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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.

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.

Purpose: To determine the disease control rate and toxicity of treating patients with aggressive cutaneous squamous cell carcinoma (CSCC) with neoadjuvant gefitinib.Experimental Design: A prospective phase II clinical trial evaluating neoadjuvant gefitinib given prior to standard treatment with surgery and/or radiotherapy. Patients with stable disease after one cycle received escalated doses. Patients who responded were given gefitinib during radiation therapy, as well as maintenance therapy after definitive treatment. We analyzed the correlation between epidermal growth factor receptor (EGFR) expression, mutation status, and gene copy number on available tissue samples and clinical response.Results: Twenty-three patients were accrued and 22 patients were evaluable for response prior to definitive local treatment; complete responses were attained by 18.2% of patients and partial responses by 27.3%. Grades 2 to 3 toxicities were observed in 59.1% of patients experiencing class-specific effects during induction therapy. After induction, 11.8% underwent surgery alone, 17.6% had definitive radiation, 11.8% were treated with radiation and concurrent gefitinib, and 47% had surgery with postoperative radiation and concurrent gefitinib. Median follow-up for the censored observations was 32 months. Two-year overall, disease-specific, and progression-free survival rates were 72.1%, 72.1%, and 63.6%, respectively. No EGFR-activating mutations were identified in tumor samples available from 10 patients. No associations between EGFR correlative studies and patient outcomes were identified.Conclusions: Gefitinib, in the neoadjuvant setting, was active and well tolerated in patients with aggressive CSCC and did not interfere with definitive treatment. In view of the 18% complete response rate we observed, EGFR tyrosine kinase inhibitors should be further explored in the treatment of aggressive CSCC. Clin Cancer Res; 18(5); 1435–46. ©2012 AACR.

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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

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.

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., Integra® bilayer wound matrix is a viable and versatile option for reconstruction of small to large intraoral oncologic surgical defects on movable and nonmoveable mucosa.

According to the entrainment hypothesis, traditional migratory routes develop in fish populations through social interactions. First-time migrants learn migratory routes by following experienced conspecifics and, by repeating the migration, contribute to guiding future cohorts along the same route. The loss of collective memory of migratory routes may be a precursor to fisheries collapse. The survival value of entrainment has not been convincingly demonstrated, and this possibly explains why there has not been greater interest in this putative migratory mechanism. I propose that the relative frequency of demonstrators of alternative contingents provides information to first-time migrants on relative survival rates. Using simulation, I show that a population in which contingent adoption is regulated by entrainment can achieve higher overall survival rates than a comparable population with fixed rates of contingent adoption in the situation where mortality rates differ among contingents. In certain cases, the advantage could be even larger in the presence of fishing mortality. I also compare the responses of the entrainment-based and fixed-rate migration populations in a scenario intended to mimic the cessation of fishing after a period of high fishing mortality, such as might occur after the collapse of a fishery.

PURPOSE: We aim to characterize the quantitative dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters associated with advanced mandibular osteoradionecrosis (ORN) compared with the contralateral normal mandible. METHODS AND MATERIALS: Patients with a diagnosis of advanced ORN after curative-intent radiation treatment of head and neck cancer were prospectively enrolled after institutional review board approval and study-specific informed consent were obtained. Quantitative maps generated with the Tofts and extended Tofts pharmacokinetic models were used for analysis. Manual segmentation of advanced ORN 3-dimensional volume was done using anatomic sequences to create ORN volumes of interest (VOIs). Subsequently, normal mandibular VOIs were segmented on the contralateral healthy mandible of similar volume and anatomic location to create control VOIs. Finally, anatomic sequences were coregistered to DCE sequences, and contours were propagated to the respective parameter maps. RESULTS: Thirty patients were included. The median time to ORN diagnosis after completion of IMRT was 38 months (range, 6–184 months), whereas median time to ORN progression to advanced grade after initial diagnosis was 5.6 months (range, 0–128 months). There were statistically significant higher K(trans) and V(e) in ORN-VOIs compared with controls (0.23 vs 0.07 min(−)(1), and 0.34 vs 0.15; P

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.

The coronavirus disease 2019 (COVID‐19) pandemic has become a major public health crisis. The diagnostic and containment efforts for the disease have presented significant challenges for the global health‐care community. In this brief report, we provide perspective on the potential use of salivary specimens for detection and serial monitoring of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), based on current literature. Oral health‐care providers are at an elevated risk of exposure to COVID‐19 due to their proximity to nasopharynx of patients, and the practice involving the use of aerosol‐generating equipment. Here, we summarize the general guidelines for oral health‐care specialists for prevention of nosocomial transmission of COVID‐19, and provide specific recommendations for clinical care management.

Author(s): MD Anderson Head and Neck Surgery Treatment Guidelines Consortium; Consortium members; Maniakas, Anastasios; Jozaghi, Yelda; Zafereo, Mark E; Sturgis, Erich M; Su, Shirley Y; Gillenwater, Ann M; Gidley, Paul W; Lewis, Carol M; Diaz, Eduardo; Goepfert, Ryan P; Kupferman, Michael E; Gross, Neil D; Hessel, Amy C; Pytynia, Kristen B; Nader, Marc-Elie; Wang, Jennifer R; Lango, Miriam N; Kiong, Kimberley L; Guo, Theresa; Zhao, Xiao; Yao, Christopher MKL; Appelbaum, Eric; Alpard, Jennifer; Garcia, Jose A; Terry, Shawn; Flynn, Jill E; Bauer, Sarah; Fournier, Danielle; Burgess, Courtlyn G; Wideman, Cayla; Johnston, Matthew; You, Chenxi; De Luna, Rolando; Joseph, Liza; Diersing, Julia; Prescott, Kaitlin; Heiberger, Katherine; Mugartegui, Lilian; Rodriguez, Jessica; Zendehdel, Sara; Sellers, Justin; Friddell, Rebekah A; Thomas, Ajay; Khanjae, Sonam J; Schwarzlose, Katherine B; Chambers, Mark S; Hofstede, Theresa M; Cardoso, Richard C; Wesson, Ruth Aponte; Won, Alex; Otun, Adegbenga O; Gombos, Dan S; Al-Zubidi, Nagham; Hutcheson, Katherine A; Gunn, G Brandon; Rosenthal, David I; Gillison, Maura L; Ferrarotto, Renata; Weber, Randal S; Hanna, Ehab Y; Myers, Jeffrey N; Lai, Stephen Y | Abstract: BackgroundCOVID-19 pandemic has strained human and material resources around the world. Practices in surgical oncology had to change in response to these resource limitations, triaging based on acuity, expected oncologic outcomes, availability of supportive resources, and safety of health care personnel.MethodsThe MD Anderson Head and Neck Surgery Treatment Guidelines Consortium devised the following to provide guidance on triaging head and neck cancer (HNC) surgeries based on multidisciplinary consensus. HNC subsites considered included aerodigestive tract mucosa, sinonasal, salivary, endocrine, cutaneous, and ocular.RecommendationsEach subsite is presented separately with disease-specific recommendations. Options for alternative treatment modalities are provided if surgical treatment needs to be deferred.ConclusionThese guidelines are intended to help clinicians caring for patients with HNC appropriately allocate resources during a health care crisis, such as the COVID-19 pandemic. We continue to advocate for individual consideration of cases in a multidisciplinary fashion based on individual patient circumstances and resource availability.

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).

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.

PURPOSE Chairside prosthesis adjustment procedures generate contaminated acrylic particle debris that include visible splatter (particles >50μm) as well as invisible aerosols (

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.

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.

Patients who have undergone a bilateral maxillectomy are particularly difficult to rehabilitate prosthetically by using a conventional obturator prosthesis, mainly because of the extensive loss of tissues for retention and support. In these situations, adapting to existing undercuts within the defect is essential. Traditional impression techniques capture certain anatomic landmarks but may fall short of the needed sinus undercuts. This article describes an alternative impression technique for capturing 3 opposing undercuts to help retain, support, and stabilize a hollow 1-piece obturator prosthesis for a patient who underwent a total maxillectomy.

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.

This clinical report describes a multidisciplinary approach in maxillofacial rehabilitation of a 61-year-old Caucasian male diagnosed with squamous cell carcinoma of the oral tongue. Following external beam radiation therapy, brachytherapy and a left neck dissection, the patient presented with bilateral osteoradionecrosis of the mandibular rami refractory to hyperbaric oxygen treatment. A subtotal mandibulectomy with a fibula free flap osteocutaneous reconstruction was subsequently performed. Prosthodontic planning and treatment considerations in a case of osteoradionecrosis refractory to hyperbaric oxygen with a reconstructed mandible is presented in this case report. (Int J Maxillofac Prosthetics 2019;1:9-13)

Background Tumor-induced osteomalacia is a rare paraneoplastic syndrome in which patients develop hypophosphatemia and osteomalacia. Methods and results Here, we report a unique case of a 42-year-old man who presented to our institution with a 1-year history of pain in his ribs, hips, lower back, and feet. Radiologic examination revealed a decrease in bone density and multiple insufficiency fractures. Laboratory evaluation revealed hypophosphatemia, low serum 1,25 dihydroxy vitamin D3 , and elevated fibroblast growth factor 23 (FGF23). A positron emission tomography/CT scan showed increased uptake in the right mandibular third molar region. Panoramic radiography and CT scanning showed a lytic expansile bone lesion. A mandibular bone biopsy revealed a mixed connective tissue tumor. A right segmental mandibulectomy was performed, followed by microvascular reconstruction. The resection was confirmed by normalization of serum phosphate and FGF23. Conclusion Successful management of this condition was achieved, with complete surgical resection of the tumor and reconstructive surgery.

Purpose: Fractionated stereotactic radiosurgery (FSRS) can be given with at least three modalities: Gamma Knife, with the noninvasive frameless extend system (GKE); linear accelerator-based volumetric modulated arc therapy (VMAT); and intensity-modulated proton therapy (IMPT). We extracted treatment plans for patients who had received FSRS with GKE for recurrent skull base or intracranial tumors, created corresponding plans for VMAT and IMPT, and compared the quality of the three sets of plans. Methods and materials: Plans were extracted for 9 patients with recurrent malignant skull-base tumors (n = 6) or large intracranial tumors (n = 3) who had received FSRS with GKE (median dose 24 Gy in 3 fractions) in 2013 through 2015. Plans for VMAT were generated with a TrueBeam STx LINAC machine using 6-MV photons, and plans for IMPT were generated with multi-field optimization. The optimized VMAT and IMPT plans were normalized to achieve the best possible target coverage while meeting the same dose-volume constraints on organs at risk (OARs) as the GKE plans. Plans were evaluated on the basis of target coverage, conformity index, homogeneity index, gradient index, and treatment efficiency. Results: The median target volume was 10.2 cm3 (range 1.9 - 33.8 cm3). The VMAT and IMPT plans met all OAR constraints, and target coverage and conformity were comparable among all plans. VMAT and IMPT plans showed significantly better target uniformity and treatment delivery efficiency (P < 0.001). The gradient index and low-dose-bath were superior in the GKE plans (P < 0.001), indicating smaller irradiated volumes. When inverse planning was used, VMAT plans could achieve a similar or steeper dose drop-off at the target-OAR boundary than GKE plans. Conclusion: FSRS for skull base and large intracranial lesions delivered by VMAT and IMPT can achieve comparable target coverage, conformity, and sparing of critical structure as the GKE while providing superior target uniformity and treatment delivery efficiency. The GKE had superior high-dose gradients outside the target and thus better protected surrounding normal structures.

PURPOSE/OBJECTIVE(S) Low and middle-income countries (LMICs) are significantly under-represented in cancer research due to a lack of research capacity rooted in historical inequalities. Training in-country physicians in clinical research is one of the most sustainable ways to address the shortage of research in LMICs. As part of an academic partnership between MD Anderson Cancer Center in Houston, TX (MDA) and Cancer Diseases Hospital in Lusaka, Zambia (CDH), an international virtual clinical research course for clinical oncology fellows at CDH was piloted in Fall 2020 to address a significant need for a structured clinical research curriculum. MATERIALS/METHODS The virtual clinical research course took place from August to November 2020 and involved 14 weekly hour-long lectures (13 by MDA faculty, one by CDH faculty) on topics including identifying a research question, study design, clinical trials, research ethics, biostatistics, and scientific writing. The course was attended by 15 clinical oncology fellows. Eight senior fellows were paired with a longitudinal MDA and CDH faculty member and MDA resident/fellow mentor in their area of interest to support a research protocol. Anonymized pre- and post-course surveys were administered with 5-point Likert scale academic self-efficacy inventories and open-ended qualitative questions. Descriptive statistics were used to summarize the findings. RESULTS A total of 12/15 participants (80%) completed the pre-course survey and 11/15 (73%) completed the post-course survey. Average scores pre- and post-course, respectively, for research interest and motivation (5.0, 4.9), comfort reading and evaluating medical literature (3.7, 4.5), developing a study question and design (2.8, 4.0), collecting and managing data (3.3, 4.0), independently performing and publishing research (2.3, 3.7), and satisfaction with mentorship and profession (3.0, 4.2) demonstrated an increase across multiple domains. As of December 2020, there were eight active research proposals led by CDH clinical oncology fellows and there had been 21 meetings and 27 hours of MDA-CDH mentorship time. Positive themes from open-ended feedback included clear lectures, meaningful relationships with mentors, and utility of presenting research proposals for feedback while constructive themes included desire for more teaching on statistical analysis and incorporation of self-assessment modules. CONCLUSION Clinical research is essential to develop effective, evidence-based interventions to the unique cancer care challenges that occur in LMICs. The results from the pilot virtual MDA-CDH research course, which led to improvements in academic self-efficacy scores, support for research proposals led by CDH clinical oncology fellows, and formation of longitudinal mentorship groups demonstrate the feasibility of conducting a virtual longitudinal research workshop model. Continued collaboration and future follow-up will be needed to demonstrate effectiveness and impact.

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.

ObjectivesTo determine the utility of low-flip angle “black bone” magnetic resonance imaging (MRI) for cortical mandibular bone assessment by comparing interdentium cortical measurements and inter-observer morphometric variability in relation to computed tomography (CT).MethodsQuantification of cortical mandible bone width was performed as per Hamada et al. at 15 cross-sectional interdentium locations on pre-treatment black bone MRI and CT for 15 oropharyngeal cancer patients, with inter-observer analyses on a subset of 3 patients by 11 observers. Bland-Altman limits of agreement and bias estimation, Lin’s concordance correlation (LCC), and Deming orthogonal regression were used to compare CT and MRI measurements. The absolute variance and intraclass correlation coefficient (ICC) were implemented for the inter-observer error quantification.ResultsBoth the Bland Altman and Deming regression analyses showed CT and black bone MRI measurements were comparable within ±0.85 mm limits of agreement, and systematically smaller for MRI. LCC (0.60[0.52;0.67]) showed moderate equivalence between modalities. The average absolute variance between the observers was similar on CT (1.13±0.06 mm) and MRI (1.15 ±0.06 mm). The ICC analyses showed that measurement consistency was significantly higher (pConclusionsBlack bone MR sequence is usable as an alternative to CT for cortical mandible bone measurements, allowing use for early detection of cortical alteration (e.g. osteonecrosis). The cortical bone measurements showed substantive but equivalent inter-observer variation on both CT and black bone MRI. (Semi)automated measurement may mitigate this in future work.

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.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.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.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%).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.

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.

The coronavirus disease 2019 (COVID-19) pandemic has become a major public health crisis. The diagnostic and containment efforts for the disease have presented significant challenges for the global healthcare community. In this brief report, we provide perspective on the potential use of salivary specimens for detection and serial monitoring of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on current literature. Oral healthcare providers are at an elevated risk of exposure to COVID-19 due to their proximity to nasopharynx of patients, and the practice involving the use of aerosol-generating equipment. Here we summarize the general guidelines for oral healthcare specialists for prevention of nosocomial transmission of COVID-19, and provide specific recommendations for clinical care management.

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.

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. 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. 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). 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.

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).

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).

This report describes the treatment of a 68-year-old man with basosquamous cell carcinoma of the left auricular area. His oncologic treatment resulted in the loss of his left ear and much of the left temporal bone. The loss of a significant portion of the temporal bone precluded the use of extraoral implants. Owing to the lack of anatomic landmarks after his surgical treatment, positioning his auricular prosthesis proved challenging. The fabrication of his prosthesis and a custom positioning aid are described.

PurposeWe aim to characterize the quantitative DCE-MRI parameters associated with advanced mandibular osteoradionecrosis (ORN) compared to the contralateral normal mandible.Experimental DesignPatients with the diagnosis of advanced ORN after curative-intent radiation treatment of head and neck cancer were prospectively enrolled after institutional-review board approval and study-specific informed consent. Eligibility criteria included; age>18 years, pathological evidence of head and neck malignancy with history of curative-intent external beam radiotherapy; patients with clinically confirmed high-grade ORN requiring surgical intervention; and no contraindications to MRI. The DCE-MRI acquisition consisted of a variable flip angle T1 mapping sequence and a multi-phase 3D FSPGR sequence. Quantitative maps generated with the Tofts and extended Tofts pharmacokinetic model were used for analysis. Motion correction was applied. Manual segmentation of advanced ORN 3-D volume was done using anatomical sequences (T1, T2, and T1+contrast) to create ORN volumes of interest (ORN-VOIs).Subsequently, normal mandibular VOIs were segmented on the contralateral healthy mandible of similar volume and anatomical location (i.e., mirror image) to create self-control VOIs. Finally, anatomical sequences were co-registered to DCE sequences, and contours were propagated to the respective quantitative parameter maps.ResultsThirty patients were included. Median age at diagnosis was 58 years (range 19-78), and 83% were men. The site of tumor origin was in the oropharynx, oral cavity, salivary glands, and nasopharynx in 13, 9, 6, and 2 patients, respectively. The median time to ORN development after completion of IMRT was 38 months (range 6-184). There were statistically significant higher Ktrans and Ve values in ORN-VOIs compared with controls (0.23 vs. 0.07 min−1, and 0.34 vs. 0.15, p trans in ORN-VOIs was 3.2 folds healthy mandibular control VOIs. Moreover, the corresponding rise of Ve in ORN-VOIs was 2.7 folds higher than the controls. Using combined Ktrans and Ve parameters, 27 patients (90%) had at least a 200% increase of either of the studied parameters in the ORN-VOIs compared with their healthy mandible control VOIs.ConclusionOur results confirm there is a quantitatively significant higher degree of leakiness in the mandibular vasculature as measured using DCE-MRI parameters of areas affected with an advanced grade of ORN versus healthy mandible. We were able to measure significant increases in quantitative metrics compared to values from the non-ORN mandibular bone. Further efforts are ongoing to validate these findings to enable the use of these DCE-MRI parameter thresholds for the early detection of subclinical cases of ORN.

Radiation-induced xerostomia (RIX) is a common, often debilitating, adverse effect of radiation therapy among patients with head and neck cancer. Quality of life can be severely affected, and current treatments have limited benefit.To determine if acupuncture can prevent RIX in patients with head and neck cancer undergoing radiation therapy.This 2-center, phase 3, randomized clinical trial compared a standard care control (SCC) with true acupuncture (TA) and sham acupuncture (SA) among patients with oropharyngeal or nasopharyngeal carcinoma who were undergoing radiation therapy in comprehensive cancer centers in the United States and China. Patients were enrolled between December 16, 2011, and July 7, 2015. Final follow-up was August 15, 2016. Analyses were conducted February 1 through 28, 2019.Either TA or SA using a validated acupuncture placebo device was performed 3 times per week during a 6- to 7-week course of radiation therapy.The primary end point was RIX, as determined by the Xerostomia Questionnaire in which a higher score indicates worse RIX, for combined institutions 1 year after radiation therapy ended. Secondary outcomes included incidence of clinically significant xerostomia (score30), salivary flow, quality of life, salivary constituents, and role of baseline expectancy related to acupuncture on outcomes.Of 399 patients randomized, 339 were included in the final analysis (mean [SD] age, 51.3 [11.7] years; age range, 21-79 years; 258 [77.6%] men), including 112 patients in the TA group, 115 patients in the SA group, and 112 patients in the SCC group. For the primary aim, the adjusted least square mean (SD) xerostomia score in the TA group (26.6 [17.7]) was significantly lower than in the SCC group (34.8 [18.7]) (P = .001; effect size = -0.44) and marginally lower but not statistically significant different from the SA group (31.3 [18.6]) (P = .06; effect size = -0.26). Incidence of clinically significant xerostomia 1 year after radiation therapy ended followed a similar pattern, with 38 patients in the TA group (34.6%), 54 patients in the SA group (47.8%), and 60 patients in the SCC group (55.1%) experiencing clinically significant xerostomia (P = .009). Post hoc comparisons revealed a significant difference between the TA and SCC groups at both institutions, but TA was significantly different from SA only at Fudan University Cancer Center, Shanghai, China (estimated difference [SE]: TA vs SCC, -9.9 [2.5]; P .001; SA vs SCC, -1.7 [2.5]; P = .50; TA vs SA, -8.2 [2.5]; P = .001), and SA was significantly different from SCC only at the University of Texas MD Anderson Cancer Center, Houston, Texas (estimated difference [SE]: TA vs SCC, -8.1 [3.4]; P = .016; SA vs SCC, -10.5 [3.3]; P = .002; TA vs SA, 2.4 [3.2]; P = .45).This randomized clinical trial found that TA resulted in significantly fewer and less severe RIX symptoms 1 year after treatment vs SCC. However, further studies are needed to confirm clinical relevance and generalizability of this finding and to evaluate inconsistencies in response to sham acupuncture between patients in the United States and China.ClinicalTrials.gov identifier: NCT01266044.

GABAA receptors containing α5 subunits (GABAAα5) are highly expressed in the hippocampus and negatively involved in memory processing, as shown by the fact that GABAAα5–deficient mice show higher hippocampus-dependent performance than wild-type mice. Accordingly, small-molecule GABAAα5 negative allosteric modulators (NAMs) are known to enhance spatial learning and memory in rodents. Here we introduce a new, orally available GABAAα5 NAM that improves hippocampal functions. ONO-8590580 [1-(cyclopropylmethyl)-5-fluoro-4-methyl-N-[5-(1-methyl-1H-imidazol-4-yl)-2-pyridinyl]-1H-benzimidazol-6-amine] binds to the benzodiazepine binding sites on recombinant human α5–containing GABAA receptors with a Ki of 7.9 nM, and showed functionally selective GABAAα5 NAM activity for GABA-induced Cl− channel activity with a maximum 44.4% inhibition and an EC50 of 1.1 nM. In rat hippocampal slices, tetanus-induced long-term potentiation of CA1 synapse response was significantly augmented in the presence of 300 nM ONO-8590580. Orally administered ONO-8590580 (1–20 mg/kg) dose-dependently occupied hippocampal GABAAα5 in a range of 40%–90% at 1 hour after intake. In the rat passive avoidance test, ONO-8590580 (3–20 mg/kg, by mouth) significantly prevented (+)-MK-801 hydrogen maleate (MK-801)–induced memory deficit. In addition, ONO-8590580 (20 mg/kg, p.o.) was also effective in improving the cognitive deficit induced by scopolamine and MK-801 in the rat eight-arm radial maze test with equal or greater activity than 0.5 mg/kg donepezil. No anxiogenic-like or proconvulsant effect was associated with ONO-8590580 at 20 mg/kg p.o. in the elevated plus maze test or pentylenetetrazole-induced seizure test, respectively. In sum, ONO-8590580 is a novel GABAAα5 NAM that enhances hippocampal memory function without an anxiogenic or proconvulsant risk.

Background Patients with metastatic breast cancer may develop oral morbidities that result from therapeutic interventions. Mammalian target of rapamycin (mTOR) inhibitor–associated stomatitis (mIAS) is a common adverse event (AE), secondary to mTOR inhibitor therapy, that can have a negative impact on treatment adherence, quality of life, and health care costs. A multidisciplinary team approach is important to minimize mIAS and to maximize treatment benefits to patients with breast cancer. In this review, we discuss the pathophysiology, diagnosis, and natural history of mIAS. Current and new management strategies for the prevention and treatment of mIAS are described in the context of fostering a coordinated team care approach to optimizing patient care. Types of Studies Reviewed The authors conducted a PubMed search from 2007 through 2017 using the terms "stomatitis," "mIAS," "everolimus," "mTOR," "metastatic breast cancer," and "oral care." They selected articles published in peer-reviewed journals that reported controlled trials and evidence-based guidelines. Results mIAS can be distinguished from mucositis caused by cytotoxic chemotherapy or radiotherapy on the basis of cause, clinical presentation, and treatment paradigms. Specific preventive and therapeutic management strategies can be implemented across the continuum of patient oral health care. Practical Implications Oral health care providers are on the frontline of oral health care for patients with metastatic breast cancer and are uniquely positioned to provide patient education, advocate accurate reporting of mIAS, and support early identification, monitoring, and prompt intervention to mitigate the severity and duration of this manageable, potentially dose-limiting AE.

To identify a clinically meaningful cut-point for the single item dry mouth question of the MD Anderson Symptom Inventory-Head and Neck module (MDASI-HN).Head and neck cancer survivors who had received radiation therapy (RT) completed the MDASI-HN, the University of Michigan Hospital Xerostomia Questionnaire (XQ), and the health visual analog scale (VAS) of the EuroQol Five Dimension Questionnaire (EQ-5D). The Bayesian information criteria (BIC) were used to test the prediction power of each tool for EQ-5D VAS. The modified Breiman recursive partitioning analysis (RPA) was used to identify a cut point of the MDASI-HN dry mouth score (MDASI-HN-DM) with EQ-5D VAS, using a ROC-based approach; regression analysis was used to confirm the threshold effect size.Two-hundred seven respondents formed the cohort. Median follow-up from the end of RT to questionnaire completion was 88 months. The single item MDASI-HN-DM score showed a linear relationship with the XQ composite score (ρ = 0.80, p 0.001). The MDASI-HN-DM displayed improved model performance for association with EQ-5D VAS as compared to XQ (BIC of 1803.7 vs. 2016.9, respectively). RPA showed that an MDASI-HN-DM score of ≥6 correlated with EQ-5D VAS decline (LogWorth 5.5).The single item MDASI-HN-DM correlated with the multi-item XQ and performed favorably in the prediction of QOL. A MDASI-HN-DM cut point of ≥6 correlated with decline in QOL.

Oral fungal infections present with atypical and varied manifestations, and distinguishing them from other entities including leukemic infiltration can be diagnostically challenging. In this report, we describe a 62 year old female with acute myeloid leukemia who presented, towards the end of her second treatment cycle of decitabine in a prolonged neutropenic state, with a month of painful, necrotic-appearing marginal gingival lesions. She was duly initiated on empiric broad spectrum antifungal treatment but did not show a clinical response with the appearance of new skin lesions concerning for progressive fungemia. Concurrent gingival and cutaneous biopsy showed fungal invasion with Fusarium. Despite changing antifungal treatment the lesions progressed, and white blood cell (WBC) transfusions were instituted. The patient had an impressive response with gradual resolution of the skin lesions and regression in gingival lesions over a week of therapy. This case illustrates the highly atypical, confounding appearance of oral fungal infections in immunocompromised hematological malignancy patients. Maxillary and mandibular marginal gingival involvement, although extremely rare, should be recognized as potential sites of fungal involvement. Accurate diagnosis entails a biopsy especially in ambiguous clinical scenarios, as presented here. The role of WBC transfusions in the management of these rare fungal pathogenic infections needs to re-established.