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BACKGROUND: Treatment at high-volume facilities (HVF) has been associated with improved prognosis of HNC patients undergoing curative treatment. Whether this systemic factor influences survival outcomes of patients with HNC undergoing palliative treatment is unknown. AIM: To investigate the impact of palliative treatment facility volume on overall survival (OS) in patients with head and neck cancer (HNC). DESIGN: The 2004 to 2018 National Cancer Database was queried retrospectively for patients with HNC undergoing palliative treatment. SETTING/PARTICIPANTS: Patients were stratified based on treatment facility volume percentile. Multivariable binary logistic and Cox proportional hazards regression models were implemented. RESULTS: Of 8682 patients included, 1661 (19.1%) underwent palliative therapy at facilities with volume ≥80th percentile. Among 972 facilities included, 643 (66.2%), 182 (18.7%), 85 (8.8%), 44 (4.5%), and 18 (1.9%) had volume <20th, 20-40th, 40-60th, 60-80th, and ≥80th percentiles, respectively. 5-year OS rates of patients undergoing palliative therapy at facilities with volume <20th, 20-40th, 40-60th, 60-80th, and ≥80th percentile was 11%, 13%, 11%, 14%, and 23%, respectively (P < .001). Facility volume ≥80th percentile was associated with higher 5-year OS on multivariable Cox regression (aHR 0.34, 95% CI 0.16-0.69, P < .001). Surgical treatment (aOR 1.34, 95% CI 1.07-1.68, P = .012) was associated with undergoing treatment at facilities with volume ≥80th percentile. CONCLUSIONS: Undergoing palliative treatment at HVFs is associated with higher OS in HNC. The survival benefit derived from high facility volume should be carefully considered in the context of other patient and facility characteristics in end-of-life management, with specific emphasis on patient-directed goals of care.
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OBJECTIVE: Mandibular plate reconstruction (MPR) is often indicated after tumor ablation, osteoradionecrosis excision, and traumatic bone loss to restore oral functionality and facial cosmetics. There are limited analyses identifying risk factors that lead to plate infection (PIn), exposure, and removal ("plate complications"). STUDY DESIGN: Retrospective cohort study. SETTING: Academic tertiary medical center. METHODS: Patients who underwent MPR from 2013 to 2022 were identified. Risk factors for plate complications were analyzed based on demographic, clinical, intraoperative, and postoperative factors. Multivariable analysis was conducted with logistic regression. Survival analysis was conducted with a Cox model. RESULTS: Of the 188 patients analyzed, 48 (25.5%) had a plate complication [infection: 22 (11.7%); exposure: 23 (12.2%); removal: 35 (18.6%)]. Multivariate analysis revealed predictive associations between at least 1 plate complication and the following variables: smoking status, soft tissue defect size, number of plates, average screw length, and various postoperative complications. Other associations approached the threshold for significance. Prior and adjuvant radiation therapy, type of free flap, stock versus custom plates, and perioperative antibiotic prophylaxis regimens were not associated with plate complications. No plate complication was independently associated with lower overall survival. PIn (hazard ratio, HR: 7.99, confidence interval, CI [4.11, 15.54]) and exposure (HR: 3.56, CI [1.79, 7.08]) were independently associated with higher rates of plate removal. CONCLUSION: Plate complications are relatively common after MPR. Smoking history, specific disease characteristics, hardware used during surgery, and postoperative complications may help identify higher-risk patients, but additional larger-scale studies are needed to validate our findings and resolve discrepancies in the current literature.
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INTRODUCTION: Chronic rhinosinusitis (CRS) can be associated with tumors involving the maxillary sinus, but outcomes after undergoing maxillectomy with free flap reconstruction remain unclear. METHODS: A retrospective analysis of medical records was performed to evaluate evidence of CRS in patients who underwent maxillectomy with free flap reconstruction at a single tertiary care academic institution from 2013 through 2020. RESULTS: Eighty-four patients were assessed. Nineteen (22.6%) patients were diagnosed with CRS after surgery, 23 (27.4%) patients were treated for sinus symptoms, and 49 (58.3%) had radiographic evidence of sinus inflammation for more than 6 months. Risk factors for requiring sinus treatment included adjuvant or neoadjuvant chemotherapy (p = 0.002) and pre-operative use of sinus medication (p < 0.001). Radiographic evidence of sinusitis 6 months after surgery is also closely associated with sinusitis treatment (p = 0.051). CONCLUSIONS: CRS may be underdiagnosed in patients undergoing maxillectomy with microvascular reconstruction. Further evaluation into patient sinus disease and symptoms following neoplastic surgery may lead to a higher quality of life in some long-term survivors.
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Head and neck squamous cell carcinomas (HNSCCs) are cancers that arise in the mucosa of the upper aerodigestive tract. The five-year patient survival rate is ~50%. Treatment includes surgery, radiation, and/or chemotherapy and is associated with lasting effects even when successful in irradicating the disease. New molecular targets and therapies must be identified to improve outcomes for HNSCC patients. We recently identified bitter taste receptors (taste family 2 receptors, or T2Rs) as a novel candidate family of receptors that activate apoptosis in HNSCC cells through mitochondrial Ca2+ overload and depolarization. We hypothesized that targeting another component of tumor cell metabolism, namely glycolysis, may increase the efficacy of T2R-directed therapies. GLUT1 (SLC2A1) is a facilitated-diffusion glucose transporter expressed by many cancer cells to fuel their increased rates of glycolysis. GLUT1 is already being investigated as a possible cancer target, but studies in HNSCCs are limited. Examination of immortalized HNSCC cells, patient samples, and The Cancer Genome Atlas revealed high expression of GLUT1 and upregulation in some patient tumor samples. HNSCC cells and tumor tissue express GLUT1 on the plasma membrane and within the cytoplasm (perinuclear, likely co-localized with the Golgi apparatus). We investigated the effects of a recently developed small molecule inhibitor of GLUT1, BAY-876. This compound decreased HNSCC glucose uptake, viability, and metabolism and induced apoptosis. Moreover, BAY-876 had enhanced effects on apoptosis when combined at low concentrations with T2R bitter taste receptor agonists. Notably, BAY-876 also decreased TNFα-induced IL-8 production, indicating an additional mechanism of possible tumor-suppressive effects. Our study demonstrates that targeting GLUT1 via BAY-876 to kill HNSCC cells, particularly in combination with T2R agonists, is a potential novel treatment strategy worth exploring further in future translational studies.
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With cancer immunotherapy and precision medicine dynamically evolving, there is greater need for pre-clinical models that can better replicate the intact tumor and its complex tumor microenvironment (TME). Precision-cut tumor slices (PCTS) have recently emerged as an ex vivo human tumor model, offering the opportunity to study individual patient responses to targeted therapies, including immunotherapies. However, little is known about the physiologic status of PCTS and how culture conditions alter gene expression. In this study, we generated PCTS from head and neck cancers (HNC) and mesothelioma tumors (Meso) and undertook transcriptomic analyses to understand the changes that occur in the timeframe between PCTS generation and up to 72 h (hrs) in culture. Our findings showed major changes occurring during the first 24 h culture period of PCTS, involving genes related to wound healing, extracellular matrix, hypoxia, and IFNγ-dependent pathways in both tumor types, as well as tumor-specific changes. Collectively, our data provides an insight into PCTS physiology, which should be taken into consideration when designing PCTS studies, especially in the context of immunology and immunotherapy.
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Perfilación de la Expresión Génica , Microambiente Tumoral , Humanos , Microambiente Tumoral/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Transcriptoma , Medicina de Precisión/métodos , Inmunoterapia/métodosRESUMEN
OBJECTIVE: To investigate the survival benefit of elective neck dissection (END) over neck observation in surgically resected cT1-4 N0M0 head and neck basaloid carcinoma (HNBC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2006 to 2017 hospital-based National Cancer Database. METHODS: Patients with surgically resected cT1-4 N0M0 HNBC were selected. Linear, binary logistic, Kaplan-Meier, and Cox proportional hazards regression models were implemented. RESULTS: Of 857 patients satisfying inclusion criteria, the majority were male (77.0%) and white (88.1%) with disease of the oral cavity (21.5%) or oropharynx (42.9%) classified as high grade (76.9%) and cT1-2 (72.9%). 389 (45.4%) patients underwent END. END utilization between 2006 and 2017 increased for cT1-2 disease (33.3% vs 56.9%, R2 = .699) but remained relatively constant for cT3-4 disease (66.7% vs 57.9%, R2 = .062). One-hundred and fifteen (29.6%) ENDs detected occult nodal metastases (ONMs). The 5-year overall survival (OS) of patients undergoing neck observation and END was 65.6% and 66.8%, respectively (P = .652). END was not associated with improved OS in survival analyses stratified by patient demographics, clinicopathologic features, and adjuvant therapy. Compared with surgery alone, adjuvant radiotherapy (adjusted hazard ratio: 0.74, 95% confidence interval [CI]: 0.57-0.97, P = .031) was associated with improved OS. END (hazard ratio [HR]: 0.96, 95% CI: 0.71-1.28, P = .770) and ONM (HR: 1.12, 95% CI: 0.78-1.61, P = .551) were not associated with OS. CONCLUSION: END is performed in nearly half of patients with HNBC but is not associated with improved OS, even after stratifying survival analyses by patient demographics, clinicopathologic features, and adjuvant therapy. The rate of ONM approaching 30%, however, justifies inclusion of END in the surgical management of HNBC.
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Procedimientos Quirúrgicos Electivos , Neoplasias de Cabeza y Cuello , Disección del Cuello , Estadificación de Neoplasias , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Neoplasias de Cabeza y Cuello/cirugía , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/mortalidad , Tasa de SupervivenciaRESUMEN
Importance: The utility of preoperative circulating tumor tissue-modified viral human papillomavirus DNA (TTMV-HPV DNA) levels in predicting human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV+ OPSCC) disease burden is unknown. Objective: To determine if preoperative circulating tumor HPV DNA (ctHPVDNA) is associated with disease burden in patients with HPV+ OPSCC who have undergone transoral robotic surgery (TORS). Design, Setting, and Participants: This cross-sectional study comprised patients with HPV+ OPSCC who underwent primary TORS between September 2021 and April 2023 at one tertiary academic institution. Patients with treatment-naive HPV+ OPSCC (p16-positive) and preoperative ctHPVDNA levels were included, and those who underwent neck mass excision before ctHPVDNA collection were excluded. Main Outcomes and Measures: The main outcome was the association of increasing preoperative ctHPVDNA levels with tumor size and lymph node involvement in surgical pathology. The secondary outcome was the association between preoperative ctHPVDNA levels and adverse pathology, which included lymphovascular invasion, perineural invasion, or extranodal extension. Results: A total of 70 patients were included in the study (65 men [93%]; mean [SD] age, 61 [8] years). Baseline ctHPVDNA levels ranged from 0 fragments/milliliter of plasma (frag/mL) to 49â¯452 frag/mL (median [IQR], 272 [30-811] frag/mL). Overall, 58 patients (83%) had positive results for ctHPVDNA, 1 (1.4%) had indeterminate results, and 11 (15.6%) had negative results. The sensitivity of detectable ctHPVDNA for identifying patients with pathology-confirmed HPV+ OPSCC was 84%. Twenty-seven patients (39%) had pathologic tumor (pT) staging of pT0 or pT1, 34 (49%) had pT2 staging, and 9 patients (13%) had pT3 or pT4 staging. No clinically meaningful difference between detectable and undetectable preoperative ctHPVDNA cohorts was found for tumor size or adverse pathology. Although the median preoperative ctHPVDNA appeared to be higher in pT2 through pT4 stages and pN1 or pN2 stages, effect sizes were small (pT stage: η2, 0.002 [95% CI, -1.188 to 0.827]; pN stage: η2, 0.043 [95% CI, -0.188 to 2.600]). Median preoperative log(TTMV-HPV DNA) was higher in active smokers (8.79 [95% CI, 3.55-5.76]), compared with never smokers (5.92 [95% CI, -0.97 to 1.81]) and former smokers (4.99 [95% CI, 0.92-6.23]). Regression analysis did not show an association between tumor dimension or metastatic lymph node deposit size and preoperative log(TTMV-HPV DNA). After univariate analysis, no association was found between higher log(TTMV-HPV DNA) levels and adverse pathology. Conclusions and Relevance: In this cross-sectional study, preoperative ctHPVDNA levels were not associated with disease burden in patients with HPV+ OPSCC who underwent TORS.
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ADN Viral , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Masculino , Femenino , Estudios Transversales , Neoplasias Orofaríngeas/virología , Neoplasias Orofaríngeas/cirugía , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/sangre , Persona de Mediana Edad , ADN Viral/análisis , ADN Viral/sangre , Infecciones por Papillomavirus/virología , Infecciones por Papillomavirus/sangre , Infecciones por Papillomavirus/complicaciones , Anciano , Procedimientos Quirúrgicos Robotizados , ADN Tumoral Circulante/sangre , Periodo Preoperatorio , Carcinoma de Células Escamosas de Cabeza y Cuello/virología , Carcinoma de Células Escamosas de Cabeza y Cuello/sangre , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carga Tumoral , Papillomaviridae/genéticaRESUMEN
BACKGROUND: Transoral robotic surgery (TORS) for oropharyngeal malignancy optimizes oncologic outcomes while preserving functionality. This study identifies patterns of functional recovery after TORS with free flap reconstruction (FFR). METHODS: Retrospective cohort study at a tertiary care center of patients with primary oropharyngeal tumors treated with TORS with FFR between 2010 and 2022. Patients were categorized into: adjuvant chemoradiation or radiation, or no adjuvant therapy (NAT). Functional outcomes were measured by functional oral intake scale (FOIS). RESULTS: 241 patients were included. FOIS declined at first postoperative appointment (median = 7.0 to 2.0, IQR = [7.0, 7.0], [2.0, 4.0]), and progressively improved to 6.0 (5.0, 6.0) after 1 year, with NAT having the highest FOIS (7.0, p < 0.05). Predictors of poor long-term FOIS included RT and hypoglossal nerve (CN XII) involvement (p < 0.05). CONCLUSIONS: TORS with FFR leads to good long-term function with minimal intake restrictions. Radiation therapy and CN XII involvement increase risk of worse functional outcomes.
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Colgajos Tisulares Libres , Neoplasias Orofaríngeas , Procedimientos de Cirugía Plástica , Procedimientos Quirúrgicos Robotizados , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Neoplasias Orofaríngeas/cirugía , Neoplasias Orofaríngeas/patología , Anciano , Procedimientos de Cirugía Plástica/métodos , Estudios de Cohortes , Resultado del Tratamiento , Recuperación de la Función , AdultoRESUMEN
Iatrogenic tracheoesophageal fistulae management and repair are difficult to manage with few resourced describing management and repair. Two cases are presented describing the approach to and repair of a tracheoesophagea fistula; one with a free flap and one with local flap reconstruction. Both cases utilized allograft material to maintain separation between the alimentary and repiratory tracts. Laryngoscope, 134:3761-3764, 2024.
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Colgajos Quirúrgicos , Fístula Traqueoesofágica , Humanos , Fístula Traqueoesofágica/cirugía , Masculino , Colgajos Quirúrgicos/trasplante , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Anciano , Enfermedad Iatrogénica , FemeninoRESUMEN
OBJECTIVE: To compare surgical and nonsurgical definitive treatment in cT4b major salivary gland cancer (MSGC). STUDY DESIGN: Retrospective cohort study. SETTING: The 2004 to 2019 National Cancer Database. METHODS: The NCDB was queried for patients with cT4b MSGC (N = 976). Patients undergoing definitive treatment with (1) surgical resection + adjuvant therapy, (2) radiotherapy (RT) alone, or (3) chemoradiotherapy (CRT) were included in Kaplan-Meier and Cox survival analyses. RESULTS: Of 219 patients undergoing definitive treatment, 148 (67.6%) underwent surgical resection + adjuvant therapy and 71 (32.4%) underwent RT or CRT. There were no documented mortalities within 90 days of surgical resection. Tumor diameter and nodal metastasis were associated with decreased odds of undergoing definitive treatment (P < 0.025). Patients with positive surgical margins (PSM) had higher 5-year overall survival (OS) than those undergoing definitive RT or CRT (48.5% vs 30.1%, P = 0.018) and similar 5-year OS as those with negative margins (48.5% vs 54.0%, P = 0.205). Surgical resection + adjuvant therapy (adjusted hazard ratio: 0.55, 95% confidence interval [CI]: 0.37-0.84) was associated with higher OS than definitive RT or CRT (P < 0.025). A separate cohort of 961 patients with cT4a tumors undergoing surgical resection + adjuvant therapy was created; cT4a and cT4b (hazard ratio: 1.02, 95% CI: 0.80-1.29, P = 0.896) tumors had similar OS. CONCLUSION: A minority of patients with cT4b MSGC undergo definitive treatment. Surgical resection + adjuvant therapy was safe and associated with higher OS than definitive RT or CRT, despite high rate of PSM. In the absence of clinical trial data, appropriately selected patients with cT4b MSGC may benefit from surgical resection.
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Neoplasias de las Glándulas Salivales , Humanos , Masculino , Femenino , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/mortalidad , Neoplasias de las Glándulas Salivales/patología , Neoplasias de las Glándulas Salivales/cirugía , Neoplasias de las Glándulas Salivales/terapia , Persona de Mediana Edad , Anciano , Estadificación de Neoplasias , Tasa de Supervivencia , Márgenes de Escisión , Quimioradioterapia , Estimación de Kaplan-Meier , AdultoRESUMEN
OBJECTIVE: Undergoing surgery and adjuvant radiotherapy (aRT) at the same facility has been associated with higher overall survival (OS) in head and neck squamous cell carcinoma. Our study investigates whether undergoing surgery and aRT at the same academic facility is associated with higher OS in major salivary gland cancer (MSGC). METHODS: The 2006-2018 National Cancer Database was queried for patients with MSGC undergoing surgery at an academic facility and then aRT. Multivariable binary logistic and Cox proportional hazards regression models were implemented. RESULTS: Of 2801 patients satisfying inclusion criteria, 2130 (76.0%) underwent surgery and aRT at the same academic facility. Residence in a less populated area (adjusted odds ratio [aOR] 1.69, 95% confidence interval [CI] 1.16-2.45), treatment without adjuvant chemotherapy (aOR 1.97, 95% CI 1.41-2.76), and aRT duration (aOR 1.02, 95% CI 1.01-1.04) were associated with undergoing surgery and aRT at different facilities on multivariable logistic regression adjusting for patient demographics, clinicopathologic features, and adjuvant therapy (p < 0.01). Five-year OS was higher in patients undergoing surgery and aRT at the same academic facility (68.8% vs. 61.9%, p < 0.001). Undergoing surgery and aRT at different facilities remained associated with worse OS on multivariable Cox regression (aHR 1.41, 95% CI 1.10-1.81, p = 0.007). CONCLUSION: Undergoing surgery and aRT at the same academic facility is associated with higher OS in MSGC. Although undergoing surgery and aRT at the same academic facility is impractical for all patients, academic physicians should consider same-facility treatment for complex patients who would most benefit from clear multidisciplinary communication. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:3620-3632, 2024.
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Neoplasias de las Glándulas Salivales , Humanos , Neoplasias de las Glándulas Salivales/radioterapia , Neoplasias de las Glándulas Salivales/mortalidad , Neoplasias de las Glándulas Salivales/cirugía , Neoplasias de las Glándulas Salivales/patología , Masculino , Femenino , Radioterapia Adyuvante/estadística & datos numéricos , Persona de Mediana Edad , Anciano , Estudios Retrospectivos , Adulto , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: To develop machine learning (ML) models predicting unplanned readmission and reoperation among patients undergoing free flap reconstruction for head and neck (HN) surgery. METHODS: Data were extracted from the 2012-2019 NSQIP database. eXtreme Gradient Boosting (XGBoost) was used to develop ML models predicting 30-day readmission and reoperation based on demographic and perioperative factors. Models were validated using 2019 data and evaluated. RESULTS: Four-hundred and sixty-six (10.7%) of 4333 included patients were readmitted within 30 days of initial surgery. The ML model demonstrated 82% accuracy, 63% sensitivity, 85% specificity, and AUC of 0.78. Nine-hundred and four (18.3%) of 4931 patients underwent reoperation within 30 days of index surgery. The ML model demonstrated 62% accuracy, 51% sensitivity, 64% specificity, and AUC of 0.58. CONCLUSION: XGBoost was used to predict 30-day readmission and reoperation for HN free flap patients. Findings may be used to assist clinicians and patients in shared decision-making and improve data collection in future database iterations.
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Colgajos Tisulares Libres , Neoplasias de Cabeza y Cuello , Aprendizaje Automático , Readmisión del Paciente , Procedimientos de Cirugía Plástica , Reoperación , Humanos , Readmisión del Paciente/estadística & datos numéricos , Masculino , Femenino , Reoperación/estadística & datos numéricos , Persona de Mediana Edad , Neoplasias de Cabeza y Cuello/cirugía , Anciano , Procedimientos de Cirugía Plástica/métodos , Bases de Datos Factuales , Complicaciones Posoperatorias/epidemiología , Adulto , Estudios RetrospectivosRESUMEN
OBJECTIVES: Determine if intensive local therapy (i.e., local surgery or radiation) has a survival benefit for patients presenting with distantly metastatic oropharyngeal squamous cell carcinoma (OPSCC). METHODS: Retrospective population-based cohort study of patients in the National Cancer Database presenting with distantly metastatic OPSCC. Overall survival (OS) was compared for patients receiving systemic therapy alone or in combination with local surgery or curative dose radiation, controlling for various clinicodemographic factors. RESULTS: Between 2010 and 2015, 627 patients presented with newly diagnosed, metastatic OPSCC and an initial treatment course including systemic chemotherapy. Multivariable analysis demonstrated that local radiation therapy was independently associated with improved OS (OR 0.64, CI [0.51-0.81]); local surgery was not independently associated with improved OS (OR 0.99, CI [0.65-1.53]). Higher T stages were associated with worse OS (OR 1.69, CI [1.14-2.50] for T3 and OR 1.77, CI [1.22-2.58] for T4 compared to T1). HPV-positive (HPV+) tumors were associated with improved OS compared to HPV- (OR 0.79, CI [0.64-0.97]). Multiagent chemotherapy was associated with improved OS compared to single-agent (OR 0.78, CI [0.62-1.00]). The best survival for the entire cohort and for HPV+ patients was for radiation with systemic therapy and the worst survival for systemic therapy alone. CONCLUSIONS: Curative dose local radiotherapy in addition to systemic therapy is associated with improved OS compared to systemic therapy alone in patients presenting with distantly metastatic OPSCC. There is not a significant survival benefit for local surgery in addition to systemic therapy in this patient population, regardless of HPV status. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:2243-2251, 2024.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/cirugía , Carcinoma de Células Escamosas de Cabeza y Cuello/complicaciones , Carcinoma de Células Escamosas/cirugía , Neoplasias Orofaríngeas/cirugía , Neoplasias Orofaríngeas/patología , Infecciones por Papillomavirus/complicaciones , Estudios Retrospectivos , Estudios de Cohortes , Neoplasias de Cabeza y Cuello/complicaciones , PronósticoRESUMEN
There is limited guidance on exploiting the genome-wide loss-of-function CRISPR screens in cancer Dependency Map (DepMap) to identify new targets for individual cancer types. This study integrated multiple tools to filter these data in order to seek new therapeutic targets specific to head and neck squamous cell carcinoma (HNSCC). The resulting pipeline prioritized 143 targetable dependencies that represented both well-studied targets and emerging target classes like mitochondrial carriers and RNA-binding proteins. In total, 14 targets had clinical inhibitors used for other cancers or nonmalignant diseases that hold near-term potential to repurpose for HNSCC therapy. Comparing inhibitor response data that were publicly available for 13 prioritized targets between the cell lines with high vs. low dependency on each target uncovered novel therapeutic potential for the PAK2 serine/threonine kinase. PAK2 gene dependency was found to be associated with wild-type p53, low PAK2 mRNA, and diploid status of the 3q amplicon containing PAK2. These findings establish a generalizable pipeline to prioritize clinically relevant targets for individual cancer types using DepMap. Its application to HNSCC highlights novel relevance for PAK2 inhibition and identifies biomarkers of PAK2 inhibitor response.
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Neoplasias de Cabeza y Cuello , Proteínas Serina-Treonina Quinasas , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Línea Celular Tumoral , Quinasas p21 Activadas/genéticaRESUMEN
INTRODUCTION: Management of the neck in oral cavity squamous cell carcinoma (OCSCC) is essential to oncologic control and survival. The rates of lymph node metastasis (LNM) vary based on oral cavity tumor site and stage and influence treatment decisions. The aim of this paper was to describe clinical LNM for different tumor subsites and stages of surgically managed OCSCC. METHODS: We conducted a retrospective analysis of 25,846 surgically managed OCSCC patients from the National Cancer Database (NCDB) stratified by tumor subsite and clinical T-stage. For cN + patients, rates of pathologic LNM and absence of pathologic LNM were determined. For cN0 patients, outcomes included the rates of elective neck dissection (END) and occult LNM and predictors of occult LNM determined by a multivariable logistic regression model. RESULTS: A total of 25,846 patients (59.1% male, mean age 61.9 years) met inclusion criteria with primary tumor sites including oral tongue (50.8%), floor of mouth (21.2%), lower alveolus (7.6%), buccal mucosa (6.7%), retromolar area (4.9%), upper alveolus (3.6%), hard palate (2.7%), and mucosal lip (2.5%). Among all sites, clinical N+ rates increased with T-stage (8.9% T1, 28.0% T2, 51.6% T3, 52.5% T4); these trends were preserved across subsites. Among patients with cN + disease, the overall rate of concordant positive pathologic LNM was 80.1% and the rate of discordant negative pathologic LNM was 19.6%, which varied based on tumor site and stage. In the overall cohort of cN0 patients, 59.9% received END, and the percentage of patients receiving END increased with higher tumor stage. Occult LNM among those cN0 was found in 25.1% of END cases, with the highest rates in retromolar (28.8%) and oral tongue (27.5%) tumors. Multivariable regression demonstrated significantly increased rates of occult LNM for higher T stage (T2 OR: 2.1 [1.9-2.4]; T3 OR: 3.0 [2.5-3.7]; T4 OR: 2.7 [2.2-3.2]), positive margins (OR: 1.4 [1.2-1.7]), and positive lymphovascular invasion (OR: 5.1 [4.4-5.8]). CONCLUSIONS: Management of the neck in OCSCC should be tailored based on primary tumor factors and considered for early-stage tumors.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Humanos , Masculino , Persona de Mediana Edad , Femenino , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estudios Retrospectivos , Estadificación de Neoplasias , Neoplasias de la Boca/patología , Carcinoma de Células Escamosas/patología , Disección del Cuello , Metástasis Linfática , Neoplasias de Cabeza y Cuello/patologíaRESUMEN
Importance: A core component of delivering care of head and neck diseases is an adequate workforce. The World Health Organization report, Multi-Country Assessment of National Capacity to Provide Hearing Care, captured primary workforce estimates from 68 member states in 2012, noting that response rates were a limitation and that updated more comprehensive data are needed. Objective: To establish comprehensive workforce metrics for global otolaryngology-head and neck surgery (OHNS) with updated data from more countries/territories. Design, Setting, and Participants: A cross-sectional electronic survey characterizing the OHNS workforce was disseminated from February 10 to June 22, 2022, to professional society leaders, medical licensing boards, public health officials, and practicing OHNS clinicians. Main Outcome: The OHNS workforce per capita, stratified by income and region. Results: Responses were collected from 121 of 195 countries/territories (62%). Survey responses specifically reported on OHNS workforce from 114 countries/territories representing 84% of the world's population. The global OHNS clinician density was 2.19 (range, 0-61.7) OHNS clinicians per 100â¯000 population. The OHNS clinician density varied by World Bank income group with higher-income countries associated with a higher density of clinicians. Regionally, Europe had the highest clinician density (5.70 clinicians per 100â¯000 population) whereas Africa (0.18 clinicians per 100â¯000 population) and Southeast Asia (1.12 clinicians per 100â¯000 population) had the lowest. The OHNS clinicians deliver most of the surgical management of ear diseases and hearing care, rhinologic and sinus diseases, laryngeal disorders, and upper aerodigestive mucosal cancer globally. Conclusion and Relevance: This cross-sectional survey study provides a comprehensive assessment of the global OHNS workforce. These results can guide focused investment in training and policy development to address disparities in the availability of OHNS clinicians.
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Otolaringología , Humanos , Estudios Transversales , Recursos Humanos , Otolaringología/educación , Encuestas y Cuestionarios , Cabeza , Salud GlobalRESUMEN
BACKGROUND: Management of the neck in laryngeal squamous cell carcinoma (LSCC) is essential to oncologic control and survival. We aim to describe patterns and rates of clinical/pathologic lymph node disease, elective neck dissection (END), and occult lymph node metastasis (LNM) in patients with surgically-managed LSCC. METHODS: Retrospective cohort study of patients in the National Cancer Database (NCDB) diagnosed with LSCC between January 2004 and December 2016 who underwent primary surgery. RESULTS: Seven thousand eight hundred and seventy-six patients met inclusion criteria. For cN0 patients, the rates of END and occult LNM both increased with tumor stage and were highest for supraglottic tumors. Predictors of occult LNM included supraglottic site, pathologic T3 and T4 stage, positive margins, and presence of lymphovascular invasion (p < 0.05). CONCLUSIONS: The propensity for cervical LNM in surgically-managed LSCC varies based on primary tumor site and stage, and a variety of disease factors increase risk of occult LNM.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias Laríngeas , Humanos , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Estudios Retrospectivos , Carcinoma de Células Escamosas/patología , Estadificación de Neoplasias , Disección del Cuello , Neoplasias Laríngeas/cirugía , Neoplasias Laríngeas/patología , Metástasis Linfática , Neoplasias de Cabeza y Cuello/patologíaRESUMEN
Objective: Although standard of care for primary nasopharyngeal carcinoma (NPC) is chemoradiotherapy, there remains no consensus on management of recurrent or metastatic disease. We characterized recent clinical trials on NPC to assess trends in NPC treatment and establish promising areas for future research. Study Design: Retrospective database study. Setting: ClinicalTrials.gov database. Methods: Retrospective review of all NPC trials from November 1999 to June 2021. For each study, the following variables were extracted: study characteristics, intervention, outcome measures, and inclusion criteria. Secondary searches via PubMed and Google scholar determined trial publication status. Results: A total of 448 clinical trials were identified: 72 (16%) observational and 376 (84%) interventional, of which there were 30 (8%) Phase I, 183 (49%) Phase II, 86 Phase III (23%), and 5 (1%) Phase IV trials. Fifty-four percent of trials included only primary NPC while 111 (25%) exclusively studied recurrent cancers. The most common interventions were cisplatin (n = 64) and intensity modulated radiation therapy (n = 54); there were 38 trials involving PD-1 monoclonal antibodies. Thirty-four studies examined quality of life measures, including xerostomia and mucositis. Of the completed studies, 53.2% have published manuscripts. Poor patient accrual was the most common reason for premature study termination. Conclusions: Novel immunotherapies have been increasingly incorporated into NPC studies in recent years, however, chemotherapy and radiation, despite their numerous side effects, are still widely used due to their clinical effectiveness. Future trials are warranted to determine the optimal therapeutic regimens to decrease relapse rates and side effects.
RESUMEN
OBJECTIVES: To describe swallowing and feeding-tube outcomes in patients with high-risk oropharyngeal cancer treated with trimodality therapy (TMT), including transoral robotic surgery (TORS) and adjuvant chemoradiotherapy. METHODS: A chart review was conducted on patients with HPV+ OPSCC receiving TMT with TORS at an academic medical center from March 2010 to March 2021. Data collected included demographics, treatment, feeding tube placement, functional oral intake scale (FOIS) scores, and swallowing-language pathology (SLP) evaluations. RESULTS: A total of 255 patients met selection criteria (mean age 61 years, 88% male). Following intraoperative nasogastric tube (NG) placement, 31% remained NG tube dependent after 3 weeks. A gastrostomy tube was placed in 19% of patients, and at 1 year after end-of-treatment (EOT), 3.5% overall remained tube-dependent. Mean FOIS scores were 6.9 (SD = 0.3) at pre-operative visit, 2.6 (1.8) at first post-operative visit, and 5.5 (1.5) after EOT. In the subset of patients with follow-up longer than 2 years (n = 118), the mean FOIS was 6.1 (SD = 1.3) at most recent visit. Clinical signs of aspiration/penetration were suspected on SLP evaluation in 18% of patients. These patients were subsequently evaluated with fiberoptic endoscopic evaluation of swallowing (FEES) and/or barium swallow study, which confirmed signs of aspiration in 2.7% of patients overall. Delayed NG tube removal after 3 weeks was predictive of (1) gastrostomy tube requirement and (2) clinical signs of aspiration on an SLP visit after EOT. CONCLUSIONS: Favorable functional and feeding-tube outcomes are demonstrated in patients with HPV-associated OPSCC undergoing TMT. In this single-institution study, we found low rates of long-term feeding tube dependence and high median FOIS following treatment. Review of routine SLP visits provides a detailed and easily accessible means for assessing swallowing function in this cohort. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:3013-3020, 2023.