Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Mepolizumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Halschirurgie (DGHNOKHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the mucous membranes of the nose and sinuses. Eosinophilic inflammation is described as a common endotype. The anti-IL5 antibody mepolizumab was approved in November 2021 as an add-on therapy to intranasal glucocorticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps when systemic glucocorticosteroids or surgery do not provide adequate disease control. While national and international recommendations exist for the use of mepolizumab in CRSwNP, it has not yet been adequately specified how this therapy is to be monitored, what follow-up documentation is necessary, and when it should be terminated if necessary. METHODS: A literature search was performed to analyze previous data on the treatment of CRSwNP with mepolizumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 10/2022 were considered. RESULTS: Based on the international literature and previous experience by an expert panel, recommendations for follow-up, adherence to therapy intervals and possible therapy breaks, as well as termination of therapy when using mepolizumab for the indication CRSwNP in the German health care system are given on the basis of a documentation sheet. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens up new non-surgical therapeutic approaches with biologics for patients with severe, uncontrolled courses. Here, we provide recommendations for follow-up, adherence to therapy intervals, possible therapy pauses, or discontinuation of therapy when mepolizumab is used as add-on therapy with intranasal glucocorticosteroids to treat adult patients with severe CRSwNP that cannot be adequately controlled with systemic glucocorticosteroids and/or surgical intervention.

Positionspapier: Empfehlungen zur Anwendung von Mepolizumab bei chronischer Rhinosinusitis mit Polyposis nasi (CRSwNP) im deutschen Gesundheitssystem ­ Empfehlungen des Ärzteverbandes Deutscher Allergologen (AeDA) und der AGs Klinische Immunologie, Allergologie und Umweltmedizin und Rhinologie und Rhinochirurgie der Deutschen Gesellschaft für HNO-Heilkunde, Kopf- und Hals-Chirurgie (DGHNO-KHC).

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the paranasal sinus mucosa with eosinophilic inflammation as the most common endotype. The anti-IL5 antibody mepolizumab was approved for the treatment of severe CRSwNP in the EU in November 2021. METHODS: A literature search was performed to analyze the immunology of CRSwNP and determine the available evidence by searching Medline, Pubmed, and the German national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to and including 12/2021 that investigated the effect of mepolizumab in CRSwNP were considered. RESULTS: Based on the international literature and previous experience, recommendations for the use of mepolizumab in CRSwNP in the German health care system are given by an expert panel on the basis of a documentation form. CONCLUSIONS: Understanding about the immunological basis of CRSwNP opens new non-surgical therapeutic approaches with biologics for patients with severe courses. Mepolizumab is approved since November 2021 for add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP who cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

Empfehlungen zur Überprüfung der Wirksamkeit und Verlaufsdokumentation von Dupilumab bei chronischer Rhinosinusitis mit Nasenpolypen (CRSwNP) im deutschen Gesundheitssystem.

BACKGROUND: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a multifactorial inflammatory disease of the nasal and paranasal mucosa. A Type-2 inflammation is described as the most common endotype. Since October 2019 the anti-IL-4/-IL-13 antibody dupilumab has been approved in Germany as an add-on therapy to intranasal corticosteroids for the treatment of adults with severe chronic rhinosinusitis with nasal polyps, when systemic corticosteroids alone or surgery do not provide adequate disease control. While recommendations for the use of dupilumab in CRSwNP exist at both national and international levels, until now it has not been adequately established, how therapy should be monitored and when it should be discontinued in the German Health Care System. METHODS: A literature search was performed analyzing previous data on the treatment of CRSwNP with dupilumab and to determine the available evidence by searching Medline, Pubmed, the national and international trial and guideline registries and the Cochrane Library. Human studies published in the period up to 05/2022 were included. RESULTS: Based on international literature and previous experience, recommendations are given by an expert panel for follow-up and possible therapy breaks, therapy intervals or termination of therapy when using dupilumab for the indication CRSwNP in the German health care system based on a documentation form. CONCLUSIONS: Understanding the immunological basis of CRSwNP opens new non-surgical therapy approaches with biologics for patients with severe courses. The authors give recommendations for follow-up, possible therapy breaks, therapy intervals and a termination for dupilumab treatment as add-on therapy with intranasal corticosteroids for the treatment of adult patients with severe CRSwNP that cannot be adequately controlled with systemic corticosteroids and/or surgical intervention.

[Dupilumab has an additional benefit in treatment of chronic rhinosinusitis with nasal polyps]. / Dupilumab besitzt einen Zusatznutzen für die Behandlung der chronischen Rhinosinusitis mit Nasenpolypen.

BACKGROUND: For patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) which cannot be controlled by continuous therapy with intranasal corticosteroids (INCS) and systemic corticosteroids and/or surgical treatment, there were no approved curative options for a long time. For CRSwNP treatment with T2-addressing biologics is possible. On October 24, 2019, the European Commission granted extended approval for dupilumab as the first biological agent for treatment of insufficiently controlled severe CRSwNP. The Federal Joint Committee (G­BA) evaluates the benefits of reimbursable drugs with new active ingredients. This includes assessment of the additional benefit and its therapeutic relevance. METHODS: A meta-analysis was performed using individual patient data based on two phase III studies. Both studies examined the safety and efficacy of dupilumab as an add-on therapy to INCS for treatment of CRSwNP in adults inadequately controlled with systemic corticosteroids and/or surgery compared to INCS alone. RESULTS: Based on the present data, the G­BA decided that there is an indication of a considerable additional benefit of dupilumab compared to mometasone furoate. CONCLUSION: For patients with severe CRSwNP inadequately controlled with INCS and systemic corticosteroids and/or surgery, there is an indication of a considerable additional benefit for the administration of dupilumab as an add-on therapy to INCS compared to mometasone furoate alone.

[Effects of the SARS-CoV­2 pandemic on the otolaryngology university hospitals in the field of research, student teaching and specialist training]. / Auswirkungen der SARS-CoV­2-Pandemie auf die universitäre Hals-Nasen-Ohren-Heilkunde im Bereich der Forschung, Lehre und Weiterbildung.

BACKGROUND: From spring 2020, SARS-CoV­2 began to spread worldwide, with what is now known as the first wave of the pandemic, starting in March 2020. This resulted in restructuring and shift of resources at many hospitals. The aim of our work was to detect the effects of the pandemic on the german Oto-Rhino-Laryngology (ORL) university hospitals in terms of research, student teaching and further specialist training. MATERIAL AND METHODS: The chairmen of the 39 ORL university hospitals in Germany were asked about the effects of the pandemic on research, student teaching and ORL specialist training (residency) in the period from March to April 2020 using a structured online survey. RESULTS: All 39 chairmen took part in the survey. Of these, 74.4% (29/39) stated that their research activities had deteriorated as a result of the pandemic. In 61.5% (24/39) pandemic-related research issues were addressed. All hospitals reported a restriction for in-house teaching and 97.5% (38/39) introduced new digital teaching methods. During the observation period, 74.4% of the chairmen did not see ORL specialist training (residency)at risk. CONCLUSION: Our results provide an insight into the heterogeneous effects of the pandemic. The fast processing of pandemic-related research topics and the introduction of innovative digital concepts for student teaching impressively demonstrates the great innovative potential and the ability of the ORL university hospitals to react quickly in order to maintain their tasks in research, student teaching and ORL specialist training in the best possible way even during the pandemic.

[Liquid biopsy-a possible key player in immuno-oncology]. / "Liquid biopsy" als Schlüsselfigur in der Immunonkologie.

BACKGROUND: Clinical application of immune checkpoint inhibitors (ICI), whether as monotherapy or in combination with established methods, is revolutionizing treatment of head and neck cancer. However, this change in therapeutic concepts requires reevaluation and further development of predictive and prognostic markers, since the survival rates for advanced and particularly human papillomavirus (HPV)-negative disease remain poor. MATERIALS AND METHODS: A selective literature review was performed in PubMed. Literature found with the keywords "cytodiagnostics, circulating tumor cells, liquid biopsy, cfDNA, exosomes" in combination with "head and neck cancer" and/or "immune checkpoint inhibitor therapy" published until March 2020 was included. The articles were selected for their relevance for the current study by the authors. RESULTS: This work provides a review of the current literature and indicates possible applications in the field of head and neck cancers. Liquid biopsy refers to the analysis of circulating tumor cells or of tumor genetic material in body fluids. This minimally invasive analysis can support therapeutic decisions and enable a personalized approach to treating head and neck cancer. DISCUSSION: Before any of these approaches can be established in clinical routine, long-term data and standardization of the methods for isolating and analyzing the markers are needed.

[Recognition function for the Freiburg monosyllabic test in noise with a signal to noise ratio (SNR) of 5 dB]. / Die Verständlichkeitskurve für den Freiburger Einsilbertest im Störschall mit einem Signal-Rausch-Abstand (SNR) von 5 dB.

OBJECTIVE: The Freiburg monosyllabic test (FBE) has been an important German speech audiometry test for years. It is nowadays also used to assess the benefit of hearing aids in noise (FBE-S). This study investigates hearing in noise using the FBE at different sound pressure levels and a signal to noise ratio of 5 dB to generate a recognition curve. METHODS: In autumn 2018, 60 normal-hearing German native speakers (age 18-31 years) participated in the study at the military hospital in Hamburg. Using one FBE test list, speech intelligibility was measured from sound pressure levels of 15 to 90 dB in 5­dB steps with a noise level 5 dB lower in each case. Subsequently, the average of all intelligibility rates and 95% confidence intervals (CI) were determined. RESULTS: Participants comprised 29 female and 31 male subjects. Average age was 24.32 years (±3.29 years). The fixed effects analysis of variance with recognition as the dependent variable demonstrated a highly significant correlation between the levels of sounds/noise and the intelligibility of speech (p < 0.0001). The average intelligibility rates with 95% CI and the frequency distributions were presented tabularly and graphically. CONCLUSION: In comparison to the normative curve, the FBE­S recognition curve is shifted to the right. The average values of the FBE­S reach the saturation area at a volume of 70/65 dB with an intelligibility rate of 90% (for comparison: the point of saturation for 100% intelligibility of the FBE without noise is reached at 55 dB). Using these averaged values of the FBE­S enables better interpretation of individual results without and with hearing aids. In the future, the benefit of hearing aids should be measured at lower noise levels than it is today.

Upper airway stimulation for obstructive sleep apnea-Can radiological position monitoring predict tongue motion one year after implantation?

BACKGROUND: Tongue motion patterns (TMP) can influence the outcome of upper airway stimulation (UAS) in the treatment of obstructive sleep apnea (OSA). As a postoperative control, the cuff position of the stimulation lead is monitored via X­ray imaging. A multidimensional X­ray assessment system was established and the association between these positional assessments and TMP was investigated 1 year after implantation. MATERIAL AND METHODS: The study on TMP and the X­ray assessments were carried out at a German ear nose and throat clinic as an implantation center. The TMPs were assessed under bipolar electrode configuration and were categorized according to the currently available literature as right-sided protrusion (RP), left-sided protrusion (LP), bilateral protrusion (BP) and mixed activation (MA). The X­ray assessment was carried out in five dimensions: the position relative to the mandible and hyoid, cuff steepness in the lateral view of the neck, the cuff position based on the single electrode, and the lead connection to the cuff in the anterior-posterior view. The analyses were performed by three raters with different medical backgrounds and knowledge regarding TMP. RESULTS: In approximately 60% of patients, the apnea-hypopnea index was reduced to below 15/h 1 year after implantation. The most common TMPs were RP and BP (82.9%). The interrater variability of the X­ray assessment was good except for one category. Furthermore, no relevant associations were found apart from the correlation between a favorable TMP and the cuff position with respect to the lateral position of the stimulation cable. CONCLUSION: Despite good interrater variability and convenient usage of the suggested X­ray assessment system, this approach did not enable the identification of any associations by which a TM and, therefore, a possible straightforward or complicated treatment pathway could be predicted. Attention should possibly be paid to a rotation of the cuff during implantation with a lateral position of the stimulation lead.

[Effects of the SARS-CoV-2 pandemic on the otorhinolaryngology university hospitals in the field of medical care]. / Auswirkungen der SARS-CoV-2-Pandemie auf die universitäre Hals-Nasen-Ohrenheilkunde im Bereich der Krankenversorgung.

INTRODUCTION: Since December 2019, the SARS-CoV-2 virus has been rapidly spreading worldwide. In Germany, an exponential increase in the number of infections was registered at the beginning of March 2020 and led to a call of the Ministry of Health to create more capacity for intensive medical treatment in hospitals. The aim of the present study was to determine the effects of the SARS-CoV-2 pandemic on Oto-Rhino-Laryngology (ORL) university hospitals regarding patient care. MATERIALS AND METHODS: An online survey was sent out to all chairmen of the 39 ORL university hospitals in Germany. The answers to the questions referred to the defined period from March 15th to April 15th 2020 and were carried out using the online survey tool "SurveyMonkey". 87 questions focused on general information, health care, and structural effects in the respective institution. RESULTS: All chairmen of the 39 university hospitals in Germany participated in the survey. The collected data prove the considerable impact on organizational, structural and medical aspects of patient care. For example, the surveyed clinics reported a decrease in outpatient cases by 73.8 % to 26.2 ±â€Š14.2 % and in surgical treatments by 65.9 % to 34.1 ±â€Š13.9 %. In contrast, emergency treatment remained unchanged or even increased in 80 % of the facilities and surgical treatment of emergency patients remained unchanged or even increased in more than 90 %. Emergency outpatient and surgical treatment of patients was provided throughout the pandemic in all facilities. In total, about 35 000 outpatients and about 12 000 surgical cases were postponed. As a result of the acute structural changes, the potential danger of falling below current treatment standards was seen in individual areas of patient care. DISCUSSION: The assessment of the impact of the SARS-CoV-2 pandemic is heterogeneous. The majority of the chairmen are critically aware of the risk of falling below current medical treatment standards or guidelines. In the phase of an exponential increase in the number of infections, significant changes in treatment processes had to be accepted for understandable reasons. However, with the currently significantly reduced number of infections, falling below treatment standards and guidelines should not be allowed to remain constant and tolerated. SUMMARY: This study shows a differentiated picture with regard to the effects of the SARS-CoV-2 pandemic on outpatient, inpatient and operative patient care at the ORL university hospitals in Germany and illustrates the importance of these institutions for ensuring patient care during this critical phase.

[Histamine receptors in chronic inflammatory diseases of the nose and paranasal sinuses]. / Histaminrezeptoren bei chronisch-entzündlichen Erkrankungen der Nase und Nasennebenhöhlen.

BACKGROUND: Release of histamine from mast cells and basophils in inflammatory diseases of the nose and paranasal sinuses has been demonstrated in allergic and non-allergic processes. METHODS: A selective literature search was conducted in PubMed and Medline, and publications in German-language journals were additionally analyzed. RESULTS: The histamine receptors H1-H4 play a role in otorhinolaryngologic inflammatory diseases. To date, the histamine receptor subtype 4 (H4R), which is functionally expressed by immune cells in chronic inflammatory diseases, has received little attention. Stimulation of H4R influences the release of cytokines and chemokines as well as the migration behavior of immune cells. In animal models blockade of H4R reduced inflammation symptoms and pruritus. CONCLUSIONS: H4R plays a key role in the pathogenesis of chronic inflammatory diseases and may represent an interesting future therapeutic target.

[Immunology of chronic rhinosinusitis with nasal polyps as a basis for treatment with biologicals]. / Immunologie der Polyposis nasi als Grundlage für eine Therapie mit Biologicals.

BACKGROUND: Chronic rhinosinusitis (CRS) is a heterogeneous and multifactorial inflammation of the nasal and paranasal mucosa. Until now, no internationally standardized classification could be developed. In most cases, CRS is phenotypically classified according to chronic rhinosinusitis with (CRScNP) and without nasal polyps (CRSsNP). However, recent studies could show that there are numerous endotypes within these phenotypes based on different inflammatory mechanisms. This review describes the important immunological mechanisms of CRScNP and highlights modern treatment options with biologicals directly addressing particular immunological processes. METHODS: Current knowledge on immunological and molecular processes of CRS, particularly CRScNP, was extracted from Medline, PubMed, national and international study- and guideline-registers, and the Cochrane library by a systematic review of the literature. RESULTS: Based on current literature, various immunological mechanisms for CRS and CRScNP could be identified. Relevant studies for the treatment of eosinophilic conditions such as asthma or CRScNP are presented and, if available, results of these studies are discussed. CONCLUSION: The growing insight into the underlying immunological mechanisms of CRScNP could pave the way for new personalized treatment options such as biologicals in the future.

[Reasons for the development of allergies in children]. / Gründe für die Entstehung von Allergien bei Kindern.

Allergies are one of the most common chronic diseases in childhood, contributing to a tremendous medical and economical burden in health care systems of most industrialized countries. The development of allergies is dependent on a complex interaction of-among others-environmental factors, nutrition, genetic and epigenetic mechanisms as well as the microbiome. These diverse factors can influence early life immune regulation including innate and adaptive immune mechanisms in a complex fashion. In case of any Childhood allergies have increased significantly in past decades. In addition to environmental factors and nutrition, genetic and epigenetic mechanisms as well as the microbiome of children play an important role. Of relevance is the way in which these diverse factors influence early immune development of the innate and adaptive immune systems of children. Their complex regulation is decisive for whether or not a child develops an allergy that manifests in most cases as atopic dermatitis, bronchial asthma, or allergic rhino conjunctivitis, or whether a child develops an immune tolerance. These influences can begin prenatally, already setting the course for later immune system development and occurrence of disease.

[The adaptive Freiburg monosyllabic test in noise : Development of a procedure and comparison of the results with the Oldenburg sentence test]. / Die adaptive Messung des Freiburger Einsilbertests im Störschall : Entwicklung einer Messmethode und Vergleich der Ergebnisse mit dem Oldenburger Satztest.

BACKGROUND: Whereas sentence tests are commonly performed using an adaptive procedure, this method has not yet been transferred to the Freiburg monosyllabic speech test, the most important word test. When using different procedures, a comparison of results between sentence and word tests is not possible. Therefore, an adaptive procedure which has proven itself in sentence tests was transferred to the Freiburg monosyllabic test in noise. The results of the new procedure were compared to the standard of sentence tests, i.e., the Oldenburg sentence test. METHODS: The adaptive Freiburg monosyllabic speech test and the Oldenburg sentence test were applied in 40 otologically normal subjects in a randomized order. Results were analyzed with respect to time requirements, possible gender differences, the influence of test order, and correlation of test results. RESULTS: The time required for the adaptive Freiburg monosyllabic speech test was significantly higher than for the Oldenburg sentence test. No significant impact of gender or test order could be shown. The mean signal-to-noise ratio for 50% speech discrimination of the Oldenburg sentence test was significantly smaller than for the adaptive Freiburg monosyllabic speech test. No correlation could be shown between the results of the two tests CONCLUSION: The Freiburg monosyllabic test can not only be used for quantifying discrimination loss in percentage terms, but also to measure the 50% speech recognition threshold with an adaptive algorithm. However, the procedure of the adaptive Freiburg monosyllabic test is more time consuming than that of the Oldenburg sentence test. Concerning a possible missing correlation between the results for 50% speech discrimination, further studies with hearing-impaired persons are needed.

[Everyday relevance of APHAB questions : Influence on answer frequency]. / Alltagsrelevanz der APHAB-Fragen : Einfluss auf die Beantwortungshäufigkeit.

BACKGROUND: The Abbreviated Profile of Hearing Aid Benefit (APHAB) questionnaire measures subjective hearing impairment in different situations. Recently, a survey demonstrated that some APHAB questions were answered more rarely than others. This study aims to evaluate the everyday relevance of each APHAB question and investigate whether this relevance for daily life influences answer frequency. METHODS: Between July 2016 and November 2017, 517 hearing impaired patients from 11 ENT practices in Schleswig-Holstein, Germany, were evaluated using the APHAB. In parallel, the everyday relevance of each APHAB question for the subjects was assessed on a four-step scale (often/sometimes/rarely/never). The answers were listed in a cross table and statistically analyzed. RESULTS: The average age of all subjects was 67.4 years (±14.0 years); 45.3% were female and 54.7% were male. One APHAB question (no. 21) was answered noticeably less often than the others. Overall, five types of distribution for the everyday relevance of APHAB questions could be determined. Using the χ2-test, no correlation between the frequency of answers and their everyday relevance could be detected (p < 0.001). CONCLUSION: No correlation between everyday relevance and answer frequency was detected. However, the five types of distribution could be used for an individual interpretation of single APHAB answers. In the future, a possible influence of everyday relevance on ranking within a specific APHAB answer should be investigated.

[T-cell immune responses in chronic inflammatory diseases of the nasal mucosa]. / T-Zell-Immunreaktionen bei chronisch entzündlichen Erkrankungen der nasalen Schleimhäute.

Acute rhinosinusitis and chronic rhinosinusitis are inflammatory diseases of the mucosal membranes due to mislead immunological reactions to aeroallergens. T­cells are divided into different groups based on their cytokine secretion: T­helper type 1 (Th1) and type 2 (Th2) cells. The allergic immune response is caused by activation of specific Th2 cells. With specific immunotherapy, the mislead hyperactivated "allergic" immune response is reduced to a reaction within the normal range. The inflammatory forms of chronic rhinosinusitis are called endotypes, and, in the future, could enable a targeted, pathomechanistic therapy. These endotype-based treatment approaches target specific signaling pathways that have already shown good effects for chronic rhinosinusitis with nasal polyps using monoclonal antibodies. However, so far, only selected patients with non-rhinologic indications, off-label treatments, or in clinical trials have benefited from these treatments.

[Upper Airway Stimulation for obstructive sleep apnea-Can radiological position monitoring predict tongue motion one year after implantation? German version]. / Die obere Atemwegsstimulation bei obstruktiver Schlafapnoe ­ Kann die radiologische Lage des Stimulation-Cuff die Zungenbewegung vorhersagen?

BACKGROUND: Tongue motion patterns (TMP) can influence the outcome of upper airway stimulation (UAS) in the treatment of obstructive sleep apnea (OSA). As a postoperative control the cuff position of the stimulation lead is monitored via X­ray imaging. A multidimensional X­ray assessment system was established and the association between these positional assessments and TMP was investigated 1 year after implantation. MATERIAL AND METHODS: The study on TMP and the X­ray assessments were carried out at a German ear nose and throat clinic as an implantation center. The TMPs were assessed under bipolar electrode configuration and were categorized according to the currently available literature as right-sided protrusion (RP), left-sided protrusion (LP), bilateral protrusion (BP) and mixed activation (MA). The X­ray assessment was carried out in five dimensions: the position relative to the mandible and hyoid, cuff steepness in the lateral view of the neck, the cuff position based on the single electrode and the lead connection to the cuff in the anterior-posterior view. The analyses were performed by three raters with different medical backgrounds and knowledge regarding TMP. RESULTS: In approximately 60% of the patients the apnea-hypopnea index was reduced to below 15/h, 1 year after implantation. The most common TMPs were RP and BP (82.9%). The interrater variability of the X­ray assessment was good except for one category. Furthermore, no relevant associations were found apart from the correlation between a favorable TMP and the cuff position with respect to the lateral position of the stimulation cable. CONCLUSION: Despite good interrater variability and convenient usage of the suggested X­ray assessment system, this approach did not enable the identification of any associations, by which a TM and therefore a possible straightforward or complicated treatment pathway could be predicted. Attention should possibly be paid to a rotation of the cuff during implantation with a lateral position of the stimulation lead.

[Immunotherapy for head and neck cancer : Highlights of the 2019 ASCO Annual Meeting]. / Immuntherapie von Kopf-Hals-Tumoren : Highlights der ASCO-Jahrestagung 2019.

BACKGROUND: In the field of immunotherapy of head and neck squamous cell carcinoma (HNSCC), a high level of study activity can still be observed. The results of the Keynote-048 study on first-line therapy with pembrolizumab were a highlight at this year's meeting of the American Society of Clinical Oncology (ASCO). MATERIALS AND METHODS: All abstracts and presentations on immunotherapy of head and neck tumors presented at ASCO 2019 were evaluated for relevance and the most interesting studies were summarized. RESULTS: The Keynote-048 study showed an improvement in overall survival with pembrolizumab monotherapy for patients with measurable programmed cell death ligand 1 (PD-L1) expression according to the combined positive score (CPS), and for the whole cohort with the combination of pembrolizumab and platin/5-fluorouracil (FU). The EAGLE study on durvalumab ± tremelimumab in second-line therapy did not demonstrate any improvement in response rates or overall survival compared to standard therapy. In addition, several new immunotherapeutic approaches and combinations were presented. CONCLUSION: The results of the Keynote-048 study have already led to the approval of pembrolizumab in the first line for platin-sensitive HNSCC in the USA and the expected approval in Europe will presumably change the therapeutic landscape in the long term. In the future, effective therapies for patients without a response to programmed cell death 1 (PD-1)/PD-L1 inhibition will be needed.

[Immunodeficiency in chronic rhinosinusitis : An important and often underestimated cause]. / Immundefekte bei chronischer Rhinosinusitis : Eine bedeutende und oft unterschätzte Ursache.

BACKGROUND: Chronic rhinosinusitis (CRS) is one of the most frequent chronic diseases. Among these patients the prevalence of immune defects is higher than in the healthy general population. METHODS: A selective review of the literature was carried out in PubMed and Medline covering the period between 2008 and 2019. Additionally, recent German publications in journals not listed in the abovementioned databases were analyzed. RESULTS: The diagnostic workflow with respect to the immunodeficiency consists of a detailed anamnesis and physical examination, laboratory tests and the antibody reaction to polysaccharide vaccines and antigens. Beside antibiotic treatment, vaccinations and immunoglobulin replacement are available. Notwithstanding the above, functional endoscopic surgery of the paranasal sinuses should be performed according to guideline recommendations. CONCLUSION: Patients with CRS who do not sufficiently respond to conservative and surgical treatment should be checked for underlying immunodeficiencies.

Induction chemotherapy (IC) followed by radiotherapy (RT) versus cetuximab plus IC and RT in advanced laryngeal/hypopharyngeal cancer resectable only by total laryngectomy-final results of the larynx organ preservation trial DeLOS-II.

Background: The German multicenter randomized phase II larynx organ preservation (LOP) trial DeLOS-II was carried out to prove the hypothesis that cetuximab (E) added to induction chemotherapy (IC) and radiotherapy improves laryngectomy-free survival (LFS; survival with preserved larynx) in locally advanced laryngeal/hypopharyngeal cancer (LHSCC). Patients and methods: Treatment-naïve patients with stage III/IV LHSCC amenable to total laryngectomy (TL) were randomized to three cycles IC with TPF [docetaxel (T) and cisplatin (P) 75 mg/m2/day 1, 5-FU (F) 750 mg/m2/day days 1-5] followed by radiotherapy (69.6 Gy) without (A) or with (B) standard dose cetuximab for 16 weeks throughout IC and radiotherapy (TPFE). Response to first IC-cycle (IC-1) with ≥30% endoscopically estimated tumor surface shrinkage (ETSS) was used to define early responders; early salvage TL was recommended to non-responders. The primary objective was 24 months LFS above 35% in arm B. Results: Of 180 patients randomized (July 2007 to September 2012), 173 fulfilled eligibility criteria (A/B: larynx 44/42, hypopharynx 41/46). Because of 4 therapy-related deaths among the first 64 randomized patients, 5-FU was omitted from IC in the subsequent 112 patients reducing further fatal toxicities. Thus, IC was TPF in 61 patients and TP in 112 patients, respectively. The primary objective (24 months LFS above 35%) was equally met by arms A (40/85, 47.1%) as well as B (41/88, 46.6%). One hundred and twenty-three early responders completed IC+RT; their overall response rates (TPF/TP) were 94.7%/87.2% in A versus 80%/86.0% in B. The 24 months overall survival (OS) rates were 68.2% and 69.3%. Conclusions: Despite being accompanied by an elevated frequency in adverse events, the IC with TPF/TP plus cetuximab was feasible but showed no superiority to IC with TPF/TP regarding LFS and OS at 24 months. Both early response and 24 months LFS compare very well to previous LOP trials and recommend effective treatment selection and stratification by ETSS. Clinical trial information: NCT00508664.

Complete concentric collapse at the soft palate in sleep endoscopy: what change is possible after UPPP in patients with CPAP failure?

PURPOSE: The aim of this work was to assess whether uvulopalatopharyngoplasty in patients with failure for positive airway pressure not only reduces the degree of obstructive sleep apnea but also to determine as well if it changes the collapse pattern of the soft palate and thereby fulfills the qualifications for implementing upper airway stimulation (UAS) as an adjunctive solution. METHOD: Fifteen patients with intolerance for positive airway pressure were included in this retrospective cohort study. Polygraphy and drug-induced sleep endoscopy were used in order to evaluate the reduction of the apnea-hypopnea index (AHI), as well as the change of collapse pattern at the soft palate level before and about 3 months after uvulopalatopharyngoplasty and tonsillectomy (TE-UPPP). RESULTS: In 93% of the patients, a postoperative change of the initially complete concentric palatal collapse pattern could be found during drug-induced sleep endoscopy. In one patient, no obstruction at all was seen at the soft palatal level. Only one patient still presented with a complete concentric collapse at velum level. AHI decreased from mean 34.7 events per hour to 20.2/h and oxygen desaturation index from 25.3 events per hour to 16.1/h. CONCLUSION: Patients seeking for positive airway pressure alternatives could not only benefit from reduction of AHI by TE-UPPP postoperatively; additionally, by changing the collapse pattern at the soft palate, they might also fulfill criteria for upper airway stimulation (UAS) in case of persistent OSA of at least moderate degree.