Oral Toxicities Associated with Immune Checkpoint Inhibitors: Meta-Analyses of Clinical Trials.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer treatment; however, their oral toxicity profile is not well elucidated. This review aimed to investigate the prevalence of oral toxicities including xerostomia, mucositis/stomatitis, dysgeusia, dysphagia, oral/oropharyngeal pain, oral infections, angular cheilitis, osteonecrosis, osteomyelitis, and oral mucosal reactions with ICIs. A review protocol was registered with PROSPERO (ID: CRD42023391674). A systematic search of ClinicalTrials.gov was conducted as of April 10, 2022. Studies were selected, assessed, and data extracted using PRISMA guidelines. Oral toxicity data were extracted from study arms using a single immunotherapy drug. Meta-analyses were conducted to summarize prevalence of oral toxicities using random-effects models. Of 750 screened records, 95 trials were included in the meta-analysis with published results. Time between study completion and first publication on ClinicalTrials.gov was 1 to 146 months (mean = 20.3, SD = 18.4). Weighted pooled prevalence was 5% (95% CI: 4-6%) for xerostomia, 3% (95% CI: 3-4%) for mucositis/stomatitis, 3% (95% CI: 2-3%) for dysgeusia, 2% (95% CI: 1-2%) for dysphagia, 3% (95% CI: 2-4%) for oropharyngeal/oral pain, 2% (95% CI: 1-3%) for oral candidiasis, and 2% (95% CI: 0-4%) for angular cheilitis. Subgroup differences based on ICI drugs were minimal. No trials reported lichenoid or pemphigoid mucosal reactions. Meta-analysis results revealed low prevalence of oral toxicities with ICIs; however, data reporting was limited and inconsistent. Limitations of study dataset reveal a significant need for systematic collection of oral morbidity data as well as improved consistency and compliance of reporting results on ClinicalTrials.gov.

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.

Genetic susceptibility to patient-reported xerostomia among long-term oropharyngeal cancer survivors.

Genetic susceptibility for xerostomia, a common sequela of radiotherapy and chemoradiotherapy for head and neck cancer, is unknown. Therefore, to identify genetic variants associated with moderate to severe xerostomia, we conducted a GWAS of 359 long-term oropharyngeal cancer (OPC) survivors using 579,956 autosomal SNPs. Patient-reported cancer treatment-related xerostomia was assessed using the MD Anderson Symptom Inventory. Patient response was dichotomized as moderate to severe or none to mild symptoms. In our study, 39.2% of OPC survivors reported moderate to severe xerostomia. Our GWAS identified eight SNPs suggestively associated with higher risk of moderate to severe xerostomia in six genomic regions (2p13.3, rs6546481, Minor Allele (MA) = A, ANTXR1, P = 4.3 × 10-7; 5p13.2-p13.1, rs16903936, MA = G, EGFLAM, P = 5.1 × 10-6; 4q21.1, rs10518156, MA = G, SHROOM3, P = 7.1 × 10-6; 19q13.42, rs11882068, MA = G, NLRP9, P = 1.7 × 10-5; 12q24.33, rs4760542, MA = G, GLT1D1, P = 1.8 × 10-5; and 3q27.3, rs11714564, MA = G, RTP1, P = 2.9 × 10-5. Seven SNPs were associated with lower risk of moderate to severe xerostomia, of which only one mapped to specific genomic region (15q21.3, rs4776140, MA = G, LOC105370826, a ncRNA class RNA gene, P = 1.5 × 10-5). Although our small exploratory study did not reach genome-wide statistical significance, our study provides, for the first time, preliminary evidence of genetic susceptibility to xerostomia. Further studies are needed to elucidate the role of genetic susceptibility to xerostomia.

Effect of vaping on past-year smoking cessation success of Australians in 2019-evidence from a national survey.

BACKGROUND AND AIMS: Previous analyses of the effect of e-cigarettes on real world smoking cessation success have mainly been based on surveys undertaken in the United States and United Kingdom, where nicotine e-cigarettes can be readily obtained. In Australia, regulations have made obtaining e-cigarettes containing nicotine difficult. The effectiveness of e-cigarette use as a smoking cessation aid in Australia might therefore be lower than survey-based estimates published to date. This study aimed to estimate the effect of using e-cigarettes for a smoking cessation attempt on past-year smoking cessation success in Australia. DESIGN: Multivariable logistic regression models for past-year smoking cessation success. SETTING AND PARTICIPANTS: Respondents to the 2019 wave of Australia's National Drug Strategy Household Survey who made a smoking cessation attempt in the 12 months leading up to the survey. MEASUREMENTS: Past-year smoking cessation success was assumed if a smoking cessation attempt resulted in abstinence of more than a month at the time of the survey. FINDINGS: In 2019, Australians who attempted to quit smoking using e-cigarettes achieved greater success than smokers attempting to quit without e-cigarettes [adjusted odds ratio (aOR) = 1.68; 95% confidence interval (CI) = 1.09-2.60]. If people who only tried e-cigarettes once or twice are considered not to have used e-cigarettes, the estimated effect was slightly stronger (aOR = 1.98; 95% CI = 1.27-3.10). Also, the estimated odds ratio was higher among vapers who acquired their e-cigarettes from overseas websites (aOR = 2.24; 95% CI = 1.02-4.93). CONCLUSIONS: Use of e-cigarettes for a smoking cessation attempt appears to be associated with greater success among Australians who attempted to quit tobacco in 2019 compared with Australians attempting to quit without e-cigarettes, after adjusting for confounding effects.

Outcomes after definitive surgery for mandibular osteoradionecrosis.

OBJECTIVES: To analyze charges, complications, survival, and functional outcomes for definitive surgery of mandibular osteoradionecrosis (ORN). MATERIALS AND METHODS: Retrospective analysis of 76 patients who underwent segmental mandibulectomy with reconstruction from 2000 to 2009. RESULTS: Complications occurred in 49 (65%) patients and were associated with preoperative drainage (odds ratio [OR] 4.40, 95% confidence interval [CI] 1.01-19.27). The adjusted median charge was $343 000, and higher charges were associated with double flap reconstruction (OR 8.15, 95% CI 2.19-30.29) and smoking (OR 5.91, 95% CI 1.69-20.72). Improved swallow was associated with age <67 years (OR 3.76, 95% CI 1.16-12.17) and preoperative swallow (OR 3.42, 95% CI 1.23-9.51). Five-year ORN-recurrence-free survival was 93% while overall survival was 63% and associated with pulmonary disease (HR [hazard ratio] 3.57, 95% CI 1.43-8.94). CONCLUSIONS: Although recurrence of ORN is rare, surgical complications are common and charges are high. Poorer outcomes and higher charges are associated with preoperative factors.

Risk factors associated with patient-reported fatigue among long-term oropharyngeal carcinoma survivors.

BACKGROUND: The study objective is to identify risk factors associated with fatigue among long-term OPC survivors. METHODS: This cross-sectional study included disease-free OPC survivors treated curatively between 2000 and 2013 who were surveyed from September 2015 to July 2016. The outcome variable was patient-reported fatigue. Multivariable logistic regression was used to identify factors associated with moderate to severe fatigue. RESULTS: Among 863 OPC survivors, 17.4% reported moderate to severe fatigue. Self-reported thyroid problems (OR: 2.01; p = 0.003), current cigarette smoking at time of survey (OR: 3.85; p = 0.001), late lower cranial neuropathy (OR: 3.44; p = 0.002), and female sex (OR: 1.91; p = 0.010) were concurrent risk factors of reporting moderate to severe fatigue. Ipsilateral intensity-modulated radiotherapy (OR: 0.18; p = 0.014) was associated with lower risk of reporting moderate to severe fatigue. CONCLUSIONS: Our study identified thyroid problems, smoking, and late lower cranial neuropathy as associated with moderate to severe fatigue. These findings should be further validated in prospective studies to address fatigue among OPC survivors.

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.

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.

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.

Factors associated with complex oral treatment device usage in patients with head and neck cancer.

PURPOSE: The objective was to identify clinical and epidemiological factors associated with utilization of a complex oral treatment device (COTD), which may decrease toxicity in patients undergoing radiation therapy for head and neck cancer (HNC). MATERIALS AND METHODS: We retrospectively reviewed data from 1992 to 2013 in the Surveillance, Epidemiology, and End Results (SEER)-Medicare databases to analyze COTD usage during intensity-modulated radiation therapy (IMRT) for patients diagnosed with cancer of the tongue, floor of mouth, nasopharynx, tonsil, or oropharynx. Patients with a radiation simulation and complex treatment device code within 4 weeks before the first IMRT claim were identified as meeting COTD usage criteria. Demographic, regional, tumor, and treatment data were analyzed. RESULTS: Out of 4511 patients who met eligibility criteria, 1932 patients (42.8%) did not utilize a COTD while 2579 (57.2%) met usage criteria. COTD utilization increased over time (36.36% usage in 1992 vs. 67.44% usage in 2013, p < .0001). Patients less likely to receive a COTD included those aged 86 years or older compared to those aged 66-70 (OR = 0.713, 95% CI: 0.528-0.962), male patients (OR = 0.817, 95% CI: 0.710-0.941), non-Hispanic Black patients compared to non-Hispanic White patients (OR = 0.750, 95% CI: 0.582-0.966), and Louisiana residents (OR = 0.367, 95% CI: 0.279-0.483). Cancer site, grade, stage, or function of IMRT had no significant association with COTD usage. CONCLUSIONS: This study serves as the first known SEER-Medicare review of COTD utilization. Despite an increase in COTD usage over time, our results indicate age, gender, and geographic disparities are associated with utilization. Further research and development into methods that increase availability of COTDs may help increase utilization in specific patient populations.

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.

Proton Therapy for Head and Neck Cancer: A 12-Year, Single-Institution Experience.

PURPOSE: To characterize our experience and the disease control and toxicity of proton therapy (PT) for patients with head and neck cancer (HNC). PATIENTS AND METHODS: Clinical outcomes for patients with HNC treated with PT at our institution were prospectively collected in 2 institutional review board-approved prospective studies. Descriptive statistics were used to summarize patient characteristics and outcomes. Overall survival, local-regional control, and disease-free survival were estimated by the Kaplan-Meier method. Treatment-related toxicities were recorded according to the Common Terminology Criteria for Adverse Events (version 4.03) scale. RESULTS: The cohort consisted of 573 patients treated from February 2006 to June 2018. Median patient age was 61 years. Oropharynx (33.3%; n = 191), paranasal sinus (11%; n = 63), and periorbital tissues (11%; n = 62) were the most common primary sites. Patients with T3/T4 or recurrent disease comprised 46% (n = 262) of the cohort. The intent of PT was definitive in 53% (n = 303), postoperative in 37% (n = 211), and reirradiation in 10% (n = 59). Median dose was 66 Gy (radiobiological equivalent). Regarding systemic therapy, 43% had received concurrent (n = 244), 3% induction (n = 19), and 15% (n = 86) had both. At a median follow-up of 2.4 years, 88 patients (15%) had died and 127 (22%) developed disease recurrence. The overall survival, local-regional control, and disease-free survival at 2 and 5 years were, respectively, 87% and 75%, 87% and 78%, and 74% and 63%. Maximum toxicity (acute or late) was grade 3 in 293 patients (51%), grade 2 in 234 patients (41%), and grade 1 in 31 patients (5%). There were 381 acute grade 3 and 190 late grade 3 unique toxicities across 212 (37%) and 150 (26%) patients, respectively. There were 3 late-grade 4 events across 2 patients (0.3%), 2 (0.3%) acute-grade 5, and no (0%) late-grade 5 events. CONCLUSIONS: The overall results from this prospective study of our initial decade of experience with PT for HNC show favorable disease control and toxicity outcomes in a multidisease-site cohort and provide a reference benchmark for future comparison and study.

Computed Tomography Radiomics Kinetics as Early Imaging Correlates of Osteoradionecrosis in Oropharyngeal Cancer Patients.

Osteoradionecrosis (ORN) is a major side-effect of radiation therapy in oropharyngeal cancer (OPC) patients. In this study, we demonstrate that early prediction of ORN is possible by analyzing the temporal evolution of mandibular subvolumes receiving radiation. For our analysis, we use computed tomography (CT) scans from 21 OPC patients treated with Intensity Modulated Radiation Therapy (IMRT) with subsequent radiographically-proven ≥ grade II ORN, at three different time points: pre-IMRT, 2-months, and 6-months post-IMRT. For each patient, radiomic features were extracted from a mandibular subvolume that developed ORN and a control subvolume that received the same dose but did not develop ORN. We used a Multivariate Functional Principal Component Analysis (MFPCA) approach to characterize the temporal trajectories of these features. The proposed MFPCA model performs the best at classifying ORN vs. Control subvolumes with an area under curve (AUC) = 0.74 [95% confidence interval (C.I.): 0.61-0.90], significantly outperforming existing approaches such as a pre-IMRT features model or a delta model based on changes at intermediate time points, i.e., at 2- and 6-month follow-up. This suggests that temporal trajectories of radiomics features derived from sequential pre- and post-RT CT scans can provide markers that are correlates of RT-induced mandibular injury, and consequently aid in earlier management of ORN.

Reconstruction of intraoral oncologic surgical defects with Integra® bilayer wound matrix.

Utilization of biologic skin substitutes for the management of soft tissue defects as an alternative to autologous skin grafts has expanded over the past 2 decades. The purpose of this case series study was to report our experience with Integra® bilayer wound matrix for reconstruction of intraoral oncologic defects. Case records of 6 patients with intraoral oncologic defects reconstructed with Integra® bilayer wound matrix were retrospectively reviewed. The surgical defect location, size, and time to removal of surgical splint varied. Clinically, normal oral epithelialization was noted for all patients. One patient demonstrated a small area of dehiscence and bone exposure after adjuvant radiation therapy which resolved with minimal intervention. Integra bilayer wound matrix is a viable and versatile option for reconstruction of intraoral oncologic surgical defects. Further exploration of wound healing with Integra® matrix, surgical techniques, and cost-effectiveness is advocated.

Medication-Related Osteonecrosis of the Jaw in Patients Treated Concurrently with Antiresorptive and Antiangiogenic Agents: Systematic Review and Meta-Analysis.

Introduction: Medication-related osteonecrosis of the jaws (MRONJ) is a known adverse event related to the use of antiresorptive (AR) drugs. More recently, an association between antiangiogenic (AA) drugs and MRONJ has been suggested. This review aimed to investigate the overall prevalence and relative risk of MRONJ in patients treated concurrently with AA and AR agents in comparison with a single AA or AR drug. Methods: A review protocol was registered with PROSPERO (ID: CRD42020214244). A systematic literature search, study selection, quality assessment, and data extraction were carried out following PRISMA guidelines. Random-effects meta-analysis models were used to summarize relative estimates for the outcomes, namely prevalence and relative risk of MRONJ. Exposure variable included type of drug, specifically AA and AR agents administered either concurrently or individually. Results: Eleven studies were included in the final qualitative and quantitative syntheses. The overall pooled weighted prevalence of MRONJ with concurrent AA-AR drugs was 6% (95% CI: 3-8%), compared with 0% (95% CI: 0-0%) for AA only and 5% (95% CI: 0-10%) for AR only. However, high heterogeneity was noted among included studies. Retrospective cohort studies showed a higher pooled prevalence of 13% (95% CI: 10-17%) for concurrent AA-AR therapy. The pooled risk ratio for MRONJ revealed a risk with concurrent AA-AR drugs 2.57 times as high as with AR only (95% CI: 0.84-7.87); however, this difference was not statistically significant. Concurrent AA-AR drugs had a risk for MRONJ 23.74 times as high as with AA only (95% CI: 3.71-151.92). Conclusions: High-quality, representative studies are needed for accurate estimation of relative risk of MRONJ with concurrent AA and AR 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).

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.