Targeted Proteomic Quantitation of NRF2 Signaling and Predictive Biomarkers in HNSCC.

The NFE2L2 (NRF2) oncogene and transcription factor drives a gene expression program that promotes cancer progression, metabolic reprogramming, immune evasion, and chemoradiation resistance. Patient stratification by NRF2 activity may guide treatment decisions to improve outcome. Here, we developed a mass spectrometry-based targeted proteomics assay based on internal standard-triggered parallel reaction monitoring to quantify 69 NRF2 pathway components and targets, as well as 21 proteins of broad clinical significance in head and neck squamous cell carcinoma (HNSCC). We improved an existing internal standard-triggered parallel reaction monitoring acquisition algorithm, called SureQuant, to increase throughput, sensitivity, and precision. Testing the optimized platform on 27 lung and upper aerodigestive cancer cell models revealed 35 NRF2 responsive proteins. In formalin-fixed paraffin-embedded HNSCCs, NRF2 signaling intensity positively correlated with NRF2-activating mutations and with SOX2 protein expression. Protein markers of T-cell infiltration correlated positively with one another and with human papilloma virus infection status. CDKN2A (p16) protein expression positively correlated with the human papilloma virus oncogenic E7 protein and confirmed the presence of translationally active virus. This work establishes a clinically actionable HNSCC protein biomarker assay capable of quantifying over 600 peptides from frozen or formalin-fixed paraffin-embedded archived tissues in under 90 min.

Clinical applications of vascularized fascia lata in head and neck reconstruction: A systematic review.

BACKGROUND: Given limitations in the current literature, the precise indications, techniques, and outcomes relevant to vascularized fascia lata free flap reconstruction remain uncertain. The objective of this study was to perform a systematic review of published literature to evaluate indications, methods, and complications for vascularized fascia lata free flap reconstruction. METHODS: A systematic review of the literature was performed using a set of search criteria to identify patients who underwent free flap reconstruction of the head and neck region using vascularized fascia lata. Articles were reviewed based on relevance, with the primary outcome being surgical complications and surgical indications. RESULTS: A comprehensive search revealed 783 articles and 5 articles were ultimately found to be appropriate to this review- 55 patients undergoing free flap reconstruction were identified. Overall complication rates were 10.9 % for major complications and 18.1 % for minor complications. Follow-up spanned 1 to 95 months with a median of 48 months. CONCLUSIONS: Microvascular reconstruction of the head and neck with vascularized fascia lata is achievable with high adaptability and reliability reported in the literature.

Free tissue reconstruction in the "vessel-depleted" neck: A multi-institutional cohort study.

OBJECTIVES: Much of the literature on free tissue reconstruction in the "vessel-depleted" neck is focused on identification of vessels outside the pretreated field and data on free flap outcomes when infield microvascular anastomosis is performed remain scarce. We aim to report on free flap outcomes and recipient vessel choice in a large cohort of patients with prior radiation and neck dissection (RTND) to the ipsilateral side of vessel anastomosis. METHODS: A retrospective review was performed including patients who received head and neck free tissue transfer following prior RTND to the ipsilateral side of vessel anastomosis. Pretreatment data, free flap type, defect site, and recipient vessel choice were reported. Recipient vessel choice was stratified according to neck dissection level and prior free flap. Primary outcome was free flap survival (total failure, partial failure, success) within 30 days after surgery. RESULTS: This study included 72 free flap cases in 68 patients. Free flap success was 94.4%; one case (1.4%) resulted in total flap loss and three cases (4%) had partial flap loss. The facial (35%), external carotid (ECA) (25%), and superior thyroid arteries (16%) were the most common recipient arteries. The external jugular (EJV) (38%), facial (30%), and internal jugular veins (IJV) (15%) were the most common recipient veins. The superior thyroid artery was used less frequently with a prior level 2-3/4 neck dissection compared to a prior level 1-3/4 neck dissection (6% vs. 17%, p = 0.83). The facial artery (7% vs. 67%, p < 0.01) and vein (13% vs. 46%, p = 0.04) were used less frequently when a prior free flap with ipsilateral anastomosis was performed. The superior thyroid, ECA, IJV, and EJV were more commonly used in this subgroup. CONCLUSION: Free tissue transfer with infield microvascular anastomosis in a neck with prior RTND can be safely done with comparable outcomes to surgically naïve, non-irradiated necks.

Evidence-Based Medicine for Ballistic Maxillofacial Trauma.

Ballistic trauma is a serious health issue with significant costs to physical, psychosocial, economic, and societal well-being. It may be caused from firearms, explosive devices, or any other projectile forces, and is characterized by severe tissue loss and evolving tissue devitalization. This review covers mechanism, diagnosis, and management of ballistic maxillofacial trauma, specifically. Initial evaluation includes stabilization of airway, bleeding, and circulation, followed by assessment of other injuries. The overall degree of tissue damage is determined by intrinsic patient factors and extrinsic projectile factors. Management of ballistic injuries has shifted toward advocation for early operative repair with the advent of antibiotics and advanced techniques in maxillofacial reconstruction. Appropriate timing and method of reconstruction should be carefully selected on a case-by-case basis. While ballistic trauma research is limited to studies biased by institutional practices, areas for further study identified from current literature include guidelines directing timing of reconstructive surgery; thresholds for free tissue transfer; handling of retained projectiles; incidence of surgical complications; and clinical outcomes for computer-aided surgical repair of these highly destructive injuries.

National analysis of positive surgical margins in oropharyngeal salivary gland malignancies.

OBJECTIVE: Positive surgical margins (PSM) are associated with worse survival in oropharyngeal salivary gland malignancies (OPSGM), but existing literature is limited to small series. Our objective was to identify risk factors for PSM using the national cancer database (NCDB), including a transoral robotic surgical (TORS) approach. METHODS: NCDB was queried for patients with T1-T4a OPSGM undergoing resection between 2010 and 2017. Risk factors for PSM were determined using logistic regression. Overall survival (OS) was analyzed using Kaplan-Meier and Cox proportional hazards models. RESULTS: Of 785 patients, 165 (21.0 %) had PSM. Age, stage T4a tumors (OR 2.00, 95 % Confidence Interval [CI]: 1.03-3.88), adenoid cystic carcinoma (OR 2.02, 95 % CI: 1.29-3.18), and treatment at lower volume institutions (OR 1.68, 95 % CI: 1.09-2.59) were all independently associated with PSM. TORS versus a non-robotic approach was not associated with PSM (23.9 % vs 20.4 %, p 0.358), respectively. Positive margins were independently associated with a worse OS than negative margins (HR 1.63, 95 % CI: 1.03-2.59). Adjuvant radiation therapy was associated with improved survival in high grade tumors with positive margins. CONCLUSION: This study represents the largest review assessing risk factors for positive margins in OPSGM. Histologic type (adenoid cystic carcinoma), age, T4a tumor stage and treatment at a lower volume institution were all predictive of positive margins. With increasing use of TORS over the last decade, there does not appear to be a greater risk of positive margins using this modality in select patients. LEVEL OF EVIDENCE: N/A.

Chronic rhinosinusitis as a risk factor for intracranial and extracranial complications after endoscopic transsphenoidal surgery.

PURPOSE: To elucidate whether chronic rhinosinusitis (CRS), usually an inflammatory-mediated rather than infectious process, is a risk factor for extracranial and intracranial complications after elective endoscopic transsphenoidal surgery (ETSS). MATERIALS AND METHODS: A single-center retrospective cohort study of consecutive patients who underwent ETSS between January 2015 and July 2019 was performed, which included chart review and computed tomography assessment. CRS was defined by symptomatology and concurrent endoscopic or radiographic findings. RESULTS: Of 292 subjects, 11% (n = 33) met criteria for CRS. Median difference in Lund-Mackay scores between the CRS and non-CRS groups was 3.0 (95% CI 2.0-4.0). Complications included acute rhinosinusitis requiring antibiotics (23%, 68/292), epistaxis (10%, 28/292), meningitis (1%, 3/292), cerebrospinal fluid (CSF) leak (7%, 20/292), revision sinonasal procedures (10%, 28/292), and frequent in-office debridement (13%, 39/292). CRS was strongly associated with postoperative acute rhinosinusitis (aRR 1.85, 95% CI 1.18-2.90) and frequent debridement (aRR 1.96, 95% CI 1.00-3.83). Conversely, CRS was not associated with epistaxis (aRR 1.52, 95% CI 0.62-3.72), postoperative CSF leak (aRR 0.91, 95% CI 0.24-3.44), or additional sinonasal procedures (aRR 0.70, 95% CI 0.21-2.29). The rate of meningitis was not significantly higher in the CRS cohort (difference 2.2%, 95% CI -1.0% to 14.5%). CONCLUSIONS: CRS was a strong risk factor for acute rhinosinusitis and need for frequent in-office debridement after ETSS. It was not associated with other postoperative complications including epistaxis, CSF leak, or revision sinonasal procedures. CRS patients had a slightly higher rate of meningitis, which is likely not clinically meaningful.

Free vascularized parascapular fat flap for parotidectomy reconstruction.

OBJECTIVE: The contour defect resulting after parotidectomy can be cosmetically unappealing. Multiple reconstructive efforts have been reported to mitigate this problem. We describe a novel technique of vascularized parascapular fat reconstruction based on the circumflex scapular vessels and evaluate its outcomes. METHODS: Consecutive patients who underwent parotidectomy with or without additional resections and vascularized parascapular fat flap reconstruction in 2020 were included. Demographic, morphologic, intraoperative, and postoperative data were assessed. RESULTS: Eight patients (3 female) were included. Median cut-to-close time was 247 (range 209-298) minutes, including tumor ablation. None of the patients had any wound complications, and all except one was discharged on postoperative day 1. Flap monitoring was not performed. None reported any significant donor site morbidity except scar formation. At last follow up, all patients reported satisfactory facial contour. CONCLUSION: Vascularized parascapular fat flap reconstruction of parotidectomy contour defects has satisfactory cosmetic outcomes with minimal morbidity and short hospitalization courses.

20 pack-year smoking history as strongest smoking metric predictive of HPV-positive oropharyngeal cancer outcomes.

OBJECTIVES: While smoking is associated with worse outcomes in HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), the magnitude of this association is unclear given the heterogenous smoking definitions and outcomes. Our objective was to investigate the association between smoking, survival, and recurrence in HPV-related OPSCC using multiple smoking metrics reported in the literature. MATERIALS AND METHODS: This was a retrospective cohort study of 375 adults with p16+ OPSCC undergoing surgical resection (n = 272) or definitive chemoradiation (n = 103) at a tertiary academic institution from 2006 to 2017. The primary outcome was overall survival (OS). Secondary outcomes included disease-free survival (DFS), disease-specific survival (DSS), and recurrence. We used multiple smoking metrics commonly cited in previous studies, including ever versus never smokers, current versus former/never smokers, ≤10 versus >10 pack-year, ≤20 versus >20 pack-year, and continuous pack-year. RESULTS: There were 375 patients, median age 58 years, with 326 (87%) males, and median follow-up of 52 months. Of all smoking metrics, >20 pack-year history was the strongest predictor of both OS (HR 2.24, 95% CI: 1.19-4.20) and DFS (HR 1.67, 95% CI: 1.04-2.66) on univariable and multivariable analysis after adjusting for age, overall stage, and comorbidities. Patients with >20 pack-year smoking history were also more likely to have recurrence (HR 1.59, 95% CI: 0.95-2.67) after adjusting for overall stage. CONCLUSION: Heavier smoking >20 pack-years was the strongest smoking metric associated with 2-times worse survival and recurrence. Our findings suggest that >20 pack-year smoking history may be a more useful cutoff for risk stratification models but requires further validation.

Axis-specific analysis and predictors of endocrine recovery and deficits for non-functioning pituitary adenomas undergoing endoscopic transsphenoidal surgery.

PURPOSE: Endoscopic transsphenoidal surgery (ETSS) is a well-established treatment for patients with nonfunctioning pituitary adenomas (NFPAs). Data on the rates of pituitary dysfunction and recovery in a large cohort of NFPA patients undergoing ETSS and the predictors of endocrine function before and after ETSS are scarce. This study is purposed to analyze the comprehensive changes in hormonal function and identify factors that predict recovery or worsening of hormonal axes following ETSS for NFPA. METHODS: A retrospective review of 601 consecutive patients who underwent ETSS between 2010 and 2018 at one institution was performed. Recovery or development of new hypopituitarism was analyzed in 209 NFPA patients who underwent ETSS. RESULTS: Patients with preoperative endocrine deficits (59.8%) in one or more pituitary axes had larger tumor volumes (P = 0.001) than those without preoperative deficits. Recovery of preoperative pituitary deficit occurred in all four axes, with overall mean recovery of 29.7%. The cortisol axis showed the highest recovery whereas the thyroid axis showed the lowest, with 1-year cumulative recovery rates of 44.3% and 6.1%, respectively. Postoperative hypopituitarism occurred overall in 17.2%, most frequently in the thyroid axis (24.3%, 27/111) and least frequently in the cortisol axis (9.7%, 16/165). Axis-specific predictors of post-operative recovery and deficiency were identified. CONCLUSIONS: Dynamic alterations in pituitary hormones were observed in a proportion of patients following ETSS in NFPA patients. Postoperative endocrine vulnerability, recovery, and factors that predicted recovery or loss of endocrine function depended on the hormonal system, necessitating an axis-specific surveillance strategy postoperatively.

The association of smoking and outcomes in HPV-positive oropharyngeal cancer: A systematic review.

PURPOSE: While smoking is linked to worse outcomes for human papillomavirus (HPV)-related oropharyngeal squamous cell cancer (OPSCC), the magnitude of this association and the amount of smoking exposure necessary to confer clinically significant differences in outcomes is unclear. Recent studies suggested that greater tobacco exposure results in higher risk of cancer progression and death. Our study objective was to perform a systematic review of the association between smoking and HPV-related OPSCC outcomes. MATERIALS AND METHODS: A literature search was conducted in April 2019 to identify relevant articles using Embase, Medline, Scopus, CENTRAL, and Cochrane databases. All studies were independently screened by two investigators to identify studies that assessed HPV-positive patients as an independent cohort, specified smoking measures, and reported locoregional recurrence (LRR), overall survival (OS), disease-specific survival (DSS), or disease-free survival (DFS) in association with smoking. RESULTS: Of 1130 studies identified, 10 met final inclusion criteria with 2321 total patients, mean age 57.5 years. Smoking measures included ever vs never, current vs never/former smokers, ≤10 vs >10 pack-year, and continuous pack-years. Of these studies, 8 (80%) showed a significant effect of smoking on increasing recurrence and mortality. Adjusted HRs for LRR ranged from 0.6 to 5.2, OS from 1.3 to 4.0, DSS from 2.3 to 7.2, and DFS from 1.02 to 4.2 among heavier smokers compared to lighter/non-smokers. CONCLUSIONS: While there was significant variability in smoking metrics and reported outcomes, all studies reporting statistically significant HRs showed that smoking was associated with worse outcomes. Further studies using uniform smoking measures are necessary to better understand this association.

Salvage of recurrence after surgery and adjuvant therapy: A systematic review.

PURPOSE: To determine the oncologic and functional outcomes of patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma after initial management with surgery and adjuvant therapy. DATA SOURCES: Ovid Medline, Embase, Scopus, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, Cochrane Database of Systematic Reviews, and Clinicaltrials.gov. REVIEW METHODS: A structured search was performed of the literature to identify studies that included patients undergoing surgical salvage for local, regional, or locoregional recurrent head and neck squamous cell carcinoma without known distant metastases who had been treated with initial surgery and post-operative adjuvant radio- or chemoradiotherapy. Studies were excluded if they did not report at least 1-year survival estimates, included patients who underwent primary non-surgical management, or included those treated with non-surgical salvage therapies or supportive care alone. RESULTS: The search strategy yielded 3746 abstracts. After applying exclusion and inclusion criteria, 126 full-texts were reviewed and six studies were included with a total of 222 patients. All studies were retrospective in design and included diverse disease subsites and stages. Complications and functional outcomes were inconsistently reported. Five-year survival estimates ranged between 10% and 40% between studies. CONCLUSIONS: Patients undergoing salvage surgery for recurrent head and neck squamous cell carcinoma after initial surgery and adjuvant therapy may have a particularly poor prognosis. Future studies are needed to determine functional and quality of life outcomes in this patient population and to identify specific prognostic factors for re-recurrence and survival.

Acellular dermal graft pharyngeal repair augmentation after laryngectomy.

PURPOSE: Pharyngocutaneous fistula (PCF) after laryngectomy continues to be a serious complication, especially after radiation. Recruitment of non-radiated tissue into the surgical defect may decrease the risk of fistula. These techniques however have significant morbidity and increases operative time. We hypothesized that using acellular dermal graft to reinforce the pharyngeal closure could decrease the risk of fistula, without the added morbidity of a vascularized flap. METHODS: We performed a retrospective chart review of all patients that underwent a laryngectomy between 2005 and 2015 at an acedemic tertiary referral center. Patients who underwent primary pharyngeal closure with Alloderm® reinforcement without any other flap reconstruction were identified. Basic demographics, previous treatment, operative technique and fistula were extracted from the medical records. The primary outcome was PCF rate. The time to closure, margin status and disease recurrence was also evaluated. RESULTS: Among 16 patients with AlloDerm® augmentation, eight had primary laryngectomy and eight had salvage laryngectomy. A total of three in the salvage laryngectomy with prior history of radiation developed PCF. The fistula closed in all three cases with conservative treatment. There was no PCF in the primary laryngectomy group without prior history of radiation. CONCLUSION: The rate of PCF among the salvage laryngectomy group with previous radiation did not differ from historical data. AlloDerm® can however, provide a simple alternative for repair in radiation patients where flap cannot be performed for pharyngeal reconstruction. In non-radiated patients, AlloDerm® augmentation may have a protective effect on fistula formation.

Chimeric Versus Multiple Simultaneous Free Flaps for Head and Neck Reconstruction.

OBJECTIVE: To describe our experience with chimeric flaps and to assess the surgical outcomes and postoperative complications associated with chimeric flaps compared to multiple flaps. STUDY DESIGN/METHODS: Patients undergoing chimeric and multiple simultaneous free tissue transfer between June 2016 and October 2023 were retrospectively reviewed. The primary outcome of interest was the complication rate. Major complications required takeback to the operating room, hospital readmission, or transfer to the intensive care unit. Minor complications were managed conservatively. Secondary outcomes included operative time, length of hospitalization, and flap survival. SETTING: Academic tertiary care center. RESULTS: Our analysis included 113 patients (chimeric n = 38, multiple n = 75). We found no significant difference in operative times or minor complications. Chimeric flaps were associated with a shorter length of hospitalization. The major complication rate was higher for chimeric flaps (42.1% vs 22.7%, P = .03), but each cohort only had 1 instance of total flap loss. CONCLUSION: The complexity of large head and neck defects poses a reconstructive challenge for microvascular surgeons. Our findings suggest that chimeric and multiple flaps both produce acceptable complication rates when used appropriately. Differences in complication rates may reflect differences in utilization. The chimeric flap remains a valuable option for those with prior radiation or radical resection, but it remains unclear the degree to which they lessen the inherent risk of postoperative complications within this population. Each technique must be weighed in context of the patient's reconstructive profile and the institution's surgical capabilities to optimize long-term outcomes.

Airway protection and outcomes after staged versus concurrent bilateral neck dissections with transoral base of tongue cancer resection.

OBJECTIVES: To assess airway, safety, and resource utilization outcomes between transoral base of tongue (BOT) surgery with staged versus concurrent bilateral neck dissections (BND). METHODS: A retrospective cohort study of patients with human papilloma virus (HPV)-related BOT cancer who underwent transoral surgery and BND from January 2015 through June 2022 was conducted. Free flap patients were excluded. RESULTS: Of 126 patients (46 [37%] staged and 80 [63%] concurrent BND), there were no significant differences in rates of postoperative intubation, tracheostomy, intensive care admission, operative takebacks, gastrostomy, and 30-day readmission. Total operative time (median difference 1.4 [95% CI 0.9-1.8] hours), length of stay (1.0 [1.0-1.0] day), and time between primary surgery and adjuvant therapy initiation (4.0 [0.0-8.0] days) were lower in the concurrent BND cohort. CONCLUSION: Concurrent BND alongside transoral BOT resection is safe with similar airway outcomes and lower total operative time, length of stay, and time to adjuvant therapy initiation compared to staged BND.

Stacked fibula flap for unilateral total maxillectomy reconstruction with orbital preservation.

Unilateral total maxillectomy is indicated for locally advanced maxillary tumors that require complete removal of the midface bony structure and inferior orbital rim. Reconstruction of this defect is challenging due to aesthetic and functional concerns. A retrospective review of patients at two tertiary-care institutions undergoing unilateral total maxillectomy reconstruction with a stacked fibula flap from 2018 to 2022 was performed. Each patient's clinical course was reviewed, and attention was focused on the demonstration of surgical steps with photos. Twenty patients underwent stacked fibula flap reconstruction for unilateral total maxillectomy orbital preservation defects. Surgical extirpation was performed for malignancy (80%, 16/20) and for osteoradionecrosis or benign tumor in 20% (4/20). The complication rate was 30% (6/20). Most flaps survived (95%, 19/20). We present a modified, reproducible method of fibula flap reconstruction for unilateral total maxillectomy with orbital preservation that only requires two segments and maintains positive aesthetic and functional results.

Poor Dental Health as a Risk Factor for Alveolar Ridge Malignancies.

OBJECTIVE: To determine the association between poor dental health and risk of oral cavity squamous cell cancer (OCSCC) at individual tumor subsites. STUDY DESIGN: Case-control and cross-sectional METHODS: A case-control study was performed using a population-based cohort in North Carolina (Carolina Head and Neck Cancer Epidemiology Study [CHANCE]). A secondary cross-sectional analysis was performed with an institutional cohort (WashU/Siteman). Cases were adults with primary OCSCC and an identifiable tumor subsite. In the CHANCE cohort, controls were adults without head and neck cancer. In the Washington University/Siteman cohort, patients with tongue cancer served as the comparator group. We used number of missing teeth (categorized 0-6, 7-24, 25-28) as a surrogate for poor dental health, which was self-reported in CHANCE and measured on a pretreatment computed tomography scan in the WashU/Siteman study. Adjusted odds ratios (aORs) for missing teeth were estimated for each tumor subsite using binomial logistic regression models. RESULTS: Near complete tooth loss (25-28 teeth) was associated with a 3.5-fold increased risk of alveolar ridge malignancy (aOR: 3.51; 95% confidence interval [CI]: 1.14-11.01, P = .03) in the CHANCE study. This association was confirmed in our cross-sectional analysis (WashU/Siteman study) where missing 25-28 teeth was associated with an increased risk of alveolar ridge compared to tongue cancer (aOR: 4.60; 95% CI: 1.97-11.10, P = .001). CONCLUSIONS: This study suggests an association between poor dental health and risk of alveolar ridge cancer independent of smoking, alcohol use, age, race, and sex. Future prospective and translational studies are needed to confirm this association and elucidate the mechanism of dental disease in alveolar ridge malignancies.

Prognostic significance of hemorrhage requiring embolization in the setting of previously treated head and neck squamous cell carcinoma: Systematic review and retrospective cohort.

BACKGROUND: The management of acute hemorrhage in patients with previously treated head and neck squamous cell carcinoma (HNSCC) is challenging due to the lack of substantial evidence to guide clinical decision making. METHODS: A systematic review and retrospective chart review were performed to identify patients with a history of HNSCC who underwent either primary or adjuvant radiation therapy (RT) and presented with hemorrhagic complications requiring embolization. Patient characteristics, history, presentation, and outcomes were reviewed. RESULTS: The systematic review included a total of 182 patients. Heterogeneity existed in outcomes reporting; 1-year overall survival approached 50%. From the retrospective chart review, 51 patients were included. Median survival time following hemorrhage was 2.2 months (range 1.2-11.4 months). Patients with malignancy at time of hemorrhage were identified as having worse survival. CONCLUSIONS: Acute hemorrhage in patients with a history of previously radiated HNSCC portends a high risk of mortality, with patients with active malignancy representing a worse prognostic group.

A hybrid epithelial/mesenchymal state in head and neck cancer: A biomarker for survival with differential prognosis by self-reported race.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is the 6th leading cause of cancer-related mortality, with racial disparities amplifying the challenges in treatment. Although the relationship between hybrid epithelial/mesenchymal (E/M) states and tumor progression is of interest, no studies have characterized the clinical relevance of hybrid E/M states in head and neck cancer outcomes among self-reported racial cohorts. METHODS: Given the overlap in gene expression between hybrid E/M malignant cells and cancer-associated fibroblasts, we utilized deconvolution of bulk RNA sequencing data from oral cavity and laryngeal squamous cell carcinoma tumors from The Cancer Genome Atlas. We utilized our previously collected single-cell profiles to generate inferred malignant profiles and then scored these for hybrid E/M. We then conducted a survival analysis on overall and disease-free survival among self-reported Black and White Americans. FINDINGS: The hybrid E/M state was differentially associated with head and neck cancer survival by self-reported race and ethnicity, with a stronger association in non-Hispanic Black patients. Black patients with a high hybrid E/M score had a higher risk of death or recurrence (hazard ratio [HR]: 4.18 [95% confidence interval (CI): 2.06, 8.49]) than White patients with a high hybrid E/M score (HR: 1.58 [95% CI: 1.11, 2.26]). CONCLUSION: Our results suggest a complex interplay of social structure, racism, and genetic diversity. We implore researchers to consider the social and biological context contributing to disparities. FUNDING: A.L.M. received support from the National Institute of Minority Health and Health Disparities (K01MD013897 [principal investigator (PI), A.L.M.]). S.V.P. received support from the National Institute of Dental and Craniofacial Research (R01DE032865 [PI, S.V.P.] and R01DE032371 [PI, S.V.P.]).

Microvascular reconstruction of midface osteoradionecrosis.

BACKGROUND: Head and neck osteoradionecrosis (ORN) of the midface requiring free flap (FF) reconstruction is uncommon. This multi-institutional study was designed to review outcomes for this rare patient population. METHODS: Retrospective multi-institutional review of FF reconstruction for midface ORN (2005-2022; n = 54). RESULTS: The FF survival rate was 87% (n = 54). Patients were less likely to be tolerating a regular diet at 3 months postoperative if they had a preoperative history of prior head and surgery (80% vs. 95%; p = 0.02), a pathologic fracture (50% vs. 90%; p = 0.04), exposed bone intraorally (43% vs. 94%; p = 0.002), or a fistula (67% vs. 96%; p = 0.03). Mean albumin was higher in patients whose FF survived (3.6 ± 0.5 vs. 2.7 ± 1.4; p = 0.03). Patients with low prealbumin were more likely to undergo a hematoma evacuation (27% vs. 0%; p = 0.02). CONCLUSION: In this series of midface ORN requiring FF reconstruction preoperative nutritional status impacted postoperative complications. Preoperative occurrence of a fistula, pathologic fracture, and intraoral bone exposure correlated with decreased tolerance of a regular diet following reconstruction.

Trends in ototoxicity monitoring among cisplatin-treated patients with cancer.

PURPOSE: This study aims to characterize patterns in ototoxicity monitoring and identify potential barriers to audiologic follow-up. METHODS: We performed a single-institution retrospective cohort study on adult (≥ 18 years old) cancer patients treated with cisplatin from January 2014 to September 2021. Our primary outcomes were rates of baseline and post-treatment audiograms at the following time points: 3, 6, 12, and greater than 12 months. Time-to-event analyses were performed to describe additional insights to ototoxicity monitoring patterns. RESULTS: Nine hundred fifty-five patients with cancer were included for analysis. The most common primary cancer sites were head and neck (64%), followed by cervical (24%). Three hundred seventy-three patients (39%) underwent baseline audiometric assessment, 38 patients (4%) received audiologic evaluation during chemotherapy, and 346 patients (36%) obtained at least one post-treatment audiogram. Audiologic follow-up was greatest within 3 months of completing chemotherapy (26%), but this tapered dramatically to less than 10% at every other post-treatment time point. Patients with head and neck cancer achieved higher rates of audiologic follow-up at every time point than patients with non-head and neck cancer except for during treatment. CONCLUSIONS: Ototoxicity monitoring is an inconsistent practice, particularly during chemotherapy and for long-term surveillance of hearing loss. Patients with non-head and neck cancer may be at increased risk for loss of audiologic follow-up. IMPLICATIONS FOR CANCER SURVIVORS: Cisplatin ototoxicity is a common occurrence that can be effectively managed with auditory rehabilitation. Therefore, referrals to audiology and counseling on treatment-related ototoxicity are recommended throughout chemotherapy and cancer survivorship.