Upfront Neck Dissection for Treatment Selection and Improvement in Quality of Life as a Novel Treatment Paradigm for Deintensification in HPV+ OPSCC.

PURPOSE: Locoregionally advanced HPV+ oropharyngeal squamous cell carcinoma (OPSCC) has excellent cure rates, although current treatment regimens are accompanied by acute and long-term toxicities. We designed a phase II deescalation trial for patients with HPV+ OPSCC to evaluate the feasibility of an upfront neck dissection to individualize definitive treatment selection to improve the quality of life without compromising survival. PATIENTS AND METHODS: Patients with T1-3, N0-2 HPV+ OPSCC underwent an upfront neck dissection with primary tumor biopsy. Arm A included patients with a single lymph node less than six centimeters, with no extracapsular spread (ECS) and no primary site adverse features underwent transoral surgery. Arm B included patients who had two or more positive lymph nodes with no ECS, or those with primary site adverse features were treated with radiation alone. Arm C included patients who had ECS in any lymph node and were treated with chemoradiation. The primary endpoint was quality of life at 1 year compared with a matched historical control. RESULTS: Thirty-four patients were enrolled and underwent selective neck dissection. On the basis of pathologic characteristics, 14 patients were assigned to arm A, 10 patients to arm B, and 9 to arm C. A significant improvement was observed in Head and Neck Quality of Life (HNQOL) compared with historical controls (-2.6 vs. -11.9, P = 0.034). With a median follow-up of 37 months, the 3-year overall survival was 100% and estimated 3-year estimated progression-free survival was 96% [95% confidence interval (CI), 76%-99%]. CONCLUSIONS: A neck dissection-driven treatment paradigm warrants further research as a deintensification strategy.

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.

Sponsorship in Otolaryngology-Head and Neck Surgery: A Pathway to Equity, Diversity, and Inclusion.

Importance: Sponsorship, distinct from mentorship or coaching, involves advancing the careers of individuals by nominating them for roles, increasing the visibility of their work, or facilitating opportunities. Sponsorship can open doors and enhance diversity; however, achieving desirable outcomes requires equitable approaches to cultivating potential in sponsees and promoting their success. The evidence on equitable sponsorship practices has not been critically examined, and this special communication reviews the literature, highlighting best practices. Observations: Sponsorship addresses an unmet need for supporting individuals who have historically been afforded fewer, less visible, or less effective opportunities for upward career mobility. Barriers to equitable sponsorship include the paucity of sponsors of underrepresented identity; smaller and underdeveloped networks among these sponsors; lack of transparent, intentional sponsorship processes; and structural inequities that are associated with recruitment, retention, and advancement of diverse individuals. Strategies to enhance equitable sponsorship are cross-functional, building on foundational principles of equity, diversity, and inclusion; patient safety and quality improvement; and insights from education and business. Equity, diversity, and inclusion principles inform training on implicit bias, cross-cultural communication, and intersectional mentoring. Practices inspired by patient safety and quality improvement emphasize continuously improving outreach to diverse candidates. Education and business insights emphasize minimizing cognitive errors, appreciating the bidirectional character of interactions, and ensuring that individuals are prepared for and supported in new roles. Collectively, these principles provide a framework for sponsorship. Persistent knowledge gaps are associated with timing, resources, and systems for sponsorship. Conclusions and Relevance: The nascent literature on sponsorship is limited but draws on best practices from various disciplines and has potential to promote diversity within the profession. Strategies include developing systematic approaches, providing effective training, and supporting a culture of sponsorship. Future research is needed to define best practices for identifying sponsees, cultivating sponsors, tracking outcomes, and fostering longitudinal practices that are sustainable at local, regional, and national levels.

Novel Immunotherapeutic Approaches to Treating HPV-Related Head and Neck Cancer.

Head and neck cancer (HNC) is the seventh most common malignancy, with oropharyngeal squamous cell carcinoma (OPSCC) accounting for a majority of cases in the western world. While HNC accounts for only 5% of all cancers in the United States, the incidence of a subset of OPSCC caused by human papillomavirus (HPV) is increasing rapidly. The treatment for OPSCC is multifaceted, with a recently emerging focus on immunotherapeutic approaches. With the increased incidence of HPV-related OPSCC and the approval of immunotherapy in the management of recurrent and metastatic HNC, there has been rising interest in exploring the role of immunotherapy in the treatment of HPV-related OPSCC specifically. The immune microenvironment in HPV-related disease is distinct from that in HPV-negative OPSCC, which has prompted further research into various immunotherapeutics. This review focuses on HPV-related OPSCC, its immune characteristics, and current challenges and future opportunities for immunotherapeutic applications in this virus-driven cancer.

Tumor immune microenvironment alterations using induction cetuximab in a phase II trial of deintensified therapy for p16-positive oropharynx cancer.

BACKGROUND: We sought to characterize early changes in CD8+ tumor-infiltrating lymphocytes and tumor transcriptomes after induction cetuximab in a cohort with p16-positive oropharyngeal cancer on a phase II clinical de-escalation trial. METHODS: Tumor biopsies were obtained before and 1 week after a single cetuximab loading dose in eight patients enrolled in a phase II trial of cetuximab and radiotherapy. Changes in CD8+ tumor-infiltrating lymphocytes and transcriptomes were assessed. RESULTS: One week after cetuximab, five patients (62.5%) had an increase in CD8+ cell infiltration with a median (range) fold change of +5.8 (2.5-15.8). Three (37.5%) had unchanged CD8+ cells (median [range] fold change of -0.85 [0.8-1.1]). In two patients with evaluable RNA, cetuximab induced rapid tumor transcriptome changes in cellular type 1 interferon signaling and keratinization pathways. CONCLUSIONS: Within 1 week, cetuximab induced measurable changes in pro-cytotoxic T-cell signaling and immune content.

Sponsorship and Negotiation for Women Otolaryngologists at Midcareer: A Content Analysis.

OBJECTIVE: To explore challenges and opportunities for supporting midcareer women otolaryngologists in the areas of negotiation and sponsorship. STUDY DESIGN: Qualitative approach using semistructured interviews. SETTING: Online multi-institutional interviews. METHODS: This study was performed from June to August 2021. Women otolaryngologists representing diverse subspecialties, training, and practice environments were recruited via a purposive criterion-based sampling approach. Semistructured interviews were transcribed, coded, and analyzed via an inductive-deductive approach to produce a thematic content analysis. RESULTS: Among the 12 women interviewees, who represented 7 subspecialties, the majority were Caucasian (58%) and in academic practice (50%). The median residency graduation year was 2002 (range, 1982-2013). Participants expressed several challenges that women otolaryngologists face with respect to negotiation, including the absence of systematic formal negotiation training, gendered expectations that women experience during negotiations, and a perceived lack of power in negotiations. Obstacles to effective sponsorship included difficulty in the identification of sponsors and the influence of gender and related systemic biases that hindered sponsorship opportunities. CONCLUSION: Notable gender disparities exist for negotiation and sponsorship in the midcareer stage for women otolaryngologists. Women start at a disadvantage due to a lack of negotiation training and access to sponsors, which is exacerbated by systemic gender bias and power differentials as women advance in their careers. This study highlights opportunities to improve negotiation and sponsorship for women, with the goal of promoting a more diverse workforce.

Randomized trial of laryngeal organ preservation evaluating two cycles of induction chemotherapy with platinum, docetaxel, and a novel Bcl-xL inhibitor.

BACKGROUND: Single cycle induction chemotherapy (IC) with platinum and 5-flurouracil (PF) and treatment based on clinical response predicts organ preservation in laryngeal cancer. Other agents offer intriguing alternatives with potentially increased ease of administration, reduced risk for severe toxicities, and increased platinum sensitivity. METHODS: We report the results of a phase II bioselection trial in advanced resectable laryngeal cancer utilizing an IC regimen of two cycles of platinum plus docetaxel (TP) with a Bcl-2 inhibitor. The primary endpoint was organ preservation rate at 12 weeks post chemoradiation. RESULTS: Fifty-four patients were enrolled. Response to IC was 72%. The organ preservation rate was 59% with a laryngectomy free survival of 46%. Induction related grade ≥3 toxicities were observed in 56% of patients with two grade 5 events. CONCLUSIONS: Two cycles of TP IC plus a Bcl-2 inhibitor did not improve laryngeal preservation compared to a single cycle of PF.

Small molecule profiling to define synergistic EGFR inhibitor combinations in head and neck squamous cell carcinoma.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is a debilitating disease with poor survival. Although epidermal growth factor receptor (EGFR)-targeting antibody cetuximab improves survival in some settings, responses are limited suggesting that alternative approaches are needed. METHODS: We performed a high throughput drug screen to identify EGFR inhibitor-based synergistic combinations of clinically advanced inhibitors in models resistant to EGFR inhibitor monotherapies, and then performed downstream validation experiments on prioritized synergistic combinations. RESULTS: From our screen, we re-discovered known synergistic EGFR inhibitor combinations with FGFR or IGF-1R inhibitors that were broadly effective and also discovered novel synergistic combinations with XIAP inhibitor and DNMT inhibitors that were effective in only a subset of models. CONCLUSIONS: Conceptually, our data identify novel synergistic combinations that warrant evaluation in future studies, and suggest that some combinations, although highly synergistic, will require parallel companion diagnostic development to be effectively advanced in patients.

TP53 mutations in head and neck cancer.

Head and neck squamous cell carcinomas (HNSCCs) arising in the mucosal linings of the upper aerodigestive tract are highly heterogeneous, aggressive, and multifactorial tumors affecting more than half a million patients worldwide each year. Classical etiological factors for HNSCC include alcohol, tobacco, and human papillomavirus (HPV) infection. Current treatment options for HNSCCs encompass surgery, radiotherapy, chemotherapy, or combinatorial remedies. Comprehensive integrative genomic analysis of HNSCC has identified mutations in TP53 gene as the most frequent of all somatic genomic alterations. TP53 mutations are associated with either loss of wild-type p53 function or gain of functions that promote invasion, metastasis, genomic instability, and cancer cell proliferation. Interestingly, disruptive TP53 mutations in tumor DNA are associated with aggressiveness and reduced survival after surgical treatment of HNSCC. This review summarizes the current evidence and impact of TP53 mutations in HNSCC.

Imaging response assessment for predicting outcomes after bioselection chemotherapy in larynx cancer: A secondary analysis of two prospective trials.

BACKGROUND AND PURPOSE: Bioselection with induction chemotherapy in larynx cancer is associated with excellent larynx preservation and disease-specific survival but requires visual inspection of the primary tumor. We retrospectively compare clinical and imaging response in bioselected patients to develop predictive models of surgeon-assessed response (SR), laryngectomy-free survival (LFS), and overall survival (OS) in bioselected patients. MATERIALS AND METHODS: In a secondary analysis of patients on two single-institution bioselection trials, model building used a regularized regression model (elastic-net) and applied nested cross-validation. Logistic regression-based model was used to predict SR and Cox proportional hazard-based models were used to predict LFS and OS. RESULTS: In 115 patients with a median age of 57 years, most patients had supraglottic tumors (73.0%) and T3/T4 disease (94.8%). Definitive treatment was chemoradiation in 76.5% and laryngectomy in 23.5%. Change in primary tumor (OR = 5.78, p < 0.001) and N-classification (OR = 1.64, p = 0.003) predicted SR (AUC 0.847). Change in tumor volume (HR = 0.58, p < 0.001) predicted LFS (c-index 0.724). N-classification (HR = 1.48, p = 0.04) and pre-chemotherapy tumor volume (HR = 1.30, p = 0.174) predicted OS (c-index 0.552). CONCLUSIONS: Imaging offers a non-invasive opportunity to evaluate response to induction chemotherapy, complementary to surgeon assessment. Further evaluation of approaches to bioselection that optimize generalizability of this paradigm are needed, and clinical trials utilizing imaging to predict outcomes including LFS are warranted.

Tumor-Infiltrating Lymphocytes in Patients With Advanced Laryngeal Cancer Undergoing Bioselection.

OBJECTIVE: Bioselection to assess tumor response after induction chemotherapy has been introduced as an alternative treatment strategy to total laryngectomy for patients with advanced larynx squamous cell carcinoma (LSCC). Tumor-infiltrating lymphocytes (TILs) have proven to serve as prognostic biomarkers in head and neck cancer but have not been evaluated as a way to select patients for treatment paradigms. The aim of this study is to evaluate the role of pretreatment TILs in patients with advanced LSCC undergoing the bioselection paradigm. STUDY DESIGN: Retrospective study. SETTING: Tertiary care hospital. METHODS: Patients with advanced LSCC treated with bioselection and available tissue were included (N = 76). Patients were stratified into CD8-low and CD8-high cohorts by using the median TIL count. Kaplan-Meier survival analysis and multivariate cox regression were performed with SPSS version 26 (IBM). RESULTS: After controlling for tobacco use, tumor site, and stage, a high CD8 TIL count was an independent predictor of improved 5-year disease-specific survival (hazard ratio, 0.17 [95% CI, 0.03-0.84]; P = .03). CD8 TIL counts did not predict response to induction chemotherapy; however, subgroup analysis of patients treated with chemoradiation therapy revealed that CD8 TIL count was significantly associated with degree of response (P = .012). CONCLUSION: These findings support prior data published by our group showing that TILs are predictive of disease-specific survival in patients with head and neck cancer. CD8 TIL counts were significantly associated with degree of clinical response after induction chemotherapy. These results suggest that pretreatment assessment of tumor-infiltrating CD8 cells could be useful in selecting patients.

Impact of Completion Lymphadenectomy on Quality of Life for Head and Neck Cutaneous Melanoma.

OBJECTIVE: Recent randomized data suggest that completion lymph node dissection after a positive sentinel lymph node biopsy (SLNB) improves locoregional control but does not improve survival for melanoma patients. Locoregional recurrences of head and neck cutaneous melanoma (HNCM) may result in significant morbidity. A better understanding of morbidity is thus important to inform decisions about whether to pursue completion neck dissection (ND). STUDY DESIGN: Cross-sectional study. SETTING: Academic tertiary care hospital. METHODS: Clinical data were collected for patients with HNCM seen between 2016 and 2019 who were at least 1-year disease free. Each patient completed the Self-administered Leeds Assessment of Neuropathic Symptoms and Signs (SLANSS), Neck Dissection Impairment Index, and SF-36 (Short Form-36). Scores were compared by surgical treatment: wide local excision (WLE) only, SLNB, and ND. Univariate and multivariable regression was performed. RESULTS: Of 474 patients, 140 returned questionnaires (29.5% response rate; WLE, n = 49; SLNB, n = 76; ND, n = 15). No significant differences in SLANSS or Neck Dissection Impairment Index scores were found between the WLE and SLNB groups. SLANSS scores differed by 2 SD (P = .001) in the ND cohort, which had a 36% rate of neuropathy. Neck impairment was worse by 1 SD (P = .01) in the ND cohort. No differences were found in SF-36 domains. CONCLUSION: Neuropathy and neck impairment are components of morbidity after ND. These risks must be balanced with potential morbidity of locoregional recurrence in HNCM.

Honesty and Transparency, Indispensable to the Clinical Mission-Part I: How Tiered Professionalism Interventions Support Teamwork and Prevent Adverse Events.

At the foundation of clinical medicine is the relationship among patients, families, and health care professionals. Implicit to that social contract, professionals pledge to bring clinical excellence to advance their patients' wellness and healing-and to prevent harm. Patients trust that those privileged to deliver care will do so unwaveringly in service of patients' best interests; however, the incentives and infrastructure surrounding health care delivery can promote or undermine individual performance, teamwork, and patient safety. Modeling professionalism and identifying slips and lapses supports pursuit of high reliability. Part 1, Promoting Professionalism, introduces the first of 3 pillars of advancing the clinical mission.

Corticosteroid Use in Otolaryngology: Current Considerations During the COVID-19 Era.

OBJECTIVE: To offer pragmatic, evidence-informed advice on administering corticosteroids in otolaryngology during the coronavirus disease 2019 (COVID-19) pandemic, considering therapeutic efficacy, potential adverse effects, susceptibility to COVID-19, and potential effects on efficacy of vaccination against SARS-CoV-2, which causes COVID-19. DATA SOURCES: PubMed, Cochrane Library, EMBASE, CINAHL, and guideline databases. REVIEW METHODS: Guideline search strategies, supplemented by database searches on sudden sensorineural hearing loss (SSNHL), idiopathic facial nerve paralysis (Bell's palsy), sinonasal polyposis, laryngotracheal disorders, head and neck oncology, and pediatric otolaryngology, prioritizing systematic reviews, randomized controlled trials, and COVID-19-specific findings. CONCLUSIONS: Systemic corticosteroids (SCSs) reduce long-term morbidity in individuals with SSNHL and Bell's palsy, reduce acute laryngotracheal edema, and have benefit in perioperative management for some procedures. Topical or locally injected corticosteroids are preferable for most other otolaryngologic indications. SCSs have not shown long-term benefit for sinonasal disorders. SCSs are not a contraindication to vaccination with COVID-19 vaccines approved by the US Food and Drug Administration. The Centers for Disease Control and Prevention noted that these vaccines are safe for immunocompromised patients. IMPLICATIONS FOR PRACTICE: SCS use for SSNHL, Bell's palsy, laryngotracheal edema, and perioperative care should follow prepandemic standards. Local or topical corticosteroids are preferable for most other otolaryngologic indications. Whether SCSs attenuate response to vaccination against COVID-19 or increase susceptibility to SARS-CoV-2 infection is unknown. Immunosuppression may lower vaccine efficacy, so immunocompromised patients should adhere to recommended infection control practices. COVID-19 vaccination with Pfizer-BioNTech, Moderna, or Johnson & Johnson vaccines is safe for immunocompromised patients.

Stage Migration and Survival Trends in Laryngeal Cancer.

BACKGROUND: During the last two decades, significant advancements in the treatment of laryngeal cancer have occurred. Although survival of head and neck cancer patients has improved over time, the temporal trend of laryngeal cancer survival is an area of controversy. METHODS: From 2004 to 2016, 77,527 patients who had laryngeal cancer treated with curative intent in the United States were identified in the National Cancer Database. Relative and observed survival rates were assessed for temporal trends. Multinomial logistic regression investigated the relationship between American Joint Committee on Cancer (AJCC) stage and increasing calendar year. RESULTS: No significant improvement in 2- or 5-year observed survival (OS) or relative survival (RS) was observed. The 5-year RS ranged from 61.72 to 63.97%, and the 5-year OS ranged from 54.26 to 56.52%. With each increasing year, the proportion of stage 4 disease increased, with risk for stage 4 disease at the time of diagnosis increasing 2.2% annually (adjusted odds ratio [aOR], 1.022; 95% confidence interval [CI], 1.017-1.028; p < 0.001). This increase was driven by a 4.7% yearly increase in N2 disease (aOR, 1.047; 95% CI, 1.041-1.053; p < 0.001), with an annual 1.2% increase in T3 disease (aOR, 1.012; 95% CI, 1.007-1.018; p < 0.001) and a 1.2% increase in T4 disease (aOR, 1.012; 95% CI, 1.005-1.018; p < 0.001). CONCLUSION: Despite advances in the field, laryngeal cancer survival in the United States is not improving over time. This may be due to an increase in the proportion of stage 4 disease, driven primarily by increasing nodal disease. To achieve survival improvement commensurate with scientific and technologic advances, efforts should be made to diagnose and treat laryngeal cancer at earlier stages to prevent further stage migration.

Patient Burden with Current Surveillance Paradigm and Factors Associated with Interest in Altered Surveillance for Early Stage HPV-Related Oropharyngeal Cancer.

INTRODUCTION: Optimal surveillance paradigms for survivors of early stage human papillomavirus (HPV)-related oropharyngeal cancer are not well defined. This study aimed to characterize patient interest in and factors associated with an altered surveillance paradigm. MATERIALS AND METHODS: We surveyed patients with Stage I or II HPV-related oropharyngeal cancer treated at a tertiary care institution from 2016 to 2019. Primary outcomes were descriptive assessment of patient knowledge, interest in altered surveillance, burdens of in-person appointments, and priorities for surveillance visits. Ordinal regression was used to identify correlates of interest in altered surveillance. RESULTS: Sixty-seven patients completed surveys from February to April 2020 at a median of 21 months since completing definitive treatment. A majority (61%) of patients were interested in a surveillance approach that decreased in-person clinic visits. Patients who self-identified as medical maximizers, had higher worry of cancer recurrence, or were in long-term relationships were less likely to be interested. Patients reported significant burdens associated with surveillance visits, including driving distance, time off work, and nonmedical costs. Patients were most concerned with discussing cancer recurrence (76%), physical quality of life (70%), mortality (61%), and mental quality of life (52%) with their providers at follow-up visits. CONCLUSION: Patients with early stage HPV-related oropharyngeal cancers are interested in altered surveillance approaches, experience significant burdens related to surveillance visits, and have concerns that are not well addressed with current surveillance approaches, including physical and mental quality of life. Optimized surveillance approaches should incorporate patient priorities and minimize associated burdens. IMPLICATIONS FOR PRACTICE: The number of patients with HPV-related oropharyngeal cancers is increasing, and numerous clinical trials are investigating novel approaches to treating these good-prognosis patients. There has been limited work assessing optimal surveillance paradigms in these patients. Patients experience significant appointment-related burdens and have concerns such as physical and mental quality of life. Additionally, patients with early stage HPV-related oropharyngeal cancers express interest in altered surveillance approaches that decrease in-person clinic visits. Optimization of surveillance paradigms to promote broader survivorship care in clinical practice is needed.

New Age Mentoring and Disruptive Innovation-Navigating the Uncharted With Vision, Purpose, and Equity.

For individuals aspiring to a career in otolaryngology-head and neck surgery, mentorship can shape destiny. Mentorship helps assure safe passage into the specialty, and it influences the arc of professional development across the career continuum. Even before the novel coronavirus disease 2019 (COVID-19) pandemic, technology and social networking were transforming mentorship in otolaryngology. Now, in an increasingly virtual world, where in-person interactions are the exception, mentorship plays an even more pivotal role. Mentors serve as trusted guides, helping learners navigate accelerating trends toward early specialization, competency-based assessments, and key milestones. However, several structural barriers render the playing field unlevel. For medical students, cancellation of visiting clerkships, in-person rotations, and other face-to-face interactions may limit access to mentors. The pandemic and virtual landscape particularly threaten the already-leaky pipeline for underrepresented medical students. These challenges may persist into residency and later career stages, where structural inequities continue to subtly influence opportunities and pairings of mentors and mentees. Hence, overreliance on serendipitous encounters can exacerbate disparities, even amid societal mandates for equity. The decision to take deliberate steps toward mentoring outreach and engagement has profound implications for what otolaryngology will look like in years to come. This article introduces the concept of new age mentoring, shining a light on how to modernize practices. The key shifts are from passive to active engagement; from amorphous to structured relationships; and from hierarchical dynamics to bidirectional mentoring. Success is predicated on intentional outreach and purposefulness in championing diversity, equity, and inclusion in the progressively technology-driven landscape.

Long-term neck and shoulder function among survivors of oropharyngeal squamous cell carcinoma treated with chemoradiation as assessed with the neck dissection impairment index.

BACKGROUND: Of interest is the long-term neck and shoulder impairment of patients treated with primary chemoradiotherapy (CRT). This is important for counseling patients regarding treatment decisions when discussing primary CRT. METHODS: A cross-sectional study to identify factors that contribute to neck and shoulder dysfunction in patients treated with primary CRT. We utilized the neck dissection impairment index (NDII). Eighty-seven patients treated between 2003 and 2010, who were free of disease, responded; 24 of these 87 underwent post-CRT neck dissection. Mean interval since completion of CRT was over 5 years (62.7 months). Mean age, 63.5 years, male:female 75:12. RESULTS: Mean NDII score was 87.4 (SD 22.1, range 5-100). Multiple linear regression revealed worse NDII scores for patients with larger pre-CRT gross tumor nodal volume (GTVnodal), controlled for age, sex, body mass index (BMI), and the presence of neck dissection (p = 0.02). There were significant associations with increasing GTVnodal and "low" scores for components of the NDII that assessed neck pain (p = 0.02), neck stiffness (p = 0.01), lifting heavy objects (p = 0.02), reaching overhead (p = 0.02), and ability to do work (p = 0.02). Physical therapy (PT) was evaluated as an "anchor" but it was prescribed "as needed." Regression revealed participation in PT was associated with higher GTVnodal, lower BMI, presence of neck dissection, and female sex (p = 0.00007). CONCLUSION: GTVnodal was an independent predictor of neck and shoulder impairment. High GTVnodal was associated with increased pain and stiffness, and increased difficulty lifting heavy objects, reaching overhead, overall ability to perform work-related tasks and was associated with participation in post-treatment PT.

CT and FDG-PET radiologic biomarkers in p16+ oropharyngeal squamous cell carcinoma patients treated with definitive chemoradiotherapy.

PURPOSE: To assess associations between imaging biomarkers from standard of care pre-treatment CT and FDG-PET scans and locoregional (LR) and distant metastatic (DM) recurrences in patients with p16+ oropharyngeal squamous cell carcinoma (OPSCC) treated with definitive chemoradiotherapy (CRT). METHODS: An institutional database from a single NCI-designated cancer center identified 266 patients with p16+ OPSCC treated with definitive CRT in our department from 2005 to 2016 with evaluable pre-treatment FDG-PET scans. Quantitative SUV metrics and qualitative imaging metrics were determined from FDG-PET and CT scans, while clinical characteristics were abstracted from the medical record. Associations between clinical/imaging features and time to LR (TTLRF) or DM (TTDMF) failure and overall survival (OS) were assessed using univariable Cox regression and penalized stepwise regression for multivariable analyses (MVA). RESULTS: There were 27 LR and 32 DM recurrences as incident failures. Imaging biomarkers were significantly associated with TTLRF, TTDMF and OS. FDG-PET metrics outperformed CT and clinical metrics for TTLRF, with metabolic tumor volume being the only significant feature selected on MVA: C-index = 0.68 (p = 0.01). Radiographic extranodal extension (rENE), positive retropharyngeal nodes (RPN+), and clinical stage were significant on MVA for TTDMF: C-index = 0.84 (p < 0.001). rENE, group stage, and RPN+ were significant on MVA for OS: C-index = 0.77 (p < 0.001). CONCLUSIONS: In the largest study to date of uniformly treated patients with CRT to evaluate both pretreatment CT and FDG-PET, radiographic biomarkers were significantly associated with TTLRF, TTDMF and OS among patients with p16+ OPSCC treated with CRT. CT metrics performed best to predict TTDMF, while FDG-PET metrics showed improved prediction for LRRFS. These metrics may help identify candidates for treatment intensification or de-escalation of therapy. STATEMENT OF TRANSLATIONAL RELEVANCE: Pre-treatment imaging features from standard-of-care PET/CT imaging show promise for predicting long-term outcomes following HPV-associated oropharynx cancer (HPV-OPC) therapy. This study comprehensively characterizes qualitative and quantitative pre-treatment imaging metrics associated with time to pattern-specific failure in a cohort of 266 patients treated uniformly with definitive chemoradiation. Multivariate analysis (MVA) for time to locoregional failure (TTLRF), time to distant metastatic failure (TTDMF), and overall survival (OS) was performed. FDG-PET metrics outperformed CT and clinical metrics for TTLRF. CT radiographic extranodal extension, positive retropharyngeal nodes, and stage strongly predicted TTDMF (combined C-index = 0.84, log rank p < 0.001). Number of smoking pack-years complemented clinical and imaging features only in patients without radiographic extranodal extension or positive retropharyngeal nodes. Time to pattern-specific failure is important for guiding treatment de-escalation strategies, which intend to reduce treatment-related toxicity in patients with relatively long expected survival times. This study suggests that PET/CT features should play a crucial role in future de-escalation trials and management of HPV-OPC patients.