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Loss or absence of hearing is common at both extremes of human lifespan, in the forms of congenital deafness and age-related hearing loss. While these are often studied separately, there is increasing evidence that their genetic basis is at least partially overlapping. In particular, both common and rare variants in genes associated with monogenic forms of hearing loss also contribute to the more polygenic basis of age-related hearing loss. Here, we directly test this model in the Penn Medicine BioBank-a healthcare system cohort of around 40,000 individuals with linked genetic and electronic health record data. We show that increased burden of predicted deleterious variants in Mendelian hearing loss genes is associated with increased risk and severity of adult-onset hearing loss. As a specific example, we identify one gene-TCOF1, responsible for a syndromic form of congenital hearing loss-in which deleterious variants are also associated with adult-onset hearing loss. We also identify four additional novel candidate genes (COL5A1, HMMR, RAPGEF3, and NNT) in which rare variant burden may be associated with hearing loss. Our results confirm that rare variants in Mendelian hearing loss genes contribute to polygenic risk of hearing loss, and emphasize the utility of healthcare system cohorts to study common complex traits and diseases.
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Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Humanos , Adulto , Surdez/genética , Perda Auditiva/genética , Perda Auditiva Neurossensorial/genética , Herança Multifatorial , Audição , MutaçãoRESUMO
Tinnitus is a common complaint that approximately three-fourths of adults will experience at some point in their life. While for many it is a mild nuisance, for some it can be debilitating, affecting cognition and quality of life, increasing stress, and leading to anxiety, depression, and in severe circumstances even suicide. Pulsatile tinnitus refers to the perception of a heartbeat-like sound without external stimulus. Although less common than nonpulsatile tinnitus, pulsatile tinnitus raises concern for underlying disease that can have a high risk of causing the patient harm if undiagnosed, and most of these patients will have positive findings at imaging. While these findings are often subtle, identifying them can have a meaningful impact on the patient's quality of life. The literature on pulsatile tinnitus is changing rapidly with improved imaging techniques and novel minimally invasive treatment options. A careful history and physical examination together with appropriate imaging are therefore critical in identifying the underlying cause. With emerging surgical, endovascular, and supportive technologies, the vast majority of patients with bothersome pulsatile tinnitus can be cured or have their symptoms ameliorated. The objective of this narrative review is to present a comprehensive analysis of the currently available literature on pulsatile tinnitus, with a focus on understanding its pathophysiologic mechanisms, diagnostic pathways, imaging findings, and the spectrum of available management strategies and ultimately to propose a structured framework that aids radiologists as well as clinicians in identifying an underlying diagnosis and guiding management of these patients. ©RSNA, 2024 Supplemental material is available for this article.
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Zumbido , Zumbido/diagnóstico por imagem , Humanos , Diagnóstico DiferencialRESUMO
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 Cabeça e Pescoço , Neoplasias Bucais , Humanos , Masculino , Pessoa de Meia-Idade , Feminino , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Estudos Retrospectivos , Estadiamento de Neoplasias , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Esvaziamento Cervical , Metástase Linfática , Neoplasias de Cabeça e Pescoço/patologiaRESUMO
PURPOSE: Comparison of audiometric measurements of commercially available smartphone audiogram application thresholds as compared to gold standard audiometric evaluation. MATERIALS AND METHODS: A single-institution, original contribution. Ninety consecutive adult patients presenting to a tertiary care auditory clinic with auditory complaints were evaluated using standard audiometric testing and an application-based hearing test. Correlation between app results and standard audiogram for air conduction pure tone thresholds was evaluated. RESULTS: Mimi™ (Berlin, Germany) results for audiometric thresholds were moderately correlated with standard audiogram (r = 0.51-0.68) depending on severity. The percentage of patients whose hearing loss severity on formal audiometry results were accurately reflected in the Mimi™ (app-based hearing test: ABHT)1 results ranged from 18.2 to 80 %. Among patients whose results were at the extremes of hearing performance, app and standard audiogram results were similar. ABHT yielded an overall sensitivity of 35.5 % and specificity of 97.1 % for normal hearing, and an overall sensitivity of 80 % and specificity of 96 % for severe hearing loss. CONCLUSIONS: Results from an audiometric smart phone application showed accurate categorization of hearing loss at the high and extremes as compared to standard audiometry. However, correlation of pure tone values was more variable and dependent on hearing level.
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Surdez , Perda Auditiva , Aplicativos Móveis , Adulto , Audiometria , Audiometria de Tons Puros/métodos , Limiar Auditivo , Perda Auditiva/diagnóstico , Humanos , Smartphone , TropanosRESUMO
PURPOSE: To evaluate the role of elective neck dissection (END) and of adjuvant radiation (aRT) in polymorphous adenocarcinoma (PAC), previously known as polymorphous low-grade adenocarcinoma (PLGA). METHODS: Retrospective cohort study of patients in the National Cancer Database with a histology of PAC (coded as PLGA) at a head and neck site diagnosed between 2004 and 2015. Multivariable Cox proportional hazard modeling was used to assess overall survival in the overall population, and in sub-analyses of clinically N0 disease, positive resection margins, and late stage disease. RESULTS: A total of 922 patients [66.8% female; mean (SD) age, 60.9 (13.9) years] met inclusion criteria. 74.7% of patients received surgery alone, and 18.0% received surgery and aRT. Only 7.6% of patients with clinically N0 disease received an END, with 10.6% of these having at least one positive node. END did not have a survival benefit compared to no END [HR 1.28 (0.61-2.68)]. Compared to surgery alone, aRT did not have significantly increased survival in the overall population or in late stage [HR 0.68 (0.39-1.19) and HR 0.46 (0.18-1.22), respectively]. On sub-analysis of patients with positive resection margins, aRT had a significant survival benefit compared to surgery alone [HR 0.37 (0.14-0.99)]. CONCLUSION: PAC is a rare, slow-growing malignant tumor typically treated with surgical excision, with undefined indications for END or aRT. Our findings show END to not have a benefit to overall survival. In patients with positive resection margins, there was a survival benefit for aRT.
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Adenocarcinoma , Esvaziamento Cervical , Adenocarcinoma/patologia , Adenocarcinoma/radioterapia , Adenocarcinoma/cirurgia , Procedimentos Cirúrgicos Eletivos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Radioterapia Adjuvante , Estudos RetrospectivosRESUMO
BACKGROUND: Given the rarity of parotid cancer, there is relatively few data published regarding outcomes. Utilizing the large sample population of the National Cancer Database (NCDB), we aim to examine the relationship between two key social determinants of health, demographics and socioeconomic status (SES), and parotid malignancy survival rates. METHODS: Our analytic sample consists of patients with a diagnosis of primary malignancy of the parotid gland between 2004 and 2012 in the NCDB. We used univariable and multivariable Cox proportional hazard models to evaluate the relationship between overall survival rate and two key social determinants of health: demographics and SES. RESULTS: 15,815 cases met inclusion criteria. Average age was 60.1â¯years and 8255 were male (52.2%). Median overall survival was 121â¯months with 5-year overall survival of 67.4%. Male sex and older age at diagnosis were associated with poorer overall survival (pâ¯<â¯0.0001). We found that Asian Americans compared to whites had better overall survival (HR 0.75; 95% CI [0.58-0.95]). Black patients had improved survival compared to whites on univariate (HR 0.71; 95% CI [0.64-0.79]); but not multivariate analysis. Hispanic ethnicity and higher education level were protective (HR 0.76 95% CI [0.63-0.91] and HR 0.84 95% CI [0.74-0.96], respectively). We found no significant survival association based on income level. CONCLUSION: In this national sample of patients with parotid malignancy, a rare form of cancer, we found a significant correlation between important social determinants of health and overall survival rate. Females, Asian-Americans, Hispanics, and patients with higher education level have better overall survival.
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Neoplasias Parotídeas/mortalidade , Determinantes Sociais da Saúde , Sobrevivência , Demografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Classe Social , Estados UnidosRESUMO
OBJECTIVE: In the setting of current national healthcare reform, it becomes especially relevant to understand the current state of healthcare disparities with regards to insurance status. To determine the impact of payer status on survival in parotid malignancy, we utilized the National Cancer Database (NCDB). STUDY DESIGN: Retrospective database review. SETTING: National Cancer Database (2004-2012). SUBJECTS AND METHODS: The NCDB was queried for cases of primary malignancy of the parotid gland between 2004 and 2012. The impact of payer status on overall survival was evaluated, as well as the relationship of insurance status with patient and tumor variables. RESULTS: 15,815 cases met inclusion criteria. A majority had private insurance (47.8%), followed by Medicare (40.9%), Medicaid (5.0%), uninsured (3.2%) and other government sources (1.3%). Medicare patients had the lowest 5 and 10-year survival rates (50.7% (95% CI [49.3-52.1]) and 27.8% (95% CI [25.0-30.9]), respectively). On multivariable analysis, uninsured, Medicare, and Medicaid patients had worse overall survival than the privately insured (HR 1.42, 95% CI [1.17-1.74]; HR 1.29, 95% CI [1.17-1.42]; HR 1.36, 95% CI [1.13-1.62], respectively). Uninsured and Medicaid patients were more likely than the privately insured to present with advanced stage disease, nodal metastasis and longer times to treatment following diagnosis. CONCLUSION: In parotid malignancy, uninsured, Medicaid, and Medicare patients have worse survival outcomes compared to those with private insurance. Uninsured and Medicaid patients also present with more advanced stage disease and have increased wait times before definitive treatment is initiated.
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Disparidades em Assistência à Saúde , Cobertura do Seguro/estatística & dados numéricos , Neoplasias Parotídeas/mortalidade , Adulto , Idoso , Bases de Dados como Assunto , Feminino , Humanos , Masculino , Medicaid/estatística & dados numéricos , Pessoas sem Cobertura de Seguro de Saúde/estatística & dados numéricos , Medicare/estatística & dados numéricos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Parotídeas/patologia , Estudos Retrospectivos , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
BACKGROUND/AIMS: To review the existing literature on pigmented villonodular synovitis (PVNS) of the temporomandibular joint (TMJ) and report a rare case of PVNS of the TMJ presenting with unilateral hearing loss. METHODS: Review of the existing literature and a description of personal experience with PVNS of the TMJ presenting with unilateral hearing loss. RESULTS: Review of the existing literature revealed 76 reported cases of PVNS of the TMJ. The most common presenting symptom was of a slowly enlarging mass or swelling of the preauricular area, with dysfunctional TMJ also frequently reported. All patients underwent surgical excision with some pursuing radiation as adjuvant therapy. Presented Patient: A 46-year-old man presented with several months of unilateral subjective hearing loss and aural fullness. Imaging revealed a mass centered along the superior TMJ with expansion through the squamous temporal bone and extra-axial intracranial extension into the middle cranial fossa. Imaging characteristics and fine-needle aspiration biopsy were consistent with PVNS. INTERVENTION: The patient underwent near-total excision of the mass via frontotemporal craniectomy and lateral temporal bone resection. FOLLOW-UP: At the 16-month follow-up there was no evidence of disease recurrence. CONCLUSION: PVNS of the TMJ represents a rare entity that can present with a variety of symptoms including unilateral hearing loss.
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Perda Auditiva Unilateral/etiologia , Sinovite Pigmentada Vilonodular/complicações , Articulação Temporomandibular/diagnóstico por imagem , Audiometria , Biópsia por Agulha Fina , Terapia Combinada , Diagnóstico Diferencial , Audição/fisiologia , Perda Auditiva Unilateral/diagnóstico , Perda Auditiva Unilateral/fisiopatologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Sinovite Pigmentada Vilonodular/diagnóstico , Sinovite Pigmentada Vilonodular/terapia , Tomografia Computadorizada por Raios XRESUMO
The development of inner ear gene carriers and delivery systems has enabled genetic defects to be repaired and hearing to be restored in mouse models. Today, promising advances in translational therapies provide confidence that targeted molecular therapy for inner ear diseases will be developed. Unfortunately, the currently available non-invasive modalities, such as Computerized Tomography scan or Magnetic Resonance Imaging provide insufficient resolution to identify most pathologies of the human inner ear, even when the current generation of contrast agents is utilized. The development of targeted contrast agents may play a critical role in determining the cause of, and treatment for, sensorineural hearing loss. Such agents should be able to pass through the cochlea barriers, possess minimal cytotoxicity, and easily conjugate to a targeting agent, without distorting the anatomic details. This review focuses on a series of contrast agents which may fit these criteria for potential clinical application.
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Orelha Interna/patologia , Perda Auditiva Neurossensorial/fisiopatologia , Imagem Molecular/métodos , Animais , Meios de Contraste/metabolismo , Orelha Interna/diagnóstico por imagem , Orelha Interna/metabolismo , HumanosRESUMO
BACKGROUND/AIMS: Cribriform adenocarcinoma of the tongue and minor salivary gland (CATMSG) is a rare, locally invasive, and poorly recognized tumor, typically occurring on the base of the tongue. This case report describes the previously unreported use of transoral robotic surgery (TORS) for the local resection of CATMSG in a novel location, the palatine tonsil, and leverages follow-up information to compare TORS to conventional surgical approaches. METHODS: We performed transoral radical tonsillectomy, limited pharyngectomy, and base-of-tongue resection with staged left selective neck dissection. RESULTS: Tumor pathology revealed an infiltrating salivary gland carcinoma with perineural invasion and a histologically similar adenocarcinoma in 1 of 64 left neck lymph nodes. TORS was performed with no perioperative complications, and the patient was subsequently discharge on postoperative day 3 with a Dobhoff tube. Postoperatively, the Dobhoff tube was removed at 1 month, the patient was advanced to soft foods by mouth at 2 months, and 3-month positron emission tomography-computed tomography scan showed no evidence of distant metastases and evolving postsurgical changes in the left tonsillectomy bed. CONCLUSIONS: This case report highlights the use of TORS resection with minimal acute and long-term morbidity compared to conventional approaches for the resection of this rare, locally invasive salivary gland carcinoma in the palatine tonsil.
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Adenocarcinoma/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias das Glândulas Salivares/cirurgia , Neoplasias da Língua/cirurgia , Carcinoma de Células Escamosas , Feminino , Neoplasias de Cabeça e Pescoço , Humanos , Pessoa de Meia-Idade , Esvaziamento Cervical , Faringectomia , Tomografia por Emissão de Pósitrons , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Tomografia Computadorizada por Raios X , Língua/patologia , Neoplasias da Língua/patologia , TonsilectomiaRESUMO
This article represents the first reported case in the external auditory canal of epithelioid fibrous histiocytoma (EFH), a rare benign cutaneous epithelioid neoplasm. Immunostaining revealed uncommon negative staining for anaplastic lymphoma kinase (ALK) expression. This case and literature review outline the diagnostic strategy for this highly unusual neoplasm. Laryngoscope, 134:3371-3373, 2024.
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Quinase do Linfoma Anaplásico , Meato Acústico Externo , Neoplasias da Orelha , Histiocitoma Fibroso Benigno , Humanos , Quinase do Linfoma Anaplásico/genética , Quinase do Linfoma Anaplásico/metabolismo , Meato Acústico Externo/patologia , Neoplasias da Orelha/patologia , Neoplasias da Orelha/cirurgia , Neoplasias da Orelha/diagnóstico , Histiocitoma Fibroso Benigno/patologia , Histiocitoma Fibroso Benigno/diagnóstico , Histiocitoma Fibroso Benigno/cirurgiaRESUMO
Subtotal petrosectomy plays a critical role in the management of late-stage cholesteatoma. This procedure is indicated either for recurrent cholesteatoma that has failed prior surgical therapies or when life-threatening infectious complications are present. By exenterating all diseased areas of the temporal bone and closing off the ear canal, subtotal petrosectomy has a much greater chance of removing cholesteatoma and preventing recidivism.
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OBJECTIVE: To design and validate a disease-specific quality of life instrument for Meniere's disease. METHODS: We used a sequential process of expert input, patient focus groups, and analyses of responses to draft questionnaires to create a 24-item Meniere's disease quality of life (MenQOL) instrument. The MenQOL and the SF-36v2 were administered to a cohort of 50 patients with Meniere's disease and 60 comparison patients with tinnitus, vertigo, or hearing loss from other causes identified at a tertiary academic center. We performed exploratory factor analysis, Cronbach's α, between group comparisons of total MenQOL scores, and regression analyses between the MenQOL and SF-36v2 to evaluate the instrument's factor structure, internal consistency, face validity, and external validity. Segregation of the instrument into domains was assessed by exploratory factor analysis. RESULTS: Exploratory factor analysis revealed that the MenQOL has a single domain. Cronbach's α = 0.914 indicated high internal consistency for the instrument as a whole. Mean MenQOL scores showing significantly worse quality of life among patients with Meniere's disease than comparison participants (52.5 ± 15.8 vs. 43.2 ± 12.6; p = 0.0051), indicating good construct validity. Significant inverse relationships in bivariate linear regressions between total MenQOL scores and SF-36v2 physical (slope = -0.94, p < 0.0001) and mental (slope = -1.16, p < 0.0001) composite scores showed acceptable concurrent validity. CONCLUSIONS: We have described the initial development of the MenQOL, a simple, valid patient-reported outcome measure that, subject to further study, may be used to assess the effects of treatment on disease-specific quality of life in patients with Meniere's disease. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:4351-4357, 2024.
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Doença de Meniere , Qualidade de Vida , Humanos , Doença de Meniere/psicologia , Masculino , Feminino , Pessoa de Meia-Idade , Inquéritos e Questionários , Reprodutibilidade dos Testes , Adulto , Idoso , Análise Fatorial , PsicometriaRESUMO
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 das Glândulas Salivares , Humanos , Masculino , Feminino , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/mortalidade , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Neoplasias das Glândulas Salivares/terapia , Pessoa de Meia-Idade , Idoso , Estadiamento de Neoplasias , Taxa de Sobrevida , Margens de Excisão , Quimiorradioterapia , Estimativa de Kaplan-Meier , AdultoRESUMO
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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Procedimentos Cirúrgicos Eletivos , Neoplasias de Cabeça e Pescoço , Esvaziamento Cervical , Estadiamento de Neoplasias , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso , Neoplasias de Cabeça e Pescoço/cirurgia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/mortalidade , Taxa de SobrevidaRESUMO
OBJECTIVE: To ascertain trends in ototoxicity observed with monoclonal antibodies (mABs) and understand the impact they may have on hearing function. DATA SOURCES: PubMed, Embase, Scopus. REVIEW METHODS: A systematic review was performed following PRISMA guidelines. Data were reviewed for demographics, utilized mABs with respective indication and dosing, audiometric outcomes, and treatment for otologic effects. RESULTS: Of 757 studies reviewed, a total of 44 were included, encompassing 18,046 patients treated with mABs. Mean age of the sample was 57.8 years old. The search yielded 18 agents of ototoxicity, with reported symptoms of ototoxicity such as hearing loss, tinnitus, and/or aural fullness occurring in 1079 of total patients. Main agents causing ototoxicity were teprotumumab (n = 17/44 studies), nivolumab (n = 10/44), ipilimumab (n = 9/44), pembrolizumab (n = 5/44), and rituximab (n = 4/44). Thirty-one of 44 studies encompassing eight agents reported audiometric data for ototoxic agents, showing sensorineural hearing loss primarily in the high-frequency range. Only two articles performed ultrahigh-frequency audiograms. CONCLUSION: Monoclonal antibody usage is expanding, but the vast majority of studies lack substantial audiometric data. Where reported, study design and inclusion criteria vary greatly. Future studies would benefit from rigid inclusion of audiometric data, prospective study design, and consideration of formal ototoxicity screening. Otolaryngologists should be aware of the cochlear immune response and potential impact of this expanding medication class on hearing function. Laryngoscope, 2024.
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IMPORTANCE: Thyroid eye disease (TED) negatively impacts quality of life. TED occurs predominantly in Graves' disease (GD). Teprotumumab improves TED but concern for hearing adverse events (AEs) has emerged. Hearing dysfunction is reported in thyroid autoimmune disease but the background prevalence in GD/TED without teprotumumab remains uncertain. OBJECTIVE: To quantify ear-related diagnostic codes/hearing AEs in GD, TED, and patients receiving teprotumumab by examining medical claims and clinical trials. DESIGN AND PARTICIPANTS: Deidentified claims for ear/labyrinth-related ICD-10 codes (KOMODO®) were examined in GD patients without TED, and TED patients without/with teprotumumab treatment. Hearing AE incidence/severity was evaluated in teprotumumab clinical trials. Graves' Ophthalmopathy QOL (GO-QOL) scores were compared in teprotumumab TED trial patients without/with hearing AEs. RESULTS: GD (469,720), TED (38,566) and teprotumumab-treated (967) patients were identified in the claims database. Ear-related codes (including those not specific for hearing) occurred in 24% GD, 33% TED, and 32% teprotumumab-treated patients. "Sensorineural hearing loss bilateral" was most frequent: 32,961/469,720 (7%) GD, 4,279/38,566 (11.1%) TED, and 104/967 (10.8%) teprotumumab patients. Pre-teprotumumab use,165 (17.1%) patients had ear-related codes while 98 (10.1%) had new ear-related codes post-treatment.Eight teprotumumab oncology trials revealed 8.1% (51/633) had Ear/Labyrinth Disorders with 2.1% (13) considered study-drug-related and 3.8% (24) hearing impairment/tinnitus-related AEs, with 1.3% (8) considered teprotumumab-related. Similar rates occurred in TED trials.GO-QOL improved in teprotumumab-treated patients without/with hearing AEs. Incidence/severity was consistent across patients with chronic and acute TED. CONCLUSIONS: These analyses indicate similar occurrence of hearing claims in patients with GD/TED alone as following teprotumumab treatment. Future analyses of incremental hearing risk from teprotumumab should utilize a priori study designs accounting for background hearing dysfunction in patients with GD/TED.
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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.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Orofaríngeas , Infecções por Papillomavirus , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/cirurgia , Carcinoma de Células Escamosas de Cabeça e Pescoço/complicações , Carcinoma de Células Escamosas/cirurgia , Neoplasias Orofaríngeas/cirurgia , Neoplasias Orofaríngeas/patologia , Infecções por Papillomavirus/complicações , Estudos Retrospectivos , Estudos de Coortes , Neoplasias de Cabeça e Pescoço/complicações , PrognósticoRESUMO
BACKGROUND: Socioeconomic variables including race, education, and income have been shown to affect vestibular schwannoma incidence, treatment, and outcomes. We sought to determine the impact of socioeconomic factors on quality of life at the time of vestibular schwannoma diagnosis. METHODS: Retrospective cohort study conducted at a tertiary academic center. All patients evaluated for vestibular schwannoma from March 1, 2010 to December 31, 2021 who completed at least one Penn Acoustic Neuroma Quality of Life (PANQOL) questionnaire at presentation or prior to any intervention were included. PANQOL scores were compared across income quintiles, racial groups, and health insurance categories. RESULTS: Two-hundred and ninety-six patients who had non-missing information on variables of interest were included. Compared to White/Caucasian patients (84.5 %), Black/African American patients (4.7 %) had significantly lower PANQOL total scores (b = -12.8[-21.7, -4.0], p = 0.005). Compared to patients with Commercial insurance (53 %), patients who were Uninsured/ Self-pay (1.7 %) had significantly lower PANQOL total scores (b = -16.7[-31.4, -1.9], p = 0.027). Patients in higher income quintiles had significantly higher PANQOL total scores (b = 11.7[3.9, 19.5], p = 0.004 comparing highest income quintile to lowest). After controlling for potential confounders, income quintile (b = 9.6[1.3, 17.9], p = 0.023 comparing highest quintile to lowest) and insurance (b = -17.0[-31.9, -21], p = 0.025 comparing Uninsured/Self-pay to Commercial insurance) remained predictors of total PANQOL score. CONCLUSIONS: Socioeconomic factors including race, health insurance, and income appear to contribute to quality of life at the time of vestibular schwannoma diagnosis. These variables are interrelated and the effects of race may be mediated in part by differences in income and health insurance coverage.
Assuntos
Neuroma Acústico , Humanos , Neuroma Acústico/diagnóstico , Neuroma Acústico/epidemiologia , Neuroma Acústico/terapia , Estudos Retrospectivos , Qualidade de Vida , Inquéritos e Questionários , Fatores SocioeconômicosRESUMO
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.