Faculty Bibliography

BACKGROUND:The early detection of oral cavity squamous cell carcinoma (OSCC) and oral potentially malignant disorders (OPMD), followed by appropriate treatment, may improve survival and reduce the risk for malignant transformation respectively. This is an update of a Cochrane Review first published in 2013. OBJECTIVES:To estimate the diagnostic test accuracy of conventional oral examination, vital rinsing, light-based detection, mouth self-examination, remote screening, and biomarkers, used singly or in combination, for the early detection of OPMD or OSCC in apparently healthy adults. SEARCH METHODS:Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 20 October 2020), MEDLINE Ovid (1946 to 20 October 2020), and Embase Ovid (1980 to 20 October 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. We conducted citation searches, and screened reference lists of included studies for additional references. SELECTION CRITERIA:We selected studies that reported the test accuracy of any of the aforementioned tests in detecting OPMD or OSCC during a screening procedure. Diagnosis of OPMD or OSCC was provided by specialist clinicians or pathologists, or alternatively through follow-up. DATA COLLECTION AND ANALYSIS:Two review authors independently screened titles and abstracts for relevance. Eligibility, data extraction, and quality assessment were carried out by at least two authors independently and in duplicate. Studies were assessed for methodological quality using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). We reported the sensitivity and specificity of the included studies. We provided judgement of the certainty of the evidence using a GRADE assessment. MAIN RESULTS:We included 18 studies, recruiting 72,202 participants, published between 1986 and 2019. These studies evaluated the diagnostic test accuracy of conventional oral examination (10 studies, none new to this update), mouth self-examination (four studies, two new to this update), and remote screening (three studies, all new to this update). One randomised controlled trial of test accuracy directly evaluated conventional oral examination plus vital rinsing versus conventional oral examination alone. There were no eligible studies evaluating light-based detection or blood or salivary sample analysis (which tests for the presence of biomarkers for OPMD and OSCC). Only one study of conventional oral examination was judged as at overall low risk of bias and overall low concern regarding applicability. Given the clinical heterogeneity of the included studies in terms of the participants recruited, setting, prevalence of the target condition, the application of the index test and reference standard, and the flow and timing of the process, the data could not be pooled within the broader categories of index test. For conventional oral examination (10 studies, 25,568 participants), prevalence in the test accuracy sample ranged from 1% to 51%. For the seven studies with prevalence of 10% or lower, a prevalence more comparable to the general population, the sensitivity estimates were variable, and ranged from 0.50 (95% confidence interval (CI) 0.07 to 0.93) to 0.99 (95% CI 0.97 to 1.00); the specificity estimates were more consistent and ranged from 0.94 (95% CI 0.88 to 0.97) to 0.99 (95% CI 0.98 to 1.00). We judged the overall certainty of the evidence to be low, and downgraded for inconsistency and indirectness. Evidence for mouth self-examination and remote screening was more limited. We judged the overall certainty of the evidence for these index tests to be very low, and downgraded for imprecision, inconsistency, and indirectness. We judged the evidence for vital rinsing (toluidine blue) as an adjunct to conventional oral examination compared to conventional oral examination to be moderate, and downgraded for indirectness as the trial was undertaken in a high-risk population. AUTHORS' CONCLUSIONS:There is a lack of high-certainty evidence to support the use of screening programmes for oral cavity cancer and OPMD in the general population. Frontline screeners such as general dentists, dental hygienists, other allied professionals, and community healthcare workers should remain vigilant for signs of OPMD and OSCC.

OBJECTIVE:Patients with non-small cell lung cancer (NSCLC) metastatic to the brain are living longer. The risk of new brain metastases when these patients stop systemic therapy is unknown. The authors hypothesized that the risk of new brain metastases remains constant for as long as patients are off systemic therapy. METHODS:A prospectively collected registry of patients undergoing radiosurgery for brain metastases was analyzed. Of 606 patients with NSCLC, 63 met the inclusion criteria of discontinuing systemic therapy for at least 90 days and undergoing active surveillance. The risk factors for the development of new tumors were determined using Cox proportional hazards and recurrent events models. RESULTS:The median duration to new brain metastases off systemic therapy was 16.0 months. The probability of developing an additional new tumor at 6, 12, and 18 months was 26%, 40%, and 53%, respectively. There were no additional new tumors 22 months after stopping therapy. Patients who discontinued therapy due to intolerance or progression of the disease and those with mutations in RAS or receptor tyrosine kinase (RTK) pathways (e.g., KRAS, EGFR) were more likely to develop new tumors (hazard ratio [HR] 2.25, 95% confidence interval [CI] 1.33-3.81, p = 2.5 × 10-3; HR 2.51, 95% CI 1.45-4.34, p = 9.8 × 10-4, respectively). CONCLUSIONS:The rate of new brain metastases from NSCLC in patients off systemic therapy decreases over time and is uncommon 2 years after cessation of cancer therapy. Patients who stop therapy due to toxicity or who have RAS or RTK pathway mutations have a higher rate of new metastases and should be followed more closely.

Despite the success of immune checkpoint blockade therapy, few strategies sufficiently overcome immunosuppression within the tumor microenvironment (TME). Targeting regulatory T cells (T_regs) is challenging, because perturbing intratumoral T_reg function must be specific enough to avoid systemic inflammatory side effects. Thus, no T_reg-targeted agents have proven both safe and efficacious in patients with cancer. Neuropilin-1 (NRP1) is recognized for its role in supporting intratumoral T_reg function while being dispensable for peripheral homeostasis. Nonetheless, little is known about the biology of human NRP1⁺ T_regs and the signals that regulate NRP1 expression. Here, we report that NRP1 is preferentially expressed on intratumoral T_regs across six distinct cancer types compared to healthy donor peripheral blood [peripheral blood lymphocyte (PBL)] and site-matched, noncancer tissue. Furthermore, NRP1⁺ T_reg prevalence is associated with reduced progression-free survival in head and neck cancer. Human NRP1⁺ T_regs have broad activation programs and elevated suppressive function. Unlike mouse T_regs, we demonstrate that NRP1 identifies a transient activation state of human T_regs driven by continuous T cell receptor (TCR) signaling through the mitogen-activated protein kinase pathway and interleukin-2 exposure. The prevalence of NRP1⁺ T_regs in patient PBL correlates with the intratumoral abundance of NRP1⁺ T_regs and may indicate higher disease burden. These findings support further clinical evaluation of NRP1 as a suitable therapeutic target to enhance antitumor immunity by inhibiting T_reg function in the TME.

PURPOSE:No standard treatment exists for platinum-refractory, recurrent/metastatic nasopharyngeal cancer (NPC). This phase II study (NCT02605967) evaluated progression-free survival (PFS) of spartalizumab, an antiprogrammed cell death protein-1 (PD-1) monoclonal antibody, versus chemotherapy, in NPC. PATIENTS AND METHODS:Patients with nonkeratinizing recurrent/metastatic NPC who progressed on/after platinum-based chemotherapy were enrolled. Spartalizumab was dosed 400 mg once every 4 weeks, and chemotherapy was received per investigator's choice. RESULTS:gene expression. CONCLUSIONS:Spartalizumab demonstrated a safety profile consistent with other anti-PD-1 antibodies. The primary endpoint of median PFS was not met; however, median overall survival and median duration of response were longer with spartalizumab compared with chemotherapy.

HYPOTHESIS/OBJECTIVE:This study tests the hypothesis that it is possible to find tone or noise vocoders that sound similar and result in similar speech perception scores to a cochlear implant (CI). This would validate the use of such vocoders as acoustic models of CIs. We further hypothesize that those valid acoustic models will require a personalized amount of frequency mismatch between input filters and output tones or noise bands. BACKGROUND:Noise or tone vocoders have been used as acoustic models of CIs in hundreds of publications but have never been convincingly validated. METHODS:Acoustic models were evaluated by single-sided deaf CI users who compared what they heard with the CI in one ear to what they heard with the acoustic model in the other ear. We evaluated frequency-matched models (both all-channel and 6-channel models, both tone and noise vocoders) as well as self-selected models that included an individualized level of frequency mismatch. RESULTS:Self-selected acoustic models resulted in similar levels of speech perception and similar perceptual quality as the CI. These models also matched the CI in terms of perceived intelligibility, harshness, and pleasantness. CONCLUSION/CONCLUSIONS:Valid acoustic models of CIs exist, but they are different from the models most widely used in the literature. Individual amounts of frequency mismatch may be required to optimize the validity of the model. This may be related to the basalward frequency mismatch experienced by postlingually deaf patients after cochlear implantation.

PURPOSE:), whereas no molecularly based stratification exists for the broad spectrum of patients with low- and intermediate-risk meningioma. METHODS:DNA methylation data and copy-number information were generated for 3,031 meningiomas (2,868 patients), and mutation data for 858 samples. DNA methylation subgroups, copy-number variations (CNVs), mutations, and WHO grading were analyzed. Prediction power for outcome was assessed in a retrospective cohort of 514 patients, validated on a retrospective cohort of 184, and on a prospective cohort of 287 multicenter cases. RESULTS:= .005). Besides the overall stratification advantage, the integrated score separates more precisely for risk of progression at the diagnostically challenging interface of WHO grade 1 and grade 2 tumors (hazard ratio 4.34 [2.48-7.57] and 3.34 [1.28-8.72] retrospective and prospective validation cohorts, respectively). CONCLUSION:Merging these layers of histologic and molecular data into an integrated, three-tiered score significantly improves the precision in meningioma stratification. Implementation into diagnostic routine informs clinical decision making for patients with meningioma on the basis of robust outcome prediction.

Neural circuits often exhibit sequences of activity, but the contribution of local networks to their generation remains unclear. In the zebra finch, song-related premotor sequences within HVC may result from some combination of local connectivity and long-range thalamic inputs from nucleus uvaeformis (Uva). Because lesions to either structure abolish song, we examine "sleep replay" using high-density recording methods to reconstruct precise song-related events. Replay activity persists after the upstream nucleus interfacialis of the nidopallium is lesioned and slows when HVC is cooled, demonstrating that HVC provides temporal structure for these events. To further gauge the importance of intra-HVC connectivity for shaping network dynamics, we lesion Uva during sleep and find that residual replay sequences could span syllable boundaries, supporting a model in which HVC can propagate sequences throughout the duration of the song. Our results highlight the power of studying offline activity to investigate behaviorally relevant circuit organization.

Hypoglossal nerve stimulation (HGNS) has evolved as a novel and effective therapy for patients with moderate-to-severe obstructive sleep apnea (OSA). Despite positive published outcomes of HGNS, there exist uncertainties regarding proper patient selection, surgical technique, and the reporting of outcomes and individual factors that impact therapy effectiveness. According to current guidelines, this therapy is indicated for select patients, and recommendations are based on the Stimulation Therapy for Apnea Reduction (STAR) trial. Ongoing research and physician experiences continuously improve methods to optimize the therapy. An understanding of the way in which airway anatomy, OSA phenotypes, individual health status, psychological conditions and comorbid sleep disorders influence the effectiveness of HGNS is essential to improve outcomes and expand therapy indications. This manuscript presents discussions on current evidence, future directions, and research gaps for HGNS therapy from the 10th International Surgical Sleep Society expert research panel.

OBJECTIVE:The role of sclerotherapy for vascular lesions of the head and neck is well established. However, the efficacy of sclerotherapy for benign cystic lesions of the head and neck is less clear. The objective of this review is to determine the efficacy and safety of sclerotherapy for benign cystic lesions of the head and neck. DATA SOURCES:PubMed/MEDLINE, Cochrane Library, and Embase. REVIEW METHODS:The PRISMA guidelines (Preferred Reporting Systems for Systematic Reviews and Meta-analyses) were followed for this systematic review. Studies of patients with benign head and neck cystic masses treated primarily with sclerotherapy were included. Thirty-two studies met criteria for inclusion. RESULTS:= .015). Fifty-three cases (11.2%) required further surgical management. One case of laryngeal edema was reported and managed nonoperatively. CONCLUSION:Sclerotherapy appears to be a safe and efficacious option for benign cystic lesions if malignancy is reliably excluded. Efficacy rates are comparable to those of sclerotherapy for vascular malformations. The rate of serious complications is low, with 1 incident of airway edema reported in the literature.