Somatic 9p24.1 alterations in HPV- head and neck squamous cancer dictate immune microenvironment and anti-PD-1 checkpoint inhibitor activity.

Somatic copy number alterations (SCNAs), generally (1) losses containing interferons and interferon-pathway genes, many on chromosome 9p, predict immune-cold, immune checkpoint therapy (ICT)-resistant tumors (2); however, genomic regions mediating these effects are unclear and probably tissue specific. Previously, 9p21.3 loss was found to be an early genetic driver of human papillomavirus-negative (HPV-) head and neck squamous cancer (HNSC), associated with an immune-cold tumor microenvironment (TME) signal, and recent evidence suggested that this TME-cold phenotype was greatly enhanced with 9p21 deletion size, notably encompassing band 9p24.1 (3). Here, we report multi-omic, -threshold and continuous-variable dissection of 9p21 and 9p24 loci (including depth and degree of somatic alteration of each band at each locus, and each gene at each band) and TME of four HPV- HNSC cohorts. Preferential 9p24 deletion, CD8 T-cell immune-cold associations were observed, driven by 9p24.1 loss, and in turn by an essential telomeric regulatory gene element, JAK2-CD274. Surprisingly, same genetic region gains were immune hot. Related 9p21-TME analyses were less evident. Inherent 9p-band-level influences on anti-PD1 ICT survival rates, coincident with TME patterns, were also observed. At a 9p24.1 whole-transcriptome expression threshold of 60th percentile, ICT survival rate exceeded that of lower expression percentiles and of chemotherapy; below this transcript threshold, ICT survival was inferior to chemotherapy, the latter unaffected by 9p24.1 expression level (P-values < 0.01, including in a PD-L1 immunohistochemistry-positive patient subgroup). Whole-exome analyses of 10 solid-tumor types suggest that these 9p-related ICT findings could be relevant to squamous cancers, in which 9p24.1 gain/immune-hot associations exist.

Capsular attachment on the anterosuperior femoral head-neck junction: A hypothesis about femoroacetabular impingement.

Femoroacetabular impingement (FAI), characterized by a pathological contact between the proximal femur and acetabulum, is a common precursor of hip osteoarthritis. Cam morphology is a bony prominence that causes FAI and frequently forms on the anterosuperior femoral head-neck junction. Despite anatomical consensus regarding the femoral head-neck junction as a boundary area covered by the articular cartilage and joint capsule, it remains unclear whether the joint capsule is continuous with the anterosuperior articular cartilage. For the anatomical consideration of cam morphology formation, this study aimed to investigate the histological characteristics of the capsular attachment on the anterosuperior femoral head-neck junction, particularly focusing on the presence or absence of continuity of the joint capsule to the articular cartilage. A total of 21 anterosuperior regions (seven hips each for the 12:00, 1:30, and 3:00 positions) from seven hips (three males and four females; mean age at death, 68.7 years) were histologically analyzed in this study for quantitative evaluation of the capsular thickness using histological sections stained with Masson's trichrome, as well as qualitative evaluation of the capsular attachment. The present study showed that the joint capsule, which folded proximally to the femoral head-neck junction from the recess, exhibited a blend of the fibrous and synovial regions. Notably, it not only continued with the superficial layer of the articular cartilage, but also attached to the articular cartilage via the fibrocartilage. This continuous region was relatively fibrous with dense connective tissue running in the longitudinal direction. The capsular thickness at the recess point (mean, 1.7 ± 0.9 mm) and those at the distal end of the articular cartilage (0.35 ± 0.16 mm) were significantly greater than the control value for the most superficial layer thickness of the articular cartilage (0.019 ± 0.003 mm) (Dunnett's T3, both p-value <0.001). Based on the fibrous continuity between the joint capsule and articular cartilage and its thickness, this study suggests the anatomical possibility that some mechanical stress can be transmitted from the joint capsule to the articular cartilage at the frequent sites of cam morphology.

A comparative dose-escalation analysis for reirradiated cancer patients with and without appropriate dose mapping.

This study aims to compare dose escalation between two groups of reirradiated cancer patients, one with the previous contour and radiotherapy plan available on the treatment planning system and the other without. First group is identified as DICOM-group, while the other one is called non-DICOM group. The current study included 89 patients, 57 in the DICOM, and 32 in the non-DICOM group, who received reirradiation for recurrent or second primary tumours between 2019 and 2021. For the DICOM group, doses to 0.2cc volume for spine, brainstem, and optic apparatus from first radiation were converted into structures and transferred to reirradiation CT using deformable registration. First, one radiotherapy plan was created using the doctor prescribed dose (baseline prescription RxD_B); further an escalated dose (RxD_E) plan, taking into account all the dose volume parameters from previous radiation, was created only for DICOM group. In non-DICOM group patients were planned only for RxD_B. The maximum accepted dose escalation was 21 Gy. Radiotherapy prescription dose during earlier (first) treatment in DICOM and non-DICOM groups were 61 ± 5.6 Gy and 30-66 Gy, respectively. DICOM and non-DICOM groups had nearly identical baseline doses: 52.5 ± 10.7 Gy and 50.6 ± 6.9 Gy (difference 1.9 ± 12.7 Gy). Dose escalation was possible for 51 out of 57 patients in the DICOM-group. Average escalated dose in DICOM-group was 59.2 ± 6.2 Gy, with an incremental dose of 6.7 ± 12.4 Gy from the baseline prescription. No dose escalation was opted for in the non-DICOM group due to the unavailability of dose volume information from previous radiation. Reirradiation for head and neck cases allowed for a moderate to high dose escalation, facilitated by the presence of pertinent DICOM information from the initial radiotherapy.

Validity and reliability of the Group for Learning Useful and Performant Swallowing (GLUPS) tool.

INTRODUCTION: To validate the Group for Learning Useful and Performant Swallowing (GLUPS), a clinical tool dedicated to videofluoroscopy swallowing study (VFSS). METHODS: Forty-five individuals were recruited from January 2022 to March 2023 from the Department of Otolaryngology Head and Neck Surgery of University Hospital Saint-Pierre (Brussels, Belgium). Subjects underwent VFSS, which was rated with GLUPS tool by two blinded otolaryngologists and one speech-therapist. VFSS were rated twice with GLUPS within a 7-day period to assess test-retest reliability. RESULTS: Twenty-four patients and twenty-one controls completed the evaluations. The internal consistency (α = 0.745) and the test-retest reliability (rs = 0.941; p = 0.001) were adequate. GLUPS reported a high external validity regarding the significant correlation with the Penetration-Aspiration Scale (rs = 0.551; p = 0.001). Internal validity was adequate, because GLUPS score was significant higher in patients compared to controls (6.21 ± 4.42 versus 2.09 ± 2.00; p = 0.001). Interrater reliability did not report significant differences in the GLUPS sub- and total score among the independent judges. The mean GLUPS score of individuals without any evidence of VFSS abnormalities was 2.09/23 (95% CI 1.23-2.95), which supported that a GLUPS score ≥ 3.0 is suggestive of pathological VFSS. CONCLUSIONS: GLUPS is a clinical instrument documenting the abnormal findings of oral and pharyngeal phases at the VFSS. GLUPS demonstrated high reliability and excellent criterion-based validity. GLUPS may be used in clinical practice for the swallowing evaluation at the VFSS.

How ChatGPT works: a mini review.

OBJECTIVE: This paper offers a mini-review of OpenAI's language model, ChatGPT, detailing its mechanisms, applications in healthcare, and comparisons with other large language models (LLMs). METHODS: The underlying technology of ChatGPT is outlined, focusing on its neural network architecture, training process, and the role of key elements such as input embedding, encoder, decoder, attention mechanism, and output projection. The advancements in GPT-4, including its capacity for internet connection and the integration of plugins for enhanced functionality are discussed. RESULTS: ChatGPT can generate creative, coherent, and contextually relevant sentences, making it a valuable tool in healthcare for patient engagement, medical education, and clinical decision support. Yet, like other LLMs, it has limitations, including a lack of common sense knowledge, a propensity for hallucination of facts, a restricted context window, and potential privacy concerns. CONCLUSION: Despite the limitations, LLMs like ChatGPT offer transformative possibilities for healthcare. With ongoing research in model interpretability, common-sense reasoning, and handling of longer context windows, their potential is vast. It is crucial for healthcare professionals to remain informed about these technologies and consider their ethical integration into practice.

Accuracy of ChatGPT-3.5 and -4 in providing scientific references in otolaryngology-head and neck surgery.

INTRODUCTION: Chatbot generative pre-trained transformer (ChatGPT) is a new artificial intelligence-powered language model of chatbot able to help otolaryngologists in practice and research. We investigated the accuracy of ChatGPT-3.5 and -4 in the referencing of manuscripts published in otolaryngology. METHODS: ChatGPT-3.5 and ChatGPT-4 were interrogated for providing references of the top-30 most cited papers in otolaryngology in the past 40 years including clinical guidelines and key studies that changed the practice. The responses were regenerated three times to assess the accuracy and stability of ChatGPT. ChatGPT-3.5 and ChatGPT-4 were compared for accuracy of reference and potential mistakes. RESULTS: The accuracy of ChatGPT-3.5 and ChatGPT-4.0 ranged from 47% to 60%, and 73% to 87%, respectively (p < 0.005). ChatGPT-3.5 provided 19 inaccurate references and invented 2 references throughout the regenerated questions. ChatGPT-4.0 provided 13 inaccurate references, while it proposed only one invented reference. The stability of responses throughout regenerated answers was mild (k = 0.238) and moderate (k = 0.408) for ChatGPT-3.5 and 4.0, respectively. CONCLUSIONS: ChatGPT-4.0 reported higher accuracy than the free-access version (3.5). False references were detected in both 3.5 and 4.0 versions. Practitioners need to be careful regarding the use of ChatGPT in the reach of some key reference when writing a report.

ChatGPT performance in laryngology and head and neck surgery: a clinical case-series.

OBJECTIVES: To study the performance of ChatGPT in the management of laryngology and head and neck (LHN) cases. METHODS: History and clinical examination of patients consulting at the Otolaryngology-Head and Neck Surgery department were presented to ChatGPT, which was interrogated for differential diagnosis, management, and treatment. The ChatGPT performance was assessed by two blinded board-certified otolaryngologists using the following items of a composite score and the Ottawa Clinic Assessment Tool: differential diagnosis; additional examination; and treatment options. The complexity of clinical cases was evaluated with the Amsterdam Clinical Challenge Scale test. RESULTS: Forty clinical cases were submitted to ChatGPT, accounting for 14 (35%), 12 (30%), and 14 (35%) easy, moderate and difficult cases, respectively. ChatGPT indicated a significant higher number of additional examinations compared to practitioners (p = 0.001). There was a significant agreement between practitioners and ChatGPT for the indication of some common examinations (audiometry, ultrasonography, biopsy, gastrointestinal endoscopy or videofluoroscopy). ChatGPT never indicated some important additional examinations (PET-CT, voice quality assessment, or impedance-pH monitoring). ChatGPT reported highest performance in the proposition of the primary (90%) or the most plausible differential diagnoses (65%), and the therapeutic options (60-68%). The ChatGPT performance in the indication of additional examinations was lowest. CONCLUSIONS: ChatGPT is a promising adjunctive tool in LHN practice, providing extensive documentation about disease-related additional examinations, differential diagnoses, and treatments. The ChatGPT is more efficient in diagnosis and treatment, rather than in the selection of the most adequate additional examination.

Accuracy of ChatGPT in head and neck oncological board decisions: preliminary findings.

OBJECTIVES: To evaluate the ChatGPT-4 performance in oncological board decisions. METHODS: Twenty medical records of patients with head and neck cancer were evaluated by ChatGPT-4 for additional examinations, management, and therapeutic approaches. The ChatGPT-4 propositions were assessed with the Artificial Intelligence Performance Instrument. The stability of ChatGPT-4 was evaluated through regenerated answers at 1-day interval. RESULTS: ChatGPT-4 provided adequate explanations for cTNM staging in 19 cases (95%). ChatGPT-4 proposed a significant higher number of additional examinations than practitioners (72 versus 103; p = 0.001). ChatGPT-4 indications of endoscopy-biopsy, HPV research, ultrasonography, and PET-CT were consistent with the oncological board decisions. The therapeutic propositions of ChatGPT-4 were accurate in 13 cases (65%). Most additional examination and primary treatment propositions were consistent throughout regenerated response process. CONCLUSIONS: ChatGPT-4 may be an adjunctive theoretical tool in oncological board simple decisions.

ChatGPT-4 accuracy for patient education in laryngopharyngeal reflux.

INTRODUCTION: Chatbot Generative Pre-trained Transformer (ChatGPT) is an artificial intelligence-powered language model chatbot able to help otolaryngologists in practice and research. The ability of ChatGPT in generating patient-centered information related to laryngopharyngeal reflux disease (LPRD) was evaluated. METHODS: Twenty-five questions dedicated to definition, clinical presentation, diagnosis, and treatment of LPRD were developed from the Dubai definition and management of LPRD consensus and recent reviews. Questions about the four aforementioned categories were entered into ChatGPT-4. Four board-certified laryngologists evaluated the accuracy of ChatGPT-4 with a 5-point Likert scale. Interrater reliability was evaluated. RESULTS: The mean scores (SD) of ChatGPT-4 answers for definition, clinical presentation, additional examination, and treatments were 4.13 (0.52), 4.50 (0.72), 3.75 (0.61), and 4.18 (0.47), respectively. Experts reported high interrater reliability for sub-scores (ICC = 0.973). The lowest performances of ChatGPT-4 were on answers about the most prevalent LPR signs, the most reliable objective tool for the diagnosis (hypopharyngeal-esophageal multichannel intraluminal impedance-pH monitoring (HEMII-pH)), and the criteria for the diagnosis of LPR using HEMII-pH. CONCLUSION: ChatGPT-4 may provide adequate information on the definition of LPR, differences compared to GERD (gastroesophageal reflux disease), and clinical presentation. Information provided upon extra-laryngeal manifestations and HEMII-pH may need further optimization. Regarding the recent trends identifying increasing patient use of internet sources for self-education, the findings of the present study may help draw attention to ChatGPT-4's accuracy on the topic of LPR.

Validity and reliability of an instrument evaluating the performance of intelligent chatbot: the Artificial Intelligence Performance Instrument (AIPI).

OBJECTIVES: To evaluate the reliability and validity of the Artificial Intelligence Performance Instrument (AIPI). METHODS: Medical records of patients consulting in otolaryngology were evaluated by physicians and ChatGPT for differential diagnosis, management, and treatment. The ChatGPT performance was rated twice using AIPI within a 7-day period to assess test-retest reliability. Internal consistency was evaluated using Cronbach's α. Internal validity was evaluated by comparing the AIPI scores of the clinical cases rated by ChatGPT and 2 blinded practitioners. Convergent validity was measured by comparing the AIPI score with a modified version of the Ottawa Clinical Assessment Tool (OCAT). Interrater reliability was assessed using Kendall's tau. RESULTS: Forty-five patients completed the evaluations (28 females). The AIPI Cronbach's alpha analysis suggested an adequate internal consistency (α = 0.754). The test-retest reliability was moderate-to-strong for items and the total score of AIPI (rs = 0.486, p = 0.001). The mean AIPI score of the senior otolaryngologist was significantly higher compared to the score of ChatGPT, supporting adequate internal validity (p = 0.001). Convergent validity reported a moderate and significant correlation between AIPI and modified OCAT (rs = 0.319; p = 0.044). The interrater reliability reported significant positive concordance between both otolaryngologists for the patient feature, diagnostic, additional examination, and treatment subscores as well as for the AIPI total score. CONCLUSIONS: AIPI is a valid and reliable instrument in assessing the performance of ChatGPT in ear, nose and throat conditions. Future studies are needed to investigate the usefulness of AIPI in medicine and surgery, and to evaluate the psychometric properties in these fields.

Effect of Femoral Head Material, Surgeon Experience, and Assembly Technique on Simulated Head-Neck Total Hip Arthroplasty Impaction Forces.

BACKGROUND: There is no standard method for assembling the femoral head onto the femoral stem during total hip arthroplasty (THA). This study aimed to measure and record dynamic 3-dimensional (3D) THA head-neck assembly loads from residents, fellows, and attending surgeons, for metal and ceramic femoral heads. METHODS: An instrumented apparatus measured dynamic 3D forces applied through the femoral stem taper in vitro for 31 surgeons (11 attendings, 14 residents, 6 fellows) using their preferred technique (ie, number of hits or mallet strikes). Outcome variables included peak axial force, peak resultant force, impulse of the resultant force, loading rate of the resultant force, and off-axis angle. They were compared between femoral head material, surgeon experience level, and the number of hits per trial. RESULTS: Average peak axial force was 6.92 ± 2.11kN for all surgeons. No significant differences were found between femoral head material. Attendings applied forces more "on-axis" as compared to both residents and fellows. Nine surgeons assembled the head with 1 hit, 3 with 2 hits, 14 with 3 hits, 2 with 4 hits, and 3 with ≥5 hits. The first hit of multihit trials was significantly lower than single-hit trials for all outcome measures except the off-axis angle. The last hit of multihit trials had a significantly lower impulse of resultant force than single-hit trials. CONCLUSION: Differences in applied 3D force-time curve dynamic characteristics were found between surgeon experience level and single and multihit trials. No significant differences were found between femoral head material.

Mix and Match Use of Revision Universal Head Neck Adapters in Hip Arthroplasty: Complications and Survival Analysis of 306 Cases.

BACKGROUND: Outcomes and safety of "mix and match" in total hip arthroplasty (THA) using universal head-neck adapters (UHNA) are a matter of ongoing discussion and concern due to legal affairs. This study aimed at analyzing the "mix and match" use of UHNA and evaluating complication and reoperation rates, possible risk factors, and the implant's survival. METHODS: A total of 306 patients treated with THA (94.1% revisions) using a UHNA at our institution between 2006 and 2022 were identified and included. Diagnoses, comorbidities, implants, and UHNA specifications were retrospectively recorded. Outcomes, complications, and survival analyses were evaluated, taking account of various possible risk factors. RESULTS: There were 19.9% of the 306 included cases (58.5% women; median age 74 years; median follow-up 57 months) that had at least 1 complication. There were 43 patients (14.1%) who had to receive ≥ 1 re-revision surgery. The most common complication was postoperative recurrent dislocation (n = 27, 8.8%). There was one case of a prosthetic stem-neck fracture that was registered. Statistically significant risk factors for postoperative recurrent dislocations and postoperative aseptic loosening were, respectively, dislocation as an indication for UHNA implantation (P < 0.001) and oversized neck lengths (≥ 2XL;P= 0.004). The overall revision-free survival was 92% after one year and 82% at ten years. Statistically significant better survival rates were registered in patients ≥ 60 years old, who had fewer comorbidities (< 2), and normal neck lengths (S to XL). CONCLUSION: The results of this study underline the overall safety of UHNA use in THA through "mix and match." Only one case of a stem-neck fracture was identified. The highlighted risk factors for failure must be kept in mind during the decision-making process with patients.

External validation of an 18F-FDG-PET radiomic model predicting survival after radiotherapy for oropharyngeal cancer.

PURPOSE/OBJECTIVE: The purpose of the study is to externally validate published 18F-FDG-PET radiomic models for outcome prediction in patients with oropharyngeal cancer treated with chemoradiotherapy. MATERIAL/METHODS: Outcome data and pre-radiotherapy PET images of 100 oropharyngeal cancer patients (stage IV:78) treated with concomitant chemotherapy to 66-69 Gy/30 fr were available. Tumors were segmented using a previously validated semi-automatic method; 450 radiomic features (RF) were extracted according to IBSI (Image Biomarker Standardization Initiative) guidelines. Only one model for cancer-specific survival (CSS) prediction was suitable to be independently tested, according to our criteria. This model, in addition to HPV status, SUVmean and SUVmax, included two independent meta-factors (Fi), resulting from combining selected RF clusters. In a subgroup of 66 patients with complete HPV information, the global risk score R was computed considering the original coefficients and was tested by Cox regression as predictive of CSS. Independently, only the radiomic risk score RF derived from Fi was tested on the same subgroup to learn about the radiomics contribution to the model. The metabolic tumor volume (MTV) was also tested as a single predictor and its prediction performances were compared to the global and radiomic models. Finally, the validation of MTV and the radiomic score RF were also tested on the entire dataset. RESULTS: Regarding the analysis of the subgroup with HPV information, with a median follow-up of 41.6 months, seven patients died due to cancer. R was confirmed to be associated to CSS (p value = 0.05) with a C-index equal 0.75 (95% CI=0.62-0.85). The best cut-off value (equal to 0.15) showed high ability in patient stratification (p=0.01, HR=7.4, 95% CI=1.6-11.4). The 5-year CSS for R were 97% (95% CI: 93-100%) vs 74% (56-92%) for low- and high-risk groups, respectively. RF and MTV alone were also significantly associated to CSS for the subgroup with an almost identical C-index. According to best cut-off value (RF>0.12 and MTV>15.5cc), the 5-year CSS were 96% (95% CI: 89-100%) vs 65% (36-94%) and 97% (95% CI: 88-100%) vs 77% (58-93%) for RF and MTV, respectively. Results regarding RF and MTV were confirmed in the overall group. CONCLUSION: A previously published PET radiomic model for CSS prediction was independently validated. Performances of the model were similar to the ones of using only the MTV, without improvement of prediction accuracy.

Prediction of plan adaptation in head and neck cancer proton therapy using clinical, radiographic, and dosimetric features.

PURPOSE: Because proton head and neck (HN) treatments are sensitive to anatomical changes, plan adaptation (re-plan) during the treatment course is needed for a significant portion of patients. We aim to predict re-plan at plan review stage for HN proton therapy with a neural network (NN) model trained with patients' dosimetric and clinical features. The model can serve as a valuable tool for planners to assess the probability of needing to revise the current plan. METHODS AND MATERIALS: Mean beam dose heterogeneity index (BHI), defined as the ratio of the maximum beam dose to the prescription dose, plan robustness features (clinical target volume (CTV), V100 changes, and V100 > 95% passing rates in 21 robust evaluation scenarios), as well as clinical features (e.g., age, tumor site, and surgery/chemotherapy status) were gathered from 171 patients treated at our proton center in 2020, with a median age of 64 and stages from I-IVc across 13 HN sites. Statistical analyses of dosimetric parameters and clinical features were conducted between re-plan and no-replan groups. A NN was trained and tested using these features. Receiver operating characteristic (ROC) analysis was conducted to evaluate the performance of the prediction model. A sensitivity analysis was done to determine feature importance. RESULTS: Mean BHI in the re-plan group was significantly higher than the no-replan group (p < .01). Tumor site (p < .01), chemotherapy status (p < .01), and surgery status (p < .01) were significantly correlated to re-plan. The model had sensitivities/specificities of 75.0%/77.4%, respectively, and an area under the ROC curve of .855. CONCLUSION: There are several dosimetric and clinical features that correlate to re-plans, and NNs trained with these features can be used to predict HN re-plans, which can be used to reduce re-plan rate by improving plan quality.

Mapping the impact of malnutrition as defined by the Global Leadership Initiative on Malnutrition and nutrition impact symptoms on the possibility of returning to work after treatment for head and neck cancer.

PURPOSE: This study aimed to investigate whether malnutrition or nutrition impact symptoms (NIS) affect the possibility of returning to work after treatment for head and neck cancer. METHODS: Patients of working age with head and neck cancer were followed up from treatment initiation to 3 months (n = 238), 1 year (n = 182), and 2 years (n = 130) after treatment completion. The observed decrease in the number of patients over time was due to retirement, lack of follow-up, or death. Returning to work was dichotomised as yes or no. Malnutrition was diagnosed 7 weeks after treatment initiation using the Global Leadership Initiative on Malnutrition (GLIM) criteria. This time-point corresponds to the end of chemoradiotherapy or radiotherapy (with or without prior surgery), except for patients who underwent exclusive surgery. NIS were scored on a Likert scale (1-5) at each follow-up using the Head and Neck Patient Symptom Checklist© (HNSC©). Nonparametric tests were used to analyse the ability of patients with/without malnutrition and high/low NIS scores to return to work. RESULTS: At 3 months, 1 year, and 2 years after treatment completion, 135/238 (56.7%), 49/182 (26.9%), and 23/130 (17.7%) patients had not returned to work. Patients with malnutrition at 7 weeks after treatment initiation were more likely to not return to work at 3 months than those without malnutrition, 70.5% compared to 47.1% (p < 0.001). At all three follow-up time-points, patients reporting high scores for a number of NIS had more often not returned to work, with this pattern being most distinct at 2 years. CONCLUSION: Malnutrition according to the GLIM criteria at 7 weeks after treatment initiation and NIS assessed by the HNSC© at subsequent follow-ups were predictors of the return-to-work process after treatment for up to 2 years. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03343236 (date of registration 17/11/2017).

ETV5 facilitates tumor progression in head-neck squamous cell carcinoma.

OBJECTIVE: E26 transformation-specific (ETS) factors have emerged as key mediators underlying human tumorigenesis. Here, we sought to characterize the expression pattern, biological roles, and clinical significance of ETS Variant Transcription Factor 5 (ETV5) in head neck squamous cell carcinoma (HNSCC). SUBJECTS AND METHODS: ETV5 expression pattern in HNSCC was determined by bioinformatics interrogations and immunohistochemical staining in primary samples. The associations between its abundance with clinicopathological parameters, and patient survival were evaluated. Colony formation, CCK-8, flow cytometry, wound healing, and Transwell invasion assays, as well as xenograft models, were utilized to determine the phenotypic changes after ETV5 silencing in vitro and vivo. The potential binding of ETV5 in the Slug promoter was determined by ChIP-qPCR. RESULTS: ETV5 was significantly overexpressed in HNSCC samples. Its overexpression is significantly associated with aggressiveness features and reduced survival. ETV5 knockdown significantly inhibited cell proliferation, migration, invasion, and induced apoptosis in vitro, and impaired tumor growth in vivo. Moreover, ETV5-activated Slug transcription by binding its promoter region in HNSCC cells. Patients with ETV5high Slughigh had the worst survival across multiple HNSCC cohorts. CONCLUSIONS: Our findings reveal that ETV5 serves as a novel prognostic biomarker and putative oncogene for HNSCC progression likely by activating Slug transcription.

Assessment of Dimensional Changes in Submandibular Glands in Head-Neck Radiotherapy Patients by Ultrasonography.

OBJECTIVES: The present study investigated the dimensional changes in the submandibular glands following radiotherapy using ultrasonography. METHODS: Twenty-three patients planned to receive head-neck radiotherapy were included in this study. The anteroposterior, superoinferior, mediolateral length, and volumes of 46 submandibular glands were measured by ultrasonography at 3 different time periods (before radiotherapy and in the second and sixth months after the radiotherapy onset) and evaluated in terms of dimensional changes and the effect of the radiation dose on these changes. The data were statistically analyzed using repeated measures analysis of variance (ANOVA) and 2-factor repeated measures ANOVA. RESULTS: Before radiotherapy and in the second and sixth months after the radiotherapy onset, mean anteroposterior length of the submandibular glands was 32.39 ± 4.55, 30.38 ± 4.80, and 31.50 ± 3.68 mm, respectively; mean superoinferior length was 9.96 ± 1.54, 8.76 ± 1.26, and 9.08 ± 1.01 mm, respectively; mean mediolateral length was 24.66 ± 3.77, 22.03 ± 3.73, and 21.76 ± 4.01 mm, respectively; and mean volume was 4.21 ± 1.01, 3.08 ± 0.77, and 3.32 ± 0.63 cm3 , respectively. Moreover, there were significant differences in the anteroposterior (P < .01), superoinferior (P < .001), and mediolateral lengths (P < .001), as well as the volumes (P < .001) of the submandibular glands measured at the 3 different time periods. CONCLUSION: In the second and sixth months after the radiotherapy onset, the sizes of the submandibular glands were markedly reduced, but it partially recovered to normal as more time elapsed after radiotherapy.

Prognostic significance of extra-nodal extension and positive surgical margins in HPV positive oropharyngeal squamous cell carcinoma.

BACKGROUND: Whether extra-nodal extension (ENE+) and surgical margin positivity (margin+) are poor prognostic factors in HPV-associated (HPV+) oropharyngeal carcinoma (OPC) remains uncertain. RESULTS: Our study evaluated if microscopic ENE+ and/or margin+ are associated poorer recurrence free survival (RFS) and overall survival (OS) in HPV+ OPC. Patients were classified as high risk (ENE+ and/or margin+) or low risk (ENE- and margins-). Of a total of 176 patients HPV+ OPC, 81 underwent primary surgery and dad data on ENE and margin status. There was no statistically significant difference in RFS (p = 0.35) or OS (p = 0.13) for high-risk versus low-risk groups. Ongoing smoking (p = 0.023), alcohol use (p = 0.044) and advanced stage (p = 0.019) were associated with higher risk of recurrence. Only advanced stage (p-value <0.0001) was associated poorer overall survival. CONCLUSIONS: The presence of ENE+ and/or margin+ was not an independent predictor of poor RFS or OS in HPV+ OPC.

Association between tooth extraction during radiotherapy and the risk of osteoradionecrosis in patients with head and neck cancers.

PURPOSE: It is commonly recommended that tooth extraction should be performed prior to radiotherapy (RT) in patients with head neck cancer to prevent osteoradionecrosis (ORN). However, doctors still occasionally encounter patients who require tooth extraction during RT. This study aimed to determine the risk of ORN in patients who undergo tooth extraction during RT. METHODS: Data were collected from Taiwan's National Health Insurance Research Database. We retrospectively enrolled 24,412 patients with head and neck cancer treated with radiotherapy between 2011 and 2017. The associations between ORN and demographic characteristics, timing of tooth extraction, and treatments were examined using univariate and multivariable Cox proportional hazards regression models. RESULTS: A total of 24,412 head and neck cancer patients were enrolled; 133 patients underwent tooth extraction during RT and 24,279 patients did not undergo tooth extraction during RT. Tooth extraction during RT was not associated with a significantly higher risk of ORN (hazard ratio [HR] = 1.303, P = 0.4862). Tumor site, RT dose ≥ 60 Gy, age < 55 y/o, mandibulectomy, chronic periodontitis, and chemotherapy were significantly associated with a higher risk of ORN. CONCLUSION: The risk of ORN in head and neck cancer is not significantly different between patients who undergo tooth extraction during RT and patients who do not undergo tooth extraction during RT.

Tele-rehabilitation in voice disorders during the pandemic: a consensus paper from the French Society of Phoniatrics and Laryngology.

OBJECTIVES: To establish a consensus protocol for telerehabilitation in speech therapy for voice disorders. METHODS: The study was conducted according to a modified Delphi method. Twenty speech therapist or laryngologist experts of the French Society of Phoniatrics and Laryngology assessed 24 statements of voice telerehabilitation with a 10-point visual analog scale ranging from 1 (totally disagree) to 10 (totally agree). The statements were accepted if more than 80% of the experts rated the item with a score of ≥ 8/10. The statements with ≥ 8/10 score by 60-80% of experts were improved and resubmitted to voting until they were validated or rejected. RESULTS: The French Society of Phoniatrics and Laryngology experts validated 10, 6, and 2 statements after the first, second and third voting round, respectively. Seven statements did not reach agreement threshold and were rejected. The validated statements included recommendations for setting (N = 4), medical/speech history (N = 2), subjective voice evaluations (N = 3), objective voice quality measurements (N = 3), and voice rehabilitation (N = 5). The experts agreed for a follow-up consisting of combined telerehabilitation and in-office rehabilitation. The final protocol may be applied in context of pandemic but could be assessed out of pandemic period for patients located in rural regions. CONCLUSIONS: This Delphi study established the first telerehabilitation protocol of the French Society of Phoniatrics and Laryngology for patients with voice disorders. Future controlled studies are needed to assess its feasibility, reliability, and the patient perception about telerehabilitation versus in-office rehabilitation.