Prospective, randomised clinical trial on the necessity of using a silicone intubarium in the context of endonasal-endoscopic dacryocystorhinostomy (EN-DCR) in patients with postsaccal lacrimal duct stenosis.

BACKGROUND: This prospective clinical study evaluates the effect of a silicone stent tube (SST) on the success rate of endonasal-endoscopic dacryocystorhinostomy (EN-DCR) to treat primary acquired nasolacrimal duct obstruction. METHODS: Patients were randomly assigned to receive EN-DCR with or without SST intubation over a period of 3 months. The surgery was performed using standardized techniques. Patients were assessed at three different timepoints: one day, 12 weeks and 24 weeks after the surgery. The results were compared in order to evaluate statistical differences. Surgical success was determined by means of positive irrigation procedures, as well as by the improvement of symptoms and a high level of patient satisfaction. RESULTS: A total of 56 randomized cases completed 24 weeks of follow up. 1 Patient dropped out due to malignant genesis of the nasolacrimal duct obstruction. After 24 weeks of follow up no statistically significant differences in levels of epiphora (p > .10) or patency (p > .16) were revealed. Comparisons regarding changes in time did not show levels of significance (p > .28). CONCLUSIONS: This study could not confirm a statistically significant benefit or disadvantage for SST Insertion in EN-DCR.

[Current Therapy Standards for Soft Tissue Sarcomas in the Head and Neck Area - Part 1]. / Weichgewebesarkome im Kopf-Hals-Bereich: Aktuelle Therapie ­ Teil 1.

The present work discusses soft tissue sarcoma in the head and neck area, due to the new published German S3-Guideline "adult soft tissue sarcoma". The head and neck surgeon plays the central role in the diagnosis and treatment of the vast majority of cases. It is crucial to admit the patients immediately to specialized centers for diagnoses and specific treatment. Regarding correct diagnostic procedures, in contrast to squamous cell carcinoma, a larger accidental excisional biopsy within the tumor tissue is strongly prognostic negative. After confirmation of histology and tumor extension, it is mandatory to discuss the interdisciplinary treatment concept. If possible, introduction of the patient in ongoing clinical studies is key.

[Current Therapy Standards for Soft Tissue Sarcomas in the Head and Neck Area - Part 2]. / Weichgewebesarkome im Kopf-Hals-Bereich: Aktuelle Therapie ­ Teil 2.

In September 2021, the first version of the German S3 guideline on adult soft tissue sarcomas, version 1.0 (AWMF register number 032/044OL) was presented as part of the oncology guideline program of the DKG, German Cancer Aid and the AWMF. After the basic features of soft tissue sarcomas were presented in Part 1, Part 2 describes the specific options for surgical therapy depending on the location in the head and neck area.

Dysphagia, voice problems, and pain in head and neck cancer patients.

PURPOSE: Head and neck cancer (HNC) and its treatment can leave devastating side effects with a relevant impact on physical and emotional quality of life (QoL) of HNC patients. The objectives were to examine the amount of dysphagia, voice problems, and pain in HNC patients, the impact of sociodemographic, behavioral, and clinical factors on these symptoms, the psychometric properties of the EAT-10, and the relationship between these symptoms and QoL variables. METHODS: HNC patients attending for regular follow-up from 07/2013 to 09/2019 completed questionnaires (Eating Assessment Tool-10 (EAT-10); questions from the EORTC QLQ-C30 and EORTC H&N35) on dysphagia, voice problems, pain, fatigue, and QoL collected with the software OncoFunction. Associations between prognostic factors and symptoms were tested with analyses of variance (ANOVAs). Associations between the symptom scales and QoL variables were expressed with Pearson correlations. RESULTS: Of 689 patients, 54.9% suffered from dysphagia, the EAT-10 proved to be a reliable measure. The mean voice score was 37.6 (± 33.9) [range 0-100], the mean pain score 1.98 (± 2.24) [range 0-10]. Trimodality treatment was associated with the highest dysphagia scores. Dysphagia, voice problems, and pain significantly correlated with each other, the highest association was found for dysphagia and pain (r = 0.51). QoL was strongly correlated with dysphagia and pain (r = - 0.39 and r = - 0.40, respectively), while the association with voice problems was weaker (r = - 0.28). CONCLUSION: Dysphagia is an important symptom in HNC patients greatly affecting patients' QoL and significantly correlating with voice problems and pain.

[Immuno oncology treatment in head and neck cancer]. / Immunonkologie bei Kopf-Hals-Tumoren.

In the near future, immunotherapy with checkpoint inhibitors will not only reach the relevant ENT clinics, but also the oncologically integrated ENT practice, since more and more patients under long-term therapy (currently up to 2 years) also have to be seen during clinical follow-up in the specialist practice. In this respect, we also consider as necessary that the basics of immuno-oncology in head and neck tumors are already taught as part of the ENT specialist training. In this review article, the background and the definitions of the therapy sections (first, second line treatment, marker, etc.) should be discussed in detail and the basic tools for understanding this new therapy option should be provided. Since 2017, we have been experiencing a high level of approval dynamics for checkpoint inhibitors in Germany, which is to be assessed as an expression of a new effective principle of action and, after surgery, radiation and chemotherapy, is establishing a fourth strong pillar in the multimodal spectrum against head and neck tumors. Right from the start, the checkpoint inhibitors in the first phase 1b, 2 and 2b studies achieved overall response rates of 16-22 % with overall survival rates of 6-8 months in seriously ill patients with HNSCC who already had a first- and/or even second-line therapy. Nivolumab and Pembrolizumab are currently approved in Germany for the first and second line therapy of relapsed/metastatic squamous cell carcinoma of the head and neck region (HNSCC), Cemiplimab for recurrent/metastatic cutaneous squamous cell carcinoma and Avelumab for metastatic recurrent Merkel-cell carcinoma. The synopsis article about immune checkpoint inhibitors is intended to convey the basic understanding of the principle of action, the indication, toxicity management and the further development within trials in head and neck oncology.

[Automatic calculation and visualization of comorbidity scores for decision-making in tumor boards]. / Automatisierte Berechnung und Visualisierung von Komorbiditätsindizes für den Tumorboard-Entscheid.

OBJECTIVE: Comorbidity reduces treatment options for patients with head and neck cancer (HNC). Utilization of ICD-10 codes instead of manual research may facilitate estimation of comorbidity relevant for decision-making in the interdisciplinary tumor board (TB). Providing this information immediately in an intuitively ascertainable way whenever registering a patient for the TB would trigger awareness for comorbidities and shows potentially missing information. MATERIAL AND METHODS: Administrative data was extracted of four databases at our clinic (hospital information system (HIS*-MED), the clinic's tumor database, OncoFlow® and OncoFunction®). After data extraction and record linkage facilitated by python libraries Pandas and Record linkage, ICD-10 codes were rated applying the Charlson Score and prepared for visualization within OncoFlow®. Coding quality was tested assessing the imported and manually researched diabetes status of a 1:1 matched cohort of 240 patients. RESULTS: 29 073 ICD-10 codes of 2087 HNC patients were extracted. Matched data are immediately made available whenever registering a patient for the TB and are visualized in a pictogram within OncoFlow® providing information about comorbidities and missing diagnostics. The precision of diagnostic coding at our clinic was 95.0 %. CONCLUSIONS: The high prevalence of comorbidities in HNC patients with impact on their eligibility for particular treatment indicates the usefulness of our algorithm for providing automatic comorbidity assessment from administrative data for clinical routine and requires high quality of coding diagnoses.

Rückkehr in das Erwerbsleben nach kurativer Therapie von Kopf-Hals-Karzinomen.

OBJECTIVE: Reintegration of cancer patients into occupational life is an important social and economic factor. Data for the "return to work" in Head and Neck Cancer (HNC) patients are sparse, especially compared with other tumor entities. MATERIAL AND METHODS: In a selective literature research, original articles dealing with the theme complex "return to work in patients with HNC", between 1997 and 2018 were included and analyzed. RESULTS: 18 relevant articles were identified. After curative therapy, 10-52 % of previously employed patients retired from their work. The influence of the predictors tumor localization, therapy modality and gender were not consistent. However, age, socioeconomic status, therapy-related impairment (e. g. fatigue, depression) and co-morbidity were significant factors for return to work. Rehabilitation exerts a positive effect. CONCLUSIONS: HNC patients have a high risk to retire from work. The heterogenous methods, the non-standardized points in time used for the assessments and inhomogeneous distribution in tumor localization make it difficult to compare these studies. There is an unmet need of further research in HNC patients to develop evidence-based concepts to facilitate their return to work.

Quality of Life Measurements: Any Value for Clinical Practice?

OPINION STATEMENT: Quality of life measurements are well established in cancer clinical trials. In daily clinical practice, where cancer patients often suffer from disease-specific symptoms and report unmet needs regarding their treatment, these measurements are not systematically implemented. The systematic (often computer-based) assessment of quality of life in daily cancer care has shown to be beneficial for patient-physician communication, symptom management, shared decision-making, and in creating a learning health system. Unfortunately, to date, routine electronic quality of life assessments are usually limited to large cancer facilities. Patient and physician barriers as well as barriers from the administrative side in particular are currently hindering the implementation of these systems into the broad spectrum of clinical cancer care. Cost-effectiveness analyses of existing systems, the inclusion of all relevant stakeholders, and clear implementation guidelines are required to introduce quality of life measurements in clinical cancer practice to improve the treatment of cancer survivors and to create a health care system that addresses all their disease-related needs.

Cancer-associated financial burden in German head and neck cancer patients.

Background: The financial toxicity of cancer causes higher morbidity and mortality. As the financial burden due to head and neck cancer (HNC) in European healthcare systems with legally established compulsory health insurance is still poorly understood, we set up an investigation to assess the financial impact of HNC. Methods: Between August 2022 and March 2023, HNC consecutive patients (n = 209) attending the cancer aftercare program of a university hospital in an outpatient setting were surveyed utilizing self-administered questionnaires about their socioeconomic situation, income loss, and out-of-pocket payments (OOPPs). Results: The majority of HNC patients (n = 119, 59.5%) reported significant financial burden as a consequence of OOPP (n = 100, 50.0%) and/or income loss (n = 51, 25.5%). HNC patients reporting financial burden due to OOPP had on average 1,716 € per year costs related to their disease, whereas patients reporting an income loss had a mean monthly income loss of 620.53 €. Advanced UICC (7th edition, 2017) stage, T3 or T4 category, and larynx/hypopharynx cancer are significant predictors of financial burden. Conclusion: HNC survivors suffer from significant financial burden after HNC treatment, even in Germany with a healthcare system with statutory health insurance. The findings from this study offer valuable insights for healthcare professionals and policymakers, helping them acknowledge the economic impact of HNC.

Improved survival of locoregional-advanced larynx and hypopharynx cancer patients treated according to the DeLOS-II protocol.

Introduction: Larynx organ preservation (LOP) in locoregional-advanced laryngeal and hypopharyngeal squamous cell carcinoma (LA-LHSCC) being only R0-resectable (clear margins > 5 mm) by total laryngectomy (TL) is desirable. Based on tumor-specific survival (TSS) and overall survival (OS) data from the RTOG 91-11 trial and meta-analyses of randomized clinical trials (RCTs), cisplatin-based concurrent radiochemotherapy (CRT) is discussed being superior to cisplatin-based induction chemotherapy followed by radiotherapy (IC+RT) and TL followed by postoperative RT (TL+PORT) or radiochemotherapy (TL+PORCT). Outside of RCTs, T4 LHSCC treated with TL+PORCT demonstrated improved OS and TSS compared to CRT alone; comparisons with docetaxel plus cisplatin (TP)-based IC+RT are unpublished. Head-to-head comparisons in RCTs of these four alternatives are missing. Materials and methods: We utilized monocentric registry data to compare the outcome in the LOP trial DeLOS-II (NCT00508664) and propensity score (PS)-matched LHSCC patients. DeLOS-II utilized endoscopic tumor staging after one cycle of TP-based IC for selecting TL+R(C)T for non-responders versus IC+RT for responders. Main risk factors for survival (localization hypopharynx, T4, N+, tobacco smoking >30 pack years, alcohol consumption >60 g/day, age, sex) were used to calculate the individual PS for each DeLOS-II patient and 330 LHSCC patients suitable for DeLOS-II according to eligibility criteria in Leipzig by CRT (78), TL+PORT (148), and TL+PORCT (104). We performed PS matching with caliper width 0.2. Results: The 52 DeLOS-II patients (whole intent-to-treat cohort) and three PS-matched cohorts (52 LHSCC patients each) had equal distribution regarding risk factors including Charlson comorbidity score (CS; all p > 0.05) but differed in outcome. During 12,498.6 months of follow-up, 162 deaths (36/41/43/42 in DeLOS-II/TL+PORCT/TL+PORT/CRT, p = 0.356) occurred; DeLOS-II patients had superior OS and TSS. Compared to DeLOS-II, the HR (95% CI) observed in TL+PORCT, TL+PORT, and CRT for OS and TSS were 1.49 (0.92-2.43), 1.49 (1.15-3.18), and 1.81 (1.11-2.96) for OS; and 2.07 (0.944-4.58), 3.02 (1.32-6.89), and 3.40 (1.58-7.31) for TSS. Conclusion: In addition potential LOP, LA-LHSCC suitable for LOP according the DeLOS-II protocol may achieve improved survival.

A Radiomics-Based Machine Learning Perspective on the Parotid Gland as a Potential Surrogate Marker for HPV in Oropharyngeal Cancer.

BACKGROUND: In treatment of oropharyngeal squamous cell carcinoma (OPSCC), human papillomavirus status (HPV) plays a crucial role. The HPV-positive subtype tends to affect younger patients and is associated with a more favorable prognosis. HPV-associated lesions have been described in the parotid gland, which is included in routine imaging for OPSCC. This work aims to explore the ability of an ML system to classify HPV status based on imaging of the parotid gland, which is routinely depicted on staging imaging. METHODS: Using a radiomics approach, we investigate the ability of five contemporary machine learning (ML) models to distinguish between HPV-positive and HPV-negative OPSCC based on non-contrast computed tomography (CT) data of tumor volume (TM), locoregional lymph node metastasis (LNM), and the parotid gland (Parotid). After exclusion of cases affected by streak artefacts, 53 patients (training set: 39; evaluation set: 14) were retrospectively evaluated. Classification performances were tested for significance against random optimistic results. RESULTS: The best results are AUC 0.71 by XGBoost (XGB) for TM, AUC 0.82 by multi-layer perceptron (MLP) for LNM, AUC 0.76 by random forest (RF) for Parotid, and AUC 0.86 by XGB for a combination of all three regions of interest (ROIs). CONCLUSIONS: The results suggest involvement of the parotid gland in HPV infections of the oropharyngeal region. While the role of HPV in parotid lesions is under active discussion, the migration of the virus from the oral cavity to the parotid gland seems plausible. The imaging of the parotid gland offers the benefit of fewer streak artifacts due to teeth and dental implants and the potential to screen for HPV in cases of an absent or unlocatable tumor. Future investigation can be directed to validation of the results in independent datasets and to the potential of improvement of current classification models by addition of information based on the parotid gland.

Immune checkpoint blockade induced shifts in cytokine expression patterns in peripheral blood of head and neck cancer patients are linked to outcome.

Background: Immune-checkpoint blockade (ICB) of programmed-death-1 (PD-1) with pembrolizumab or nivolumab is approved for treating recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). NadiHN and ADRISK are phase IIB trials investigating in locally advanced (LA) HNSCC having low or high risk of recurrence the potential benefits from adding nivolumab to post-operative radiotherapy or pembrolizumab to cisplatin-based radio-chemotherapy. Methods: Along five randomized controlled ICB trials including NadiHN and ADRISK, blood samples were taken before and after starting ICB in n=25 patients. Concentrations of vascular endothelial growth factor A (VEGF), CCL2 (MCP-1), interleukin-6 (IL-6), IL-8, interferon-gamma (IFN-γ), and CXCL10 (IP-10) pre- and post-ICB in EDTA-anticoagulated plasma and serum were compared. We used receiver operating characteristic (ROC) curves to identify optimal cutoff for defining subgroups before analyzing overall survival (OS) applying Kaplan-Meier plots and multivariate Cox regression. Results: We detected huge heterogeneity between cytokine patterns in pre-and post-ICB plasma and serum. We observed high correlation between concentrations of some cytokines. Despite absent systematic OS differences after ICB with pembrolizumab or nivolumab or between LA-HNSCC versus R/M HNSCC patients, we noticed improved outcome of patients having lower IFN-γ concentrations pre- and post-ICB and following ICB reduced concentrations of VEGF, IL-6, and IL-8 but not MCP-1. Contrarily, increases in IL-6, IL-8, and VEGF levels correlated with impaired outcome. Multivariate Cox regression revealed five independent OS predictors among cytokines; using natural logarithms of their hazard ratios to estimate an individual's risk of dying, three cytokine-expression pattern (CEP)-risk groups with no death within mean (95% confidence interval) follow-up of 29.2 (22.1-36.2) months and median OS of 11.3 (8.8-13.8) and 2.9 (0.4-5.4) months were found. Conclusion: Whereas individual pre- or post-ICB cytokine concentrations in serum or plasma alone failed to predict the survivor group, CEP-risk groups may support the identification of individual patients with long-lasting benefit from ICB.

Outcome differences in HPV-driven head and neck squamous cell carcinoma attributable to altered human leukocyte antigen frequencies.

Background: Effective immune surveillance requires a functioning immune system and natural killer (NK) and T cells for adequate innate and antigen-specific immune responses critically depending on human leukocyte antigens (HLAs) and haplotypes representing advantageous combinations of HLA antigens. Recently, we reported a link between altered frequencies of HLA alleles and haplotypes and developing head and neck squamous cell carcinoma (HNSCC). Whereas the majority of HNSCCs seem to be related to classical risk factors alcohol and tobacco, a subset of HNSCC and especially oropharyngeal squamous cell carcinoma (OPSCC) were etiologically linked to human papillomavirus (HPV) recently. Here, we demonstrate in HPV-driven (p16-positive high risk-HPV DNA-positive) HNSCC a deviating distribution of HLA antigens and haplotypes and their relevance to outcome. Methods: Leukocyte DNA of n = 94 HPV-driven HNSCC patients (n = 57 OPSCC, n = 37 outside oropharynx) underwent HLA SSO typing, allowing allele, antigen (allele group), and haplo-typing. Besides comparing these frequencies with those of German blood donors, we analyzed their impact on outcome using Kaplan-Meier plots and Cox proportional hazard regression. Results: Antigen and haplotype frequencies demonstrate enrichment of rare antigens and haplotypes. The HLA score for unselected HNSCC patients was not predictive for outcome here. However, together with alcohol consumption, tobacco smoking, T category, and extranodal extension of locoregional metastases and treatment applied, eight HLA traits allow for predicting progression-free and tumor-specific survival. Conclusion: Patients can be categorized into low, intermediate-low, intermediate-high, and high risk groups. Using a new PFS risk score for HPV-driven HNSCC may allow to improve prognostication.

Frailty Assessed with FRAIL Scale and G8 Questionnaire Predicts Severe Postoperative Complications in Patients Receiving Major Head and Neck Surgery.

INTRODUCTION: Frailty represents a complex geriatric syndrome associated with elevated rates of postoperative complications as shown for several malignant entities, including head and neck cancer. A specific screening instrument to assess frailty in head and neck patients does not exist. Both the FRAIL Scale and the G8 questionnaire are well-established and easy to use as screening tools. The present study's aim was to assess the potential of frailty screening to predict postoperative complications in head and neck patients prior to surgery. PATIENTS AND METHODS: We recorded demographic data, pre-existing medical conditions and clinical characteristics in a prospective cohort of 104 head and neck cancer patients undergoing major head and neck surgery and assessed frailty prospectively on the day of admission utilizing the G8 questionnaire and the FRAIL Scale. We analyzed the link between occurrence of postoperative complications up to the twenty-first postoperative day and age, frailty and other covariates using χ2 tests and receiver operating characteristic (ROC) curves. RESULTS: There was no significant correlation between patients' pre-existing medical conditions and postoperative complications. Whereas chronological age alone did not predict the occurrence of postoperative complications, frailty posed the highest risk for complications. Frailty according to either the G8 questionnaire or the FRAIL Scale predicted occurrence of complications with an area under the curve (AUC) of 0.64 (p = 0.018) and 0.62 (p = 0.039) and severe complications with an AUC of 0.72 (p = 0.014) and 0.69 (p=0.031), respectively. Neither frailty score correlated with age or with each other. CONCLUSION: Prospective screening using the FRAIL Scale or the G8 questionnaire reliably detected frailty in our sample group. Frailty is linked to increased risk of postoperative complications. The correct prediction of severe postoperative complications as shown identifies vulnerable cases and triggers awareness of potential complications. Anticipating risk allows for a more comprehensive view of the patient and triggers decision making towards risk adjustment, and therefore a selective view of alternative treatment modalities.

Web-Based Patient-Reported Outcomes for ENT Patients-Evaluation of the Status Quo, Patients' View, and Future Perspectives.

BACKGROUND: Patient-reported outcomes (PRO) assess disease burden and indicate unmet needs. Home-based electronic PRO measures (ePROMs) can support tumor aftercare (TAC). Creating an ePROM is the next step after implementing the software "OncoFunction" to assess PROs during TAC of head- and neck-cancer patients (HNC). Therefore, internet use and perception on ePROMs of ENT and TAC patients were evaluated. METHODS: From May-July 2020, ENT patients at a high-volume outpatient department aged >18 without need for emergency treatment were invited to complete a questionnaire concerning internet use and access, hardware, and opinion on the chances, requirements, and designs of ePROMs. RESULTS: 415 questionnaires were evaluated; 46.3% of the respondents visited the common consultation hour (CCH) and 44.3% TAC; 71.9% were internet users, being younger than non-internet users; and 36.4% of TAC patients were non-internet users and 16.3% of them were without a web-enabled device. Significant differences existed in age and assessment of future perspectives between internet-/non-internet users and TAC/CCH patients, respectively. Regarding the design of ePROMs, patients preferred quarterly and short surveys. Data safety and feedback were important. CONCLUSIONS: ePROMs are not suitable for everyone because of missing internet access and experience. A tailored approach to implement ePROMs in TAC is needed.

High-Risk Human Papillomavirus (HR-HPV) DNA Detection in Mouthwashes for Diagnosis of HPV-Driven Oropharynx Cancer and Its Curative Therapy-A Feasibility Study.

Detection of p16 through immunohistochemistry (IHC) is the standard for determining the HPV status of the tumor according the TNM eighth edition released in 2017 and has become crucial for determining the HPV status of oropharyngeal squamous cell carcinomas (OPSCC) with direct impact on staging and prognostication. In recent years, detection of HPV DNA in mouthwashes has been proposed as a noninvasive alternative, both for OPSCCs and for other head and neck squamous cell carcinomas (HNSCCs). However, the prospect of using the mouthwashes to monitor the response to therapy is unclear. To evaluate the effect of curative therapy on the detection of HPV DNA, we performed a prospective study comparing the detection frequency of high-risk HPV DNA (HR-HPV-DNA) in pre- and post-therapy mouthwashes. We collected 137 mouthwashes from 88 pathologically confirmed HNSCC patients for DNA isolation and HPV genotyping with the Inno-LiPA assay. We show that HPV DNA in pretherapeutic mouthwashes can detect HPV-driven HNSCCs with a sensitivity of 50.0% and specificity of 85.4%, alongside a high negative predictive value of 79.5% and an accuracy of 74.5%. Furthermore, we observed a notable decrease in the detection frequency of HR-HPV-DNA after successful treatment (pre-therapy 50.0% (9/18) versus post-therapy 9.7% (3/28)). However, the comparatively low sensitivity regarding detection of HPV-driven OPSCC argues against its use in clinical routine.

Standardization and Feasibility of Voice Range Profile Measurements in Epidemiological Studies.

OBJECTIVES: The voice range profile (VRP) is composed of the speaking VRP (spVRP) and the singing VRP (siVRP). Different examination methods of VRP and effects of interobserver variability were evaluated to define a standard operating procedure (SOP) suitable for the specific use in epidemiological studies. Subsequently the feasibility of the SOP was investigated in a larger number of participants. STUDY DESIGN: Cross-sectional study. METHODS: In a first phase both the spVRP and the siVRP of 51 female students were measured by four differently experienced examiners. Using a cross-over study design the effects of two different recording methods (manual vs automatic) and three different types of instructions given by the examiner (none vs before vs during recording) were investigated. In a second phase, the SOP for VRP recording was tested in the framework of a feasibility study in 110 (55 female and 55 male) participants. RESULTS: The average total investigation time was significantly (P = 0.001) higher for the manual recording method (6.1 minutes ± 1.0) in comparison to the automated (5.5 minutes ± 0.7) recording method. The manual recording method led to significantly lower values of minimum frequency (F0min) (P = 0.013) and minimum intensity (SPLmin) (P < 0.001) and higher values of the maximum frequency (F0max) (P = 0.005) of the siVRP. The maximum phonation time, F0max, SPLmax of the siVRP and the frequency and intensity of the shouting voice (Level IV) of the spVRP showed significantly (P < 0.001) higher values when the examiner was allowed to give instructions and advise during the recording. Voice parameters of the siVRP did not show significant associations with the experience of the examiner. CONCLUSIONS: Standardization of VRP measurements is important to obtain correct and reproducible data in a reasonable examination time. The SOP proposed here proved to be feasible in the setting of an epidemiological study.

Cytokine Profiles of Head and Neck Squamous Cell Carcinoma Undergoing Dual Immunotherapy With Cetuximab and Pembrolizumab Identify Interferon Gamma-Induced Protein 10 as Novel Biomarker.

Background: Pembrolizumab and cetuximab are antibodies under investigation in head and neck squamous cell carcinoma (HNSCC) either as single agents or combined with cisplatin and other chemotherapeutic drugs, e.g., 5-fluorouracil and/or docetaxel. However, also the combination of both antibodies may have potential in recurrent/metastatic (R/M) HNSCC, in particular in cisplatin-resistant or -refractory cases or patients with comorbid disease, e.g. patients with impaired renal function. Methods: To clarify potential benefit that may result from such combination, we used the FLAVINO assay, a short-time ex vivo assay to compare responsiveness of HNSCC to pembrolizumab, cetuximab and both combined regarding colony formation of epithelial cells of biopsy-derived tumor samples and their cytokine production within three days either without or with stimulation with 10 ng/mL interferon gamma (IFN-γ). Vascular endothelial growth factor A (VEGF), monocyte chemoattractant protein 1 (MCP-1 or CCL2), interleukin 6 (IL-6), IL-8, IFN-γ, and interferon gamma-induced protein 10 (IP-10 or CXCL10) in supernatants were measured by ELISA. Results: We detected huge heterogeneity in response to cetuximab, pembrolizumab and both combined with and without IFN-γ stimulation. Moreover, we detected a link between IFN-γ induced IP-10 release and improved outcome in those HNSCC patients who were capable to respond to IFN-γ and pembrolizumab, cetuximab and both combined with a further increase in IP-10 production. We derived an "IP-10 score" that independent from clinical characteristics of HNSCC patients and therapy regimens applied was able to predict their outcome. Conclusions: The heterogeneity in the ex vivo response of cetuximab, pembrolizumab and both combined with and without IFN-γ stimulation identifies subgroups of HNSCC patients with deviating OS.

Invasive Growth of Ailanthus altissima Trees is Associated with a High Rate of Sensitization in Atopic Patients.

Purpose: Ailanthus altissima is one of the world's most invasive species with a globally problematic spread. Pollen is dispersed locally and partially airborne. We aimed at investigating if (i) A. altissima pollen can be detected in relevant quantity in the air and if (ii) sensitization to A. altissima can be detected in patients with seasonal exacerbation of atopic diseases. Patients and Methods: We recorded distribution of A. altissima in Leipzig, Germany. In 2019 and 2020, pollen was collected with a Hirst-type pollen trap placed on the roof of the University Hospital. Specific IgE investigations were performed in children and adults with history of atopic diseases with deterioration between May and July. We analysed specific IgE for A. altissima, Alternaria sp., birch, grasses, profilins, polcalcins and crossreacting carbohydrates. Results: We found abundant growth of A. altissima and pollen was detected from early June to mid-July with a maximum pollen concentration of 31 pollen/m3. Out of 138 patients (63 female, 69 children/adolescents), 95 (69%) had seasonal allergic rhinitis, 84 (61%) asthma, and 43 (31%) atopic dermatitis. Sensitization to A. altissima was shown in 59 (42%). There were no significant differences between age groups. In 59% of patients sensitized (35/59), there was no sensitization to possibly cross-reacting structures. Conclusion: Sensitization to A. altissima pollen could be detected in 42% of our patients with atopic diseases, suggesting allergenic potential of this neophyte. In the context of further spread with climate change, eradication strategies and population-based sensitization studies are needed.