[Surgical Treatment of Oropharyngeal Cancer - Recommendations of the Current German S3 Guideline, Part I]. / Chirurgische Therapie des Oropharynxkarzinoms: Empfehlungen der aktuellen S3-Leitlinie ­ Teil I.

In general, a trend towards transoral resection (as opposed to classic open approaches) + neck dissection + adjuvant radio- (chemo-) therapy has been observed for oropharyngeal carcinoma over the last 20 years. Techniques of transoral surgery (TOS), including transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) have been propagated in retrospective comparisons with conventional surgery or primary radiochemotherapy as gentle, minimally invasive procedures with good late functional results. Meta-analyses of mostly uncontrolled retrospective analyses suggest that TORS may have better disease-free survival (DFS) and a reduced risk of free flap reconstruction compared with open surgery. TORS (TOS) was associated with fewer tumor-positive resection margins (R1), a lower number of recurrences, fewer intraoperative tracheostomies, a shorter inpatient stay and a shorter duration of postoperative nasal tube feeding compared to open surgery. In principle, based on the best evidence currently available from registry studies, stage I-II oropharyngeal carcinomas can be treated either with primary surgery or radiochemotherapy with a comparable chance of survival. With comparable evidence for stage III and IVa, p16neg. oropharyngeal carcinomas, the majority of authors advocate primary surgery followed by adjuvant radiotherapy or radiochemotherapy as the treatment of first choice. For p16pos. patients the results of registry studies are inconsistent, although the largest registry study on 450 HPV-positive stage III patients shows a significant superiority of primary surgery + adjuvant radiochemotherapy. Since all registry studies did not adjust for smoking status, among other factors, the current data situation should be evaluated with the necessary caution.

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.

[BIOPASS hybrid navigation for endoscopic sinus surgery - an assistance system]. / BIOPASS-Hybrid-Navigation für die endoskopische Nasennebenhöhlenchirurgie ­ ein Assistenzsystem.

Previous navigation systems can determine the position of the "tracked" surgical instrument in CT images in the context of functional endoscopic sinus surgery (FESS), but do not provide any assistance directly in the video endoscopic image of the surgeon. Developing this direct assistance for intraoperative orientation and risk reduction was the goal of the BIOPASS project (Bild Ontologie und prozessgestütztes Assistenzsystem). The Project pursues the development of a novel navigation system for FESS without markers. BIOPASS describes a hybrid system that integrates various sensor data and makes it available. The goal is to abandon tracking and exclusively provide navigation information directly in the video image. This paper describes the first step of the development by collecting and structuring the surgical phases (workflows), the video endoscopic landmarks and a first clinical evaluation of the model version. The results provide the important basis and platform for the next step of the project.

Complications of injections in conservative treatment of degenerative spine disease: a prospective unicentric study.

BACKGROUND: Spinal injection has been an accepted part of conservative therapy for degenerative diseases. The drugs used can cause side effects and severe complications. The aim of this study was to determine the occurrence of general side effects (GSE) and complications when performing consecutive different types of spinal injections and to evaluate pain reduction. METHODS: Prospective data evaluation of patients with degenerative spine disease at hospital admission, discharge, and six and 12 weeks after discharge. All patients received a specific injection protocol depending on their symptoms and radiological findings. The injections performed were dorsal sacroiliac joint injections, perineural injections, epidural interlaminar and epidural periradicular injections, and facet joint injections. Potential complications were categorized and recorded as GSE and complications. In addition, the Numerical Analog Scale (NAS) for pain, the Oswestry Disability Index (ODI) were evaluated. RESULTS: Forty-eight patients were enrolled. There were 282 spinal injections performed. A total of 131 common treatment-related events were recorded. Depending on the type of injection, transient pain at the injection site (32.4-73.5%), radiating pain (9.4-34.7%), and nerve root irritation (2-18.4%) were the most common. One complication with postpuncture syndrome occurred with epidural-interlaminar injection. No persistent neurologic deficits occurred. The highest rate of GSE was observed with periradicular injections (relative frequency (RF) = 0.8), followed by epidural-interlaminar injections (RF = 0.65), least frequently with FJ injections (RF = 0.32). From the time of admission to discharge, NAS scores were significantly decreased and ODI score significantly improved at discharge (p < 0.001), but relapse occurred at the 12-week follow-up. CONCLUSIONS: Various consecutive spinal injections for conservative treatment of degenerative spine diseases are safe and lead to a decrease in pain and improvement in quality of life. GSE are common, but not persistent. Although complications are rare, they can have serious consequences for the patient.

[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.

[Presentation and evaluation of the haptic-visual ear surgery training system "HaptiVisT"]. / Vorstellung und Evaluation des haptisch-visuellen, ohrchirurgischen Trainingssystems "HaptiVisT".

BACKGROUND: Operations on the temporal bone are a special challenge for ENT surgeons. The aim of the BMBF-funded project was to develop a realistic training system for ear operations in the form of a "serious game". METHODS: The presented prototype of the HaptiVisT system functions as a training system for ear surgeries with visual feedback through a glasses-free 3D monitor and feedback by means of a haptic arm simulating the drill. A variety of training options is guaranteed by three available surgical procedures (antrotomy, mastoidectomy, posterior tympanotomy). A weighted point system enables the measurability of the training success. Following the technical development of the prototype, a prospective evaluation was carried out by eight ENT physicians and four students regarding "learning content" and "user experience". A standardized questionnaire was used (ordinal scale: 1=very good to 5=very bad). RESULTS: Regarding the learning content, the aspects "strengthening anatomy (mean=1.58)", "training hand-eye coordination (1.67)", "transferability into practice (1.83)", "usefulness for practice (1.33)" yielded good to very good scores. "User experience" also showed good results for the aspects "realism (2.29)", "interaction of haptics and optics (2.33)" and "immersion in the training system (1.89)". The "motivation factor" was very high for all test subjects (1.2). CONCLUSIONS: The training system for ear surgeries "HaptiVisT" offers the possibility of immersive training. Integration into the daily clinical routine and in particular into the medical training to become an ENT specialist therefore seems to make sense.

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.

[Evaluation of an integrated OR based on open standards in Cochlea Implant surgery]. / Evaluation eines integrierten OP-Saals auf Basis offener Standards in der Cochlea-Implantat-Chirurgie.

BACKGROUND: Digitalization in surgery makes it necessary to develop modern surgical concepts. New approaches to system networking with integration and open standardized communication of all medical devices are being pursued. METHODS: At the University Hospital Leipzig, a demonstration of the integrated OR was carried out together with the Innovation Center for Computer Assisted Surgery (ICCAS) using the example of a cochlea implantation. The preoperative management, technical preparation, surgical procedure and postoperative documentation by a total of n = 30 study participants (2 expert groups) were evaluated. In addition to the collection of objective parameters, qualitative questionnaires and quantitative, interval-scaled questions were used. RESULTS: Preoperatively, the digital presentation of the patient's clinical data was considered as helpful by both groups (group 1: median = 5, group 2: median = 4). This also applies to the personalized OR settings, the intraoperative display options and the dynamic, surgeon-centered visualization (median = 4). Similar positive conclusions were drawn for postoperative documentation and postoperative follow-up (median = 4). A significant difference in the final evaluation of the integrated surgical concept between the two expert groups could not be determined (p > 0.05). CONCLUSIONS: The positive study results show that the theoretical idea of system networking based on open standards can be successfully implemented in practice using the example of a cochlea implantation. Thus, the intelligent "operating room of the future" no longer seems to be a fictitious idea, but a realistic image of modern surgical medicine.

The Intelligent ENT Operating Room of the Future. / Der intelligente HNO-Operationssaal der Zukunft.

The increasing plurality and complexity of technical assistance systems pose a challenge for clinically active physicians. Particularly in the operating theater, there is a growing need to integrate medical systems and software solutions into a holistic clinical infrastructure. The primary goal of building a "digital (ENT) operating room of the future" is not just the pure technical improvement of the individual computer-aided equipment and instruments, but rather their dynamic networking and system integration in an open modular system. Promising scientific projects address the question of how to improve the quality, safety and user-friendliness of technical systems in the health care system of the 21st century. The work on SCOT, MD PnP and OR.NET show the various components that make the vision of the ENT operating room of the future tangible and realistic in the overall context.

Functional and cosmetic donor site morbidity of the radial forearm-free flap: comparison of two different coverage techniques.

BACKGROUND: The use of the radial forearm-free flap is a well-established and reliable reconstruction method in head and neck surgery. Usually, the defect of the donor site is covered with full or split-thickness skin grafts. Since 09/2013, a direct closure of the radial forearm donor site has been performed at the ENT University Hospital Leipzig to avoid secondary donor site morbidity. However, few data are available in the literature on long-term cosmetic and functional results compared to the established indirect donor site defect coverage. METHODS: This study investigated patients with radial forearm-free flap harvest from 01/2012 until 03/2015. A total of n = 39 patients were included, with n = 18 being operated by indirect (group 1) and n = 21 by direct closure technique (group 2). For the validation of surgical revisions and wound healing disorders, we carried out clinical investigations as well as interviews. The "POSAS Observer and Patient Scale" was used for assessing the cosmetic outcome and the "Michigan Hand Outcome Questionnaire (MHQ)" for functional criteria. RESULTS: Group 2 showed an increased rate of wound healing problems, however it was not statistically different compared to group 1. Revision surgery was necessary in both groups only each in one case. Using the POSAS, there were no significant differences between both groups in the observer scale for the items vascularity, pigmentation, thickness, relief, pliability, surface area and even for pain, scar itching, color, stiffness, thickness and relief in the patient scale. The functional results (MHOQ) also showed no significantly inferior results for group 2. CONCLUSIONS: The direct closure procedure is quick, simple and can be performed without secondary donor site morbidity. For wound healing, cosmetic and function of the forearm and hand, no inferior results can be measured for the direct procedure compared to the indirect coverage technique.

[Current Status of therapy and prophylaxis of oropharyngeal carcinoma]. / Aktueller Status der Therapie und Prophylaxe des Oropharynxkarzinoms.

Incidence of oropharyngeal carcinoma (OPSCC) is increasing significantly worldwide. Due to its association with chronic tobacco/alcohol consumption, but increasingly also with the human papillomavirus HPV-16, oropharyngeal carcinoma is a genetically heterogeneous tumor group with high prognostic diversification. HPV-associated OPSCC respond significantly better to previous treatment concepts than non-HPV-associated. Both after primary surgical as well as after radiotherapie, radiochemotherapie and anti-EGFR treatment, this tumor group shows a significantly better survival. There is no evidence that in HPV association only primary radiotherapy concepts should be used. Currently, in the 8th edition of the TNM classification (UICC, AJCC), the HPV-associated different prognostic consideration with a rearrangement of the tumor stages and the N status was taken into account. Regardless of the known blur, p16 status detection is the most practicable and least expensive method of detection today, and is therefore consistently recommended (also by the AJCC and UICC TNM committees). HPV16 positive non-smokers differ from HPV-16 negative smokers by nearly 50 % in 5-year survival. Transoral robot surgery (TORS), which is highly acclaimed in the US today, with the Da Vinci Telemanipulator (Intuitive Surgical) has triggered a downright euphoric discussion on the minimally invasive surgery of resectable OPSCC. Based on a stable data set, it is now clear that an R0 resection must be sought regardless of the surgical procedure. Resection margins < 5 mm (R0 < 5 mm) are considered to be an "intermediate risk" situation and, like the N status, influence the adjuvant concept (radiochemotherapy). During and after transoral surgical procedures, the risk of rebleeding should never be underestimated and can not be ruled out with the utmost care.

An observational, prospective study to evaluate the preoperative planning tool "CI-Wizard" for cochlear implant surgery.

"CI-Wizard" is a new, three-dimensional software planning tool for cochlear implant surgery with manual and semi-automatic algorithms to visualize anatomical risk structures of the lateral skull base preoperatively. Primary endpoints of the study represented the evaluation of the CI-Wizards usability, accuracy, subjectively perceived and objectively measured time in clinical practice. In a period from January 2014 to March 2015, n = 36 participants were included in this study. These members were divided into three groups of equal number (n = 12), but different level of experience. Senior doctors and consultants (group 1), residents (group 2) and medical students (group 3) segmented 12 different CT-scan data sets of the CI-Wizard (four per participant). In total, n = 144 data sets were collected. The usability of the CI-Wizard was measured by the given questionnaire with an interval rating scale. The Jaccard coefficient (JT) was used to evaluate the accuracy of the anatomical structures segmented. The subjectively perceived time was measured with an interval rating scale in the questionnaire and was compared with the objectively mean measured time (time interact). Across all three groups, the usability of the CI-Wizard has been assessed between 1 ("very good") and 2 ("with small defects"). Subjectively, the time was stated as "appropriate" by questionnaire. Objective measurements of the required duration revealed averages of t = 9.8 min for creating a target view. Concerning the accuracy, semi-automatic anatomical structures such as the external acoustic canal (JT = 0.90), the tympanic cavity (JT = 0.87), the ossicles (JT = 0.63), the cochlea (JT = 0.66), and the semicircular canals (JT = 0.61) reached high Jaccard values, which describes a great match of the segmented structures between the partcipants and the gold standard. Facial nerve (JT = 0.39) and round window (JT = 0.37) reached lower Jaccard values. Very little overlap tendency was found for the chorda tympani (JT = 0.11). This software program represents a further important step in the development of preoperative planning tools in cochlear implant surgery. The study revealed a high level of satisfaction in the usability. The subjectively required time was considered as "appropriate" and the objectively mean measured time was t = 9.8 min short enough, so that a clinical application seems realistic. Particularly for semi-automatically segmented structures, it represented a good accuracy. For purely manual segmented structures, further improvements are desirable. Finally, this program also provides a good learning tool for medical students and residents to become familiar with the anatomy of the lateral skull base.

[Implantable Bone Conduction and Active Middle Ear Devices]. / Implantierbare Knochenleitungs- und aktive Mittelohrhörsysteme.

In case of audiological and/or anatomical limitations in the provision of conventional hearing aids, semi- or fully-implantable hearing systems represent a modern therapy alternative. These hearing systems are divided according to their mode of action into active middle ear implants when stimulating the auditory ossicles or the round window, into bone conduction devices while stimulating the skull directly, into cochlear implants with direct acoustic stimulation to the cochlea with its auditory nerve and finally into auditory brainstem implants by bridging the peripheral auditory structures. Taking careful criteria of indications and anatomical specificities into account, significant improvements can be achieved in comfort, speech understanding and thus quality of life for a large number of patients.

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.

The European Larynx Organ Preservation Study [MK-3475-C44].

The European Larynx Organ Preservation Study (ELOS; NCT06137378) is a prospective, randomized, open-label, two-armed parallel group controlled, phase II multicenter larynx organ preservation (LOP) trial in locoregionally advanced (LA) stage III, IVA/B head and neck squamous cell carcinoma of the larynx or hypopharynx (LHSCC) amenable for total laryngectomy (TL) with PD-L1 expression within tumor tissue biopsy, calculated as CPS ≥ 1. Induction chemotherapy (IC) with docetaxel and cisplatin (TP) followed by radiation will be compared to TP plus PD-1 inhibition by pembrolizumab (MK-3475; 200 mg i.v. starting day 1 q3w for 17 cycles). After a short induction early response evaluation (ERE) 21 ± 3 days after the first cycle of IC (IC-1), responders achieving endoscopic estimated tumor surface shrinkage (ETSS) ≥30% will get an additional two cycles of IC followed by intensity-modulated radiotherapy 70-72 Gy (EQD2/α/ß = 10) aiming at LOP. Nonresponders (ETSS < 30% or progressing disease) will receive TL and bilateral neck dissection followed by postoperative radiation or chemoradiation as recommended by the clinic's multidisciplinary tumor board. Pembrolizumab treatment will be continued in the intervention arm regardless of ETSS status after IC-1 in both responders and laryngectomized nonresponders, independent of subsequent decisions on adjuvant therapy after TL. Clinical Trial Registration: clinicaltrials.gov, identifier NCT06137378.

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.