI, 1.37-41.1) were independently associated with increased risk of postoperative gastrostomy tube dependence at 1 year on multivariable analysis. CONCLUSIONS: Long-term gastrostomy tube dependence following TORS is rare, particularly in patients that receive surgery alone. Patients with advanced T stage tumors have poorer functional outcomes. Early functional outcomes, as early as discharge from the hospital, are a strong predictor for long-term functional outcomes.

Patient experiences of sialendoscopy with monitored anesthesia care versus general anesthesia.

OBJECTIVE: To compare the experiences of patients who received sialendoscopy under general anesthesia (GA) with those who received monitored anesthesia care (MAC). METHODS: Patients who underwent sialendoscopy for sialadenitis or sialolithiasis from July 1, 2020, to July 31, 2021, were offered inclusion to this prospective observational study. A survey was sent to consenting patients on post-operative day 1 to record aspects of their pre-, intra-, and post-operative experience. The primary outcome was overall satisfaction. Secondary outcomes included pain tolerability and preference for similar anesthetic modality in the future. RESULTS: Seventy-five patients completed the post-operative survey (86% response rate), of which 39 patients received GA and 36 received MAC. Patient overall satisfaction was similar between groups (GA: "Poor/Average/Good" = 23%, "Excellent" = 77%; MAC: "Poor/Average/Good" = 25%, "Excellent" = 75%, p = 1.00). Tolerability of immediate post-operative pain was likewise similar between the GA (82%) and MAC (97%) groups (p = 0.058). Patients who received MAC reported intra-operative pain as "none/tolerable" 72% of the time and "uncomfortable" 28% of the time. Patients who received GA would prefer the same anesthetic in the future more often than in the MAC group (85% versus 61%, respectively, OR 3.50, 95% CI 1.17-10.50, p = 0.035). CONCLUSION: In regard to patient satisfaction, both MAC and GA are acceptable anesthetic choices in sialendoscopy for appropriate cases. Patients report similar overall satisfaction and post-operative pain tolerance under either anesthetic modality. Patients who undergo GA report higher rates of preference for similar anesthetic modality in the future. Further study is needed to determine the most appropriate criteria for anesthesia modality selection.

Recurrence of premalignant oral cavity and oropharynx lesions after pulsed diode laser treatment.

PURPOSE: Leukoplakia is common with a 1 % incidence in the population and may harbor preneoplastic changes. Diode lasers provide both precision and coagulation for excision of superficial lesions in clinical and operative settings with little damage to deeper tissue. We aim to determine the rate of oral and oropharyngeal hyperkeratosis and dysplasia recurrence after treatment with diode laser. MATERIALS AND METHODS: Patients with oral or oropharyngeal hyperkeratotic or mild dysplastic lesions treated with pulsed diode laser between 2013 and 2020 at a tertiary academic institution were analyzed. The main outcome measure was recurrence of hyperkeratosis and dysplasia after treatment. RESULTS: Fourteen patients received diode laser treatment for hyperkeratotic or mild dysplastic lesions of the oral cavity or oropharynx. Demographic features included 9 (64.3 %) females and mean age of 66.6 years. In these 14 patients, 18 distinct lesions were identified. Eleven (61.1 %) lesions were located on the oral tongue, 4 (22.2 %) on the buccal mucosa, 2 (11.1 %) on the hard palate, and 1 (5.6 %) on the soft palate. Average time from lesion clinical diagnosis to the first diode laser treatment was 8.3 months with an average number of 1.4 treatments per lesion. Three (16.7 %) lesions experienced recurrence after the most recent treatment. None of the lesions underwent malignant transformation. None of the patients experienced bleeding, tethering, or dysarthria after treatment. One patient developed pyogenic granuloma and reported chronic tongue pain. CONCLUSIONS: Pulsed diode laser treatment of leukoplakia was well tolerated with low complication rates and reasonable control of precancerous lesions.

Improved efficiency of sialendoscopy procedures at an ambulatory surgery center.

OBJECTIVES: To compare time spent on day of surgery and post-surgical outcomes for sialendoscopy procedures at an ambulatory surgery center versus in a hospital operating room. METHODS: Retrospective chart review for patients who underwent sialendoscopy for sialadenitis or sialolithiasis from March 2017 to May 2020 were included. Surgery location (ambulatory surgery center or hospital operating room) was compared. Primary outcomes included total time in hospital, operative time, total time in operating room. and recovery time. Secondary outcomes included rate of symptoms resolutions, requiring further medical management, and requiring further surgical intervention. RESULTS: A total of 321 procedures were included. Sialendoscopy in an ambulatory surgery center compared to main operating room decreased median hospital time (166 min reduction, p < 0.001), operative time (18 min reduction, p < 0.001), total time in operating room (34 min reduction, p < 0.001), and recovery time (64 min reduction, p < 0.001). Sialendoscopy in an ambulatory surgery center had similar rates of post-operative resolution of symptoms and further medical or surgical intervention compared to procedures in a hospital operating room. CONCLUSION: Sialendoscopy can be safely performed in an ambulatory surgery center for sialadenitis or appropriate sialolithiasis cases while decreasing hospital time, operative time, total time in operating room time, and recovery time.

Comparison of general anesthesia and monitored anesthesia care for sialendoscopy procedures.

OBJECTIVES: The literature remains scarce in terms of comparing different anesthesia modalities in sialendoscopy. Due to the lack of a standard of care or guidelines to anesthetic care, it is generally accepted that surgeons perform these surgeries under the anesthetic modality in which they are most comfortable. In this study, we evaluate time spent on the day of surgery and post-surgical outcomes for patients receiving sialendoscopy under monitored anesthesia care versus general anesthesia. MATERIALS AND METHODS: We retrospectively assessed patients who underwent sialendoscopy using a solely endoscopic approach for sialadenitis or sialolithiasis from March 2017 to December 2019. Anesthesia modality (monitored anesthesia care versus general anesthesia) was compared. Main outcomes included total time in hospital, operative time, total time in operating room, anesthesia time, and recovery time. Secondary outcomes included rate of resolution of symptoms, requiring further medical management, requiring further surgical intervention, and complications. RESULTS: A total of 172 procedures were included. Sialendoscopy under monitored anesthesia care center compared to general anesthesia decreased median hospital time (141 min reduction), anesthesia time (46 min reduction), operative time (24 min reduction), time in operating room (43 min reduction), and recovery time (56 min reduction). Utilizing monitored anesthesia care demonstrated similar rates of post-operative resolution of symptoms, complications, and further medical or surgical intervention compared to the general anesthesia cohort. CONCLUSION: Sialendoscopy can be safely performed under monitored anesthesia care for appropriate sialadenitis or sialolithiasis cases while decreasing hospital time, operative time, time in operating room, anesthesia time, and recovery time while maintaining similar post-operative outcomes. Monitored anesthesia care should be considered for solely endoscopic cases as guided by surgeon and patient comfort.

Evaluating the impact of smoking on disease-specific survival outcomes in patients with human papillomavirus-associated oropharyngeal cancer treated with transoral robotic surgery.

BACKGROUND: When treated nonsurgically with definitive chemoradiation, smokers with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC) have a worse prognosis compared with their nonsmoking counterparts. To the authors' knowledge, the prognostic significance of smoking in surgically treated patients is unknown. METHODS: The current study is a retrospective case series of patients with HPV-positive OPSCC who underwent upfront transoral robotic surgery at a single institution from 2010 through 2017. Exclusion criteria were nonoropharyngeal primary tumors, histology other than SCC, HPV-negative tumors, previous history of head and neck cancer, and/or previous head and neck radiotherapy. Recurrence-free survival (RFS), overall survival, and disease-specific survival were compared using the Kaplan-Meier method and the log-rank test. Smoking history was categorized as never smokers (<1 pack-year), current smokers (smoking at the time of the cancer diagnosis), and former smokers. RESULTS: A total of 258 patients met the study criteria. The average age was 60 years, and approximately 87% of patients were male. A total of 148 patients (57.4%) were smokers whereas 110 (42.6%) reported never smoking. There were 44 active smokers (17.1%) and 104 former smokers (40.3%). The median follow-up was 3.23 years. There were 17 patients of disease recurrence. Smoking pack-year history was not found to be significant for RFS (hazard ratio, 1.01; 95% CI, 0.99-1.03 [P = .45]). There was no significant difference in RFS noted between never and ever smokers (92% vs 89.8%; P = .85) nor was there a difference observed between never, former, and current smokers (92% vs 91.5% vs 86.1%, respectively; P = .69). CONCLUSIONS: A smoking history is common in patients with HPV-positive OPSCC. In the current study, HPV-positive smokers were found to have excellent survival and locoregional control, similar to their nonsmoking counterparts. The results of the current study do not support the exclusion of smokers with early-stage, HPV-positive OPSCC from transoral robotic surgery-based deintensification trials.

Functional outcomes of temporomandibular joint reconstruction with vascularized tissue.

OBJECTIVE: To determine how current temporomandibular joint (TMJ) reconstruction methods affect functional outcomes. METHODS: Retrospective review from January 2006 to July 2017 at a single tertiary care center. All patients who underwent mandibulectomy with subsequent reconstruction with vascularized free tissue were included in the study. Condylar segments were reconstructed with vascularized free tissue flap in conjunction with autologous tissue or allograft in the joint space. Preoperative, 3 month, 1 year, and 2 year postoperative records were assessed for trismus, need for tube feeds, and Functional Oral Intake Scale (FOIS). RESULTS: Joint space was reconstructed with autologous tissue (n = 10), allograft (n = 15) or both (n = 9). At three months, FOIS scores significantly decreased from 5.4 preoperatively to 4.8 post operatively (P = .024) and need for tube feeds significantly increased from 15.8% preoperatively to 35.1% (P ≤0.027). Trismus significantly decreased from 63.2% to 27% (P = .006). At one-year, there were no significant changes in functional status compared to pre-operative state. Patients who had previous RT had significantly worse FOIS scores preoperatively (p = .002), at three months (p < .001), one year (p < .001), and two years (p = .008). There was no significant difference in postoperative functional status of patients based on the method of TMJ reconstruction. CONCLUSION: Reconstruction of the TMJ with vascularized free tissue is a viable option and yields acceptable long-term outcomes. While functional status may improve or worsen in the immediate postoperative period, long term results mirror preoperative function. Preoperative trismus will likely improve. LEVEL OF EVIDENCE: Level 3; Retrospective Comparative Study.

Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes.

Extracellular vesicles (EVs) are nanoscale membrane-derived vesicles that serve as intercellular messengers carrying lipids, proteins, and genetic material. Substantial evidence has shown that cancer-derived EVs, secreted by tumor cells into the blood and other bodily fluids, play a critical role in modulating the tumor microenvironment and affecting the pathogenesis of cancer. Here we demonstrate for the first time that squamous cell carcinoma (SCC) EVs were enriched with the C-terminal fragment of desmoglein 2 (Dsg2), a desmosomal cadherin often overexpressed in malignancies. Overexpression of Dsg2 increased EV release and mitogenic content including epidermal growth factor receptor and c-Src. Inhibiting ectodomain shedding of Dsg2 with the matrix metalloproteinase inhibitor GM6001 resulted in accumulation of full-length Dsg2 in EVs and reduced EV release. When cocultured with Dsg2/green fluorescence protein-expressing SCC cells, green fluorescence protein signal was detected by fluorescence-activated cell sorting analysis in the CD90+ fibroblasts. Furthermore, SCC EVs activated Erk1/2 and Akt signaling and enhanced fibroblast cell proliferation. In vivo, Dsg2 was highly up-regulated in the head and neck SCCs, and EVs isolated from sera of patients with SCC were enriched in Dsg2 C-terminal fragment and epidermal growth factor receptor. This study defines a mechanism by which Dsg2 expression in cancer cells can modulate the tumor microenvironment, a step critical for tumor progression.-Overmiller, A. M., Pierluissi, J. A., Wermuth, P. J., Sauma, S., Martinez-Outschoorn, U., Tuluc, M., Luginbuhl, A., Curry, J., Harshyne, L. A., Wahl, J. K. III, South, A. P., Mahoney, M. G. Desmoglein 2 modulates extracellular vesicle release from squamous cell carcinoma keratinocytes.

A Survey of Microvascular Technique Preferences Among American Head Neck Society Members.

OBJECTIVE: To identify practices in microvascular techniques in routine and challenging scenarios. STUDY DESIGN: Cross-sectional study. METHODS: A national survey addressing practices related to microvascular free flap reconstruction was distributed to AHNS members between October and November 2021. RESULTS: The respondents encompassed 95 microvascular surgeons. Median years of practice was 6 (interquartile range, 2-13) and median flaps per year was 35 (22-50). Common practices in arterial anastomosis included limited cleaning of artery (84.2%), use of a double approximating clamp (64.2%), and use of interrupted suture (88.4%). Common practices in venous anastomosis included limited cleaning (89.5%), downsizing the coupler (53.7%), and coupling to two independent venous systems (47.4%). In arterial anastomosis, respondents felt that kinking (50.5%) and tension (24.2%) were the riskiest challenges. Kinking was handled by loose sutures or native tissue/dissolvable biomaterial to orient pedicle. Excess tension was handled by additional dissection. With regards to associated practices, most surgeons perform anastomosis after partial inset (52.6%), give aspirin immediately postoperatively (66.3%), reserve transfusion for hemodynamic instability (69.5%), and utilize intraoperative pressors when needed (72.6%). More senior surgeons reported placing more suture to address leaks (p = 0.004) and perform end to side anastomosis on larger vein in case of venous mismatch (p = 0.012). In cases of tension, higher volume surgeons perform more extensive dissection (p = 0.035) and end to side coupling (p = 0.029). CONCLUSIONS: This survey of AHNS members indicates patterns of microvascular techniques in routine and challenging scenarios. There exists a variation in approaches amongst surgeons based on volume and practice length. LEVEL OF EVIDENCE: 5 Laryngoscope, 134:1265-1277, 2024.

Altered extracellular matrix correlates with an immunosuppressive tumor microenvironment and disease progression in younger adults with oral cavity squamous cell carcinoma.

Introduction: Oral cavity squamous cell carcinoma (OSCC) occurs most frequently in patients >60 years old with a history of tobacco and alcohol use. Epidemiological studies describe increased incidence of OSCC in younger adults (<45 years). Despite its poor prognosis, knowledge of OSCC tumor microenvironment (TME) characteristics in younger adults is scarce and could help inform possible resistance to emerging treatment options. Methods: Patients with OSCC were evaluated using TCGA-HNSC (n=121) and a stage and subsite-matched institutional cohort (n=8) to identify differential gene expression focusing on the extracellular matrix (ECM) and epithelial-mesenchymal transition (EMT) processes in younger (≤45 years) vs. older adults (≥60 years). NanoString nCounter analysis was performed using isolated total RNA from formalin-fixed paraffin-embedded (FFPE) tumor samples. Stained tumor slides from young and old OSCC patients were evaluated for CD8+ T-cell counts using immunohistochemistry. Results: Younger OSCC patients demonstrated significantly increased expression of ECM remodeling and EMT process genes, as well as TME immunosuppression. Gene set enrichment analyses demonstrated increased ECM pathways and concurrent decreased immune pathways in young relative to old patients. Transcripts per million of genetic markers involved in ECM remodeling including LAMB3, VCAN, S100A9, COL5A1, and ITGB2 were significantly increased in tumors of younger vs. older patients (adjusted p-value < 0.10). Young patient TMEs demonstrated a 2.5-fold reduction in CD8+ T-cells as compared to older patients (p < 0.05). Conclusion: Differential gene expression impacting ECM remodeling and TME immunosuppression may contribute to disease progression in younger adult OSCC and has implications on response to evolving treatment modalities, such as immune checkpoint inhibitor therapy.

Obesity and Survival After Immune Checkpoint Inhibition for Head and Neck Squamous Cell Carcinoma.

Importance: For patients treated with immune checkpoint inhibitors (ICIs), recent data suggest that obesity has a beneficial effect on survival outcomes in various cancer types. Reports on this association in head and neck cancer are limited. Objectives: To compare overall survival (OS) to 5 years and functional outcomes in patients with head and neck squamous cell carcinoma (HNSCC) treated with ICIs based on pretreatment body mass index (BMI). Design, Setting, and Participants: This retrospective population-based cohort study used data obtained from the TriNetX Global Collaborative Network database to identify patients with HNSCC who received ICI treatment between January 1, 2012, and December 31, 2023, resulting in a total of 166 patients (83 with BMI of 20.0-24.9 [normal BMI] and 83 with BMI of ≥30.0 [obesity BMI]) after propensity score matching (PSM) for pretreatment medical comorbidities and oncologic staging. Exposure: Normal BMI vs obesity BMI. Main Outcomes and Measures: Overall survival and functional outcomes (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) were measured to 5 years after ICI treatment and compared between patients with obesity BMI and normal BMI. Additional analyses compared OS and functional outcomes in the cohort with normal BMI and cohorts with overweight BMI (25.0-29.9) and underweight BMI (<20.0). Results: Among the 166 patients included in the PSM analysis (112 men [67.1%]; mean [SD] age, 62.9 [15.4] years), obesity BMI was associated with significantly improved OS at 6 months (hazard ratio [HR], 0.54 [95% CI, 0.31-0.96]), 3 years (HR, 0.56 [95% CI, 0.38-0.83]), and 5 years (HR, 0.62 [95% CI, 0.44-0.86]) after ICI treatment, compared with patients with normal BMI. Obesity BMI was also associated with decreased risk of gastrostomy tube dependence at 6 months (odds ratio [OR], 0.41 [95% CI, 0.21-0.80]), 1 year (OR, 0.41 [95% CI, 0.21-0.78]), 3 years (OR, 0.35 [95% CI, 0.18-0.65]), and 5 years (OR, 0.34 [95% CI, 0.18-0.65]). Obesity was also associated with decreased risk for tracheostomy dependence at 1 year (OR, 0.52 [95% CI, 0.28-0.90]), 3 years (OR, 0.45 [95% CI, 0.45-0.90]), and 5 years (OR, 0.45 [95% CI, 0.45-0.90]). There were no differences in rates of dysphagia or immune-related adverse events between cohorts at any points. Conclusions and Relevance: Using population-level data for patients with HNSCC treated with ICIs, these results suggest that having obesity was associated with improved 6-month, 3-year, and 5-year OS compared with having normal BMI. Additionally, obesity was associated with decreased gastrostomy and tracheostomy tube dependence compared with normal BMI. Further investigation is required to understand the mechanism of these findings.

Predictive capacity of immune-related adverse events and cytokine profiling in neoadjuvant immune checkpoint inhibitor trials for head and neck squamous cell carcinoma.

OBJECTIVES: Certain low-level immune-related adverse events (irAEs) have been associated with survival benefits in patients with various solid tumors on immune checkpoint inhibitors (ICIs). We aimed to investigate the association between irAEs and response to neoadjuvant ICIs in patients with head and neck squamous cell carcinoma (HNSCC) and to identify differences in circulating cytokine levels based on irAE status. METHODS: This was a retrospective cohort study including three neoadjuvant clinical trials from July 2017 to January 2022: NCT03238365 (nivolumab ± tadalafil), NCT03854032 (nivolumab ± BMS986205), NCT03618654 (durvalumab ± metformin). The presence and type of irAEs, pathologic treatment response, and survival were compared. Canonical linear discriminant analysis (LDA) was performed to identify combinations of circulating cytokines predictive of irAEs using plasma sample multiplex assay. RESULTS: Of 113 participants meeting inclusion criteria, 32 (28.3%) developed irAEs during treatment or follow-up. Positive p16 status was associated with irAEs (odds ratio [OR] 2.489; 95% CI 1.069-6.119; p = 0.043). irAEs were associated with pathologic treatment response (OR 3.73; 95% CI 1.34-10.35; p = 0.011) and with higher OS in the combined cohort (HR 0.319; 95% CI 0.113-0.906; p = 0.032). Patients with irAEs within the nivolumab cohort had significant elevations of select cytokines pre-treatment. Canonical LDA identified key drivers of irAEs among all trials, which were highly predictive of future irAE status. CONCLUSIONS: irAEs are associated with response to neoadjuvant ICI therapy in HNSCC and can serve as clinical indicators for improved clinical outcomes. irAEs can be predicted by concentrations of several circulating cytokines prior to treatment.

Feasibility of collagen matrix tiles with cesium-131 brachytherapy for use in the treatment of head and neck cancer.

BACKGROUND: Locoregional failure is a unique and challenging problem in head and neck cancer with controversy surrounding the use of re-irradiation in the treatment. We aimed to evaluate the dosimetry and technical parameters in utilizing a collagen matrix with embedded Cesium-131 (Cs-131) radioactive isotope seeds as it relates to dose distribution and dose to carotid artery. METHODS AND MATERIALS: Cadaveric feasibility study randomizing Cs-131 strands alone or Cs-131 with collagen matrix to be placed into neck dissection defects. For the dose computation, physicists employed the TG-43 dosimetry calculation algorithm with a point source assumption to compute the dose. Carotid arteries were contoured in MIM-Symphony software and the carotid artery maximum and mean doses were calculated in accordance with TG-43 specifications. Ease of use of collagen matrix tiles on a 7-point Likert scale and mean radiation dose to the carotid artery. RESULTS: Ease of use score was higher in collagen matrix compared to stranded seeds with a mean score of 6.3 +/- 1.2 compared to 4.5 +/- 0.87. Time of implantation was statistically significantly, p = 0.031, lower in the collagen matrix group (M = 5.17 min, SD = 4.62) compared to stranded seeds (M = 15.83 min, SD = 3.24). Mean radiation dose to the carotid artery was 62.8 Gy +/- 9.46 in the collagen matrix group compared to 108.2 Gy +/- 55.6 in the traditional Cs-131 seeds group. CONCLUSIONS: We present a feasibility and concept cadaveric study using a collagen matrix with Cesium-131 demonstrating preliminary evidence to support its ease of use, decreased time to implantation, and decreased dose delivered to the carotid artery.

Impact of Head and Neck Cancer Diagnosis and Treatment on Patient-Partner Intimacy.

OBJECTIVE: To determine the effects of head and neck squamous cell carcinoma diagnosis and treatment on patient- and partner-perceived intimacy and to understand if a diagnosis of HPV-related head and neck squamous cell carcinoma influences patient-partner intimacy. STUDY DESIGN: Prospective observational. SETTING: Single tertiary care center. METHODS: An investigator-developed questionnaire was used to prospectively survey patients and partners in 2 groups based on human papillomavirus (HPV) status: HPV+ and HPV- at diagnosis (visit 1) and after treatment (visit 2). Surveys were scored on a 60-point scale, and results were categorized as follows: loss of intimacy (0-30), stable relationship (31-41), or improvement in intimacy (42-60). Responses of couples who participated together were assessed for concordance. Responses were considered discordant if patient and partner scores equated to different levels of perceived intimacy. Median patient and partner scores were compared via Mann-Whitney U test, and concordance was assessed with a chi-square test. RESULTS: Thirty-four patients and 28 partners completed surveys at visit 1 and 28 patients and 15 partners at visit 2. Median scores among patients and partners were similar at the first time point (HPV+, 45 vs 45, P = .64; HPV-, 42.6 vs 40.8, P = .29) and the second (HPV+, 44.5 vs 44, P = .87; HPV-, 40.2 vs 39.6, P = .90). Concordance rates between HPV+ and HPV- couples were 63% vs 44% (P = .43) for the first time point and 89% vs 50% (P = .24) for the second. CONCLUSION: Patients and partners reported stable or improved intimacy at both time points, and most couples tended to agree on their levels of perceived intimacy. A diagnosis of HPV did not appear to significantly affect intimacy scores.

Postoperative opioid-prescribing practices in otolaryngology: Evidence-based guideline outcomes.

Objectives: We previously reported that >50% of postoperative opioids prescribed at our institution went unused for common otolaryngologic procedures. Based on these findings, we instituted multimodal, evidence-based guidelines for postoperative pain management. In the second part of our multiphasic study, we evaluated the effects of these guidelines on (1) quantity of unused opioids, (2) patient satisfaction, and (3) institutional perceptions toward the opioid epidemic and prescribing guidelines. Methods: Standardized, procedure-specific opioid prescription guidelines were created using prospective data from the first phase of our study and evidence from current literature. Again, we examined sialendoscopy, parotidectomy, parathyroidectomy/thyroidectomy, and transoral robotic surgery (TORS). Patients were surveyed at their first postoperative appointment. Groups from Phases I and II were compared. Attending physicians were surveyed before the start of the multiphasic project and after prescribing guidelines were implemented. Results: Prescribing guidelines led to an average reduction in prescribed morphine milligram equivalents (MME) per patient by: 48% (sialendoscopy), 63% (parotidectomy), 60% (para/thyroidectomy), and 42% (TORS). Average used MME per patient for parotidectomy was significantly reduced (64%). The proportion of unused MME per patient and patient satisfaction scores did not significantly change after guidelines were implemented. Conclusion: Implementation of opioid-prescribing guidelines and the use of multimodal analgesia substantially reduced the amount of opioids prescribed across all procedures without impacting patient satisfaction. Level of Evidence: 2.

Postoperative analysis of osseous midface reconstructions: The value of imaging and a novel scoring system for complexity and operative success.

BACKGROUND: Few standardized methods exist for evaluating the postoperative outcomes of osteocutaneous free flaps. We propose an anatomic-based scoring system for midface free flap reconstruction. METHODS: One hundred and twelve patients across four institutions underwent osteocutaneous reconstruction of the midface. Postoperative scans were scored based on the number of independent osseous subunits reconstructed (Subunit Score), the number of different bony appositions with bony contact (Contact Score), and the number of osseous segments in anatomic position (Position Score). These were added together to create a Total Score. RESULTS: Osteocutaneous radial forearm flaps had the lowest Subunit Score (p = 0.001). Fibula flaps had the highest Contact Score (p = 0.0008) and Position Score (p = 0.001). Virtual surgical planning was associated with an increased Subunit Score (p = 0.02) and Total Score (p = 0.04). CONCLUSIONS: We propose a novel scoring system for osseous midface reconstruction based on postoperative imaging scans. This can help guide management decisions and create a common language to compare outcomes.