Search Results (3,267)

Cutaneous T-cell lymphoma (CTCL) is a chronic, generally incurable group of non-Hodgkin lymphomas associated with substantial symptom burden, yet receipt of palliative-intent treatment in this population remains uncharacterized. We conducted a cross-sectional retrospective study of 13,215 patients with CTCL using the National Cancer Database (2004–2023) to evaluate receipt of palliative-intent treatment by sociodemographic and disease characteristics using χ² tests, Wilcoxon rank sum tests, Fisher’s exact tests, and multivariable logistic regression. Only 355 patients (2.7%) received palliative-intent treatment. In multivariable analysis, the strongest factors associated with palliative-intent treatment receipt were regional stage (OR, 3.19; 95% CI, 2.43–4.17) and distant stage (OR, 2.49; 95% CI, 1.86–3.31). Treatment at academic facilities was associated with significantly lower odds of NCDB-defined palliative care receipt (OR, 0.59; 95% CI, 0.47–0.76). Medicare insurance, primary cutaneous CD30+ histology, higher comorbidity burden, head and neck primary site, and more recent diagnosis were also independently associated with receipt of palliative-intent treatment. Sex, race, income, and distance to the facility were not significant. Palliative-intent treatment receipt is markedly low in CTCL despite guideline recommendations supporting early integration. Systematic screening for palliative care needs is warranted, particularly for patients with advanced-stage disease or high symptom burden. Full article

Objectives: 18F-FDG PET/CT is central to head and neck cancer (HNC) care, yet most radiomic models use PET or CT alone. We quantified the discrimination of fused PET/CT models and what fusion adds. Methods: Following PRISMA 2020 and a registered protocol (PROSPERO CRD420261319855), seven sources were searched, supplemented by citation and proceedings searching. Reports sharing patients were grouped into independent cohort lineages, which served as the unit of analysis, and every synthesis included one analysis per lineage. The estimand was each report’s within-study difference between its fused model and its own comparator. Two confirmatory hypotheses were specified in the statistical analysis plan, with a Bonferroni threshold of 0.025. Random-effects models used REML with Hartung-Knapp; risk of bias used PROBAST+AI, reporting completeness METRICS v1.0 and diagnostic accuracy QUADAS-3. Results: 100 studies were included, arising from 31 independent cohort lineages. Fused models exceeded PET-only models by 0.042 (95% CI 0.014 to 0.070) on the concordance index (6 lineages; p = 0.0115), meeting the confirmatory threshold, and CT-only models by 0.037 (0.002 to 0.072; p = 0.0429), which did not. Pooled absolute discrimination was 0.711 (95% CI 0.659 to 0.763). Diagnostic evidence was reported by task and not pooled. Only 25 studies could contribute to any pooled estimate, chiefly because 71 of 100 fused estimates lacked a recoverable measure of precision; all were at high risk of bias in the analysis domain. Conclusions: Fusing PET and CT radiomic information improves survival discrimination in HNC, most securely against the PET-only baseline. The advantage over CT-only models was smaller and did not meet the multiplicity-adjusted criterion, and none was established for diagnostic classification. Incremental benefit depends on the comparator, the cohort and the endpoint; it does not follow from fusion itself. Full article

Background/Objectives: Evidence regarding changes in oral and oropharyngeal squamous cell carcinoma (SCC) care across the COVID-19 pandemic remains limited, particularly in Eastern Europe. This study evaluated temporal changes in surgical admission volume, operative complexity, and comorbidity burden before, during, and after the pandemic at a Romanian tertiary maxillofacial center. Methods: This retrospective mixed-methods study included 248 admissions for oral and oropharyngeal SCC between 2018 and 2024. A structured administrative database was deterministically linked to narrative discharge summaries. Admissions were grouped into pre-pandemic (n = 117), pandemic (n = 93), and post-pandemic (n = 38) periods. Statistical analyses included between-period comparisons, segmented interrupted time-series analysis, and multivariable logistic regression. Qualitative thematic analysis was used to contextualize surgical and perioperative complexity. Results: Mean monthly admissions decreased from 4.9 before the pandemic to 2.6 during the pandemic and 1.6 in the post-pandemic period. Interrupted time-series analysis identified a significant declining baseline monthly trend (IRR 0.973, 95% CI 0.950–0.996; p = 0.024), without a significant immediate level change or post-onset slope change. Neck dissection increased from 23.9% before the pandemic to 39.8% during the pandemic (p = 0.045) and was independently associated with the pandemic/post-pandemic period (adjusted OR 1.87, 95% CI 1.06–3.29; p = 0.030). Qualitative findings identified recurrent codes related to surgical complexity, reconstruction, extensive nodal surgery, comorbidity burden, and perioperative management. Conclusions: Oral and oropharyngeal SCC surgical admissions showed a significant declining baseline trend between 2018 and 2024, while patients treated during and after the pandemic had higher adjusted odds of undergoing neck dissection. The findings support sustained oncological surveillance, timely referral, and multidisciplinary perioperative planning. Further multicenter studies incorporating standardized tumor–node–metastasis (TNM) staging and human papillomavirus (HPV) documentation are required to confirm these observations. Full article

Background: Biomedical spectroscopy offers a non-invasive way to characterise disease, but the large number of spectral variables, redundancy, and limited interpretability can hinder the creation of compact diagnostic models. This study presents the Spectral Linear Series Decomposition Learner (Spectral-LSDL), an adaptive framework for spectral information localisation and representation that combines established spectral transformations with threshold-based decomposition and morphology-based feature extraction. The framework tests whether disease-related discriminative information can be preserved within specific spectral decompositions rather than requiring representation of the full measured spectrum. Methods: Spectral-LSDL combines complementary spectral representations, adaptive upper/lower threshold decomposition, localisation-depth optimisation, and morphology-based feature extraction to produce compact 50-feature representations of spectral structure. The framework was tested on three biomedical spectroscopy datasets: Raman spectroscopy for head and neck cancer, near-infrared (NIR) spectroscopy for skin-lesion classification, and ATR-FTIR spectroscopy for type 2 diabetes. Model training and evaluation used biological-group-aware partitioning so that spectra from the same participant or lesion did not appear in both development and hold-out sets. Spectral-LSDL was compared with Raw-LDA, PCA-LDA, PLS-DA, and a 1D-CNN. Performance was measured using balanced accuracy, macro-F1, and ROC-AUC, with paired biological-group bootstrap inference. Preferential spectral localisation was examined separately through size-matched random-region Monte Carlo analysis. The Information Localisation Index (ILI) and its dimension-normalised form (nILI) were used descriptively to assess compression efficiency and predictive retention. Results: Spectral-LSDL achieved marked dimensional reduction while maintaining competitive predictive performance across all three modalities. Group-independent hold-out ROC-AUC values were 0.739 for Raman, 0.809 for NIR, and 0.940 for ATR-FTIR, with corresponding nILI values of 1.184, 0.976, and 0.946, respectively. Paired inference showed no statistically significant differences between Spectral-LSDL and the conventional comparators for Raman or NIR after correction for multiple testing. For ATR-FTIR, Raw-LDA significantly outperformed Spectral-LSDL in balanced accuracy (ΔBA = −0.050, 95% CI −0.088 to −0.014; Holm-adjusted p = 0.016) and ROC-AUC (ΔAUC = −0.040, 95% CI −0.073 to −0.012; Holm-adjusted p = 0.020). Size-matched random-region analysis provided evidence of preferential localisation for Raman (balanced accuracy: p = 0.049; ROC-AUC: p = 0.002), whereas significant localisation enrichment was not seen for NIR or ATR-FTIR. Conclusions: Spectral-LSDL offers an adaptive framework for spectral information localisation and representation based on established analytical components, allowing compact representations of biomedical spectra while preserving predictive information. The results show that adaptive decomposition can be used to examine where predictive spectral structure is concentrated, but they do not demonstrate consistent predictive superiority, distinct biochemical regions, or clinical usefulness. These findings support further study of Spectral-LSDL as an interpretable approach to spectroscopy modelling, although external prospective validation and independent biochemical confirmation are needed to establish the reproducibility, biological specificity, and clinical relevance of the identified spectral localisations. Full article

Dental implant-supported rehabilitation is a key component of functional survivorship care for patients with head and neck cancer (HNC) treated with radiotherapy (RT). Despite its importance, implant outcomes in this population are frequently interpreted through simplified paradigms such as irradiated versus non-irradiated status, prescribed tumor dose, pre-RT versus post-RT placement, and arbitrary post-RT waiting intervals. This narrative review proposes a radiobiology-informed, implant-bed-specific framework for assessing implant viability following HNC RT. The biologically relevant exposure is best defined as the localized radiation dose delivered to the implant bed, considered in conjunction with fractionation, equivalent dose in 2-Gy fractions, recipient substrate, soft-tissue condition, prosthetic loading, systemic host factors, and late toxicity risk. Distinctions among early osseointegration, implant survival, implant success, prosthetic rehabilitation, and patient-centered functional benefit are essential, as retained implants do not necessarily equate to durable or meaningful rehabilitation. Post-RT timing should be understood as a contextual variable rather than a universal chronological determinant, since longer intervals do not inherently indicate progressive biological recovery and may be confounded by survivor and clinician selection. Future research should prioritize implant-bed-specific dosimetry, continuous modeling of dose and timing, standardized outcome measures, cluster-adjusted statistical approaches, time-to-event analyses, and explicit reporting of osteoradionecrosis as a distinct implant-relevant late toxicity endpoint. Shifting from chronological waiting rules to implant-bed-specific risk stratification may enhance the safety, interpretability, and clinical relevance of dental implant rehabilitation following HNC RT. Full article

Objectives: To characterize the frequency and temporal patterns of anterior segment findings after radiotherapy for sinonasal and nasopharyngeal cancer, with particular focus on anterior segment neovascularization and its association with superselective intra-arterial cisplatin infusion with concurrent radiotherapy (RADPLAT). Methods: We retrospectively reviewed 113 patients treated with intensity-modulated radiotherapy between 2019 and 2022. Anterior segment findings were evaluated using the whole cohort as the denominator and among patients referred for ocular symptoms. Cumulative incidence was estimated with death as a competing risk using the Aalen–Johansen estimator and compared using Gray’s test. Results: Median follow-up was 1666 days. Forty-seven patients (41.6%) were referred to ophthalmology. Anterior segment findings occurred in 16/60 patients (26.7%) with nasal cavity cancer and 13/31 (41.9%) with maxillary sinus cancer (p = 0.16); 5-year cumulative incidences were 27.7% and 46.1%, respectively (p = 0.018). Anterior segment neovascularization occurred in 7/113 patients (6.2%), including 6/21 (28.6%) treated with RADPLAT and 1/92 (1.1%) without RADPLAT (p < 0.001); 5-year cumulative incidences were 31.4% and 1.4%, respectively (p < 0.001). Among patients with maxillary sinus cancer, neovascularization occurred in 5/19 RADPLAT-treated patients and 0/12 non-RADPLAT patients (p = 0.13); however, median follow-up was substantially shorter in the non-RADPLAT group (385 vs. 1784 days). Neovascularization developed late (median, 975 days), and four affected patients had final best-corrected visual acuity below 0.05. Conclusions: Anterior segment findings showed distinct temporal patterns after radiotherapy. Late, vision-threatening neovascularization was strongly associated with RADPLAT, although causality cannot be established because treatment selection was confounded by tumor site, disease extent, orbital invasion, and radiotherapy characteristics. These findings identify anterior segment neovascularization as an important safety signal warranting prospective evaluation. Standardized baseline ophthalmological assessment, long-term surveillance, and patient-level ocular dosimetry are needed to clarify mechanisms and define appropriate follow-up strategies. Full article

Background and Objectives: Basal cell carcinoma (BCC) is the most common non-melanoma skin cancer, and its global incidence rate constantly rises. However, there are no current epidemiological data for many regions, including Małopolska in southern Poland. This study aimed to characterize the clinical and histological profile of patients with BCC and to identify factors associated with local recurrence and the presence of multiple tumors. Materials and Methods: We performed a single-center, retrospective observational study consistent with STROBE guidelines at the Department of Dermatology and Allergology, University Hospital in Cracow. The included patients were adults with at least one histologically confirmed BCC treated between 2015 and 2025. Demographic, clinical, histopathological, and follow-up data were collected at patient and lesion levels. The results were evaluated using univariable tests, multivariable logistic regression, Kaplan–Meier survival analysis, and generalized estimating equations. Results: We included 108 patients (median age at first diagnosis, 73 years; 52% male) with 418 BCCs; the median follow-up duration was 84 months. Superficial BCC was the most common subtype among lesions with available histological subtype information (56%). The head and neck region was the most frequent anatomical site in this group (51%). Multiple BCCs were present in 62% of patients. Longer follow-up was independently associated with the presence of multiple BCCs. A history of actinic keratoses showed a positive but statistically nonsignificant association with multiple BCCs. Recurrence was observed in 15 lesions (3.6%). Female sex and H-zone involvement showed higher odds of recurrence. Conclusions: In this elderly cohort, multiple BCC tumors may reflect longer follow-up and cumulative actinic damage. Recurrence was relatively infrequent but associated with clinically relevant features, including H-zone involvement and female sex. These findings support an individualized, multifactorial approach to treatment and follow-up, taking into account age, sex, lesion burden, anatomical location, and histological subtype. Full article

Background: Comorbidity is an important determinant of treatment selection and in-hospital complications in patients with head and neck cancer (HNC) and thyroid cancer (TC), yet population-based evidence on this relationship remains limited. Methods: We analyzed nationwide Diagnosis-Related Groups (DRG) data from 1,552,028 inpatient HNC and TC treatments of patients aged ≥30 years in Germany between 2005 and 2021. The aim was to characterize the association of comorbidity and severe treatment-related procedure-coded inpatient events (IEs) with gender, age, tumor subsite, and treatment type. Results: The largest proportion of treatments occurred in patients aged 60–69 years (33.5%). The most frequent tumor subsites were the oropharynx, thyroid gland, oral cavity, larynx, and hypopharynx, with 35.52, 33.84, 33.60, 26.12, and 15.76 treatments per 100,000 population per year, respectively. Overall, 38% of cases had a Charlson Comorbidity Index (CCI) ≥ 1, with the highest mean CCI observed for C14 (other sites of the lip, oral cavity and pharynx) and C12 (piriform sinus). IEs requiring additional in-hospital treatment occurred in 19.3% of cases. After adjustment for age, tumor location, and treatment type, men had a lower risk of IEs than women (OR 0.929; CI 0.919–0.939; p < 0.001). Increasing comorbidity was associated with a higher IE risk, reaching a plateau at CCI ≥ 4 (OR 2.135; CI 2.029–2.246; p < 0.001). IE risk was high during chemotherapy/immunotherapy (OR 29.527; CI 28.897–30.170; p < 0.001), followed by surgery (OR 3.465; CI 3.433–3.498; p < 0.001), whereas radiotherapy showed the lowest risk (OR 1.339; CI 1.313–1.366; p < 0.001). Conclusions: These findings highlight substantial heterogeneity in comorbidity and IE risk among patients with HNC or TC. Full article

Background/Objectives: Surgical pulmonary resection in lung cancer remains the cornerstone of curative treatment; however, it is associated with considerable postoperative pulmonary complications. Patients previously treated for head and neck cancer (HNC) have a significantly increased risk of developing second primary lung cancer (LC) and a higher incidence of adverse pulmonary outcomes after LC resective surgery due to increased baseline frailty. Methods: A retrospective observational longitudinal study was conducted on 1679 patients who underwent surgical resection with curative intent for LC at the Thoracic Surgery Department of Hospital Clínico San Carlos, Madrid, Spain, between December 1989 and December 2024. Patients were divided into two groups based on the presence or absence of prior HNC: 87 with HNC vs. 1592 without. Special attention was paid to respiratory complications, particularly bronchopleural fistula (BPF), empyema, atelectasis, and pneumonia. Variables significantly associated with BPF and HNC in univariate analyses (excluding those related to other complications to avoid collinearity), as well as clinically relevant baseline differences between groups, were included in a stepwise multivariable logistic regression modeling procedure to identify independent risk factors associated with BPF. Results: In comparison with the control group, significantly higher rates of postoperative BPF (12.6% vs. 3.6%), empyema (10.3% vs. 2.8%), atelectasis (14.9% vs. 8.3%) and need of reintervention (10.3% vs. 4.2%) were found in the HNC group under unadjusted approach and stratified by surgery period. Sex, history of HNC, chronic obstructive pulmonary disease (COPD) and length of preoperative hospital stay were independently associated with BPF according to several multivariable logistic regression fits, which showed a moderate discriminatory capacity (AUC values ranging from 0.723 to 0.732). In particular, the presence of HNC was significantly associated with BPF, with adjusted odds ratio (aOR) estimates ranging from 3.562 (95% CI: 1.773 to 7.156) to 3.789 (95% CI: 1.863 to 7.709). Conclusions: In our study, COPD, male sex, preoperative hospital stay as well as HNC history were found independently associated with an increased odds of BPF after surgical treatment for LC. In particular, patients previously treated for HNC had more than threefold higher odds of developing BPF than those without a history of HNC, with this association remaining consistent over the 35-year study period. Full article

Background: Oral cavity cancer is a clinically relevant subgroup of head and neck malignancies and is associated with substantial treatment burden and healthcare utilization. Hospital length of stay (LOS) is an important indicator of inpatient resource use and complexity of care, yet large multicenter data from Germany are limited. Methods: This retrospective multicenter analysis used anonymized inpatient administrative data from 49 German hospitals; eligible oral cavity cancer hospitalizations were contributed by 34 of these hospitals. Adult inpatient hospitalizations (≥18 years) with malignant neoplasms of the oral cavity, defined using ICD-10-GM codes C00–C06, recorded between January 1 2019 and 31 December 2024 were included. The primary outcome was hospital LOS in days. Multimorbidity was quantified using the van Walraven-weighted Elixhauser Comorbidity Score. Prolonged hospitalization was defined as LOS ≥ 7 days and LOS ≥ 14 days. Associations between demographic, clinical, and treatment-related variables and LOS were examined using multivariable Poisson regression models. Because overdispersion was present, a negative binomial mixed model was additionally fitted as a sensitivity analysis. To account for inter-hospital variability, hospital was included as a random intercept in all multivariable models. Associations with prolonged LOS were analyzed using multivariable logistic regression models. All analyses were performed at the hospitalization level. Results: A total of 3957 inpatient hospitalizations for oral cavity cancer were included. Mean age was 65.6 years, and 66.2% of hospitalizations involved male patients. The median LOS was 6 days (interquartile range [IQR] 3–13; mean 10.2 days, standard deviation 11.8). Overall, 49.4% of hospitalizations had an LOS ≥ 7 days and 23.5% had an LOS ≥ 14 days. Older age, particularly >80 years, and higher comorbidity burden were associated with longer LOS (adjusted Poisson rate ratio [RR] for age > 80 years 1.17, 95% CI 1.13–1.21; high comorbidity burden RR 1.58, 95% CI 1.54–1.63). Several treatment-related variables, including surgical procedures in the oral and facial region, lymphatic system operations, blood transfusions, and complex intensive care treatment, were associated with prolonged hospitalization (e.g., blood transfusion RR 1.80, 95% CI 1.76–1.85; complex intensive care RR 1.70, 95% CI 1.65–1.75). Chemotherapy-related hospitalizations were associated with shorter LOS. Conclusions: LOS varied substantially across inpatient hospitalizations for oral cavity cancer in Germany. Older age, higher comorbidity burden, and markers of more complex inpatient treatment were associated with extended hospital stay. These findings may help identify hospitalizations at increased risk of prolonged LOS and inform inpatient planning and resource allocation. Full article

Background/Objectives: Radiation-induced hypothyroidism (RIHT) is a frequent complication in head and neck cancer (HNC) patients following radiotherapy, significantly impacting quality of life. This study aimed to develop and validate an interpretable machine learning model for predicting RIHT, with a focus on providing individualized risk assessment. Methods: The study included a development cohort (n = 256) from the Second Affiliated Hospital of Harbin Medical University and an independent external validation cohort (n = 296) from the First Affiliated Hospital of Kunming Medical University. Using 18 predictive features, six machine learning algorithms—Random Forest, Support Vector Machine, Multi-Layer Perceptron, Logistic Regression, XGBoost, and LightGBM—were constructed. Model performance was evaluated using AUC, balanced accuracy, F1 score, PR-AUC, Brier score, and Brier skill score. SHapley Additive exPlanations (SHAP) was applied for model interpretability. Results: In internal validation, LightGBM achieved the highest performance (AUC = 0.872, balanced accuracy = 0.703, PR-AUC = 0.712, and Brier skill score = 0.371), outperforming logistic regression. In external validation, Random Forest achieved the highest AUC (0.769), while XGBoost and LightGBM achieved AUCs of 0.721 and 0.716, respectively. SHAP analysis identified pre-treatment thyroid volume, T-stage, tumor site, mean thyroid dose (Dmean), and V50 as the most influential features for model prediction. Notably, dose–volume parameters (V30–V60) were highly correlated (r = 0.75–0.98); therefore, they should be interpreted as a cluster rather than as independent predictors. We caution against overinterpreting individual Vx thresholds as rigid clinical cutoffs. Conclusions: Machine learning models, particularly tree-based ensemble methods (LightGBM and XGBoost), demonstrate good predictive performance for RIHT. Combined with SHAP analysis, these models provide transparent, individualized risk assessments. However, the dose–response relationship for RIHT is continuous, and no single dose threshold should be used as a rigid clinical cutoff. Model code is available from the corresponding author upon reasonable request. Future prospective studies with time-to-event analysis are needed to further validate clinical utility. Full article

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) remains a challenging complication of bisphosphonate therapy because jaw extraction sockets exposed to bisphosphonates represent impaired wound environments rather than ordinary bone defects. This narrative review summarizes clinical, cellular, animal, and biomaterial evidence on the mechanisms that limit BRONJ repair and discusses how these pathological barriers can inform local material design. Current evidence suggests that BRONJ repair is constrained by impaired osteoclast-mediated remodeling, osteocyte and osteoblast dysfunction, oxidative stress, unresolved inflammation, angiogenic insufficiency, microbial challenge, mucosal instability, and changes in bone material properties. Biomaterial strategies investigated to date include local delivery of regenerative factors, restoration of remodeling activity, extracellular vesicles, nucleic acid nanostructures, platelet-derived matrices, antibacterial and ion-releasing hydrogels, angiogenic or lymphangiogenic systems, and mechanically adaptive scaffolds. Most studies remain preclinical and are based on rodent extraction or mandibular defect models, and few establish a direct causal link between a specific material property and durable BRONJ resolution. Future materials should be judged not only by their ability to enhance bone formation, but also by whether they can re-establish a sealed, vascularized, immune-balanced, and remodeling-competent socket capable of sustained jawbone repair. Full article

In this paper, we propose a new flexible modification of the Lomax distribution within the Bilal-G family generated through the T-X framework, referred to as the Lomax–Bilal distribution. The proposed model offers greater flexibility for modeling-skewed and heavy-tailed phenomena that frequently arise in survival and reliability studies. A comprehensive set of statistical properties is derived, as moments, order statistics, reliability measures, the quantile function, stochastic ordering, and maximum likelihood estimation. Furthermore, several information measures are obtained to characterize the uncertainty structure of the distribution, namely Shannon entropy, Rényi entropy, extropy, cumulative residual extropy, and generalized weighted extropy. Also, the Lorenz, Bonferroni, Zenga curves and Gini index are presented. The practical applicability and effectiveness of the proposed distribution are illustrated through analyses of two real datasets: survival times of patients with head and neck cancer treated with chemotherapy and radiation therapy, and repair times of an airborne communication transceiver. The empirical results showed that the Lomax–Bilal distribution consistently provides a better fit than several well-established lifetime distributions according to goodness-of-fit statistics and information criteria, particularly in modeling tail behavior. These findings suggest that the Lomax–Bilal distribution constitutes a flexible and competitive alternative for analyzing complex lifetime data in reliability engineering and medical survival studies. Full article

Background: Radiotherapy-induced xerostomia is a prevalent and disabling complication in patients with head and neck cancer, leading to persistent oral pain, impaired salivary function, and substantial deterioration in quality of life. Photobiomodulation (PBM) has emerged as a supportive therapeutic strategy with potential anti-inflammatory, analgesic, and tissue-preserving effects; however, its clinical effectiveness remains incompletely defined. Methods: We conducted a systematic review and meta-analysis of randomized controlled trials evaluating PBM for the management of radiotherapy-induced xerostomia in adults with head and neck cancer. MEDLINE (PubMed), Embase, Scopus, and Web of Science were searched from inception to October 2025. Eligible studies assessed intraoral and/or extraoral PBM using predefined laser parameters and reported outcomes related to oral pain, salivary flow, or xerostomia-related quality of life. Risk of bias was assessed using the Cochrane RoB 2.0 tool. Random-effects meta-analyses were performed using the Paule–Mandel estimator. Certainty of evidence was appraised using the GRADE framework. Results: Seven randomized trials were included. PBM significantly reduced oral pain compared with control interventions (mean difference [MD] −0.76; 95% CI −1.33 to −0.20), with moderate heterogeneity. For stimulated and unstimulated salivary flow, pooled estimates favored PBM but did not reach statistical significance, and heterogeneity was considerable (I² > 90%). Substantial variability in laser wavelength, energy density, treatment frequency, anatomical targeting, and radiation exposure of salivary glands contributed to inconsistent effects across studies. The certainty of evidence was rated as moderate for pain reduction and low to very low for salivary flow outcomes. Conclusions: Photobiomodulation provides a clinically meaningful reduction in radiotherapy-related oral pain and may confer symptomatic benefit in xerostomia; however, its effect on salivary flow restoration remains uncertain. Standardized PBM protocols, improved methodological rigor, and adequately powered trials are required to clarify its role in supportive care for head and neck cancer patients. Full article

Background/Objectives: Head and neck squamous cell carcinomas (HNSCC) are a heterogenous group of tumors, which are usually treated with surgery and radiotherapy, while chemotherapy (e.g., cisplatin), anti-EGFR, or immune checkpoint inhibitors are used to treat locoregionally advanced and recurrent cases. However, survival outcomes are still unsatisfactory, and novel augmenting treatments are required. Recently, histone lysine demethylases (KDMs) emerged as promising anti-cancer targets. In order to further characterize KDM4–6 as pharmacological targets in HNSCC, we evaluated changes in KDM4/5/6 expression in HNSCC patients, and we experimentally assessed the biological effects of inhibitors of KDM4/5/6 in HNSCC cell lines. Methods: We used online tools (TIMER, GEPIA3, UALCAN) to analyze TCGA data from HNSCC patients. Then, we used resazurin assay to assess the effect of ML324, GSK-J4, and JIB-04 (the inhibitors of KDM4, KDM6, and KDM4–6, respectively) on cell viability in two-dimensional (2D) and three-dimensional (3D) culture of FaDu, SCC-152, and Detroit-562 cells. The potential for cisplatin sensitization was also assessed. Gene/protein expression was evaluated by qPCR and antibody array. Results: We found that the majority of the analyzed KDMs were overexpressed in HNSCC, except KDM4C, KDM5D, and KDM6A. All three studied inhibitors significantly reduced cell viability in 2D and 3D cell cultures. Moreover, the pre-treatment of cells with KDM inhibitors showed moderate potential for cisplatin sensitization. In addition, the chemicals significantly reduced the expression of pluripotency markers, especially SOX2. Conclusions: In conclusion, KDM4–6 inhibitors significantly affected HNSCC cell growth, and exerted the potential for epigenetic priming in combination with cisplatin. Full article