To examine the use of treatments with antibacterial properties as prophylaxis prior to radiotherapy (RT), either alone or in combination with chemotherapy (CT), to prevent and reduce radiation-induced oral mucositis (RIOM) in patients with head and neck cancer (HNC). A systematic search following PRISMA guidelines was conducted across PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant studies published in English through March 2025. Eligible studies assessed prophylactic antibacterial interventions aimed at preventing RIOM. From 86 retrieved citations, 9 articles met inclusion criteria. Antibacterial agents assessed included polymyxin, tobramycin, amphotericin (PTA), povidone iodine, SAMITAL, and Nigella sativa (NS). Evidence supporting povidone iodine, PTA, and SAMITAL was inconclusive or failed to demonstrate statistically significant reductions in RIOM severity. Several studies reported discordant findings, with statistically significant improvements in patient-reported symptoms or quality-of-life measures despite nonsignificant clinician-assessed scores. NS demonstrated potential benefits in reducing RIOM incidence and severity compared with standard of care and other antibacterial agents. The systematic review highlights limited and inconsistent evidence supporting antibacterial prophylaxis for preventing and reducing RIOM severity in patients with HNC undergoing RT. Discrepancies between patient-reported outcomes and clinical-assessed grading suggest some treatments may provide symptomatic benefit not captured by traditional scoring systems. NS mouthwashes showed preliminary promise; however, evidence remains insufficient to establish superiority, and safety and regulatory concerns are persistent, particularly in immunosuppressed patients. Given the role of bacterial colonization and microbial dysbiosis in RIOM pathogenesis, larger, well-designed clinical trials with rigorous safety evaluations are warranted to investigate bacterial-directed preventive therapies.

BackgroundTime to treatment initiation (TTI) delays result in worse cancer outcomes. Patients in under-resourced communities may experience TTI delays due to structural challenges and social determinants of health (SDOH), impacting access to timely care. We conducted a qualitative study in breast cancer patients with and without delayed TTI from an under-served community to explore barriers and facilitators to TTI from the patient perspective.MethodsWe interviewed 30 patients who received curative intent breast cancer treatment at Montefiore Medical Center from 2019 to 2024. Half of the patients had delayed TTI (≥45 days), while the other half were not delayed. Interviews addressed barriers and facilitators of timely TTI, perceived timeliness of care, emotional well-being, and perceptions of the healthcare team and communication. Interviews were coded based on recurring ideas and patterns, and framework analysis was used to finalize themes.ResultsOur cohort (n=30) had a mean age of 60.9 years, all whom identified as female. Most participants identified as Black or African-American (56.7%), and 16.7% identified as Hispanic/Latino. Age, race, ethnicity, tumor stage, and first treatment modality were similar between delayed and non-delayed TTI groups, whereas the distribution of pathologic diagnoses approached borderline significance. The mean TTI in delayed participants was 55.1 days and 32.7 days in the non-delayed group. Three main themes were identified: (1) Facilitators and Barriers, (2) Coping in the Interim: Waiting for Treatment Initiation, and (3) Patient Perceptions of Timeliness. Delayed patients faced financial burdens, transportation issues, and childcare challenges, hindering ability to adhere to schedules. Approximately half of the full cohort (delayed and non-delayed patients) wished their treatment began sooner, while half of the delayed TTI group expressed preference for longer TTI that afforded them time to prepare for treatment, make important decisions and seek opinions. Frequently participants found significant emotional and logistical support through family, social networks, and religion as well.ConclusionsOur study revealed that delayed patients faced financial and logistical barriers to initiating treatment. Findings from our work highlight the need for healthcare systems to better equip and engage patients in the care timeline to avoid delayed TTI.

BACKGROUND:Two-month outcomes of advanced pneumatic compression device (APCD) and usual care (UC) in Head and Neck Cancer survivors with previously untreated lymphedema were compared. METHODS:Participants in this multisite, randomized clinical trial were randomized to APCD or UC. The primary endpoint was severity of lymphedema symptoms. Secondary endpoints were anatomical lymphedema changes, biopsychosocial outcomes, and barriers to care. RESULTS:Two hundred thirty-six participants were enrolled (119 APCD, 117 UC). Analysis was intention-to-treat. Lymphedema-associated symptom burden measured using the VHNSS and LSIDS was improved to a similar degree in both groups. APCD demonstrated a statistically significant improvement in external soft tissue swelling assessed by digital photography. No difference in CT imaging measures of lymphedema was noted. UC participants experienced barriers to care. CONCLUSIONS:APCD is an effective treatment for lymphedema in HNCS. The APCD addresses clinically significant barriers to therapist guided treatment. A hybrid approach may be complementary and optimize patient outcomes. TRIAL REGISTRATION:NCT04797390.

PURPOSE:We previously reported short-term efficacy (2-months) results of an advanced pneumatic compression device (APCD) versus usual care (UC) for treatment of head and neck cancer survivors (HNCS) with symptomatic treatment naïve lymphedema (HNLEF). Herein we report the long-term (4 & 6-month) outcomes of that trial. METHODS AND MATERIALS:This multi-site, prospective randomized clinical trial was conducted at academic and community-based sites. Eligibility criteria included: HNCS without evidence of cancer, previously untreated HNLEF evaluable on exam or imaging, and at least 1 associated symptom with severity of ≥4 out of 10. Participants were randomized 1:1 to either daily use of an APCD for 6-months or UC per institutional standards. Measurement tools included: Patient-reported outcome (PRO) measures, Clinician reported outcome (CRO) measures, digital photographs, and computed tomography (CT). Measures were at baseline 2, 4 (no CT) and 6-months. RESULTS:236 participants were enrolled (119 APCD, 117 UC). Tumor distribution by group was as follows: APCD=Larynx 29.4%, Salivary Glands 1.7%, Oral Cavity 37.8%, Paranasal Sinuses 1.7%, Pharynx 25.2%, Unknown Primary 4.2%); UC=Larynx 16.2%, Salivary Glands 5.1%, Oral Cavity 48.7%, Paranasal Sinuses 1.7%, Pharynx 21.4%, Unknown Primary 6.8%. Of the UC group, 17.1% (n= 20) underwent neck bilateral dissection, as did 12.6% (n=15) of the APCD group. Symptom improvement garnered during initial treatment was maintained over time in both groups with no significant difference between groups. CRO measures demonstrated improvement in internal HNLEF (Modified Patterson Scale, p <0.01 both groups) and external HNLEF (grading criteria, APCD p<0.01; UC p=0.06) in the APCD group. Statistically significant differences at two of 19 anatomic subsites favored the APCD group. At 6-months the digital photography showed improvement with no between group difference. CT findings at 6-months verified significant improvement in soft tissue swelling in both groups (p<0.01 both groups) that was not present at 2-months with no between group difference. CONCLUSIONS:At 6-months, the analysis indicated that APCD and UC resulted in improved symptom control of similar magnitude. CROs, imaging and digital photography demonstrated improvement in anatomic lymphedema in both groups over time. Select CRO outcome measures demonstrated marginal differences between groups that favored the APCD. Both interventions provided long-term benefit to patients with treatment naïve lymphedema. CLINICAL TRIAL REGISTRATION:NCT04797390.

BACKGROUND:Oral tongue squamous cell carcinoma (OTSCC) incidence is rising in the United States. While early-stage (pT1-2N0M0) OTSCC is primarily managed with surgery, the role of postoperative radiotherapy (PORT) remains debated, particularly in moderate-to-poor differentiation. Current guidelines do not recommend PORT based on histologic grade alone, yet a retrospective study by Tian et al. found PORT improved survival in moderately-to-poorly differentiated OTSCC in a Chinese cohort. We aimed to validate these findings in a US population. METHODS:A retrospective cohort study using the National Cancer Database (2004-2022) identified patients with pT1-2N0M0 OTSCC treated with surgery or surgery plus PORT. After stringent inclusion criteria, 3562 patients remained, including 456 (12.8%) who received PORT. Propensity score matching (PSM) balanced key prognostic factors, and survival was assessed using Kaplan-Meier analysis and multivariable Cox proportional hazards models. RESULTS:PORT did not improve OS in well- or moderately differentiated tumors. However, in poorly differentiated tumors, PORT was associated with a significant survival benefit (HR: 0.53, 95% CI: 0.30-0.92, p = 0.025) before and after PSM. This effect persisted in multivariable analysis (HR: 0.56, 95% CI: 0.31-0.99, p = 0.047) and after excluding patients with lymphovascular invasion (HR: 0.48, 95% CI: 0.27-0.87, p = 0.016). CONCLUSIONS:These findings validate and extend prior international data, demonstrating a PORT-associated survival benefit in poorly differentiated early-stage OTSCC. The lack of benefit in well- and moderately differentiated tumors underscores the need for individualized treatment approaches. Prospective studies are warranted to refine risk stratification and optimize clinical guidelines.

e13797 Background: Challenges with social determinants of health (SDoH) have been shown to increase the risk of delays in cancer treatment initiation and may adversely affect therapy completion rates. In addition, exposure to chronic stress can lead to systemic immune dysregulation, which may worsen treatment response and outcomes. To elucidate these relationships, we evaluated the associations between self-reported SDoH challenges, systemic inflammation index (SII) score, and cancer survival, among historically disadvantaged patients. Objective: To study the influence of unmet social needs and elevated systemic inflammation on overall survival in cancer patients. Methods: We utilized our well-characterized retrospective cohort study of adult patients diagnosed with cancer at an urban medical center that serves an ethnically diverse population. Patients who met our inclusion criteria were diagnosed with various solid tumors and hematologic malignancies from 2018 to 2022, and filled out a self-reported, validated SDoH questionnaire that screens for 10 social needs. Univariate testing (chi-squared and t-tests, where appropriate), followed by Cox proportional hazards modeling, were used to estimate the associations between systemic inflammation index (SII) score prior to treatment, clinical and demographic data, and staging and survival outcomes. Results: Among our 1776 patients (mean age 61.3 ± 11.6), the top three cancer sites were genitourinary (n = 362, 20.4%), breast (n = 312, 17.6%), and hematologic malignancies (n = 183, 10.3%). 336 screened positive for at least one unmet social need, predominately being money for food (n = 139, 41.4%), housing situation (n = 105, 31.3%) and healthcare transportation (n = 101, 30.1%). Over half of these patients experienced >2 unmet needs (n = 188, 56.0%). Patients with unmet needs were younger (mean age 58.0 vs 61.7, p < 0.0001) and more likely to identify as Hispanic (p = 0.04) and/or African American (p = 0.03). Further, patients with unmet social needs had a significant decrease in overall survival (HR = 1.14; 95% CI: 1.02-1.27). In addition, lack of access to healthcare transportation was independently predictive of mortality (HR = 1.91; 95% CI: 1.21-3.03), when adjusting for age, stage of disease, and SII. Patients with high immune dysregulation (SII score > 913.51) also had worse overall survival in the multivariable analysis (HR = 2.27, 95% CI: 1.72-3.00). Conclusions: Cancer patients withunmet social needs may be at risk of worse outcomes. SII and SDoH were not colinear, and may independently influence survival outcomes in cancer patients. Our Bronx population is predominantly of low socio-economic status, historically marginalized patients with a high burden of unmet social needs. Should our results be confirmed, SII values and unmet social needs may be targets for interventions to mitigate cancer health disparities.

BACKGROUND:This study elucidated sex disparities in head and neck squamous cell carcinoma (HNSCC) outcomes and investigated their interaction with race. METHODS:A total of 452 patients diagnosed with HNSCC were grouped by sex and race. Survival was analyzed using Kaplan-Meier curves with log rank tests and multivariable Cox models to assess sex/race associations while adjusting for confounders. RESULTS:Males were more likely to have advanced-stage cancer (79.6%, n = 257 vs. 70.5%, n = 91; p = 0.040). African American females had the best 5-year overall survival, followed by White females and Hispanic males. African American males had the worst survival (p = 0.0334). This sex disparity within the African American population persisted when controlling for confounding variables (HR = 0.343; 95% CI: 0.154-0.766; p = 0.0090) and was more pronounced in HPV-negative cases (HR = 0.184, 95% CI = 0.043-0.786). CONCLUSIONS:Race-stratified analysis revealed a survival advantage for African American females over males. Further analysis shows that HPV status, alongside race, moderates the effect of sex on HNSCC outcomes. LEVEL OF EVIDENCE: 3:

BACKGROUND/OBJECTIVES:HNSCC is a highly aggressive malignancy marked by the dysregulation of the cell cycle. In HPV- HNSCC, mutations in the CDKN2A gene frequently result in the loss of the p16 protein, a key inhibitor of the cyclin D1/CDK4/6 complex. This loss results in unchecked G1/S phase progression. The CDK4/6 inhibitor palbociclib has shown therapeutic potential in HPV- HNSCC by inducing G1 phase arrest and reducing cell viability. In this study, we investigated the molecular mechanisms by which palbociclib affects cell viability in HPV- HNSCC. METHODS:Four HPV- HNSCC cell lines were treated with palbociclib, and RNA sequencing was performed to assess changes in gene expression. Cell viability was measured using the MTT assay. To further investigate protein localization, interactions, and function, we used immunofluorescence staining, co-immunoprecipitation, small molecule inhibitors, and siRNA-mediated knockdown. RESULTS:We demonstrate that palbociclib downregulates survivin, a protein that plays dual roles in mitosis and apoptosis, thereby inhibiting cell proliferation. We also found that survivin is overexpressed in HPV- HNSCC. Inhibiting survivin dimerization using the compound LQZ-7i significantly reduces cell viability and promotes its export from the nucleus to the cytoplasm. Additionally, we identified USP1, a deubiquitinase, as both a downstream target of CDK4/6 and a key regulator of survivin stability. Inhibiting USP1 activity or silencing its expression significantly reduces survivin levels. CONCLUSIONS:Our findings highlight survivin as a critical mediator of cell proliferation in HPV- HNSCC and suggest that targeting the CDK4/6-USP1-survivin axis may offer a promising therapeutic strategy.

121 Background: Time to treatment (TTI) delays result in increased morbidity and mortality for cancer patients. These treatment delays disproportionately occur within marginalized communities due to structural challenges with social determinants of health (SDoH), disengagement with the healthcare system and limited or low health literacy that impacts their ability to obtain timely, appropriate care. We conducted semi-structured interviews with patients treated for breast cancer about their care treatment trajectories to further understand barriers and facilitators for timely treatment from the patient perspective. Methods: We conducted semi-structured interviews with 30 patients in 2023 who received curative intent breast cancer treatment at Montefiore Medical Center from 2019 to 2023. Interviews addressed barriers and facilitators of timely TTI, perceived timeliness and salience of timeliness, emotional well-being, and perceptions of the healthcare team and communication. We analyzed interviews using framework analysis. Results: A total of 30 patients were interviewed (mean age 58.9 year ± 10.6, 75% Non-Hispanic Black, 25% Non-Hispanic White). The median TTI was 52.5 days (49, 62 IQR). First treatment modality included surgery (75%) and chemotherapy (25%). Many participants found significant emotional and logistical support through family, social networks, religion, and connecting with survivors. Several patients faced transportation issues hindered their ability to adhere to schedules, childcare challenges, and difficulty managing numerous appointments, with some wishing transportation services had been offered at diagnosis. Some participants experienced unique cancer presentation, required clearances, involvement of non-oncologic providers and consultants, and time for decision-making about treatment options that may have contributed to delays. Some patients faced financial burdens including personal expenses, family support needs, and difficulties accessing third-party assistance (i.e., short-term disability, Supplemental Security Income). Some patients valued mental health counseling and other resources like group therapy and social workers, though some wished for earlier, more specialized support, indicating gaps in the support timeline. A few patients expressed preference for longer TTI that afforded them time to make important decisions and seek opinions. Conclusions: The study revealed that many patients faced logistical, emotional, and informational challenges while awaiting treatment and highlighted a need for more tailored assistance and timely interventions. Findings from our work highlight the need for further study on how healthcare systems can better equip and engage patients early in the care timeline to avoid delayed TTI.

Evasion of apoptosis promotes tumor survival and contributes to resistance to cancer therapeutics in head and neck squamous cell carcinoma (HNSCC). Our recent work has demonstrated that HNSCC’s highly express pro-survival anti-apoptotic proteins Bcl-xL and Mcl-1. Nevertheless, the mechanism of HNSCC to evade apoptosis is still not well understood. We used BH3 profiling, a functional assay which measures mitochondrial depolarization in response to the introduction of BH3 peptides, to evaluate apoptosis competency and dependency upon BCL-2 family anti-apoptotic proteins in a panel of immortalized and patient-derived HNSCC lines. We assessed response to BH3 mimetics including ABT-263 (navitoclax), an inhibitor of Bcl-2/Bcl-xL/Bcl-w, and S63845, an inhibitor of Mcl-1, both as single agents and in combination. We demonstrate that apoptosis signaling appears to be intact in the majority of HNSCC cells, and they are co-dependent upon Bcl-xL and Mcl-1 for survival. We found the combination to be highly synergistic in 2D culture and in 3D organoid models of HHNSCC. Given our findings that co-dependency on Bcl-xL and Mcl-1 is common, and co-inhibition of these molecules is synergistic for growth suppression in HNSCC cells, these results elucidate the therapeutic potential of BCL-xL and MCL-1 inhibition in HNSCC.

90 Background: Delays in time to treatment initiation (TTI) for gynecologic malignancies have been associated with worse survival. Worsened outcomes and presentation with more advanced disease are more common for gynecologic cancer patients who come from socioeconomically disadvantaged populations and whose healthcare is negatively impacted by their social determinants of health (SDoH). There is a need to characterize the particular social determinants of health that are associated with delays in treatment initiation in patients with gynecologic malignancy, particularly in underserved urban populations. Methods: Retrospective cohort study at an urban community-based academic center. Participants were 257 patients with primary gynecologic malignancy either of the cervix, ovary, uterus, vulva/vagina or NOS diagnosed between January 2017 and August 2022, identified through the Montefiore Medical Center Cancer Registry. The primary exposure was TTI, defined as the duration between histopathological diagnosis and initial treatment. Univariate and multivariate logistic regression analyses were conducted to examine the association between delays in TTI and SDoH. Multivariate Cox proportional hazard regression was used to obtain hazard ratios and 95% confidence intervals associated with TTI. Results: Among 257 patients with gynecologic malignancy (median [IQR] age 63 [56-72] years), 205 patients were treated within 45 days of diagnosis, and 52 were treated at or after 45 days. Predictors of delayed TTI (defined as ≥45 days) included positive SDoH screening in univariate logistic regression (OR = 3.12, 95% CI 1.39-6.98, p = 0.0061) and in multivariate logistic regression (OR = 3.06, 95% CI 2.62-3.57, p<0.001) as well as increased age in multivariate logistic regression (OR = 1.02, 95% CI 1.02-1.03, p<0.001). Multivariate logistic regression showed that protective factors for delayed TTI were Non-Hispanic Black race/ethnicity (OR = 0.87, 95% CI 0.77-0.99, p = 0.0351), non-Hispanic white race/ethnicity (OR = 0.37, 95% CI 0.30-0.46, p<0.001), inpatient stay within 30 days of diagnosis (OR = 0.74, 95% CI 0.62-0.88, p=0.001) and AJCC clinically late stage (OR = 0.57, 95% CI 0.50-0.66, p<0.001). Conclusions: In patients with gynecologic malignancies, greater SDoH burden increases risk for delays in treatment ≥ 45 days from diagnosis. Non-Hispanic race/ethnicity, inpatient stay within 30 days of diagnosis and clinically late-stage diagnoses are protective factors for expedited treatment initiation. Identification of predictive and protective factors for treatment delay will help identify at-risk patients and facilitate earlier intervention in hospitals with underserved populations.

Introduction: Drug development is systemically inefficient. Research and development costs for novel therapeutics average hundreds of millions to billions of dollars, with the overall likelihood of approval estimated to be as low as 6.7% for oncology drugs. Over half of these failures are due to a lack of drug efficacy. This pervasive and repeated low rate of success exemplifies how preclinical models fail to adequately replicate the complexity and heterogeneity of human cancer. Therefore, new methods of evaluation, early in the development trajectory, are essential both to rule-in and rule-out novel agents with more rigor and speed, but also to spare clinical trial patients from the potentially toxic sequelae (high risk) of testing investigational agents that have a low likelihood of producing a response (low benefit).Methods: The clinical in vivo oncology (CIVO®) platform was designed to change this drug development paradigm. CIVO precisely delivers microdose quantities of up to 8 drugs or combinations directly into patient tumors 4–96 h prior to planned surgical resection. Resected tissue is then analyzed for responses at each site of intratumoral drug exposure.Results: To date, CIVO has been used safely in 6 clinical trials, including 68 subjects, with 5 investigational and 17 approved agents. Resected tissues were analyzed initially using immunohistochemistry and in situ hybridization assays (115 biomarkers). As technology advanced, the platform was paired with spatial biology analysis platforms, to successfully track anti-neoplastic and immune-modulating activity of the injected agents in the intact tumor microenvironment.Discussion: Herein we provide a report of the use of CIVO technology in patients, a depiction of the robust analysis methods enabled by this platform, and a description of the operational and regulatory mechanisms used to deploy this approach in synergistic partnership with pharmaceutical partners. We further detail how use of the CIVO platform is a clinically safe and scientifically precise alternative or complement to preclinical efficacy modeling, with outputs that inform, streamline, and de-risk drug development.

AbstractObjectiveThe onset of the coronavirus disease 2019 (COVID‐19) pandemic changed practice patterns throughout medicine. The purpose of this study is to evaluate changes in the volume and location setting of laryngology procedures after the onset of COVID‐19.Study DesignRetrospective database cohort study.SettingReg‐ENT registry.MethodsRetrospective review from 2017 to 2022 of patients who underwent a laryngology procedure identified by procedure code categorized by site of service code—“ambulatory surgical” versus “office” setting. Based on March 2020 as the cutoff point, the procedures were designated as pre‐COVID versus COVID time period.ResultsA total of 5989 patients underwent laryngology procedures. Forty‐two percent more procedures were performed in the COVID period (n = 3780) versus pre‐COVID (n = 2209). Pre‐COVID, the procedure distribution between office and ambulatory surgical setting was 70% (n = 1546) compared with 30% (663). This shifted to 77% (n = 2920) and 23% (n = 860) during COVID, P = .9. The most common diagnoses associated with laryngology procedures during the study period were vocal fold paralysis 47% (n = 2831), dysphonia 33% (n = 1392), and laryngotracheal stenosis 14% (n = 838). These trends remained in both pre‐COVID and COVID time periods. After the start of the pandemic, among patients undergoing laryngology procedures, there was a 93% increase (n = 284‐549) in the diagnosis of laryngotracheal stenosis, 70% increase (n = 520‐882 patients) in dysphonia and 69% increase (n = 1054‐1777) in vocal fold paralysis.ConclusionAn increase in laryngology procedures performed after the onset of the COVID‐19 pandemic was identified with an overall procedural shift to the office‐setting.

PURPOSE Delays in oncologic time to treatment initiation (TTI) independently and adversely affect disease-specific mortality. Social Determinants of Health (SDoH) are increasingly recognized as significant contributors to patients' disease management and health outcomes. Our academic center has validated a 10-item SDoH screener, and we elucidated which specific needs may be predictive of delayed TTI. METHODS This is a retrospective cohort study at an urban academic center of patients with a SDoH screening and diagnosis of breast, colorectal, endocrine/neuroendocrine, GI, genitourinary, gynecologic, head and neck, hematologic, hepatobiliary, lung, or pancreatic cancer from 2018 to 2022. Variables of interest included household income, tumor stage, and emergency department (ED) or inpatient admission 30 days before diagnosis. Factors associated with delayed TTI ≥45 days were assessed using multivariable logistic regression. RESULTS Among 2,328 patients (mean [standard deviation] age, 64.0 (12.8) years; 66.6% female), having >1 unmet social need was associated with delayed TTI (odds ratio [OR], 1.68; 95% CI, 1.54 to 1.82). The disparities most associated with delay were legal help, transportation, housing stability, and needing to provide care for others. Those with ED (OR, 0.49; 95% CI, 0.44 to 0.54) or inpatient (OR, 0.54; 95% CI, 0.50 to 0.58) admission 30 days before diagnosis were less likely to experience delay. CONCLUSION Delays in oncologic TTI ≥45 days are independently associated with unmet social needs. ED or inpatient admissions before diagnosis increase care coordination, leading to improved TTI. Although limitations included the retrospective nature of the study and self-reporting bias, these findings more precisely identify targets for intervention that may more effectively decrease delay. Patients with SDoH barriers are at higher risk of treatment delay and could especially benefit from legal, transportation, caregiver, and housing assistance.

Purpose of Review To help clinicians gain an understanding of quality improvement (QI) and value-based care (VBC) in healthcare, with a specific emphasis on otolaryngology. This review also attempts to examine the future landscape of QI and VBC, and emphasize the need for active physician participation.Recent Findings Many efforts are underway to help define quality otolaryngologic care including otolaryngology-specific reporting measures, clinical practice guidelines, and a large, specialty-specific patient database (Reg-ent). Certain subspecialties (facial plastics and laryngology) and populations are underrepresented in the current literature.Summary QI and VBC will become increasingly important as more alternative payment models (APMs) are investigated and implemented by governmental and commercial payors. Physician participation will be integral in ensuring appropriateness of these APMs, specifically with regard to defining quality care and optimizing value for patients.

BACKGROUND:Delay in time to treatment initiation (TTI) is associated with worsened survival outcomes in laryngeal squamous cell carcinoma (LSCC). It is unclear whether this is due to tumor growth or an increased risk of metastatic disease. METHODS:This retrospective cohort study at one academic center included patients with LSCC who underwent radiotherapy/chemoradiotherapy between 2005 and 2017. We examined the association between tumor growth rate (TGR) and survival outcomes. RESULTS:Among 105 patients (mean age, 63.8 ± 11.1 years; 72% male), the threshold between "slow-growing" and "fast-growing" tumors was >0.036 mL/day (survival) and >0.082 mL/day (recurrence). Faster growth was associated with worse overall survival (OS) (hazard ratio, 1.97; 95% confidence interval [CI], 0.94-4.13) and increased recurrence (odds ratio, 9.10; 95% CI, 2.40-34.4). CONCLUSIONS:TGR >0.036 mL/day during TTI was associated with decreased OS, and >0.082 mL/day was associated with increased recurrence. Tumor measurement in patients experiencing delay may identify those who could benefit from escalated therapy.

Abstract Introduction/Objective Parathyroid Carcinomas are rare malignant neoplasms, accounting for less than 1% of primary hyperparathyroidism cases. Parathyroid carcinomas are characterized by markedly elevated levels of PTH, severe hypercalcemia and established target organ damage. The authors report the experience of a single center regarding the clinic-pathologic and genetic analysis of parathyroid carcinoma cases. Methods/Case Report The study is a retrospective review of all patients with parathyroid carcinoma that were evaluated at a tertiary oncologic center from 2001 until 2023. Results (if a Case Study enter NA) A total of nine cases (6 male and 3 female) were identified, with a mean age at diagnosis of 52 ± 16 years and a median follow-up of 16.5 years. Most patients presented with hypercalcemia (n = 7), with a mean serum calcium concentration of 13.5 mg/dl (9.6-16.5) and a mean PTH of 1123 pg/ml (276-2500). En bloc surgical resection was performed in 6 patients and 3 patients underwent adjuvant radiotherapy. Recurrence was observed in 4 cases (44.4%) after a median of 24 months following surgery. Negative immunohistochemical staining of parafibromin was noted in 3/4 cases of recurrence. Parathyroid carcinoma was diagnosed on the basis of finding lesions with vascular or perineural invasion, capsular penetration, and/or documented metastases. Immunohistochemical staining for parafibromin, Ki-67, and E-cadherin was performed on formalin-fixed, paraffin-embedded tissue samples. Next generation sequencing (NGS) was performed in 6/9 cases and CDC73 mutations were present in 38.5% of analyzed patients. Loss of TP53 and RB1 alleles and CCND1 amplification were other reported genetic alterations in the study cohort. Conclusion Parathyroid carcinoma is associated with a significant rate of recurrence and limited effective treatment beyond initial complete surgical resection. Inactivating CDC73 alterations which include truncating or frameshift mutations, as well as missense mutations lead to the loss of parafibromin immunoreactivity. Other molecular alterations like PTEN and PIK3CA mutations may represent potential targets for molecular therapy. An IHC panel of parafibromin, Ki-67 and E-cadherin may help to distinguish parathyroid carcinoma from other parathyroid neoplasms.