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.

Artery Grafting for Arterial Anastomoses in Head and Neck Free Tissue Transfer Reconstruction.

BACKGROUND: Vessel grafting is an important technique in head and neck free tissue transfer (FTT) reconstruction when a tension-free anastomosis is not otherwise feasible. To our knowledge, there are limited data regarding interposition artery grafts for arterial anastomoses in head and neck reconstruction. Here, we present a multi-institutional cohort of arterial interposition grafts for FTT reconstruction for head and neck defects. METHODS: A retrospective review was conducted at four tertiary care institutions for patients who underwent FTT reconstruction for head and neck defects which utilized an interposition artery graft for the arterial anastomosis. Charts were reviewed for type and length of artery grafts harvested, surgical indication, indication for artery graft, types of flaps harvested, and various preoperative characteristics (including history of radiation or previous FTT reconstruction surgery). Postoperative complications within postoperative day 30 were measured and reported. RESULTS: Nine patients met inclusion criteria. The lateral circumflex femoral artery (either transverse or descending branches) (n = 3) and facial artery (n = 3) were the most commonly harvested arteries. The scalp (n = 5) was the most common primary defect site. Seven grafts were harvested initially and in a planned fashion, while two were harvested as salvage techniques (either for flap salvage or vein graft failure). In planned grafts, arteries were the preferred interposition grafting method due to either size match preferences (n = 4) or similarities in wall thickness (n = 3) between graft and recipient artery. There were no reported cases of unplanned readmission, postoperative hematoma, fistula formation, wound infection, or donor site morbidities. Two patients required unplanned return to the operating room for flap compromise, both of which ultimately resulted in flap failure secondary to clot formation at both arterial and venous anastomoses. CONCLUSIONS: When arterial pedicle length is insufficient, interposition artery grafting is both a feasible and viable technique to achieve tension-free arterial anastomoses for select cases of highly complex head and neck free tissue reconstruction.

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.

Oncologic outcomes of human papillomavirus-associated oropharynx carcinoma treated with surgery alone: A 12-institution study of 344 patients.

BACKGROUND: The oncologic outcomes of surgery alone for patients with American Joint Committee on Cancer 7th edition (AJCC 7th) pN2a and pN2b human papillomavirus-associated oropharynx squamous cell carcinoma (HPV+OPSCC) are not clear. METHODS: The authors performed a 12-institution retrospective study of 344 consecutive patients with HPV+OPSCC (AJCC 7th pT0-3 N3 M0) treated with surgery alone with 6 months or more of follow-up using univariate and multivariate analyses. RESULTS: The 2-year outcomes for the entire cohort were 91% (182 of 200) disease-free survival (DFS), 100% (200 of 200) disease-specific survival (DSS), and 98% (200 of 204) overall survival (OS). The 18 recurrences within 2 years were 88.9% (16 of 18) local and/or regional recurrences and 11.1% (2 of 18) distant metastases. Recurrences were not significantly associated with smoking, pT stage, or pN stage. The 16 patients with locoregional recurrences within 2 years all underwent successful salvage treatments (median follow-up after salvage: 13.1 months), 43.8% (7 of 16) of whom underwent salvage surgery alone for a 2-year overall salvage radiation need of 4.5% (9 of 200). The 2-year outcomes for the 59 evaluable patients among the 109 AJCC 7th pT0-2 N2a-N2b patients with 1 to 3 pathologic lymph nodes (LNs) were as follows: local recurrence, 3.4% (2 of 59); regional recurrence, 8.4% (5 of 59); distant metastases, 0%; DFS, 88.1% (52 of 59); DSS, 100% (59 of 59); OS, 96.7% (59 of 61); and salvage radiation, 5.1% (3 of 59). CONCLUSIONS: With careful selection, surgery alone for AJCC 7th pT0-T2N0-N2b HPV+OPSCC with zero to 3 pathologic LNs without perineural invasion, extranodal extension, or positive margins results in high DFS, DSS, OS, and salvage treatment success. Because of the short-term follow-up, these data support further investigation of treatment de-escalation in this population.

Predicting transient hypocalcemia in patients with unplanned parathyroidectomy after thyroidectomy.

OBJECTIVE: To assess the utility of rapid parathyroid hormone (PTH) values in predicting transient post-operative hypocalcemia in patients with unplanned parathyroidectomy during total or completion thyroidectomy. METHODS: All patients who underwent total or completion thyroidectomy between January 2010 and January 2015 were reviewed. Incidences of post-operative hypocalcemia were compared in patients with and without unplanned parathyroidectomy. Unplanned parathyroidectomy was defined as intra-operative incidental or intentional parathyroidectomy. Logistic regression assessed for predictors of hypocalcemia and optimum amount of calcium supplementation. RESULTS: Thirty-eight (13.6%) patients had evidence of incidental parathyroidectomy and 39/280 (13.9%) patients had parathyroid autotransplantation intra-operatively. Central neck dissection and malignancy were identified as risk factors for unplanned parathyroidectomy (p = 0.001, p = 0.060). Patients with unplanned parathyroidectomy were more likely to have hypocalcemia (p = 0.002) and hypoparathyroidism (p < 0.0005). PTH value was the only significant predictor of hypocalcemia in these patients. In patients with a post-operative PTH of ≤15, initial calcium supplementation ≥ 1000 mg decreased the risk of hypocalcemia (p < 0.05). CONCLUSION: Post-operative PTH value predicts hypocalcemia in patients undergoing total and completion thyroidectomy with unplanned parathyroidectomy. In patients with a post-operative PTH < 15, initial calcium supplementation with ≥1000 mg of elemental calcium is recommended.

Trends and Future Directions in Margin Analysis for Head and Neck Cancers.

Margin status in head and neck cancer has important prognostic implications. Currently, resection is based on manual palpation and gross visualization followed by intraoperative specimen or tumor bed-based margin analysis using frozen sections. While generally effective, this protocol has several limitations including margin sampling and close and positive margin re-localization. There is a lack of evidence on the association of use of frozen section analysis with improved survival in head and neck cancer. This article reviews novel technologies in head and neck margin analysis such as 3-dimensional scanning, augmented reality, molecular margins, optical imaging, spectroscopy, and artificial intelligence.

Complications and Functional Outcomes After Esophageal Reconstruction with an Intact Larynx.

BACKGROUND: Esophageal defects can result from primary pathologies such as malignancy or stricture, or secondary ones such as perforation due to trauma or iatrogenic injury. Techniques, management, and outcomes of reconstruction in this setting are poorly understood. Herein, we aim to highlight surgical outcomes in patients undergoing local and free flap reconstruction of esophageal defects in the setting of an intact larynx. METHODS: Retrospective review of patients who underwent esophageal reconstruction with an intact larynx between 2009 and 2022 at our institution was performed. RESULTS: Ten patients met inclusion criteria. Esophageal reconstruction was performed for extruded spinal hardware (n = 8), and esophageal stricture (n = 2). Four patients underwent reconstruction with free tissue transfer, and six with local pedicled flaps. There were no cases of flap failure, esophageal fistula, hematoma, or wound dehiscence. One patient had post-operative bleeding requiring return to the operating room. Three patients had a postoperative wound infection, two of whom required washout. There were no unplanned 30-day readmissions. At three months after operation, all patients who were not tube feed-dependent prior to surgery returned to oral intake. Of the four patients who were tube feed-dependent preoperatively, three were tolerating oral intake at nine months postoperatively. Nine patients (90%) had stable flexible laryngoscopy exams pre- and postoperatively with no voice changes. CONCLUSIONS: Reconstruction of esophageal defects in the setting of an intact larynx can be challenging. In this series, surgical intervention with free tissue transfer and local pedicled flaps was effective in returning patients to oral intake with low long-term morbidity. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:1227-1233, 2024.

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.

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.

Functional and Symmetry Outcomes After Forehead Flap Reconstruction of Medial Peri-Ocular Defects.

BACKGROUND: Orbital defects have a profound impact on orbital function and symmetry of the face and are difficult to reconstruct given the complexity of this area. The paramedian forehead flap (PMFF) has not been well studied in reconstruction of orbital defects. METHODS: Retrospective review of patients who underwent reconstruction of periorbital defects with PMFF between 2016 and 2021. Variables were ocular adnexal asymmetry, functional outcomes, and orbital complications. RESULTS: Eighteen patients met inclusion criteria. Mean defect size was 11.1 ± 7.5 cm. The most common subsite involved was medial canthus in 88.9% of patients. There was no statistically significant difference between mean medial canthus to midline ratio and mean medial brow to midline ratio when compared to the assumed normal of 1. The medial canthus to pupil ratio and medial canthus to lateral canthus ratio had a statistically significant mean difference from 1.0 (p = 0.003 for both). In 22.2% of patients, the orbit was functional with impairment; the remaining had no impairment. Surgical sequelae occurred in 12/18 (66.7%) of patients, most commonly epiphora in 9/18 (50%) of patients, and ectropion in 5/18 (27.7%). CONCLUSION: The PMFF is feasible for medial periorbital reconstruction with acceptable functional and symmetrical outcomes and low morbidity. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2584-2589, 2023.

Trends in Positive Surgical Margins in cT3-T4 Oral Cavity Squamous Cell Carcinoma.

OBJECTIVE: Positive surgical margins in oral cavity squamous cell carcinoma are associated with cost escalation, treatment intensification, and greater risk of recurrence and mortality. The positive margin rate has been decreasing for cT1-T2 oral cavity cancer over the past 2 decades. We aim to evaluate positive margin rates in cT3-T4 oral cavity cancer over time, and determine factors associated with positive margins. STUDY DESIGN: Retrospective analysis of a national database. SETTING: National Cancer Database 2004 to 2018. METHODS: All adult patients diagnosed between 2004 and 2018 who underwent primary curative intent surgery for previously untreated cT3-T4 oral cavity cancer with known margin status were included. Logistic univariable and multivariable regression analyses were performed to identify factors associated with positive margins. RESULTS: Among 16,326 patients with cT3 or cT4 oral cavity cancer, positive margins were documented in 2932 patients (18.1%). Later year of treatment was not significantly associated with positive margins (odds ratio [OR] 0.98, 95% confidence interval [CI] 0.96-1.00). The proportion of patients treated at academic centers increased over time (OR 1.02, 95% CI 1.01-1.03). On multivariable analysis, positive margins were significantly associated with hard palate primary, cT4 tumors, advancing N stage, lymphovascular invasion, poorly differentiated histology, and treatment at nonacademic or low-volume centers. CONCLUSION: Despite increased treatment at academic centers for locally advanced oral cavity cancer, there has been no significant decrease in positive margin rates which remains high at 18.1%. Novel techniques for margin planning and assessment may be required to decrease positive margin rates in locally advanced oral cavity cancer.

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.

Effects of Prior Tracheostomy on Total Laryngectomy Outcomes.

OBJECTIVE: To assess whether preoperative tracheostomy (PreOT) increases risk of complications after total laryngectomy (TL) and to determine if timing of tracheostomy creation is associated with an increased risk. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary care hospital between 2007 and 2020. METHODS: Inclusion criteria were patients who underwent primary or salvage TL for oncologic treatment. Dependent variables of interest included surgical complications, such as wound dehiscence, infection, hematoma, complete flap failure, fistula formation, and stoma stenosis, as well as medical complications. Categorical variables were compared with chi-square test or Fisher exact test, and continuous variables were compared with an independent t test. Multivariable regression was conducted to assess predictors of complications after laryngectomy. RESULTS: A total of 306 patients were included. Primary TL was performed in 161 (53%) patients and salvage in 145 (47%) patients. Of the patients undergoing primary laryngectomy, 105 (65%) received a PreOT. Of the patients undergoing salvage laryngectomy, 86 (59%) received a PreOT. In both primary and salvage cases, there was no association between PreOT and surgical or medical complications. Additionally, there was no significant association between timing of tracheostomy and surgical complications. On multivariable analysis, the presence of a PreOT was not associated with surgical complications. In salvage cases, those with a PreOT had a significantly longer average length of stay than those without a PreOT (12 vs 9 days, P = .008). CONCLUSION: PreOT in patients undergoing primary and salvage laryngectomies was not associated with surgical or medical complications postlaryngectomy. Timing of tracheostomy in relation to laryngectomy was not found to adversely affect clinical outcomes.

Evaluating the impact of hemodynamic support measures on head and neck free tissue transfer outcomes: A population-based analysis.

OBJECTIVES: This study sought to analyze the effects of perioperative blood transfusions and vasopressors on 30-day surgical complications and 1-year mortality after reconstructive surgery in head and neck free tissue transfer (FTT) and to identify predictors of administration of perioperative blood transfusions or vasopressors. MATERIALS AND METHODS: TriNetX (TriNetX LLC, Cambridge, USA), an international population-level electronic health record database, was queried to identify subjects that underwent FTT requiring perioperative (intraoperative to postoperative day 7) vasopressors or blood transfusions. Primary dependent variables were 30-day surgical complications and 1-year mortality. Propensity score matching was used to control for population differences, and covariate analysis was used to identify preoperative comorbidities associated with perioperative vasopressor or transfusion requirements. RESULTS: 7,631 patients met inclusion criteria. Preoperative malnutrition was associated with increased odds of perioperative transfusion (p = 0.002) and vasopressor requirement (p < 0.001). Perioperative blood transfusion (n = 941) was associated with increased odds of any surgical complication (p = 0.041) within 30 days postoperatively and specifically increased odds of wound dehiscence (p = 0.008) and FTT failure (p = 0.002), respectively. Perioperative vasopressor was (n = 197) was not associated with 30-day surgical complications. Vasopressor requirement was associated with increased hazards-ratio of mortality at 1-year (p = 0.0031). CONCLUSION: Perioperative blood transfusion in FTT is associated with increased odds for surgical complications. Judicious use as a hemodynamic support measure should be considered. Perioperative vasopressor use was associated with an increased risk of one-year mortality. Malnutrition is a modifiable risk factor for perioperative transfusion and vasopressor requirement. These data warrant further investigation to assess causation and potential opportunity for practice improvement.

Factors Impacting Discharge Destination Following Head and Neck Microvascular Reconstruction.

OBJECTIVE: Determine which variables impact postoperative discharge destination following head and neck microvascular free flap reconstruction. STUDY DESIGN: Retrospective review of prospectively collected databases. METHODS: Consecutive patients undergoing head and neck microvascular free flap reconstruction between January 2010 and December 2019 (n = 1972) were included. Preoperative, operative and postoperative variables were correlated with discharge destination (home, skilled nursing facility [SNF], rehabilitation facility, death). RESULTS: The mean age of patients discharged home was lower (60 SD ± 13, n = 1450) compared to those discharged to an SNF (68 SD ± 14, n = 168) or a rehabilitation facility (71 SD ± 14, n = 200; p < 0.0001). Operative duration greater than 10 h correlated with a higher percentage of patients being discharged to a rehabilitation or SNF (25% vs. 15%; p < 0.001). Patients were less likely to be discharged home if they had a known history of cardiac disease (71% vs. 82%; p < 0.0001). Patients were less likely to be discharged home if they experienced alcohol withdrawal (67% vs. 80%; p = 0.006), thromboembolism (59% vs. 80%; p = 0.001), a pulmonary complication (46% vs. 81%; p < 0.0001), a cardiac complication (46% vs. 80%; p < 0.0001), or a cerebral vascular event (25% vs. 80%; p < 0.0001). There was no correlation between discharge destination and occurrence of postoperative wound infection, salivary fistula, partial tissue necrosis or free flap failure. Thirty-day readmission rates were similar when stratified by discharge destination. CONCLUSION: There was no correlation with the anatomic site, free flap donor selection, or free flap survival and discharge destination. Patient age, operative duration and occurrence of a medical complication postoperatively did correlate with discharge destination. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:95-104, 2023.

CD8+ and FoxP3+ T-Cell Cellular Density and Spatial Distribution After Programmed Death-Ligand 1 Check Point Inhibition.

OBJECTIVES: To analyze CD8+ and FoxP3+ T-cell cellular density (CD) and intercellular distances (ID) in head and neck squamous cell carcinoma (HNSCC) samples from a neoadjuvant trial of durvalumab +/- metformin. METHODS: Paired pre- and post-treatment primary HNSCC tumor samples were stained for CD8+ and FoxP3+. Digital image analysis was used to determine estimated mean CD8+ and FoxP3+ CDs and CD8+-FoxP3+ IDs in the leading tumor edge (LTE) and tumor adjacent stroma (TAS) stratified by treatment arm, human papillomavirus (HPV) status, and pathologic treatment response. A subset of samples was characterized for T-cell related signatures using digital spatial genomic profiling. RESULTS: Post-treatment analysis revealed a significant decrease in FoxP3+ CD and an increase in CD8+ CDs in the TAS between patients receiving durvalumab and metformin versus durvlaumab alone. Both treatment arms demonstrated significant post-treatment increases in ID. Although HPV+ and HPV- had similar immune cell CDs in the tumor microenvironment, HPV+ pre-treatment samples had 1.60 times greater ID compared with HPV- samples, trending toward significance (p = 0.05). At baseline, pathologic responders demonstrated a 1.16-fold greater CD8+ CDs in the LTE (p = 0.045) and 2.28-fold greater ID (p = 0.001) than non-responders. Digital spatial profiling revealed upregulation of FoxP3+ and cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) in the TAS (p = 0.006, p = 0.026) in samples from pathologic responders. CONCLUSIONS: Analysis of CD8+ and FoxP3+ detected population differences according to HPV status, pathologic response, and treatment. Greater CD8+-FoxP3+ ID was associated with pathologic response. CD8+ and FoxP3+ T-cell distributions may be predictive of response to immune checkpoint inhibition. CLINICALTRIALS: gov (Identifier NCT03618654). LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1875-1884, 2023.

Effect of p16 Status on Survival Outcomes in Sinonasal Squamous Cell Carcinoma.

OBJECTIVE: Evaluate the effect of p16 status on disease-free survival (DFS) and overall survival (OS) in patients with sinonasal squamous cell carcinoma (SCC) undergoing treatment with curative intent; and to assess how p16 status may affect patterns of recurrence. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary medical center. METHODS: Patients with sinonasal SCC treated with curative intent from 2012 to 2018 were identified. Independent variable of interest was p16 status, which was assessed using immunohistochemistry (IHC) with a 70% staining cutoff for positivity. Kaplan Meier survival curve was plotted to assess correlation between p16 status and DFS and OS. Association between recurrence patterns and p16 status was conducted using chi square and fisher's exact tests. Multivariable Cox proportional hazard analysis was conducted to assess association between independent variables and DFS. RESULTS: Fifty patients with sinonasal SCC met inclusion criteria. Patients were p16 positive in 28/50 (56%) of cases. Kaplan Meier survival curve revealed no statistically significant association between p16 status and DFS or OS survival (P = .780, P = .474). There was no difference in recurrence patterns in patients with p16 positive versus negative tumors. CONCLUSION: p16 status did not have prognostic value on DFS and OS in our cohort of patients with sinonasal SCC undergoing treatment with curative intent. There was no difference in recurrence patterns between the 2 populations. Based on the results of this study, p16 status should not impact counseling of patients as it relates to their prognosis from SNM.

Factors Leading to Gastrostomy Tube and Tracheostomy Requirements in Patients Treated Initially With Radiotherapy and Salvaged With Surgery and Free Flap Reconstruction.

OBJECTIVE: Patients with recurrent oropharyngeal cancer can achieve survival benefits from surgical salvage, and often require simultaneous free-flap reconstruction. Resection and reconstruction can impact function, leading to tube dependence. PRIMARY OBJECTIVE: describe rates of tracheostomy and gastrostomy tube dependence after oropharyngeal resection and free flap after prior radiation. SECONDARY OBJECTIVE: evaluate patient, tumor, and treatment factors associated with tube dependence. STUDY DESIGN: Retrospective, multi-institutional cohort study. Patients treated from 2003 to 2020. Average follow-up 21.4 months. SETTING: Five tertiary care centers. METHODS: Consecutive cohort of patients undergoing resection and simultaneous free-flap reconstruction for oropharyngeal squamous cell carcinoma after head and neck radiation. PRIMARY OUTCOMES: gastrostomy tube dependence and tracheostomy or tracheostoma 1 year after surgery. Univariable and multivariable logistic regression were performed to identify factors associated with dependence. RESULTS: 89 patients underwent oropharyngectomy and free-flap reconstruction; 18 (20%) underwent total laryngectomy as part of tumor extirpation. After surgery, 51 patients (57%) lived 12 months. Among patients alive at 12 months, 22 (43%) were at least partially-dependent on gastrostomy tube, and 15 (29%) had either tracheostomy or tracheostoma. On multivariable analysis, extensive glossectomy (OR 16.6, 95% CI 1.83-389, p = 0.026) and total laryngectomy (OR 11.2, 95% CI 1.71-105, p = 0.018) were associated with long-term gastrostomy tube. No factors were associated with long-term tracheostomy on multivariable analysis. CONCLUSION: Even among long-term survivors after salvage resection and free-flap reconstruction, rates of tube dependence are significant. This multi-institutional review is the largest such study to the date and may help inform shared decision-making. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:2141-2147, 2023.

Differences in Functional and Survival Outcomes Between Patients Receiving Primary Surgery vs Chemoradiation Therapy for Treatment of T1-T2 Oropharyngeal Squamous Cell Carcinoma.

Importance: Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear. Objectives: To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT. Design, Setting, and Population: This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform. Exposure: Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy. Main Outcomes and Measures: Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT. Results: Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79). Conclusions and Relevance: This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.

Trends in Adjuvant Therapy After Surgery for Oropharyngeal Squamous Cell Carcinoma.

OBJECTIVES/HYPOTHESIS: We aim to 1) evaluate trends in adjuvant treatment of human papilloma virus (HPV)-related oropharyngeal cancer; 2) assess change in complications and functional outcomes over time; and 3) assess change in overall and disease-free survival (DFS) over time. STUDY DESIGN: Retrospective analysis. METHODS: Charts of patients who underwent transoral robotic surgery for HPV-related oropharyngeal cancer between 2011 and 2019 were reviewed. Trend analysis was used to compare rate of adjuvant treatment over time. The Kaplan-Meier method was conducted to analyze overall survival (OS) and DFS. RESULTS: Three hundred and forty-two patients met inclusion criteria. One hundred and sixty-three (47.7%) patients underwent adjuvant radiation, and 90 (26.3%) patients underwent adjuvant chemoradiation. Rate of extranodular extension decreased significantly from 38.9% to 24.0% (P = .004). Rate of adjuvant therapy decreased significantly from 90.9% to 62.5% between 2011 and 2019 (P = .001). In patients who received adjuvant treatment, rate of adjuvant chemoradiation therapy decreased significantly from 40.0% to 20.0% (P < .0005). There was a decrease in rate of 1-year gastrostomy tube dependence in patients treated in 2015 to 2019 versus 2011 to 2014 (2.2% vs. 7.1%, P = .025). In 2011 to 2014, 2-year OS and DFS were 96% and 89%, respectively; in 2015 to 2019, 2-year OS and DFS were 96% and 94%, respectively. There was no difference in OS or DFS between the two time periods. CONCLUSIONS: The rate of adjuvant therapy, particularly chemotherapy, has decreased over time. One-year gastrostomy tube dependence rate has decreased significantly from 2011 to 2014 to 2015 to 2019. There was no change in OS and DFS over this time period. LEVEL OF EVIDENCE: 3 Laryngoscope, 132:806-812, 2022.