Search Results (399)

We evaluated global radiotherapy practices in the management of early-stage (AJCC/UICC 8th edition stages I-II) glottic cancer (ESGC). A cross-sectional online survey was conducted in March 2025 across centers worldwide. Data was collected on clinical practices, including staging, CT simulation, target volumes delineation, organs-at-risk contouring, radiotherapy techniques, dose and fractionation schedules, treatment delivery techniques, and image guidance practices. A total of 181 responses were received, primarily from Asia (41.4%) and Europe (24.3%). Most respondents were from non-academic public centers (44.2%), with multidisciplinary team involvement reported by 84.5%. Head and neck CT scan was the most used staging modality (80.1%). Intensity-Modulated Radiation Therapy was the most common planning technique (82.9%). Hypofractionated radiotherapy schedules predominated for T1 (84%) and T2 (72.4%) disease. T1a was typically treated with whole-larynx target volume (72.4%). Use of ipsilateral involved vocal cord irradiation varied by geographical region (p = 0.015), being most common in North America (44.8%) and Europe (38.6%). Accelerated fractionation for T2 also differed significantly (p < 0.001), with the highest use reported in North America (41.4%). Daily Cone-Beam Computed Tomography was acquired by (58.2%). In total, 70% of respondents expressed interest in the results of a future phase III randomized trial comparing stereotactic body radiation therapy to conventional radiotherapy. Significant global variations in radiotherapy practices for ESGC were observed, likely reflecting disparities in access and differences in institutional protocols. The development and implementation of standardized, evidence-based global guidelines are essential to harmonize care, minimize toxicity, and improve outcomes for patients with ESGC. Full article

Laryngeal squamous cell carcinoma (LSCC) remains a major clinical challenge within head and neck oncology, with five-year survival rates showing minimal improvement over recent decades despite advances in surgical and multimodal therapeutic strategies. Increasing evidence identifies metabolic reprogramming as a central driver of tumor progression, therapeutic resistance, and immune evasion in LSCC. Beyond the classical Warburg effect, LSCC exhibits profound metabolic reprogramming, involving coordinated alterations in carbohydrate, amino acid, lipid, and iron metabolism that support adaptation to hypoxic and nutrient-deprived microenvironments. Hypoxia-inducible factors, particularly HIF-1α, coordinate these key biochemical pathways and enzymatic steps by integrating glycolysis, glutaminolysis, folate-dependent one-carbon pathways, lipid synthesis, and mitochondrial remodeling, while also influencing stromal and immune components of the tumor microenvironment. Metabolic crosstalk between tumor cells, cancer-associated fibroblasts, and immune populations promotes immunosuppression through nutrient competition and accumulation of metabolites such as lactate and lipid-derived mediators. In parallel, dysregulated iron handling and altered ferroptosis susceptibility emerge as key determinants of tumor aggressiveness and treatment response. This review synthesizes current evidence on metabolic rewiring in laryngeal squamous cell carcinoma, highlighting how alterations in metabolic pathways create targetable vulnerabilities that drive tumor biology, immune modulation, and resistance to conventional and emerging therapies. Elucidating these metabolic dependencies may support the development of metabolism-based biomarkers and therapeutic strategies in laryngeal squamous cell carcinoma, providing an integrated and translational perspective that links tumor metabolism with microenvironmental interactions and immune modulation, while highlights emerging therapeutic vulnerabilities. Full article

Acoustic divergence is widely recognized as a key driver of speciation and niche differentiation in vocal animals. In echolocating horseshoe bats (Rhinolophus), the larynx is specialized for producing high-duty-cycle signals used in foraging, navigation, and species recognition. While the ecological role of echolocation is established, the molecular mechanisms regulating laryngeal frequency remain unclear. We compared the laryngeal transcriptomes of three closely related, sympatric Rhinolophus species with distinct resting frequencies (RFs): R. episcopus (~46 kHz), R. siamensis (~66 kHz), and R. osgoodi (~85 kHz). This comparison identified 511 differentially expressed genes. High-frequency species upregulated genes involved in cytoskeletal dynamics and muscle contraction, such as cell adhesion molecules and motor proteins, while low-frequency species upregulated genes related to cellular homeostasis and metabolic maintenance. Weighted gene co-expression network analysis revealed two RF-correlated modules: a high-frequency module enriched in aerobic respiration and carbon metabolism and a low-frequency module enriched in lipid metabolism. Protein–protein interaction analysis identified ACTC1, vital for muscle contraction, as a hub gene. Evolutionary analysis showed that ACTC1 is highly conserved, with no significant positive selection, indicating that transcriptional regulation, rather than coding-sequence divergence, is the primary driver of the observed functional differences. These findings suggest that RF variation likely results from transcriptional remodeling in laryngeal superfast muscles. This study provides the first transcriptomic evidence linking laryngeal gene expression with acoustic divergence and offers new insights into the genetic basis of bat echolocation. Full article

Background/Objectives: The human larynx exhibits marked sexual dimorphism and undergoes age-related structural remodeling, both of which influence voice characteristics and have important implications for diagnostic assessment. While sex-related differences in laryngeal size are well recognized, the extent to which aging contributes to dimensional versus qualitative structural changes remains incompletely defined. This study aimed to analyze sex- and age-related morphometric and histological characteristics of the human larynx, with a focus on features relevant to voice evaluation and diagnostic interpretation. Methods: A cross-sectional anatomical study was conducted on 80 cadaveric human larynges preserved in 10% buffered formalin. Specimens were stratified by sex and age (<30, 30–60, and ≥60 years). Direct morphometric measurements included anteroposterior laryngeal length, thyroid cartilage height, thyroid angle, and relative glottic area. Epiglottic morphology and the presence of laryngeal cartilage calcification/ossification (binary classification: present vs. absent) were recorded. Histological analysis of vocal fold tissue was performed on a stratified subset of specimens. Statistical analysis included t-tests, chi-square tests, two-way ANOVA, effect size estimation, and logistic regression. Results: Male specimens showed significantly greater anteroposterior length, thyroid cartilage height, and relative glottic area, along with a narrower thyroid angle, compared with females (all p < 0.001), with large effect sizes. Age did not significantly influence overall laryngeal dimensions. In contrast, cartilage calcification/ossification increased markedly after the age of 60. Logistic regression identified age ≥ 60 years as the only independent predictor of calcification (OR = 4.37, p = 0.039), while sex was not significant. Epiglottic morphology demonstrated a sex-dependent distribution. Histology revealed age-related muscle atrophy and reduced collagen and elastin density. Conclusions: Sex defines the baseline morphometric framework of the adult larynx, whereas aging, particularly beyond 60 years, drives qualitative structural degeneration. These findings provide a reproducible anatomical reference for distinguishing sex-related variation from age-related changes in diagnostic assessment. Full article

Background: Extranodal extension (ENE) is a critical prognostic factor in head and neck squamous cell carcinoma (HNSCC) and was incorporated into the AJCC eighth-edition staging system. However, the concordance between clinical (cENE) and pathological (pENE) ENE remains poorly understood in real-world practice. Methods: We conducted a retrospective analysis using Taiwan Cancer Registry (TCR) long-form data from 2018 to 2022, focusing on four major HNSCC sites (oral cavity, oropharynx, hypopharynx, and larynx). The diagnostic gap was defined as the difference between pENE and cENE positivity rates. Results: Among 29,830 patients, a persistent diagnostic gap was observed across all sites: laryngeal (20.8%), hypopharyngeal (20.4%), oropharyngeal (11.5%), and oral cavity (9.9%). For oral cavity cancer, the gap did not narrow over the 5-year period (p = 0.9788). Furthermore, in oral cavity cancer, medical centers demonstrated a larger gap than non-medical centers (10.5% vs. 8.4%), a phenomenon we term the “Quality-Gap Paradox”. Conclusions: A significant diagnostic gap persists in HNSCC, highlighting the limitations of current imaging. The Quality-Gap Paradox, observed in oral cavity cancer, suggests this is driven by a complex interplay of factors including superior pathological detection in high-volume centers. Our findings underscore the need for advanced, personalized risk-stratification tools to bridge this gap and improve patient management. Full article

Background: Laryngomalacia is the most common cause of inspiratory stridor in infancy. While most mild cases resolve spontaneously, severe cases may require surgical intervention. We report a case of severe laryngomalacia successfully treated with correction of glosso-larynx (CGL), a surgical procedure originally developed for ankyloglossia with deviation of the epiglottis and larynx (ADEL). Methods: A 2-month-old infant with severe symptoms was evaluated using objective anatomical and functional metrics. The patient underwent CGL under local anesthesia to release restrictive tension on the hyoid-larynx complex. Results: The patient showed rapid and sustained improvement in respiratory symptoms. At the one-month follow-up, endoscopic examination confirmed functional airway expansion with limited to no morbidity. Conclusions: This case demonstrates that CGL may represent a feasible and minimally invasive therapeutic option for selected cases of severe laryngomalacia, particularly those involving complex tongue–larynx dynamics. Full article

Head and neck cancer (HNC) encompasses tumors located within the oral cavity, sinonasal cavity, pharynx, and larynx. It is the sixth most common cancer worldwide. Current treatment methods in HNC patients involve radical surgery, radical radiotherapy, and concomitant chemoradiotherapy, along with adjuvant and induction therapies. Accumulating trials examine the role of immunotherapy in patients with HNC. The results of the CheckMate-141 and KEYNOTE-048 trials demonstrated the benefits of using immunotherapy in patients with metastatic or recurrent HNC. Subsequently, numerous other immunotherapy-based protocols have been evaluated. Then, KEYNOTE-689 successfully implemented immunotherapy in patients with locally advanced disease. This review aims to comprehensively present the landscape of immunotherapy opportunities in patients with HNC. It summarizes completed key clinical trials that led to the approval of immunotherapy in HNC and presents currently performed trials with highly expected results. Furthermore, it discusses methods to improve immunotherapy outcomes in the cohort of HNC patients, describes the current role of immunotherapy in HNC, and presents future perspectives of this type of treatment. Full article

Recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN) carries a poor prognosis; however, immune checkpoint inhibitors have emerged as critical therapeutic options. Although the KEYNOTE-048 trial established the efficacy of pembrolizumab, the population was restricted to major sites (e.g., oral cavity, oropharynx, hypopharynx, and larynx), excluding subsites such as the paranasal sinuses and nasopharynx. To evaluate outcomes in these populations, we conducted a multicenter retrospective study of 167 patients with R/M SCCHN treated with pembrolizumab between December 2019 and February 2022. The cohort comprised 127 patients with tumors in included sites and 27 in excluded subsites. Primary endpoints included overall survival (OS), progression-free survival (PFS), overall response rate (ORR), disease control rate (DCR), and immune-related adverse events (irAEs). In the excluded subsite group, median OS was 15.2 months (1-year rate: 70.6%), and median PFS was 4.9 months (1-year rate: 21.2%). The ORR was 22.2% and the DCR was 59.3%. The incidence of irAEs was 25.9%, with Grade ≥ 3 events in 3.7%. Survival outcomes did not differ significantly from those in included sites. These findings suggest the potential efficacy and safety of pembrolizumab in subsites excluded from KEYNOTE-048, warranting validation in prospective trials. Full article

Background/Objectives: Radiomics, the high-throughput extraction of quantitative features from medical imaging, offers a promising method for identifying laryngeal cancer imaging biomarkers. We aim to systematically review the literature on radiomics in laryngeal squamous cell carcinoma, assessing applications in tumour staging, prognosis, recurrence prediction, and treatment response evaluation. PROSPERO ID: CRD420251117983. Methods: MEDLINE and EMBASE databases were searched in May 2025. Inclusion criteria: studies published between 1 January 2010 and 31 January 2024, extracted radiomic features from CT, PET/CT, or MRI, and analysed outcomes related to diagnosis, staging, survival, recurrence, or treatment response in laryngeal cancer. Exclusion criteria: case reports, abstracts, editorials, reviews, or conference proceedings, exclusive focus on preclinical or animal models, lack of a clear radiomics methodology, or did not include imaging-based feature extraction. Results were synthesised narratively by modelling objective, alongside formal assessment of methodological quality using the Radiomics Quality Score (RQS). Results: Twenty studies met the inclusion criteria, with most using CT-based radiomics. Seven incorporated PET/CT. Radiomic models demonstrated moderate-to-high accuracy across tasks including T-staging, thyroid cartilage invasion, survival prediction, and local failure. Key predictive features included first-order entropy, skewness, and texture metrics such as size zone non-uniformity and GLCM correlation. Methodological variability, limited external validation, and small samples were frequent limitations. Conclusions: Radiomics holds strong promise as a non-invasive biomarker for laryngeal cancer. However, methodological heterogeneity identified through formal quality assessment indicates that improved standardisation, reproducibility, and multicentre validation are required before widespread clinical implementation. Full article

Background/Objectives: Premalignant laryngeal lesions carry a variable risk of malignant transformation to squamous cell carcinoma. Identifying reliable biomarkers that predict malignant transformation could improve patient management and surveillance strategies. The objective of this work is to perform a systematic review of the literature on biomarkers that predict malignant transformation of premalignant laryngeal lesions. Methods: We conducted a systematic review following PRISMA 2020 guidelines. The PubMed, Scopus and Embase databases, and Google Scholar were searched for studies published between January 2011 and November 2025. Studies investigating biomarkers that predict malignant transformation of histopathologically confirmed premalignant laryngeal lesions were included. Risk of bias was assessed using the ROBINS-I tool. Results: From 166 initially identified records, 11 studies met the inclusion criteria, including 730 patients. These studies investigated diverse biomarker categories such as protein markers (cortactin, FAK, NANOG, SOX2, CSPG4), immune markers (tumor-infiltrating lymphocytes, immune gene signatures), microRNAs (miR-183-5p, miR-155-5p, miR-106b-3p), and genetic markers (chromosomal instability, PIK3CA amplification and mutations, FGFR3 mutations). Five studies provided adequate follow-up data on transformation outcomes. Most studies showed a moderate to serious risk of bias primarily due to limited confounder control and incomplete reporting. Conclusions: While several promising biomarker candidates have been identified, the evidence base remains limited due to small sample sizes, heterogeneous methodologies, and inadequate follow-up data. Cortactin/FAK protein expression and immune signatures are the most promising but require validation in larger, well-designed prospective cohorts. Full article

Background/Objectives: Since 1988, the IARC has classified alcohol as a type 1 carcinogen, causally linked to seven types of cancer (oral cavity, pharynx, larynx, esophagus, colorectum, liver and breast carcinomas). Several agencies, such as the WHO and the IARC, hold that there is a direct monotonic association between any gram of alcohol consumed and the risk of cancer, regardless of the drinking pattern. On the other hand, an expanding body of evidence indicates that drinking pattern may substantially modify the effect of alcohol consumption. The Mediterranean alcohol-drinking pattern (MADP) includes different aspects of alcohol consumption, such as preference for red wine, moderate alcohol consumption with meals, spreading consumption over the week and avoiding binge drinking. Conformity to this pattern has shown inverse associations with all-cause mortality, cardiovascular disease and diabetes. However, its relationship with cancer incidence has not been studied yet. Our objective was to assess how alcohol consumption patterns, with particular emphasis on the MADP, relate to the incidence of the seven alcohol-related cancers. This information is needed to support cancer prevention recommendations that may go beyond the amount of alcohol consumed to also include the drinking pattern. Methods: We prospectively followed 19,541 participants in the SUN (“Seguimiento Universidad de Navarra”) cohort for a median of 13.8 years. We classified participants into four groups, namely, abstainers and three further groups according to their adherence to the MADP score (low, moderate and high). Results: A substantial reduction in the risk of alcohol-related cancer incidence was observed only in men for high versus low adherence to the MADP, with an adjusted hazard ratio (HR) of 0.44 (95% confidence intervals (CIs) (0.21–0.92)). The category of moderate adherence to the MADP showed a lower risk of cancer incidence with a tendency towards statistical significance (HR = 0.56, 95% CI, 0.30–1.06). For women, no result reached statistical significance. Conclusions: Based on the available evidence, separate messages by sex should be delivered. In men, the association between alcohol and cancer goes beyond the amount of alcohol consumed, and a Mediterranean drinking pattern may be beneficial even for alcohol-related cancers. Men should, therefore, receive an additional message: among alcohol consumers, greater adherence to the MADP may help lower their risk of developing alcohol-related cancers. No benefit is supported for the MADP against alcohol-related cancers in women. Full article

Background/Objectives: Financial toxicity (FT) refers to the financial burden directly or indirectly caused by a patient’s medical care. Patients with head and neck cancer (HNC) are particularly vulnerable to FT due to lower rates of return to work and higher out-of-pocket payments (OOPP). In this cross-sectional study, we assessed the amount and types of OOPP, as well as the prevalence of FT, in HNC patients who had completed curative radiotherapy. Methods: We included HNC patients who underwent curative-intent radiotherapy at four private clinics in Romania, within 12 months of completing treatment. Participants completed a 25-item questionnaire capturing sociodemographic information, insurance status, income, and OOPP. To assess subjective FT, we used the validated nine-item Financial Index of Toxicity (FIT), which measures three FT domains: financial stress, financial strain, and lost productivity. Each domain and the total score range from 0 to 100, with higher scores indicating greater financial toxicity. Descriptive statistics were used to summarize patient characteristics. Pearson’s chi-square, t-tests, and one-way ANOVA were used to assess statistical associations, with a significance threshold of p < 0.05. Results: Among 113 patients (mean age: 59), the majority were male (74.3%) and married (74.3%), with 40% having completed university or higher education. The most frequent tumor sites were the oropharynx (29 cases), larynx (22), and oral cavity (21). Concurrent chemoradiation was the most common treatment modality (47%). The mean total FT score was 18.8. Overall, 39.8% of patients experienced financial toxicity, and 29.2% scored above the mean in financial stress. Moderate financial strain (score > 21) was reported by 39.8% of participants, and approximately one-third reported loss of productivity. Transportation and nutritional supplements were the most common OOPP categories. Notably, 42% of patients spent at least 400 euros—equivalent to Romania’s monthly minimum income—on transportation during radiotherapy. FT was significantly associated with employment and marital status, but not with tumor site or treatment type. Conclusions: Among Romanian HNC patients treated with curative radiotherapy, we found substantial OOPP, particularly for transportation and nutritional supplements. While overall FT levels were moderate, divorced patients and those retired due to other chronic conditions were the most vulnerable to financial distress. Financial toxicity can directly affect treatment adherence, survival, and quality of life. By integrating financial counseling, social support, and broader coverage of treatment-related expenses, healthcare systems can mitigate FT for these patients. Full article

This study examines the impact of vocal fold (VF) lesions located on the superior surface on glottal airflow dynamics and tissue oscillatory behaviors using biomechanical simulations of a two-layered realistic VF model. It is hypothesized that morphological changes in the VFs due to the presence of a lesion cause changes in tissue elasticity and rheological properties, contributing to dysphonia. Previous research has lacked the integration of lesions in computational simulations of anatomically accurate larynx-VF models to explore their effects on phonation and contribution to voice disorders. Addressing the current gap in literature, this paper considers a computational model of a two-layered VF structure incorporating a lesion that represents a hemorrhagic polyp. A three-dimensional, subject-specific, multilayered geometry of VFs is constructed based on STL files derived from a human larynx CT scan, and a fluid–structure interaction (FSI) methodology is employed to simulate the coupling of glottal airflow and VF tissue dynamics. To evaluate the effects of the lesion’s presence, two FSI models, one with a lesion embedded in the cover layer and one without, are simulated and compared. Analysis of airflow dynamics and tissue vibrational patterns between these two models is used to determine the impact of the lesion on the biomechanical characteristics of phonation. The polyp is found to slightly increase airflow resistance through the glottis and disrupt vibratory symmetry by decreasing the vibration frequency of the affected fold, leading to weaker and less rhythmic oscillations. The results also indicate that the lesion increases tissue stress in the affected fold, which agrees with clinical observations. While quantitative ranges depend on lesion size and tissue properties, these consistent and physically meaningful trends highlight the biomechanical mechanisms by which lesions influence phonation. Full article

Low-permeability sandstone oil reservoirs, as an important type of oil and gas resource, feature high reservoir density and low permeability. The utilization of pore throats of different scales during their development process is crucial for enhancing oil recovery. Based on nuclear magnetic resonance and CT scanning techniques, this paper systematically studies the utilization limits and energy contribution of pore larynx under different displacement methods. The results show that during the water injection development process, the main pore–throat radius used by water flooding is between 1 and 20 μm. Among them, the contribution of the small pore tends to stabilize after the pressure rises to a certain stage, the contribution of the medium pore increases with the rise in pressure, while the contribution of the large pore gradually decreases with the increase in pressure. After switching to CO₂ gas flooding, the application range of the pore throat was further expanded to a smaller scale. The contribution of the small pore and the middle pore significantly increased in a specific pressure range, while the large pore made a greater contribution at a lower pressure. This paper has certain reference significance for the study of the limit and contribution of pore–throat exploitation in low-permeability sandstone oil reservoirs. Full article