Immunoprofiles and Oncologic Outcomes of 15 Patients with Androgen Receptor-Positive Salivary Duct Carcinoma.

BACKGROUND: Salivary duct carcinomas (SDC) are a rare and aggressive subtype of salivary gland neoplasm. They can present with distinct immunoprofiles, such as androgen receptor (AR) and HER-2/Neu-positivity. To date, no consensus exists on how to best manage this entity. METHODS: All patients diagnosed with nonmetastatic AR+ SDC of the parotid from 2013 to 2019 treated with curative intent were included. Immunologic tumor profiling was conducted using 24 distinct markers. Kaplan-Meier analyses were used to estimate locoregional recurrence (LRR), distant control, and overall survival (OS). RESULTS: Fifteen patients were included. Nine (60%) patients presented with T4 disease and eight (53%) had positive ipsilateral cervical lymphadenopathy. Ten (67%) patients underwent trimodality therapy, including surgery followed by adjuvant radiation and concurrent systemic therapy. The median follow-up was 5.5 years (interquartile range, 4.8-6.1). The estimated 5-year rates of LRR, distant progression, and OS were 6%, 13%, and 87%, respectively. CONCLUSION: Despite only including AR+ SDC of the parotid, immunoprofiles, such as expression of HER-2, were highly variable, highlighting the potential to tailor systemic regimens based on individual histologic profiles in the future. Studies with larger patient numbers using tumor-specific molecular profiling and tumor heterogeneity analyses are justified to better understand the biology of these tumors. Molecularly informed treatment approaches, including the potential use of AR- and HER-2/Neu-directed therapies upfront in the definitive setting, may hold future promise to further improve outcomes for these patients.

Scalp Irradiation with 3D-Milled Bolus: Initial Dosimetric and Clinical Experience.

BACKGROUND AND PURPOSE: A bolus is required when treating scalp lesions with photon radiation therapy. Traditional bolus materials face several issues, including air gaps and setup difficulty due to irregular, convex scalp geometry. A 3D-milled bolus is custom-formed to match individual patient anatomy, allowing improved dose coverage and homogeneity. Here, we describe the creation process of a 3D-milled bolus and report the outcomes for patients with scalp malignancies treated with Volumetric Modulated Arc Therapy (VMAT) utilizing a 3D-milled bolus. MATERIALS AND METHODS: Twenty-two patients treated from 2016 to 2022 using a 3D-milled bolus and VMAT were included. Histologies included squamous cell carcinoma (n = 14, 64%) and angiosarcoma (n = 8, 36%). A total of 7 (32%) patients were treated in the intact and 15 (68%) in the postoperative setting. The median prescription dose was 66.0 Gy (range: 60.0-69.96). RESULTS: The target included the entire scalp for 8 (36%) patients; in the remaining 14 (64%), the median ratio of planning target volume to scalp volume was 35% (range: 25-90%). The median dose homogeneity index was 1.07 (range: 1.03-1.15). Six (27%) patients experienced acute grade 3 dermatitis and one (5%) patient experienced late grade 3 skin ulceration. With a median follow-up of 21.4 months (range: 4.0-75.4), the 18-month rates of locoregional control and overall survival were 75% and 79%, respectively. CONCLUSIONS: To our knowledge, this is the first study to report the clinical outcomes for patients with scalp malignancies treated with the combination of VMAT and a 3D-milled bolus. This technique resulted in favorable clinical outcomes and an acceptable toxicity profile in comparison with historic controls and warrants further investigation in a larger prospective study.

National Trends in 30-Day Readmission Following Transoral Robotic Surgery for Oropharyngeal Squamous Cell Carcinoma.

Importance: As the incidence of oropharyngeal squamous cell carcinoma (OPSCC) continues to rise in the US, an increasing number of patients are being treated with transoral robotic surgery (TORS). Readmission following surgery can potentially delay initiation of adjuvant treatment and affect survival outcomes. Objective: To identify risk factors for 30-day postoperative readmission in patients undergoing TORS for OPSCC. Design, Setting, and Participants: This retrospective, population-based cohort study used data from the Nationwide Readmissions Database from 2010 to 2017. All patients undergoing TORS for OPSCC were identified using International Classification of Diseases codes and included. Exclusion criteria were age younger than 18 years or incomplete information regarding index admission or readmission. The analysis was performed from April to October 2023. Exposure: TORS for OPSCC. Main Outcomes and Measures: Univariate and multivariate analyses were performed to determine factors associated with 30-day readmission. Covariates included demographics and medical comorbidities, socioeconomic factors, hospital characteristics, and surgical details. Trends in readmission over time, reasons for readmission, and characteristics of the readmission were also examined. Results: A weighted total of 5544 patients (mean [SD] age, 60.7 [0.25] years; 4475 [80.7%] male) underwent TORS for OPSCC. The overall readmission rate was 17.5% (n = 971), and these rates decreased over the study period (50 of 211 patients [23.7%] in 2010 vs 58 of 633 patients [9.1%] in 2017). Risk factors associated with readmission included male sex (adjusted odds ratio [AOR], 1.54; 95% CI, 1.07-2.20) and a diagnosis of congestive heart failure (AOR, 2.42; 95% CI, 1.28-4.58). Factors associated with decreased rate of readmission included undergoing concurrent selective neck dissection (AOR, 0.30; 95% CI, 0.22-0.41). Among the 971 readmissions, the most common readmission diagnoses were bleeding (151 [15.6%]), electrolyte and digestive problems (44 [4.5%]), pneumonia (44 [4.5%]), and sepsis (26 [2.7%]). Conclusions and Relevance: In this cohort study, readmission rates following TORS for oropharynx cancer decreased over time; however, a subset of patients required readmission most commonly related to bleeding, infection, and electrolyte imbalance. Concurrent neck dissection may be protective against readmission. Elucidation of risk factors for readmission after TORS for OPSCC offers opportunities for evidence-based shared decision-making, quality improvement initiatives, and improved patient counseling.

Y-27632 acts beyond ROCK inhibition to maintain epidermal stem-like cells in culture.

Conditional reprogramming is a cell culture technique that effectively immortalizes epithelial cells with normal genotypes by renewing epidermal stem cells. Y-27632, a compound that promotes conditional reprogramming through an unknown mechanism, was developed to inhibit the two Rho-associated kinase (ROCK) isoforms. We used human foreskin keratinocytes (HFKs) to study the role of Y-27632 in conditional reprogramming and learn how ROCKs control epidermal stem cell renewal. In conditional reprogramming, Y-27632 increased HFK adherence to culture dishes, progression through S, G2 and M phases of the cell cycle, and epidermal stem cell marker levels. Although this correlated with ROCK inhibition by Y-27632, we generated CRISPR-Cas9-mediated HFK ROCK knockouts to test the direct role of ROCK inhibition. Knockout of single ROCK isoforms was insufficient to disrupt ROCK activity or promote HFK propagation without Y-27632. Although ROCK activity was reduced, HFKs with double knockout of ROCK1 and ROCK2 still required Y-27632 to propagate. Y-27632 was the most effective among the ROCK inhibitors we tested at promoting HFK proliferation and epidermal stem cell marker expression. Thus, the ability of Y-27632 to promote an epidermal stem cell state in conditional reprogramming not only depends upon ROCK inhibition but also acts via as-yet-unidentified mechanisms. Epidermal stem cell renewal might in part be regulated by ROCKs, but also involves additional pathways.

Demographic and Academic Productivity Trends Among American Head & Neck Society Fellows Over a 20-Year Period.

Importance: Historical data reveal that, compared with women, men are more likely to pursue a head and neck surgical oncology fellowship, but little is known about possible gender differences in academic productivity. Objective: To assess demographic trends and academic productivity among American Head & Neck Society (AHNS) fellowship graduates. Design, Setting, and Participants: This cross-sectional study used electronically published data from the AHNS on fellowship graduates in the US and Canada from July 1, 1997, to June 30, 2022. Scopus was used to extract h-indices for each graduate. Exposure: Scholarly activity. Main Outcomes and Measures: Main outcomes were changes in demographic characteristics and academic productivity among AHNS graduates over time. Data analysis included effect size, η2, and 95% CIs. Results: A total of 691 AHNS fellowship graduates (525 men [76%] and 166 women [24%]) were included. Over the study period, there was an increase in the number of programs offering a fellowship (η2, 0.84; 95% CI, 0.68-0.89) and an increase in the absolute number of women who completed training (η2, 0.66; 95% CI, 0.38-0.78). Among early-career graduates pursuing an academic career, there was a small difference in the median h-index scores between men and women (median difference, 1.0; 95% CI, -1.1 to 3.1); however, among midcareer and late-career graduates, there was a large difference in the median h-index scores (midcareer graduates: median difference, 4.0; 95% CI, 1.2-6.8; late-career graduates: median difference, 6.0; 95% CI, 1.0-10.9). A higher percentage of women pursued academic positions compared with men (106 of 162 [65.4%] vs 293 of 525 [55.8%]; difference, 9.6%; 95% CI, -5.3% to 12.3%). Conclusions and Relevance: This cross-sectional study suggests that women in head and neck surgery begin their careers with high levels of academic productivity. However, over time, a divergence in academic productivity between men and women begins to develop. These data argue for research to identify possible reasons for this observed divergence in academic productivity and, where possible, develop enhanced early faculty development opportunities for women to promote their academic productivity, promotion, and advancement into leadership positions.

CDK4/6 and autophagy inhibitors synergize to suppress the growth of human head and neck squamous cell carcinomas.

Head and neck squamous cell carcinoma (HNSCC) accounts for over 10,000 deaths in the United States annually. Approximately 80% of HNSCC are human papillomavirus (HPV)-negative which have an overall poorer prognosis compared to the HPV-positive disease. Treatment options are mainly nontargeted chemotherapy, radiation, and surgery. The cyclin-d-CDK4/6-RB pathway, which regulates cell cycle progression, is often deregulated in HNSCC, making it an attractive therapeutic target. In the current study, we investigated the therapeutic effects of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in preclinical models of HNSCCs. Our results show that the specific CDK4/6 inhibitor, abemaciclib, inhibited cell growth, and induced apoptosis in HNSCC cell lines. We also demonstrated that both the pro-survival autophagy pathway and the ERK pathway in HNSCC cells were activated with abemaciclib treatment through the generation of reactive oxygen species (ROS). Coinhibition of CDK4/6 and autophagy synergistically decreased cell viability, induced apoptosis, and inhibited tumor growth in both in vitro and in vivo preclinical HNSCC models. These results reveal a potential therapeutic strategy that supports the rationale for further clinical development of a combination of CDK4/6 and autophagy inhibitors in HNSCC.

Inferring early genetic progression in cancers with unobtainable premalignant disease.

Analysis of premalignant tissue has identified the typical order of somatic events leading to invasive tumors in several cancer types. For other cancers, premalignant tissue is unobtainable, leaving genetic progression unknown. Here, we demonstrate how to infer progression from exome sequencing of primary tumors. Our computational method, PhylogicNDT, recapitulated the previous experimentally determined genetic progression of human papillomavirus-negative (HPV-) head and neck squamous cell carcinoma (HNSCC). We then evaluated HPV+ HNSCC, which lacks premalignant tissue, and uncovered its previously unknown progression, identifying early drivers. We converted relative timing estimates of driver mutations and HPV integration to years before diagnosis based on a clock-like mutational signature. We associated the timing of transitions to aneuploidy with increased intratumor genetic heterogeneity and shorter overall survival. Our approach can establish previously unknown early genetic progression of cancers with unobtainable premalignant tissue, supporting development of experimental models and methods for early detection, interception and prognostication.

Immediate resection of positive margins improves local control in oral tongue cancer.

OBJECTIVES: This study investigates the impact of immediate resection of positive margins on local control of oral tongue cancer. MATERIALS AND METHODS: We analyzed 273 consecutive oral tongue cancers resected from 2013 to 2018. Additional resection was performed in cases during the initial operation based on surgeon inspection of the specimen and/or frozen margins. Positive margins were defined as invasive carcinoma/high-grade dysplasia < 1 mm from the inked edge. Patients were grouped as follows: negative margin (Group 1); positive margin with immediate additional tissue resection (Group 2); and positive margin without additional tissue resection (Group 3). RESULTS: Overall, the rate of local recurrence was 7.7 % (21/273), and the rate of positive main specimen margin was 17.9 %. Of these patients, 38.8 % (19/49) underwent immediate additional resection of the presumed positive margin. Group 3 had higher local recurrence rates than Group 1 after adjustment for T-stage (aHR 2.8 [95 % CI 1.0-7.7], p = 0.04). Group 2 had similar rates of local recurrence (aHR 0.45 [95 % CI 0.06-3.6], p = 0.45). Three year local recurrence free survival for Groups 1, 2, and 3 were 91 %, 92 % and 73 %, respectively. Compared to the main specimen margin, sensitivity of intraoperative frozen tumor bed margins was 17.4 %, and specificity was 95 %. CONCLUSION: In patients with positive main specimen margins, anticipation and detection in real-time with immediate additional tissue resection reduced local recurrence to rates similar to those with negative main specimen margins. These findings support the use of technology to provide real-time intraoperative margin data and guide additional resection for improved local control.

Cellular states are coupled to genomic and viral heterogeneity in HPV-related oropharyngeal carcinoma.

Head and neck squamous cell carcinoma (HNSCC) includes a subset of cancers driven by human papillomavirus (HPV). Here we use single-cell RNA-seq to profile both HPV-positive and HPV-negative oropharyngeal tumors, uncovering a high level of cellular diversity within and between tumors. First, we detect diverse chromosomal aberrations within individual tumors, suggesting genomic instability and enabling the identification of malignant cells even at pathologically negative margins. Second, we uncover diversity with respect to HNSCC subtypes and other cellular states such as the cell cycle, senescence and epithelial-mesenchymal transitions. Third, we find heterogeneity in viral gene expression within HPV-positive tumors. HPV expression is lost or repressed in a subset of cells, which are associated with a decrease in HPV-associated cell cycle phenotypes, decreased response to treatment, increased invasion and poor prognosis. These findings suggest that HPV expression diversity must be considered during diagnosis and treatment of HPV-positive tumors, with important prognostic ramifications.

Hypothyroidism as an Independent Predictor of 30-day Readmission in Head and Neck Cancer Patients.

OBJECTIVES: To define the role of hypothyroidism and other risk factors for unplanned readmissions after surgery for head and neck cancer. STUDY DESIGN: Retrospective cohort study. METHODS: The Nationwide Readmission Database (NRD) was used to identify patients who underwent surgery for mucosal head and neck cancer (oral cavity, oropharynx, larynx, and hypopharynx) between 2010 and 2017. Univariate and multivariate logistic regression were performed to determine patient, tumor, and hospital related risk factors for 30-day readmission. Readmitted patients were stratified by preoperative diagnosis of hypothyroidism to compare readmission characteristics. RESULTS: For the 131,013 patients who met inclusion criteria, the readmission rate was 15.9%. Overall, 11.91% of patients had a preoperative diagnosis of hypothyroidism. After controlling for other variables, patients with a preoperative diagnosis of hypothyroidism had 12.2% higher odds of readmission compared to those without hypothyroidism (OR: 1.12, 1.03-1.22, p = 0.008). Patients with hypothyroidism had different reasons for readmission, including higher rates of wound dehiscence, fistula, infection, and electrolyte imbalance. Among readmitted patients, the length of stay for index admission (mean 10.5 days vs. 9.2 days, p < 0.001), readmission (mean 7.0 vs. 6.6 days, p = 0.05), and total hospital charge were higher for hypothyroid patients ($137,742 vs. $119,831, p < 0.001). CONCLUSION: Hypothyroidism is an independent risk factor for 30-day readmission following head and neck cancer resection. Furthermore, hypothyroid patients are more likely to be readmitted for wound complications, infection, and electrolyte imbalance. Targeted interventions should be considered for hypothyroid patients to decrease readmission rates and associated patient morbidity, potentially leading to earlier initiation of adjuvant treatment. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:2988-2998, 2023.

High surgical volume is associated with improved survival in head and neck cancer.

OBJECTIVES: Examine the relationship between hospital volume and overall mortality in a surgical cohort of head and neck squamous cell carcinoma (HNSCC) patients. MATERIALS & METHODS: A retrospective review of the NCDB was completed for adults with previously untreated HNSCC diagnosed between 2004 and 2016. Mean annual hospital volume was calculated using the number of head and neck cancer cases treated at a given facility divided by the number of years the facility reported to the NCDB. Facilities were separated into three categories based on their volume percentile, informed by inflection points from a natural cubic spline: Hospital Group 1 (<50%); Hospital Group 2 (50-90%); Hospital Group 3 (90%+). Cox proportional hazard models were used to examine the association between volume percentiles (continuous or categorical) with patient overall survival, adjusting for important patient and facility variables known to impact survival. RESULTS: Risk of death decreased by 2.97% for every 10% increase in facility percentile after adjusting for other risk factors. Patients treated at facilities in Hospital Group 1 had a 23.1% increase in risk of mortality (HR 1.231 [95% CI 1.12-1.35]) relative those at facilities in Hospital Group 3. No significant difference in mortality risk was found between Hospital Group 2 versus Hospital Group 3 (HR 1.031 [95% CI 0.97-1.10]). CONCLUSIONS: Survival of HNSCC patients is significantly improved when treated at facilities >50th percentile in annual hospital volume. This may support the regionalization of care to high volume head and neck centers with comprehensive facilities and supportive services to maximize patient outcomes.

Defining the psychiatric and financial burden of mental and substance use disorders in cancer patients.

PURPOSE: To identify the proportion of Emergency Department (ED) visits in cancer patients associated with a mental and substance use disorder (MSUD) and the subsequent healthcare costs. METHODS: Nationally representative data on ED visits from 2009 to 2018 was obtained from the Nationwide Emergency Department Sample (NEDS). We identified cancer-related visits with or without a MSUD using the Clinical Classifications Software diagnoses documented during the ED visit. Survey-adjusted frequencies and proportions of ED visits among adult cancer patients with or without a MSUD was evaluated. Survey-adjusted multivariable logistic regression models were used to examine demographic and clinical predictors of the presence of an MSUD and the likelihood of hospital admission for patients with a primary MSUD. RESULTS: Among 54,004,462 ED visits with a cancer diagnosis between 2009 and 2018, 11,803,966 (22%) were associated with a MSUD. Compared to a primary diagnosis of cancer, patients who presented to the ED with a chief complaint of MSUD were more likely to be female (54% vs. 49%), younger (median: 58 vs. 66), more likely to have Medicaid insurance, and more likely to be discharged home. The three most common MSUD diagnoses among cancer patients were alcohol-related disorders, anxiety disorders, and depressive disorders. The total costs associated with a primary MSUD from 2009 to 2018 was $3,133,432,103, of which alcohol-related disorders claimed the largest majority. Younger age (OR per 10-year increase: 0.86, 95% CI: 0.85, 0.86) and female sex (OR: 1.34, 95% CI: 1.33-1.35) were associated with higher odds of having an MSUD. CONCLUSIONS: Our findings demonstrate a high burden of psychiatric and substance use illness in the cancer population and provide the rationale for early psychosocial intervention to support these patients.

The Impact of the Affordable Care Act on Insurance Coverage and Stage Among Head and Neck Squamous Cell Carcinoma Patients.

The purpose was to examine the change in percent uninsured and if there is change in T-stage, N-stage and overall-stage among nonelderly patients with newly diagnosed head and neck squamous cell carcinoma after the Affordable Care Act (ACA). The National Cancer Database was used for this study. Patients were divided between pre-ACA and post-ACA implementation with stratification between areas of ACA expansion versus non-expansion. A quasi-experimental difference-in-difference study design was undertaken. A total of 15,037 patients met the inclusion criteria. Between the pre-ACA and post-ACA periods, there was increase in proportion of percent insured with Medicaid coverage in patients residing in expansion region. There was a decrease in the proportion of patients who had advanced Tumor stage and Nodal stage decreased after implementation of ACA. With the implementation of ACA expansion, there is increased Medicaid coverage, corresponding to a decreased proportion of patients presenting with advanced T-stage and N-stage.

The role of computer aided design/computer assisted manufacturing (CAD/CAM) and 3- dimensional printing in head and neck oncologic surgery: A review and future directions.

Microvascular free flap reconstruction has remained the standard of care in reconstruction of large tissue defects following ablative head and neck oncologic surgery, especially for bony structures. Computer aided design/computer assisted manufacturing (CAD/CAM) and 3-dimensionally (3D) printed models and devices offer novel solutions for reconstruction of bony defects. Conventional free hand techniques have been enhanced using 3D printed anatomic models for reference and pre-bending of titanium reconstructive plates, which has dramatically improved intraoperative and microvascular ischemia times. Improvements led to current state of the art uses which include full virtual planning (VP), 3D printed osteotomy guides, and patient specific reconstructive plates, with advanced options incorporating dental rehabilitation and titanium bone replacements into the primary surgical plan through use of these tools. Limitations such as high costs and delays in device manufacturing may be mitigated with in house software and workflows. Future innovations still in development include printing custom prosthetics, 'bioprinting' of tissue engineered scaffolds, integration of therapeutic implants, and other possibilities as this technology continues to rapidly advance. This review summarizes the literature and serves as a summary guide to the historic, current, advanced, and future possibilities of 3D printing within head and neck oncologic surgery and bony reconstruction. This review serves as a summary guide to the historic, current, advanced, and future roles of CAD/CAM and 3D printing within the field of head and neck oncologic surgery and bony reconstruction.

Update of a prognostic survival model in head and neck squamous cell carcinoma patients treated with immune checkpoint inhibitors using an expansion cohort.

BACKGROUND: Immune checkpoint inhibitors (ICI) treatment in recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) offers new therapeutic venues. We have previously developed a predictive survival model in this patient population based on clinical parameters, and the purpose of this study was to expand the study cohort and internally validate the model. METHODS: A single institutional retrospective analysis of R/M HNSCC patients treated with ICI. Clinical parameters collected included p-16 status, hemoglobin (Hb), albumin (Alb), lactate dehydrogenase (LDH), neutrophil, lymphocyte and platelet counts. Cox proportional hazard regression was used to assess the impact of patient characteristics and clinical variables on survival. A nomogram was created using the rms package to generate individualized survival prediction. RESULTS: 201 patients were included, 47 females (23%), 154 males (77%). Median age was 61 years (IQR: 55-68). P-16 negative (66%). Median OS was 12 months (95% CI: 9.4, 14.9). Updated OS model included age, sex, absolute neutrophil count, absolute lymphocyte count, albumin, hemoglobin, LDH, and p-16 status. We stratified patients into three risk groups based on this model at the 0.33 and 0.66 quantiles. Median OS in the optimal risk group reached 23.7 months (CI: 18.5, NR), 13.8 months (CI: 11.1, 20.3) in the average risk group, and 2.3 months (CI: 1.7, 4.4) in the high-risk group. Following internal validation, the discriminatory power of the model reached a c-index of 0.72 and calibration slope of 0.79. CONCLUSIONS: Our updated nomogram could assist in the precise selection of patients for which ICI could be beneficial and cost-effective.

T cell repertoire in peripheral blood as a potential biomarker for predicting response to concurrent cetuximab and nivolumab in head and neck squamous cell carcinoma.

BACKGROUND: T cell receptor (TCR) signaling profile is a fundamental property that underpins both adaptive and innate immunity in the host. Despite its potential clinical relevance, the TCR repertoire in peripheral blood has not been thoroughly explored for its value as an immunotherapy efficacy biomarker in head and neck squamous cell carcinoma (HNSCC). The purpose of the present study is to characterize and compare the TCR repertoire in peripheral blood mononuclear cells (PBMC) from patients with HNSCC treated with the combination of cetuximab and nivolumab. METHODS: We used the immunoSEQ assay to sequence the TCR beta (TCR-B) chain repertoire from serially obtained PBMC at baseline and during the treatments from a total of 41 patients who received the combination (NCT03370276). Key TCR repertoire metrics, including diversity and clonality, were calculated and compared between patients with different therapy responses and clinical characteristics (eg, human papillomavirus (HPV) status and smoking history). Patient survival outcomes were compared according to patient groups stratified by the TCR-B clonotyping. To confirm the observed patterns in TCR spectrum, samples from patients who achieved complete response (CR) and partial response (PR) were further profiled with the immunoSEQ deep resolution assay. RESULTS: Our data indicated that the patients who achieved CR and PR had an increased TCR sequence diversity in their baseline samples, this tendency being more pronounced in HPV-negative patients or those with a smoking history. Notably, the CR/PR group had the lowest proportion of patients with oligoclonal TCR clones (2 out of 8 patients), followed by the stable disease group (9 out of 20 patients) and lastly the progressive disease group (7 out of 10 patients). An overall trend toward favorable patient survival was also observed in the polyclonal group. Finally, we reported the shared TCR clones across patients within the same response group, as well as the shared clones by aligning immunoSEQ reads with TCR data retrieved from The Cancer Genome Atlas- head and neck squamous cell carcinoma (TCGA-HNSC) cohort. CONCLUSIONS: Our data suggest that, despite the great clinical heterogeneity of HNSCC and the limited responders in the present cohort, the peripheral TCR repertoires from pretreatment PBMC may be developed as biomarkers for the benefit of immunotherapy in HNSCC.

Outcomes with culture-directed antibiotics following microvascular free tissue reconstruction for osteonecrosis of the jaw.

OBJECTIVES: Radiation (ORNJ) and bisphosphonate-related (BRONJ) osteonecrosis of the jaw represent challenging entities to treat, with many patients requiring segmental resection and reconstruction with microvascular free tissue transfer (MFTT) in the setting of failed conservative therapy. Microvascular reconstruction is associated with higher post-operative complication rates when performed for advanced osteonecrosis versus oncologic defects. We hypothesize that basing antibiotic therapy on cultures obtained from the healthy bone marrow following resection during MFTT for ORNJ or BRONJ reduces rates of post-operative wound and surgical complications. MATERIALS AND METHODS: In a retrospective cohort study spanning January 2016 to October 2018, 44 patients undergoing MFTT for ORNJ or BRONJ were identified. Patients were categorized into two cohorts: residual healthy marrow culture (n = 11; RHM), treated with antibiotics guided by cultures from healthy appearing mandible, and all others (n = 33; AO), treated with antibiotics guided by cultures from resected necrotic bone or purulent drainage. Patient, reconstruction, and outcome variables were compared via appropriate statistical tools. RESULTS: 81.8% of the RHM cohort versus 24.2% of the AO cohort received long-term IV antibiotics. Rates of post-operative wound complications, including those necessitating operative management, were significantly lower in the RHM cohort. Rates of flap failure were similar across both groups. CONCLUSION: Administration of long-term IV antibiotics directed by native mandible cultures may decrease complication rates following MFTT for ORNJ or BRONJ by treating residual, smoldering infection. Concurrently, transplantation of well-vascularized free tissue likely improves antibiotic delivery. Findings are crucial for the development of a standardized treatment algorithm following microvascular reconstruction for advanced osteonecrosis.