Oral Pre-malignancy: An Update on Novel Therapeutic Approaches.

PURPOSE OF REVIEW: This review aims to provide a comprehensive overview of the current advances in managing and preventing progression of oral potentially malignant disorders (OPMDs), focusing on their histological and clinicopathological features, and management. RECENT FINDINGS: Recent studies, including a multicenter cross-sectional study, have identified oral leukoplakia as the most prevalent form of OPMD, comprising over half of the cases examined. Advances in histological grading, specifically the World Health Organization's three-tier system (mild, moderate, and severe dysplasia), have significantly enhanced the accuracy of risk assessment for malignant transformation. Additionally, treatments such as surgical interventions, photodynamic therapy, and chemopreventive and molecularly targeted agents are being evaluated for their safety and efficacy as well as, immune checkpoint inhibitors being evaluated as potential preventive strategies to halt the progression of OPMDs. The management of OPMDs remains challenging due to the lack of standardized screening protocols and varied clinical management approaches. Despite this, recent advancements in diagnostic grading and therapeutic interventions provide a framework for improved treatment outcomes. Continued research into the molecular and cellular mechanisms driving development and progression of OPMDs and innovative treatment trials are essential to optimize strategies that prevent malignant progression and thereby reduce the global health burden of oral cancer.

Effect of in vivo aging on the surface and electrochemical properties of magnetic attachments used in facial prostheses: A retrieval analysis study.

STATEMENT OF PROBLEM: Reasons associated with the failure of facial prosthesis are of major concern and may be associated with deterioration of both elastomeric materials and magnetic attachments. However, the extent of deterioration of these components is unclear. PURPOSE: The purpose of this in vitro study was to evaluate selected retrieved facial prostheses and provide information regarding the electrochemical characterization of the recovered magnetic attachments. MATERIAL AND METHODS: Five facial prostheses (RP1, RP2, RP3, RP4, RP5) fabricated at the University of Texas, M.D. Anderson Cancer Center were retrieved following clinical use. The intaglio and external surfaces of the prostheses along with the incorporated magnetic attachments were photographed. The areas with the detected failures on the retrieved prostheses, as well as the recovered magnetic attachments, were evaluated under a reflected light stereomicroscope at ×16 nominal magnification and photographed with a digital camera. Five magnetic attachments recovered from the prostheses (retrieved group RT) were evaluated for degradation of their corrosion resistance after electrochemical testing in artificial sweat solution and were compared with 5 unused magnetic attachments (control group, CT). To identify the elemental composition of the intact magnet surface, 1 specimen from the control group was investigated by X-ray energy dispersive spectroscopy (EDS). Means and standard deviations of the open circuit potential (EOCP), the zero-circuit potential (Ecorr), and Icorr were calculated and statistically analyzed by a t test (α=.05 for all tests). RESULTS: The main reasons of failure were discoloration, degradation and rupture of the silicone elastomer, marginal misfit, and delamination of the polyurethane sheet. Additional findings were tarnish and discoloration of the magnetic attachments accompanied by considerable smear build-up. EDS results verified the Ni plating of tested magnets. Electrochemical testing revealed that retrieved magnets showed significantly lower OCP (P<.001) and Ecorr (P<.001) but similar Icorr (P=0.083) while the pseudopassivity region of unused magnets vanished in the retrieved group, denoting a degradation of electrochemical properties after clinical use. CONCLUSIONS: In vivo aging exerts extended degradation on the elastomer part of facial prostheses as well as deterioration of their surface integrity and electrochemical properties.

Many leveled ordinal models for frequency of alcohol and drug use.

Background: The numbers of days people consume alcohol and other drugs over a fixed interval, such as 28 days, are often collected in surveys of substance use. The presence of an upper bound on these variables can result in response distributions with "ceiling effects." Also, if some peoples' substance use behaviors are characterized by weekly patterns of use, summaries of substance days-of-use over longer periods can exhibit multiple modes.Objective: To highlight advantages of ordinal models with a separate level for each distinct survey response, for bounded, and potentially multimodal, count data.Methods: We fitted a Bayesian proportional odds ordinal model to longitudinal cannabis days-of-use reported by 443 individuals who used illicit drugs (206 female, 214 male, 23 non-binary). We specified an ordinal level for each unique response to allow the exact numeric distribution implied by the predicted ordinal response to be inferred. We then compared the fit of the proportional odds model with binomial, negative binomial, hurdle negative binomial and beta-binomial models.Results: Posterior predictive checks and the leave one out information criterion both suggested that the proportional odds model gave a better fit to the cannabis days-of-use data than the other models. Cannabis use among the target population declined during the COVID-19 pandemic in Australia, with the odds of a member of the population exceeding any specified frequency of cannabis use in Wave 4 estimated to be 73% lower than in Wave 1 (median odds ratio 0.27, 90% credible interval 0.19, 0.38).Conclusion: Ordinal models can be suitable for complex count data.

Effect of spatial arrangement and clinical service lifetime simulation on the retention of magnetic units used in implant-anchored orbital prostheses.

STATEMENT OF PROBLEM: Evidence for the optimal spatial arrangement of magnetic attachments in implant-supported orbital prostheses is lacking. PURPOSE: The purpose of this in vitro study was to assess the effect of 6 different spatial arrangements on the retentive force of magnetic attachments following the in vitro simulation of clinical service by insertion-removal test cycles and the contribution of artificial aging to the morphological alterations induced on the magnetic surfaces. MATERIAL AND METHODS: Ni-Cu-Ni plated disk-shaped neodymium (Nd) magnetic units (d=5 mm, h=1.6 mm) were secured on leveled (50×50×5 mm, n=3) and angled (40×45×40 mm, interior angle=90 degrees, n=3) pairs of test panels in 6 different spatial arrangements: triangular_leveled (TL), triangular_angled (TA), square_leveled (SL), square_angled (SA), circular_leveled (CL), and circular_angled (CA) generating corresponding test assemblies (N=6). TL and TA arrangements included 3 magnetic units (3-magnet groups) and SL, SA, CL, and CA 4 (4-magnet groups). The retentive force (N) was measured at a mean crosshead speed of 10 mm/min (n=10). Each test assembly was subjected to insertion-removal test cycles with a 9-mm amplitude, ν=0.1 Hz, and n=10 consequent retentive force measurements at a crosshead speed of 10 mm/min at 540, 1080, 1620, and 2160 test cycles. Surface roughness alterations following the 2160 test cycles were measured by calculating the Sa, Sz, Sq, Sdr, Sc, and Sv parameters with an optical interferometric profiler with 5 new magnetic units used as a control group. Data were analyzed with 1-way ANOVA and Tukey HSD post hoc tests (α=.05). RESULTS: The 4-magnet groups had statistically significantly higher retentive force than the 3-magnet ones at baseline and following the 2160 test cycles (P<.05). In the 4-magnet group, the ranking at baseline was SA.05). CONCLUSIONS: Four magnetic attachments placed on an SL spatial arrangement resulted in the highest retention force but presented with the highest force reduction following the in vitro simulation of clinical service by insertion-removal test cycles.

Colocation of Lipids, Drugs, and Metal Biomarkers Using Spatially Resolved Lipidomics with Elemental Mapping.

Elemental imaging is widely used for imaging cells and tissues but rarely in combination with organic mass spectrometry, which can be used to profile lipids and measure drug concentrations. Here, we demonstrate how elemental imaging and a new method for spatially resolved lipidomics (DAPNe-LC-MS, based on capillary microsampling and liquid chromatography mass spectrometry) can be used in combination to probe the relationship between metals, drugs, and lipids in discrete areas of tissues. This new method for spatial lipidomics, reported here for the first time, has been applied to rabbit lung tissues containing a lesion (caseous granuloma) caused by tuberculosis infection. We demonstrate how elemental imaging with spatially resolved lipidomics can be used to probe the association between ion accumulation and lipid profiles and verify local drug distribution.

Bilabial-protruding, mouth-opening and tongue-depressing stent for proton radiation therapy.

Custom intraoral radiation devices protect normal tissues, minimizing the adverse effects of radiation therapy. These devices also help immobilize the target by placing the patient's head in a precise, repeatable position. This clinical report describes the fabrication and benefits of a modified mouth opening, tongue depressing radiation stent with bilabial protrusion of the lips that was used in proton radiation therapy for a malignancy of the upper lip.

Floor of mouth prosthesis with removable depressible tongue: A clinical report.

The rehabilitation of a patient with a total glossectomy with a prosthetic device is challenging and depends on the individual patient. Ablation of a tongue tumor leaves defects that can be either surgically reconstructed or replaced by a prosthesis to help recreate normalcy and balance in the oral cavity. This clinical report describes a prosthetic design to rehabilitate a patient after a total glossectomy. This approach successfully recreated the glossal surface with a soft, hollow, depressible structure that emulates the tongue during speech and a solid structure to facilitate swallowing. The components were joined by magnets.

Combined rehabilitation of a lower lip defect after resection of floor of mouth cancer: A clinical report.

This clinical report describes the successful prosthetic rehabilitation of a deficient lower lip in an edentulous patient who had undergone surgery for removal of a squamous cell carcinoma of the anterior floor of the mouth and vestibule. The rehabilitation used a combined approach of an extraoral lip prosthesis joined by 3 magnets to an intraoral implant-retained mandibular resection prosthesis. The outcome demonstrated rehabilitation of the lower third of the face by eliminating loss of fluids and by improving the facial profile, lip contour and competence, esthetics, the patient's eating ability, speech intelligibility, and reported quality of life.

Effectiveness of a Chairside Acrylic Adjustment Cabinet in Reducing Dental Acrylic Debris and Aerosols.

PURPOSE: Chairside prosthesis adjustment procedures generate contaminated acrylic particle debris that include visible splatter (particles >50 µm) as well as invisible aerosols (<50 µm). The purpose of this study was to evaluate the effectiveness of a chairside acrylic adjustment cabinet (CAAC) in reducing airborne aerosol particles (<10 µm) and visible acrylic debris, time required for airborne aerosols to return to baseline levels after an acrylic adjustment procedure, and the effect on operatory turnover time. MATERIALS AND METHODS: A total of 40 acrylic adjustment procedures were carried out in a simulated setting with (experiment) and without (control) a CAAC. Standardized acrylic samples of self-polymerized, and heat polymerized polymethylmethacrylate resins, Triad™ and Fastray™ custom tray materials were evaluated. Airborne aerosol measurements were done using a handheld Lase.r Particle Counter for absolute particle counts of sizes 0.3, 0.5, 1.0, 2.5, 5.0, and 10.0 µm before, during, and immediately after adjustment and 10 minutes postadjustment. Spread of aerosols was assessed at three distinct locations within the dental operatory specific to the provider, the patient, and the caregiver/guest. Visible acrylic debris and operatory turnover time were evaluated immediately postadjustments by a blinded investigator. Repeated measures ANOVA was used to estimate group effect, time effect and interaction between group and time for air particle analysis. Independent samples T-tests were used for group differences between operatory turnover time, and time for aerosols to return to baseline. Chi-square test was used for visible surface analysis. RESULTS: In the control group, total aerosol particle counts increased from 6542.7 ± 162.6 particles at baseline to 598378.7 ± 586363.2 and 367569.9 ± 432220.8 particles during and immediately postadjustment, respectively. Adjustments made in the experiment group led to significantly reduced aerosol counts during (97738.9 ± 97866.5) and immediately postadjustment (19786.5 ± 14004.9; F = 17.8, p = 0.006). Similar trends were noted for the patient and guest positions. Time for aerosol particles to return to baseline was significantly lower in the experiment group (20.56 ± 14.5 minutes) compared to the control group (37.9 ± 31.96 minutes; p = 0.03). Visible acrylic debris analysis showed a significant decrease of 78% in the experiment group (p < 0.001). No significant differences were noted in operatory turnover time between the two groups (p = 0.61). CONCLUSIONS: Acrylic adjustment procedures generated aerosols of particle sizes less than 10 µm and were measured in significant quantities throughout the dental operatory for up to 115 minutes. Chairside acrylic adjustment cabinets significantly decreased airborne aerosols, visible acrylic particle debris, and reduced the time for airborne aerosols to return to baseline levels.

Determinants of patient-reported xerostomia among long-term oropharyngeal cancer survivors.

BACKGROUND: This study was conducted to identify clinicodemographic risk factors for xerostomia among long-term oropharyngeal cancer (OPC) survivors. METHODS: This cross-sectional study included 906 disease-free, adult OPC survivors with a median survival duration at the time of survey of 6 years (range, 1-16 years); self-reported xerostomia scores were available for 877 participants. Study participants had completed curative treatment between January 2000 and December 2013 and responded to a survey administered from September 2015 to July 2016. The primary outcome variable was cancer patient-reported xerostomia measured with the MD Anderson Symptom Inventory Head and Neck Cancer Module. Clinicodemographic risk factors for moderate to severe xerostomia were identified via multivariable logistic regression. RESULTS: Moderate to severe xerostomia was reported by 343 of the respondents (39.1%). Female sex (odds ratio [OR], 1.82; 95% CI, 1.22-2.71; P = .003; Bayesian false-discovery probability [BFDP] = 0.568), high school or lower education (OR, 1.73; 95% CI, 1.19-2.52; P = .004; BFDP = 0.636), and current cigarette smoking at the time of survey (OR, 2.56; 95% CI, 1.19-5.47; P = .016; BFDP = 0.800) were risk factors for moderate to severe xerostomia, and bilateral intensity-modulated radiotherapy (IMRT) combined with proton therapy and ipsilateral IMRT were protective. CONCLUSIONS: In this large xerostomia study, modern radiotherapy was a protective factor, and continued cigarette smoking at the time of survey, female sex, and high school or lower education were identified as other contributing risk factors associated with moderate to severe xerostomia. Importantly, these findings need to be confirmed in prospective studies. These results can inform future research and targeted patient-centered interventions to monitor and manage radiation therapy-associated xerostomia and preserve quality of life among patients with OPC.

Correlative Imaging of Trace Elements and Intact Molecular Species in a Single-Tissue Sample at the 50 µm Scale.

Elemental and molecular imaging play a crucial role in understanding disease pathogenesis. To accurately correlate elemental and molecular markers, it is desirable to perform sequential elemental and molecular imaging on a single-tissue section. However, very little is known about the impact of performing these measurements in sequence. In this work, we highlight some of the challenges and successes associated with performing elemental mapping in sequence with mass spectrometry imaging. Specifically, the feasibility of molecular mapping using the mass spectrometry imaging (MSI) techniques matrix-assisted laser desorption ionization (MALDI) and desorption electrospray ionization (DESI) in sequence with the elemental mapping technique particle-induced X-ray emission (PIXE) is explored. Challenges for integration include substrate compatibility, as well as delocalization and spectral changes. We demonstrate that while sequential imaging comes with some compromises, sequential DESI-PIXE imaging is sufficient to correlate sulfur, iron, and lipid markers in a single tissue section at the 50 µm scale.

The use of the cellular thermal shift assay for the detection of intracellular beta-site amyloid precursor protein cleaving enzyme-1 ligand binding.

Inhibition of the Alzheimer's disease associated protein ß-site amyloid precursor protein cleaving enzyme-1 (BACE1) remains a potential avenue for treatment of this disease. The cellular thermal shift assay (CETSA) is an attractive method of screening for protein binding molecules due to its ability to detect intracellular binding while avoiding the need to purify the protein in question. Here, the CETSA was carried out using the known BACE1 inhibitor verubecestat, where an increase in Tagg to 53.27 ± 0.89 °C from 49.53 ± 0.69 °C was observed. Three test compounds from the ChemBridge DiverSet compound library, identified to bind BACE1 using differential scanning fluorimetry, were then screened using the CETSA. Only compound C34 yielded a significant increase in Tagg (p value ≤ 0.05), indicative of intracellular binding. This is the first description of the cellular thermal shift assay being used to detect BACE1 binding molecules, with one novel BACE1 binding molecule being validated.

Self-Reported Trismus: prevalence, severity and impact on quality of life in oropharyngeal cancer survivorship: a cross-sectional survey report from a comprehensive cancer center.

OBJECTIVE: The purpose of this study was to estimate prevalence/severity of self-reported trismus, determine association with quality of life (QOL), and examine clinical risk factors in a large population of patients treated for oropharyngeal cancer. MATERIALS AND METHODS: A cross-sectional survivorship survey was conducted among patients who completed definitive treatment for oropharyngeal carcinoma, disease-free ≥ 1-year post-treatment (median survival, 7 years among 892 survivors). Associations between trismus and QOL were also analyzed using MDASI-HN, EQ-5D, and MDADI. Dietary and feeding tube status were also correlated to trismus status. RESULTS: Trismus was self-reported in 31%. Severity of trismus positively correlated (r = 0.29) with higher mean interference scores reflecting a moderate association with quality of life (p < 0.0001). There was a negative correlation for MDADI composite scores (r = - 0.33) indicating increased perceived dysphagia related to trismus severity (p < 0.0001). EQ-5D VAS scores were also negatively correlated with trismus severity (r = - 0.26, p < 0.0001). Larger T-stage (p ≤ 0.001), larger nodal stage (p = 0.03), tumor sub-site (p = 0.05), and concurrent chemoradiation (p = 0.01) associated with increased prevalence of trismus. Diet negatively correlated (r = - 0.27) with trismus severity (p = < 0.0001), and survivors with severe trismus were also more likely to be feeding tube-dependent. CONCLUSION: Severity of trismus appears to negatively impact quality of life and associate with various adverse functional outcomes in long-term oropharyngeal cancer survivorship. Trismus remains associated with advanced disease stages, tumor sub-site (tonsil), and addition of chemotherapy. Further investigation is merited for the dose-effect relationship to the muscles of mastication.

Prevalence of medication related osteonecrosis of the jaw in patients treated with sequential antiresorptive drugs: systematic review and meta-analysis.

BACKGROUND: Antiresorptive drugs (ARD) are associated with a known serious adverse event, known as medication-related osteonecrosis of the jaws (MRONJ). Transition from one ARD to another has become common clinical practice with the advent of more potent or safer agents; however, the influence of sequential antiresorptive therapy as a risk factor for MRONJ has not been established. OBJECTIVES: To investigate the prevalence of MRONJ in oncology or osteoporosis patients treated with two or more sequential ARDs as opposed to a single antiresorptive drug. MATERIAL AND METHODS: Systematic electronic literature searches were conducted using Ovid MEDLINE, Ovid EMBASE, and Cochrane Central Register of Controlled Trials. Two review authors retrieved studies using pre-determined eligibility criteria and conducted quality assessment and data extraction. Fixed or random-effects meta-analysis models were used to summarize relative estimates for prevalence of MRONJ. RESULTS: A total of 483 titles and abstracts were screened, and 18 full texts were retrieved for review. Twelve studies were included in the final qualitative and quantitative synthesis. Random effects meta-analysis models revealed a weighted pooled MRONJ prevalence of 19% (95% CI 10-27%) for sequential pamidronate-zoledronate therapy, 10% (95% CI 3-22%) for sequential ibandronate-zoledronate therapy. Pooled weighted prevalence of MRONJ was 13% (95% CI 3-22%) for sequential bisphosphonate-denosumab therapy while bisphosphonates only was 5% (95% CI 0-9%) and denosumab only was 4% (95% CI 3-5%). CONCLUSIONS: The present systematic review suggests an increased prevalence of MRONJ associated with sequential ARD therapy for pamidronate-zoledronate and bisphosphonate-denosumab administration when compared to single ARD therapy.

Immune-Related Oral, Otologic, and Ocular Adverse Events.

Emerging immunotherapeutic agents, including immune checkpoint inhibitors targeting cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1), and programmed cell death protein ligand 1 (PD-L1), have revolutionized cancer treatment. The first immune checkpoint inhibitor (ICI) ipilimumab, an anti-CTLA-4, was approved in 2011. Since then, the US Food and Drug Administration (FDA) has approved more than half a dozen immune checkpoint inhibitors to treat various malignancies. These agents are part of a broader class of chemotherapy agents termed immunotherapy, which selectively target different steps in the immune response cascade to upregulate the body's normal response to cancer. While the effects of traditional chemotherapy are well known, the toxicity profile of emerging immune therapies is not fully elucidated. They have been associated with atypical side effects labeled collectively as immune-related adverse events (irAEs).

ANTIBIOTIC RESISTANCE IN ESCHERICHIA COLI AND ENTEROCOCCUS SPP. ISOLATED FROM UNGULATES AT A ZOOLOGICAL COLLECTION IN THE UNITED KINGDOM.

Increase of antimicrobial resistance (AMR) is a global threat to health. The AMR profile of bacteria isolated from domesticated animals and free-ranging wildlife has been studied, but there are relatively few studies of bacteria isolated from captive wild animals. Understanding the dynamics of AMR in different populations is key to minimizing emergence of resistance and to preserve the efficacy of antimicrobials. In this study, fecal samples were collected from 17 species of healthy ungulates from a zoological collection in southeast England, which yielded 39 Escherichia coli and 55 Enterococcus spp. isolates for further analysis. Antibiotic sensitivity was investigated using agar disk diffusion. Escherichia coli isolates were resistant to a range of antibiotics, with resistance to ampicillin being the most common (28%). All E. coli isolates were susceptible to apramycin, enrofloxacin, chloramphenicol, and florfenicol. None tested positive for extended-spectrum beta-lactamase or AmpC activity. Seven of 39 (18%) E. coli isolates were resistant to three or more antibiotic classes. The E. coli isolates were further analyzed using multilocus sequence typing, which identified four pairs of identical sequence type isolates and 27 diverse strains. The Enterococcus spp. isolates were resistant to a range of antibiotics, with resistance to cefpodoxime seen in 95% of isolates. All Enterococcus spp. isolates were susceptible to ampicillin, gentamicin, chloramphenicol, and vancomycin. This study identified multidrug-resistant phenotypes in enterobacterial isolates that were like those commonly found in domestic ungulates. There was no apparent spatial clustering of the resistance profiles within the zoo. Review of the medical records of individual animals showed no direct relation to the AMR profiles observed. Observed resistance to antibiotics rarely or never used may have been due to coselection or directly acquired from other sources.

Oral microbiome and onset of oral mucositis in patients with squamous cell carcinoma of the head and neck.

BACKGROUND: Oral mucositis (OM) is a debilitating sequela for patients treated for squamous cell carcinoma of the head and neck (HNSCC). This study investigated whether oral microbial features before treatment or during treatment are associated with the time to onset of severe OM in patients with HNSCC. METHODS: This was a cohort study of newly diagnosed patients with locoregional HNSCC who received chemotherapy with or without radiotherapy from April 2016 to September 2017. OM was based on the National Cancer Institute's Common Terminology Criteria for Adverse Events, version 4.0. The oral microbiome was characterized on the basis of the 16S ribosomal RNA V4 region with the Illumina platform. A mixture cure model was used to generate hazard ratios for the onset of severe OM. RESULTS: Eighty-six percent of the patients developed OM (n = 57 [33 nonsevere cases and 24 severe cases]) with a median time to onset of OM of 21 days. With adjustments for age, sex, and smoking status, genera abundance was associated with the hazard for the onset of severe OM as follows: 1) at the baseline (n = 66), Cardiobacterium (P = .03) and Granulicatella (P = .04); 2) immediately before the development of OM (n = 57), Prevotella (P = .03), Fusobacterium (P = .03), and Streptococcus (P = .01); and 3) immediately before the development of severe OM (n = 24), Megasphaera (P = .0001) and Cardiobacterium (P = .03). There were no differences in α-diversity between the baseline samples and Human Microbiome Project data. CONCLUSIONS: Changes in the abundance of genera over the course of treatment were associated with the onset of severe OM. The mechanism and therapeutic implications of these findings need to be investigated in future studies.

The effects of zinc on radiation-induced dysgeusia: a systematic review and meta-analysis.

PURPOSE: Many head and neck cancer patients who receive radiation therapy experience radiation-induced dysgeusia (RID), which has no standard treatment. The only supplement controlled clinical trials have evaluated for the treatment of RID is zinc. However, the results of these and other studies investigating the use of zinc for RID have been inconsistent. To assess the validity of zinc as a treatment for RID, we conducted a systematic literature search and performed a meta-analysis to determine the extent to which zinc affects RID incidence and the degree to which ongoing RID responds to zinc. METHODS: We searched the Ovid MEDLINE, Ovid Embase, PubMed, and Cochrane Library databases to identify studies investigating the use of zinc-based therapy for RID in head and neck cancer patients treated with radiation that were published between January 1, 2003, and November 9, 2017. Using American Society of Clinical Oncology criteria, we selected studies with a high level of evidence for inclusion in the meta-analysis. RESULTS: Of the 32 full-text articles eligible for inclusion, three were included in the final review and meta-analysis. The meta-analysis showed that, compared with placebo, zinc reduces the incidence of RID (risk ratio, 0.72; 95% confidence interval, 0.67-0.92) but does not improve taste acuity more rapidly following radiation therapy (risk ratio, 2.58; 95% confidence interval, 0.97-6.88). CONCLUSION: Our findings indicate that zinc-based therapy reduces the incidence of RID but has a minimal effect on ongoing RID. Our findings also highlight the need for additional evidence-based research on this topic.

Minocycline for symptom reduction during radiation therapy for head and neck cancer: a randomized clinical trial.

PURPOSE: Local/systemic symptoms during cancer therapy may be exacerbated by dysregulated inflammation and its downstream toxic effects. Minocycline can suppress proinflammatory cytokine release; therefore, we investigated its potential to reduce patient-reported symptom severity during radiotherapy (RT) for head and neck cancer (HNC). METHODS: Eligible patients for this blinded, placebo-controlled trial were adults with T0-3, N-any, and M0 HNC receiving single-modality RT. Participants were randomized 1:1 to either minocycline (200 mg/day) or placebo during RT. The primary endpoint was the area under the curve (AUC) of 5 prespecified symptoms (pain, fatigue, disturbed sleep, poor appetite, difficulty swallowing/chewing) during RT, assessed with the MD Anderson Symptom Inventory for HNC (MDASI-HN). RESULTS: We analyzed data from 20 evaluable patients per arm. Overall, 75% had oropharyngeal cancer and 78% were male. No grade 3+ adverse events potentially related to study medication were observed. Two minocycline patients required a feeding tube during RT vs 5 placebo patients (P = 0.21). The average daily AUC during RT for the 5 MDASI-HN symptoms was 3.1 (SD = 1.0) for minocycline and 3.7 (SD = 1.7) for placebo (P = 0.16); the 0.37 effect size was less than our 0.70 target. AUC comparisons for several individual symptoms and symptom interference favored minocycline but were not statistically significant. The greatest numerical differences occurred for systemic symptoms, larger toward treatment end, and in early post-RT recovery. CONCLUSIONS: Minocycline was feasible, well tolerated, and achieved a positive signal toward reducing patient-reported symptom severity during RT for HNC, particularly for systemic symptoms. This justifies additional study and informs future trial design.

Immune-Related Oral, Otologic, and Ocular Adverse Events.

Emerging immunotherapy agents, such as immune checkpoint inhibitors, have shown remarkable promise in the treatment of various malignancies. These drugs selectively target different steps in the immune response cascade to upregulate the body's normal response to cancer. Due to the novelty of these therapeutic agents, their toxicity profile is less well understood.Meta-analysis results reveal that the overall prevalence of oral mucositis, stomatitis, and xerostomia is lower with checkpoint inhibitors compared to conventional chemotherapy, and head and neck radiation therapy. However, the widespread use of immunotherapy reveals new oral mucosal barrier adverse events, including bullous pemphigoid, mucous membrane pemphigoid, and lichenoid mucositis. Audiovestibular dysfunction can occur from autoimmune-mediated pathways of immunotherapy (adoptive cell) with limited treatment options. Such auditory complications can lead to speech recognition deficits and sensorineural hearing loss. Ocular toxicities are among the most common adverse events resulting from the use of these agents. The majority of ocular immune-related adverse events (irAEs) are mild, low-grade, non-sight threatening, such as blurred vision, conjunctivitis, and ocular surface disease. Serious and sight-threatening events, including corneal perforation, optic neuropathy, and retinal vascular occlusion, can occur but are infrequent. In this chapter, we review the current evidence on the clinical manifestations of oral, audiovestibular, and ocular immune-related adverse events (i.e., irAEs).