HYPOTHESIS:The pH of an intratympanic gel influences the level of protection against the ototoxic effects of systemic cisplatin. BACKGROUND:Nucleophiles reduce cisplatin-induced ototoxicity by chemically inactivating cisplatin and counteracting oxidative stress. pH is a factor influencing cisplatin's reactivity. Here, intratympanic administration of a hyaluronan-based gel containing the nucleophile sodium thiosulfate (STS) was used to investigate the role of pH in otoprotection. METHODS:Guinea pigs (n=32) received a unilateral transtympanic injection of a hyaluronan-based gel (0.10 to 0.15 mL) with either STS at pH 6.5 or pH 8.0, or NaCl at pH 6.5 or pH 8.0. The contralateral ear served as control. After 30 minutes, cisplatin (8 mg/kg b.w., i.v.) was administered. Cochleae were harvested 4 days later for hair cell quantification. RESULTS:Mean percentage of outer hair cell (OHC) loss per mm in the region ≤10 mm from the round window had a median absolute intraindividual difference of 6.0% (quartiles 1 and 2: 3.8% to 11%; P =0.012; n=8) in group STS pH 6.5 and 5.8% (1.8% to 18%; P =0.046; n=6) in group STS pH 8.0, favoring the gel-treated ear. The corresponding numbers in the NaCl groups were -0.2% (-2.2 to 8.7%; P =1.000; n=8) in group NaCl pH 6.5 and 3.3% (-8.1% to 22%; P =0.237; n=7) in group NaCl pH 8.0. The difference between nontreated and gel-treated ears did not differ significantly between the 2 STS groups. CONCLUSION:STS in a hyaluronan-based gel reduced OHC loss equally well at both pH levels, while NaCl was ineffective.

BACKGROUND:Patients with smaller vestibular schwannoma (VS) with preserved hearing can be subjected to hearing preservation surgery using the Middle Cranial Fossa (MCF) approach. AIMS/OBJECTIVES:We aimed to evaluate hearing outcome postoperatively and more than 10 years after MCF surgery. MATERIALS AND METHODS:Eighty-four patients with sporadic unilateral VS treated with MCF surgery between 1998 and 2020 at a single tertiary centre, were retrospectively studied. Pure tone audiometry and word recognition scores (WRS) preoperatively, postoperatively, and after > 10 years of follow-up, were analysed. RESULTS:Sixty (71%) patients had preserved hearing function after MCF surgery. Twenty-three of the 60 patients were followed up for >10 years after surgery. Hearing outcomes of the tumour ear after >10 years of follow up were as follows: median pure tone average (PTA): 61 decibel hearing level (dB HL) (range 6-94 dB HL), and median WRS 71% (range: 0-98%). The age-related decline in pure tone audiometry thresholds was not significantly different between the tumour and contralateral ears. CONCLUSIONS AND SIGNIFICANCE:MCF surgery offers the possibility of retaining hearing function even after >10 years of surgery in patients with preserved hearing. Additional hearing loss at the long-term follow-up was bilateral and symmetrical.

Head and neck cancer comprises a heterogeneous group of tumours affecting anatomical sites of the upper aerodigestive tract. Treatment often involves surgery and either radiotherapy or chemoradiotherapy. These treatments are associated with substantial morbidity and may have long-lasting adverse effects on oral health. Oral complications can negatively affect health-related quality of life, nutritional status, and social and work-related functioning. The aim is to evaluate an oral health care programme designed to prevent or mitigate late oral sequalae, and to assess its impact on health-related quality of life, oral health, work ability, nutritional status, healthcare-related economic costs, and psychological well-being. This is a study protocol for a Swedish multicentre, two-armed, superiority randomised controlled trial that has been ethically approved by the Swedish Ethical Review Authority. Patient inclusion commenced in September 2025, with an intended sample of 300 participants. Adult patients (≥ 18 years) planned for curative-intent treatment for head and neck cancer (oral cavity, oropharynx, larynx stage III and IV, hypopharynx, nasopharynx, salivary gland, or unknown primary) are randomised (1:1) to either an oral health care programme (intervention) or standard of care. Exclusion criteria: severe alcoholism, cognitive impairment, or inability to understand the Swedish language. Participants are followed before the start of cancer treatment and at 4 follow-ups: 6 months after completion of treatment, and 1, 2, and 3 years after the 6-month follow-up. The primary outcome measure is health-related quality of life. Secondary outcomes include quantitative oral health indicators, return to work, nutritional status, healthcare-related economic costs, and patient-reported outcome measures focusing on self-reported oral health and psychological well-being (depression, anxiety and stress), and self-efficacy. Oral health follow-up for head and neck cancer survivors often lacks consistency and uniformity. To date, few oral health care interventions for head and neck cancer survivors have been evaluated within the framework of a randomised controlled trial. The findings have the potential to inform clinical practice and contribute to the development of more integrated, evidence-based oral healthcare strategies within routine follow-up for head and neck cancer survivors, with the overarching goal of improving their oral health and long-term quality of life. ClinicalTrials.gov NCT07173270, date 15/9/2025.

Long-term patient-reported outcomes (PROMs) may provide insight into the impact of advances in the treatment of oropharyngeal squamous cell carcinoma (OPSCC). The main aim of the study was to assess and compare PROMs in OPSCC patients treated during two different periods (1998–2006 vs. 2015–2021), reflecting advances in treatment strategies and developments in care. The present study is based on data from two Swedish multicentre studies: the randomised controlled trial ARTSCAN1 (1998–2006) and the observational study NIPHNC (2015–2021). Patients received curative-intent radiotherapy as part of the ARTSCAN or NIPHNC studies. All patients completed PROMs at multiple time points up to 24 months post-treatment. PROMs were assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire EORTC QLQ-H N35 and the Hospital Anxiety and Depression Scale HADS. A total of 363 patients were included, with 161 and 202 patients from ARTSCAN1 and NIPHNC, respectively. At baseline and at all post-radiotherapy time points, the NIPHNC cohort reported fewer symptoms and lower anxiety/depression. At 2 years, both groups showed improvement, though persistent issues like dry mouth and sticky saliva remained common. Comparison of two treatment protocols demonstrates improvements in short- and long-term PROMs over time. Long-term salivary symptoms remain prevalent in patients with OPSCC.

Persistent taste dysfunction is frequently reported in individuals with post-acute sequelae of infection by SARS-CoV-2 (Long COVID). The mechanisms and pathological correlates underlying this taste dysfunction are unknown. This study investigates the underlying pathology in 28 non-hospitalized subjects diagnosed with COVID-19 and who experienced taste disturbances more than 12 months after testing positive for SARS-CoV-2. To objectively establish the nature of taste deficit, we used the WETT taste test, which quantifies the subject's ability to taste each of the five taste qualities: sweet, umami, bitter, sour, and salty. We then biopsied five to eight fungiform taste papillae (FP) in 20 of the 28 subjects. The FPs were analyzed histologically for overall taste bud structure and innervation, and by quantitative PCR (qPCR) for mRNA expression of markers for different taste receptor cells. Although all subjects had reported taste dysfunction, only three showed overall taste scores below the 10th percentile for a normal population adjusted for age and sex. However, 11 of the 28 subjects exhibited total loss of one or more taste qualities. Loss of PLCβ2-dependent taste qualities (sweet, umami, bitter) was significantly more common and was correlated with reduced expression of PLCβ2 and Tas1R3 mRNAs. Histological analysis revealed generally preserved taste bud structure and innervation, but with occasional disorganized taste buds and abnormal, isolated PLCβ2-positive cells in the epithelium. Our findings suggest long-term taste dysfunction after COVID-19 occurs rarely -- more frequently involving PLCβ2-dependent taste qualities -- but is not due to wholesale disruption of the taste periphery.

Despite advances in the management of head and neck squamous cell carcinoma (HNSCC), mortality within 6 months of diagnosis remains a substantial clinical challenge. The objectives of this study are: (i) to develop a machine learning (ML) model using data from the Surveillance, Epidemiology, and End Results (SEER) program to assess the influence of patient characteristics, tumor features, and treatment modalities on early mortality in HNSCC; (ii) to explore and compare the prognostic potentials of patient-, tumor, and treatment-related factors across distinct mortality time points-6-month mortality (early mortality), 24-month mortality, and 5-year mortality; and (iii) to externally and independently validate the early mortality model using multicenter data from the Thuringian Cancer Registry (Jena, Germany) and a prospective observational cohort from the Helsinki University Hospital (Helsinki, Finland). We identified 4802 patients with HNSCC from the SEER for model development. Permutation-based feature importance was used to identify risk factors associated with early mortality. External validation was conducted using 1952 cases from the Thuringian Cancer Registry and 58 cases from the Helsinki University Hospital. The ML model achieved a weighted area under curve (AUC) of 0.75 for predicting early mortality in the SEER cohort. External validation yielded weighted AUC values of 0.70 (Germany) and 0.60 (Finland). Aggregate feature importance for early mortality indicated that higher age at diagnosis, presence of earlier primary malignant tumors besides HNSCC, unmarried patients with T1-T3 HNSCC, T3 stage, and having hypopharyngeal or laryngeal cancer, in decreasing order of significance, were important. For 24-month mortality, the associated risk factors in decreasing order of significance were T3 stage, being elderly in terms of age at diagnosis, presence of earlier primary malignant tumors besides HNSCC, having hypopharyngeal or oral cavity cancer, and N3 stage. The associated risk factors for 5-year mortality were found to be the same with those of early mortality with the additional inclusion of T2 stage. Identification of patients at elevated risk of early death supports timely intervention and individualized therapeutic decision-making. The developed ML model identified several risk factors associated with early death and may aid in clinical decision-making with the potential to improve survival outcomes.

Background: Diagnosis and treatment of head and neck squamous cell carcinoma (HNSCC) induces psychological variables and treatment-related toxicity in patients. The evaluation of outcomes is warranted for effective treatment planning and improved disease management. Objectives: This study aimed to build a prognostic system by combining clinicopathological parameters, treatment-related factors, and sociodemographic factors as integrative inputs to build a machine learning (ML) model to estimate the overall survival (OS) of patients with HNSCC. Furthermore, we explored the complementary prognostic potentials of these input parameters. We provide explainability and interpretability using Local Interpretable Model-agnostic Explanations (LIME) and SHapley Additive exPlanations (SHAP) techniques. Methods: A total of 419 patients with HNSCC were recruited from three University Hospitals in Sweden. We compared the performance of TabNet, a state-of-the-art deep learning algorithm for tabular data, with extreme gradient boosting (XGBoost) and voting ensemble to predict OS in patients with HNSCC. Results: Both TabNet and XGBoost showed comparable performance accuracies, with TabNet and XGBoost showing a performance accuracy of 88.1% each and voting ensemble showing an accuracy of 88.7%. The aggregate feature importance showed that p16 (a tumor suppressor protein that plays a crucial role in cell cycle regulation), cancer stage, hemoglobin, age at diagnosis, T class, N class, smoking pack-years, body mass index (BMI), treatment modality, erythrocyte count, and human papillomavirus (HPV) status were the most important parameters for the predictive ability of the model for OS. Furthermore, we found survival trends in this cohort by individually considering parameters such as p16, cancer stage, hemoglobin, age at diagnosis, HPV status, Tumor Nodal Metastasis staging, and socioeconomic factors (marital status, housing, and level of education). In addition, both the LIME and SHAP techniques showed the contribution of each feature to the prediction made by the model. Conclusions: The clinical implementation of an ML model can lead to individualized risk-based therapeutic decision-making. Therefore, validating these models with multiinstitutional datasets and testing them in the context of clinical trials is warranted for safe clinical implementation.

Most head and neck squamous cell carcinoma (HNSCC) cases are diagnosed late, with an increased risk of recurrence and distant metastasis. In recent years, there has been a surge in the development of prognostic and predictive machine learning (ML) models for personalized treatment planning. However, only a small number of these have been externally validated. This study aimed to build a prognostic system by combining clinicopathological parameters and treatment-related factors as integrative inputs to build a machine learning (ML) model using data from the Surveillance, Epidemiology, and End Results (SEER, United States) program. We further validated the developed model using multicenter data obtained from the Thuringian Cancer Registry (Germany) and a multicenter prospective observational study obtained from the Uppsala University Hospital (Sweden) to estimate the overall survival (OS) of patients with HNSCC. Additionally, we explored the complementary prognostic potentials of these input parameters using permutation feature importance (PFI). A total of 40,164 patients with HNSCC were recruited from the SEER database and validated with 3950 cases obtained from the Thuringian Cancer Registry and 323 cases recruited from three University Hospitals in Sweden. We evaluated the prognostic significance of the input variables to predict OS in patients with HNSCC using permutation feature importance. The voting ensemble ML algorithm gave an area under receiving operating characteristics curve (AUC) of 0.76 and an accuracy of 70.0%. Independent external validation of the validation model with data from the Thuringian Cancer Registry and the Uppsala University Hospital gave AUCs of 0.68 and 0.76, with decreased performance accuracy in both cohorts. The PFI analysis of the base model showed that age at diagnosis, T stage, tumor site, marital status, and surgical treatment were the most important parameters for the predictive ability of the model for OS. External independent geographic validation is important for performance reproducibility and model generalization before recommending the model for further clinical evaluation. External independent geographic validation may not necessarily increase the performance accuracy. However, it can reveal and demonstrate the performance of the model outside the development data. A generalized ML can lead to individualized risk-based therapeutic decision-making. While independently validating the model may be possible during model development, data privacy and security-related issues may prevent including it as a prerequisite in the ML model development pipeline.

ObjectiveThe aim of this world-wide survey was to evaluate the currently applied treatment options for the six most frequent peripheral vestibular disorders: benign paroxysmal positional vertigo (BPPV), acute unilateral vestibulopathy (AUVP)/vestibular neuritis, Menière’s disease (MD), bilateral vestibulopathy (BVP), vestibular paroxysmia (VP) and superior canal dehiscence syndrome (SCDS).BackgroundFor the therapy of vestibular disorders, there are four treatment options: vestibular physical therapy (canalith repositioning maneuvers or balance training), pharmacotherapy, surgery, and psychotherapy. Since there are very few state-of-the-art RCTs, the treatment of vestibular disorders is so far not standardized and various methods are applied with heterogeneous efficacy.Design/methodsA web-based standardized survey questionnaire on the treatment of the six most frequent peripheral vestibular disorders was used to collect data.Results234 replies from five continents, 47 countries, 162 cities and 188 centers were received: (% from all 234 replies; multiple answers possible): BPPV: posterior canal BPPV: 71% Epley, 40% Semont, and 12% others. Horizontal canal BPPV canalolithiasis: 58% Lempert (roll-over) maneuver, 33% Gufoni, 7% prolonged rest, and 9% others. Horizontal canal BPPV cupulolithiasis: 35% Gufoni, 27% Lempert (roll-over) maneuver, 9% Zuma, and 7% head shaking: AUVP: 79% pharmacotherapy, namely 47% glucocorticoids, 39% antiemetics, and 24% betahistine; 67% vestibular physical therapy. MD: 85% pharmacotherapy, namely 65% betahistine, 21% diuretics, 20% steroids, 16% antiemetics, 14% gentamicin; 37% surgery. VP: 65% pharmacotherapy, namely 57% anticonvulsants; 7% surgery. BVP: 77% vestibular physical therapy. SCDS: 50% surgery, namely 38.8% canal plugging, 23.3% capping and 15.5% resurfacing.ConclusionIn this world-wide survey with 234 replies from 188 centers, widely heterogeneous applied treatment options were reported for the six most frequent peripheral vestibular disorders. This study shows in particular that certain drugs are often used despite low or very low evidence. Namely in AUVP, MD and VP well-designed controlled trials with clinically meaningful endpoints are needed.

BACKGROUND:Radiotherapy (RT) has been the treatment of choice for T1 glottic squamous cell carcinomas with curative intent; however, transoral microsurgery (MLS) has gradually taken its place. The objective of this study was to compare the outcomes of the two treatment modalities. METHODS:The Swedish Head and Neck Cancer Register contains records for 783 patients who had T1 glottic squamous cell carcinomas and planned to undergo either RT or MLS with curative intent from 2008 until 2019. These included 652 patients with T1a tumors and 125 patients with T1b tumors, resulting in 777 eligible patients. RESULTS:Surgical treatment led to an increased risk of recurrence compared with RT for patients who had both T1a and T1b tumors (p < .001). Forty-seven patients (6.0%) underwent laryngectomy after primary treatment. Patients with T1b tumors had a higher risk of undergoing laryngectomy (p = .01), but no significant difference in the frequency of laryngectomy was noted between the treatment modalities. Patients who had T1b tumors had a significantly worse 5-year overall survival rate compared with those who had T1a tumors, but treatment modality did not influence the overall survival rate. CONCLUSIONS:In this population-based study of 777 patients with T1 glottic squamous cell carcinomas, no significant difference in overall survival was observed at 5 years based on treatment modality (MLS or RT). Overall survival was worse for patients with T1b carcinomas, and these patients were at an elevated risk of requiring laryngectomy. An increased risk of recurrence within 3 years was observed after surgical treatment for both T1a and T1b tumors.

BACKGROUND:In general, survival outcomes for patients with Head and Neck Cancer (HNC) has improved over recent decades. However, mortality within six months after diagnosis for curative patients remains at approximately 5%. The aim of this study was to identify risk factors for early death among patients with curative treatment, and furthermore, to analyze whether the risk of early death changed over recent years. MATERIAL AND METHOD:This real-world, population-based, nationwide study from the Swedish Head and Neck Cancer Register (SweHNCR) included all patients ≥18 years diagnosed with HNC with a curative treatment intent at the multidisciplinary tumor board from 2008 to 2020. A total of 16,786 patients were included. RESULTS:During the study period a total of 618 (3.7%) patients with curative-intended treatment died within six months of diagnosis. Patients diagnosed between 2008 and 2012 had a six-month mortality rate of 4.7% compared to 2.5% for patients diagnosed between 2017 and 2020, indicating a risk reduction of 53% (p <0.001) for death within six months. The mean time to radiation therapy from diagnosis in the 2008-2012 cohort was 38 days, compared to 22 days for the 2017-2020 cohort, (p <0.001). The mean time to surgery from diagnosis was 22 days in 2008-2012, compared to 15 days for the 2017-2020 cohort, (p <0.001). Females had a 20% lower risk of dying within six months compared to males (p = 0.013). For every year older the patient was at diagnosis, a 4.8% (p <0.001) higher risk of dying within six months was observed. Patients with a WHO score of 1 had approximately 2.4-times greater risk of early death compared to WHO 0 patients (p <0.001). The risk of early death among WHO 4 patients was almost 28 times higher than for WHO 0 patients (p <0.001). Patients with a hypopharyngeal tumor site had a 2.5-fold higher risk of dying within six months from diagnosis compared to oropharyngeal tumor patients (p <0.001). CONCLUSIONS:We found that the risk of early death decreased significantly from 2008 to 2020. During this period, the mean time to the start of treatment was significantly reduced both for surgery and oncological treatment regimes. Among patients with a curative treatment intention, increased risk of early death was associated with male sex, older age, advanced disease, increased WHO score, and a hypopharyngeal tumor site.

BACKGROUND:A significant proportion of patients with head and neck squamous cell carcinoma (HNSCC) are malnourished at diagnosis. In this study, we investigated how pretreatment body mass index (BMI) and fat-free mass index (FFMI) correlate with early death, and whether these measurements are useful markers of prognosis for risk stratification of head and neck cancer patients. METHODS:Patients (n = 404) with newly diagnosed, curable HNSCC and WHO performance status 0-2 were prospectively included and met with a study representative before treatment initiation, as well as up to four follow-up visits. All patients provided an estimate of body weight at 6 months prior to diagnosis. Bioelectrical impedance analysis (BIA) was performed for all patients before treatment initiation. RESULTS:Most patients had oropharyngeal (46%), oral cavity (28%), or laryngeal cancer (12%). Forty-five (11%) patients met the standardized criteria for malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) at diagnosis. FFMI at diagnosis was lower in patients who died within 6 and 12 months after the start of treatment than in patients who survived these time points (p = 0.035 and p = 0.005, respectively). CONCLUSIONS:In this study, pretreatment FFMI was an independent prognostic factor for death within 6 and 12 months after the start of treatment in patients with HNSCC. Pretreatment BMI was not an independent risk factor for death within 6 and 12 months after treatment termination. Thus, FFMI may be useful for risk stratification of patients with head and neck cancer.

This study examined the association between hearing loss in sporadic vestibular schwannoma patients and the proteome of perilymph (PL), cerebrospinal fluid (CSF), and vestibular schwannoma. Intraoperative sampling of PL and of CSF, and biopsy of vestibular schwannoma tissue, was performed in 32, 32, and 20 patients with vestibular schwannoma, respectively. Perilymph and CSF in three patients with meningioma and normal hearing were also sampled. The proteomes were identified by liquid chromatography coupled to high-resolution tandem mass spectrometry. Preoperative hearing function of the patients was evaluated with pure tone audiometry, with mean values at frequencies of 500, 1000, 2000, and 4000 Hz (PTA4) in the tumor-affected ear used to delineate three hearing groups. Analysis of the PL samples revealed significant upregulation of complement factor H-related protein 2 (CFHR2) in patients with severe to profound hearing loss after false discovery rate correction. Pathway analysis of biofunctions revealed higher activation scores in the severe/profound hearing loss group of leukocyte migration, viral infection, and migration of cells in PL. Upregulation of CFHR2 and activation of these pathways indicate chronic inflammation in the cochlea of vestibular schwannoma patients with severe to profound hearing loss compared with patients with normal hearing or mild hearing loss.

Background: The Head and Neck Patient Symptom Checklist (HNSC) is a validated 2-part instrument used to ask patients with head and neck cancer about the nutrition impact symptoms they experience (part 1) and how these interfere with their eating (part 2). Purpose: The purpose of this work was to translate and culturally adapt the HNSC into Swedish in accordance with the guidelines of the International Society for Health Economics and Outcomes Research (ISPOR). Methods: The ISPOR guidelines include 10 steps, and these were thoroughly followed. In step 7, 9 health care professionals from the field of head and neck cancer assessed the perceived relevance (content validity) of each item in the HNSC, as well as the full HNSC. A total of 522 participants with head and neck cancer were included and followed up on 7 occasions using the HNSC to assess internal consistency. Results: The HNSC was translated from English into Swedish, ensuring accuracy through forward and backward translation and harmonization in the research team. Content validity for each part of the HNSC was rated excellent (scale content validity index 0.96). Internal consistency demonstrated a good Cronbach's alpha score (>0.8) across the 7 follow-up time points (from baseline [before the start of treatment] and up to 24 months posttreatment). Conclusions: The HNSC has been successfully translated and culturally adapted into Swedish. The HNSC can be used in both clinical practice and research to screen for nutrition impact symptoms and symptoms that interfere with eating in patients with head and neck cancer. Trial registration: ClinicalTrials.gov NCT03343236 (date of registration: November 17, 2017)

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).

Vestibular schwannoma can cause vestibular dysfunction; however, conflicting evidence exists regarding whether this affects the incidence of fall-related injuries in this patient population. This matched cross-sectional and cohort study assess the risk of fall-related injuries in patients with vestibular schwannoma. The study included patients with vestibular schwannoma treated at a tertiary referral hospital in Sweden between 1988 and 2014. Information on fall-related injuries was obtained from the National Patient Register, and matched population comparisons were randomly selected in a 1:25 ratio. Fall-related injuries occurring pre- (within 5 years before the diagnosis of vestibular schwannoma) and post-diagnostically (up to 3 years after diagnosis or intervention) were registered. The association between vestibular schwannoma and fall-related injuries was estimated using logistic regression and Cox proportional hazards analyses. We identified 1153 patients with vestibular schwannoma (569 [49%] women and 584 [51%] men), and 28815 population comparisons. Among the patients, 9% and 7% had pre- and post-diagnostic fall-related injuries, respectively, and among the comparisons, 8% and 6% had pre- and post-diagnostic fall-related injuries, respectively. There was no increased risk of pre- (OR 1.14; CI 0.92-1.41) or post-diagnostic 1 year (HR 1.16; CI 0.87-1.54) or 3 years (HR 1.11; CI 0.89-1.29) fall-related injury among the total patient cohort. In age-stratified analyses, we found an increased risk of pre-diagnostic fall-related injury among patients aged 50-69 years (OR 1.42; CI 1.10-1.88). Patients who underwent middle fossa surgery, regardless of age, had an increased risk of post-surgery fall-related injury within 3 years of follow-up (HR 2.68; CI 1.06-6.81). We conclude that patients with vestibular schwannoma have a low risk of enduring fall-related injuries. Middle-aged patients with dizziness and fall-related injuries should be considered for a vestibular clinical evaluation. Our results highlight the importance of rehabilitation in avoiding future fall-related injuries among patients undergoing middle fossa surgery.

AIMS:To examine the prognostic value of F-18 fluorodeoxyglucose (FDG) uptake in the bone marrow (BM) for disease recurrence and survival in patients with oropharyngeal squamous cell carcinoma (OP-SCC). The secondary aims were to evaluate the prognostic value of PET/CT parameters for the primary oropharyngeal tumor and total tumor burden, and to assess the correlation between FDG uptake variables and serum inflammatory markers. METHODS:This was an observational study of 91 patients with OP-SCC who underwent pretreatment FDG-PET/CT. The patients' blood samples were collected before treatment, and treatment was administered with the intention to cure. The median follow-up time was 40 months. The PET parameters measured were SUVmeanBM for the assessment of BM FDG uptake, SUVmean, SUVmax, total lesion glycolysis (TLG), and metabolic tumor volume (MTV) for the evaluation of primary oropharyngeal tumor and total tumor burden. Blood samples were analyzed to determine each patient's white cell, red cell, and platelet cell counts, hemoglobin, and C-reactive protein level. In a subgroup of 33 patients, blood serum was analyzed to evaluate the expression of serum immune proteins using a proximity extension assay (Olink Proteomics). RESULTS:The univariate analysis revealed that SUVmeanBM and tumor-specific parameters (SUVmaxtumor, SUVmeantotal, SUVmaxtotal, MTVtotal, TLGtotal) were significantly associated with recurrence-free survival (RFS). After adjusting for age, sex, and stage only SUVmeanBM remained significantly associated with RFS. Spearman's correlation identified several correlations between PET parameters and inflammatory markers. CONCLUSIONS:Our results show that several FDG-PET/CT parameters may have a prognostic value of treatment outcome in patients with OP-SCC. However, SUVmeanBM was the only independent PET parameter that showed a prognostic value for RFS in the study cohort. Moreover, the study findings might suggest an association between systemic inflammation and the metabolic activity in the BM.

The main prognostic factors for patients with head and neck cancer are the tumour site and stage, yet immunological and metabolic factors are certainly important, although knowledge is still limited. Expression of the biomarker p16INK4a (p16) in oropharyngeal cancer tumour tissue is one of the few biomarkers for the diagnosis and prognosis of head and neck cancer. The association between p16 expression in the tumour and the systemic immune response in the blood compartment has not been established. This study aimed to assess whether there is a difference in serum immune protein expression profiles between patients with p16+ and p16- head and squamous cell carcinoma (HNCC). The serum immune protein expression profiles, using the Olink® immunoassay, of 132 patients with p16+ and p16- tumours were compared before treatment and one year after treatment. A significant difference in the serum immune protein expression profile was observed both before and one year after treatment. In the p16- group, a low expression of four proteins: IL12RB1, CD28, CCL3, and GZMA before treatment conferred a higher rate of failure. Based on the sustained difference between serum immune proteins, we hypothesise that the immunological system is still adapted to the tumour p16 status one year after tumour eradication or that a fundamental difference exists in the immunological system between patients with p16+ and p16- tumours.

Measures of adiposity and the risk of HNC in the EPIC study, excluding Oxford participants with calibrated self-reported anthropometry