Purpose:The objective of this study was to evaluate the prognostic significance of CT-based body composition markers in patients with head and neck squamous cell cancer (HNSCC) treated with immunotherapy. Material and methods:Forty-five HNSCC patients (24.4% female, median age: 66 years) treated with Nivolumab or Pembrolizumab were retrospectively assessed. Automated body composition analysis was performed on thoracic CT scans. The analysis included skeletal muscle (SM), bone (B), visceral adipose tissue (VAT), and volumes of various adipose tissue compartments. Overall survival (OS) was estimated using the Kaplan-Meier method, and hazard ratios (HR) were calculated using the Cox proportional hazards model. In the multivariate analysis, the strongest body composition parameter was entered into the model. Results:The median OS was 8.13 months (95% CI: 4.8-21.9). Univariate analysis identified baseline high SM/B ratio, high (SM+VAT)/B ratio, albumin levels >3.4g/dl, low Eastern Cooperative Oncology Group (ECOG) performance status, body mass index ≥18.5 kg/m2, and male sex as significant prognostic factors for longer OS. In multivariate analysis, SM/B ratio (HR: 0.25, 95% CI: 0.1-0.64, p=0.004) and albumin ≤3.4 g/dl (HR: 0.31, 95% CI: 0.12-0.76, p=0.01) remained independent. Patients with both high SM/B and albumin survived the longest (median not reached) compared to either high SM/B or high albumin (9.6 months) vs. low SM/B and albumin (2.7 months). A decrease in SM/B of ≥ 8% after three months was associated with a lower median OS of 6.7 vs. 26.2 months, p=0.032. Conclusions:Automated CT-based body composition analysis, particularly the thoracic SM/B ratio and serum albumin level, provide valuable prognostic information on OS for HNSCC patients receiving immunotherapy and may guide clinical decision-making in this patient population.

To investigate the prognostic significance of pretreatment inflammatory markers and their association with computed tomography (CT)-based body composition (BC) metrics in patients with recurrent and/or metastatic head and neck squamous cell cancer (HNSCC) treated with immunotherapy. This retrospective, single-center study included 49 patients with HNSCC (20.4

Background/Objectives: To evaluate the prognostic significance of automated, volumetric body composition analysis (BCA) derived from pretreatment thoracic computed tomography (CT) scans in patients with head and neck cancer (HNC). Methods: We retrospectively assessed 160 patients (median age: 63 years; 26.9% women) undergoing primary treatment. BCA quantified various tissue volumes, including bone (B), skeletal muscle (SM), and subcutaneous adipose tissue (SAT). Optimal sex-specific cutoffs for BCA metrics were established via maximally selected log-rank tests. Internal validation of BCA cutoffs was conducted via bootstrap resampling. Kaplan-Meier survival analysis and Cox proportional hazards modeling were used to investigate progression-free survival (PFS). Results: The median PFS for all patients was 51.7 months (95% confidence interval (CI): 31.4-68.8). Among the continuous BCA parameters, only SM/B was significant across the total cohort (hazard ratio (HR): 0.23; 95%CI: 0.12-0.46; p < 0.0001, males (p = 0.0009), females (p = 0.004)). Internal validation of gender-specific cutoffs demonstrated strong-to-intermediate stability for SM/B across both sexes and for SAT/B in males. In contrast, SAT/B exhibited only weak stability among female participants. In univariate PFS analysis, dichotomized SM/B, SAT/B, Union for International Cancer Control (UICC) stage, Eastern Cooperative Oncology Group (ECOG) status, higher body mass index (BMI), normal albumin, and Charlson Comorbidity Index were identified as significant predictors of PFS. Multivariable analysis identified high SM/B (HR: 0.53; 95% CI: 0.3-0.93; p = 0.026) and high SAT/B (HR: 0.58; 95% CI: 0.35-0.95; p = 0.029) as independent prognostic factors, alongside lower UICC stage (p = 0.045) and lower Charlson Comorbidity Index (p = 0.038). Patients with high SM/B and SAT/B ratios had the longest median PFS (65.9 months, 95%CI: 51.7-.), compared to 36.4 months (95%CI: 19.4-.) for high SM/B or SAT/B and 12.6 months (95%CI: 4.2-25.1) for low SM/B and SAT/B (p < 0.0001). Conclusions: Although the BCA parameters SM/B and, to a lesser extent, SAT/B appear to be promising biomarkers, external validation and investigation within well-defined patient subgroups are warranted to establish their generalizability in clinical practice.

BACKGROUND:In functional endoscopic sinus surgery, the intricate anatomy and the use of minimally invasive endoscopic techniques may hinder comprehensive patient understanding in the informed consent process. AIMS/OBJECTIVES:Evaluation of the impact of personalized 3D CT computed tomography (CT) imaging supplementing informed consent in sinus surgery. MATERIAL AND METHODS:In this prospective randomized study, patients scheduled for paranasal sinus surgery were allocated to standard informed consent using two-dimensional (2D) CT imaging or to counseling supplemented with individualized three-dimensional (3D) CT reconstructions. All patients received a questionnaire prior- and postsurgery to assess disease comprehension, perception of risks and benefits, and satisfaction with the informed consent process. RESULTS:Twenty-two patients were included, with equal distribution between groups. The 3D group demonstrated significantly greater understanding of expected recovery and recurrence (p = 0.03) and improved knowledge transfer (p = 0.04). Postoperatively, the 3D group reported significantly higher understanding scores (4.50 vs. 2.73). The composite outcome-encompassing disease understanding, surgical comprehension, and overall satisfaction-was superior in the 3D group (16.00 vs. 11.64; p < 0.01). CONCLUSIONS AND SIGNIFICANCE:Patient-specific 3D CT reconstructions may enhance informed consent in sinus surgery, improving comprehension, shared decision-making, and satisfaction with preoperative counseling.

BACKGROUND:Head and neck squamous cell carcinoma (HNSCC) is a globally significant disease with poor survival outcomes. Immune checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab have improved treatment paradigms, yet their real-world efficacy and the factors influencing treatment outcomes remain underexplored. AIMS:This study aimed to evaluate real-world outcomes of pembrolizumab and nivolumab therapy in patients with HNSCC and to identify clinical and laboratory factors associated with overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). METHODS AND RESULTS:We conducted a retrospective analysis of 45 HNSCC patients treated with pembrolizumab or nivolumab at the University Medical Center Mannheim. Patient-specific factors, including tumor characteristics, PD-L1 expression, and laboratory parameters, were assessed using Kaplan-Meier estimation, log-rank tests, and multivariate regression models. The median OS and PFS were 10.4 months and 7.4 months, respectively, with an ORR of 22%. A tumor proportion score (TPS) ≥ 50% and absence of smoking or alcohol abuse significantly improved ORR, while female sex, high neutrophil-to-lymphocyte ratio (NLR), and elevated leukocyte counts were associated with inferior OS and PFS. Real-world outcomes largely aligned with the pivotal trials Keynote-048 and CheckMate 141. CONCLUSION:This study underscores the predictive value of TPS and patient lifestyle factors in ICI treatment for HNSCC. The findings also highlight sex-specific differences, as well as NLR and leukocyte count as potential prognostic factors. Larger, more diverse cohorts are needed to confirm these results and refine patient selection strategies.

Fractionated irradiation causes premature senescence of tumor cells. Interactions between senescence, the immune system and survival signaling are poorly understood to date. As MAP kinases are implicated in immune resistance, the present study addressed the detection of senescence‑associated modulation of postradiogenic programmed death‑ligand 1 (PD‑L1) and MAP kinase ERK1/2 expression in an in vitro and ex vivo model for head and neck squamous cell carcinoma (HNSCC). Established HNSCC cell  lines (UM-SCC-11B, UM-SCC-14C and UM-SCC-22B) were employed to study the expression levels of p21, histone  H2AX (γH2AX), PD-L1 and phosphorylated (p)ERK1/2 via immunohistochemistry following application of 4x2 Gy. Using senescence‑associated β‑galactosidase (SA‑ß‑Gal) staining, postradiogenic induction of senescence was additionally assessed. Results were validated in a 3D ex vivo HNSCC model with vital explants. Upon ionizing radiation (IR), senescence‑like subpopulations were observed in all cell lines, showing upregulation of PD‑L1 and pERK1/2 as well as of established senescence markers p21 and γH2AX. SA‑β‑Gal‑positive cells were found in all lines. These results were supported in a 3D tumor model. Fractionated IR can generate a subpopulation of HNSCC cells characterized by senescence‑typical cellular changes and marked expression of PD‑L1 and pERK1/2. Postradiogenic senescence in both 2D and 3D cancer models was possibly related to survival signaling and immune checkpoint regulation, crucial elements in tumor development and progress.

Patient-derived head and neck squamous cell carcinoma (HNSCC) explant models have been shown to retain the original tumour microenvironment and morphological characteristics. To enhance the human relevance of models and improve clinical outcomes, there is an emerging move toward preclinical models that are cultured in xeno-free media (i.e. media containing no non-human animal-derived components). Fetal bovine serum (FBS) has been the standard cell culture medium supplement in most in vitro systems. However, growing emphasis on ethical concerns, animal welfare considerations and reproducibility, as well as the need to implement the Three Rs principles, have driven substantial efforts to identify viable xeno-free alternatives to FBS. In this study, an ex vivo culture model for HNSCC was developed, based on the use of xeno-free media. Human platelet lysate (hPL)-supplemented medium and a commercially available xeno-free human mesenchymal stromal cell (MSC) expansion medium were evaluated, comparing HNSCC explant model growth to that in the 'standard' FBS-supplemented medium, over a 10-day culture period. To best reflect clinical conditions, the tissues were treated with radiochemotherapy (RCT) comprising cisplatin and fractionated irradiation. After 10 days, the tissues were formalin-fixed, paraffin-embedded, and assessed for the expression of key biomarkers, including PD-L1, Ki-67 and vimentin. The upregulation of PD-L1, as well as the downregulation of Ki-67 and vimentin, were consistent across all media, thus validating hPL-supplemented medium and MSC medium as viable alternatives to FBS-supplemented medium, for use in the culture of humanised HNSCC preclinical models.

BACKGROUND AND OBJECTIVES:Reconstruction of head and neck defects using free flaps is successful, but complications occur. This study aims to identify factors preventing complications to support clinical decision-making. METHODS:Retrospective study for free flap reconstructions (2019 to 2022, tertiary referral center). Univariate and multivariate regression models assessed predictors of complication-free survival (CFS) and odds ratios (OR) measured risk correlations. RESULTS:Of 125 identified cases, most patients were male (71.8%) with a median age of 66 years (37-93 years). Common complications were wound healing disorders (10.9%), hematoma (10%), total (7.3%) or partial (1.8%) flap necrosis, cardiovascular events (5.5%), and pulmonary artery embolism (4.5%). 30-day CFS was 63%. On multivariable analysis, female gender (HR: 9.4, CI: 2.6-33.5), alcohol abuse (HR: 3.5, CI: 1.4-8.4), N2-3 (HR: 2.4, CI: 1.3-4.4), obesity (HR: 2.1, CI: 0.9-5.1), preoperative anticoagulation (HR: 2.5, CI: 1.1-5.9) were significant prognosticators. Positive factors increasing CFS included high albumin (OR 0.21, p = 0.02), intraoperative i.v. heparin bolus (OR 0.15, p = 0.08), intraoperative catecholamine treatment (OR 0.15, p = 0.009), and nonsmoking (OR 0.18, p = 0.1). CONCLUSION:Key preventive measures against complications include optimizing nutritional status and albumin levels, administering intraoperative heparin and catecholamines, and abstaining from alcohol. Females should also be screened for undiagnosed cardiovascular risks.

Head and neck squamous cell carcinoma (HNSCC) are invasive solid tumors accounting for high mortality. To improve the clinical outcome, a better understanding of the tumor and its microenvironment (TME) is crucial. Three -dimensional (3D) bioprinting is emerging as a powerful tool for recreating the TME in vitro. To establish long-term HNSCC bioprinted constructs for personalized drug-testing, this proof-of-principle study aims to compare two different innovative tunicate-derived nanocellulose (NC) hydrogels against the widely used semi-synthetic gelatin methacryloyl (GelMA). Cell lines of different tumor origin sites are printed in TEMPO and Carboxy-NC, and GelMA in alginate (GelMAA). Both NC hydrogels show higher bioprintability than GelMAA. Carboxy-NC supported long-term HNSCC survival, proliferation, and maintenance of epithelial phenotype in 3D bioprinted constructs similar to GelMAA. The hydrogel microstructure revealed differences in pore size. Importantly, the established HNSCC bioprinted model allowed the testing of radiochemotherapy (RCT) both in cell lines and patient-derived cultures. Compared to a spheroid model, the cytotoxic effects are less, better reflecting the response in patients. The proof-of-principle findings indicate that Carboxy-NC is a viable alternative to gelatin-based bioink with improved bioprintability allowing personalized drug-testing. By adding other cell-types of the TME, this model can be advanced to a heterotypic one.

Introduction Despite therapeutic benefits of immune checkpoint inhibition (ICI) in many tumor types, single-agent IC blockade has a low objective response rate. Combined treatment strategies are needed, so we aimed to closely characterize the immune microenvironment of head and neck squamous cell carcinoma (HNSCC). HNSCC- linked inhibitory receptors CTLA-4, TIM-3, TIGIT, PD-1 mediate immunosuppression. CD14 is expressed as a surface protein by monocytes and macrophages.

Introduction Olfactory neuroblastoma (ONB constitutes 3-6% of sinonasal tumors. Despite surgical approaches adjuvant and systemic targeted treatment options for advanced ONBs are rare.

Einleitung Das olfaktorische Neuroblastom (ONB) macht 3-6% der sinonasalen Tumoren aus. Neben chirurgischen Ansätze sind adjuvante und systemische zielgerichtete Behandlungsmöglichkeiten für fortgeschrittene ONBs selten.

Einleitung Trotz des Erfolges von Immun-Checkpoint-Inhibition (ICI) hat die IC-Monotherapie eine niedrige Ansprechrate. Kombinationsstrategien sind notwendig, daher haben wir die immunologische Mikroumgebung des Kopf-Hals-Plattenepithelkarzinoms (HNSCC) näher charakterisiert. Die mit HNSCC verknüpften inhibitorischen Rezeptoren CTLA-4, TIM-3, TIGIT und PD-1 vermitteln Immunsuppression. CD14 wird als Oberflächenprotein von Monozyten und Makrophagen exprimiert.

IntroductionCheckpoint inhibitors, such as PD1 inhibitors, represent an important pillar in the therapy of advanced malignancies of the head and neck region. The most relevant complications are immune-related adverse effects (irAEs), which represent an immense burden for patients. Currently, no sufficient stratification measures are available to identify patients at increased risk of irAEs. The aim of this retrospective study was to examine whether demographic, histopathological, clinical, or laboratory values at the start of CPI therapy represent a risk factor for the later occurrence of autoimmune complications.Material and methodsData from 35 patients between 2018 and 2021 who received therapy with nivolumab or pembrolizumab for head and neck malignancy were analyzed and assessed for any associations with the subsequent occurrence of irAEs.ResultsIrAE developed in 37% of patients, with pneumonitis being the most common form (14%). Pneumonitis was found in patients with an average significantly lower T-stage of primary tumors. An increase in basophilic leukocytes was found in patients with dermatitis later in the course. When thyroiditis developed later, the patients had a higher CPS score and lower monocyte levels.DiscussionEven though individual laboratory values at the beginning of therapy might show a statistical association with the later occurrence of irAEs, neither demographic, histopathological, nor laboratory chemistry values seem to be able to generate a sound and reliable risk profile for this type of complication. Therefore, patients need to be educated and sensitized to irAEs, and regular screening for irAEs should be carried out.

Introduction The kinetic of C-reactive protein (CRP) in the early phase of therapy with checkpoint inhibitors (CPI) and its prognostic value has already been investigated in several tumor entities. In particular, flare dynamics have been described as a positive prognostic parameter. The aim of this retrospective study is to examine the extent to which such an application can also be transferred to patients with recurrent or metastatic squamous cell carcinoma of the head and neck region (R/M-HNSCC). Material and Methods All patients treated with CPI for R/M-HNSCC at our clinic between 2018 and 2023 were included (n = 44). Demographic, clinical, histopathologic and laboratory data were extracted from the digital patient records and statistically analyzed. We then examined the CRP kinetic using two previously published classifications and proposed a new classification ourselves. Subsequently, correlation analyses were performed with the overall survival (OS) of the patients. Results Of the two CRP kinetic classifications previously published, only one showed a correlation with the result of the first re-staging, and neither showed a correlation with the OS of R/M-HNSCC patients. Our new CRP kinetic classification showed a significant association with OS in R/M-HNSCC patients (p = 0.05). In a multivariate analysis, our CRP kinetic classification (p = 0.007) and the outcome of the first re-staging (p = 0.002) were significant independent factors for OS. Discussion Our novel CRP kinetic classification significantly correlates with OS in R/M-HNSCC patients, indicating a potential prognostic marker. Existing classifications from other cancer entities showed limited prognostic significance, emphasizing the need for tailored markers. For validation, however, testing on larger R/M-HNSCC patient collectives is necessary.

Introduction Free and pedicled flap reconstructions of head and neck defects are highly successful. However, postoperative complications are common. The aim of this study is to investigate risk factors associated with complications after flap reconstruction.

Introduction The importance of prognostic factors in the treatment of head and neck squamous cell carcinoma (HNSCC) is increasing due to expanding individualized treatment options. Since the introduction of checkpoint inhibitors in head and neck oncology, a new group of patients is developing who can establish a stable disease burden over a long period of time and for whom an individualized prognosis assessment is becoming increasingly relevant. The laboratory chemical parameters regularly collected before and during therapy appear particularly attractive. In a retrospective study, their prognostic potential for the later course of the disease was evaluated.

Introduction 3D-bioprinted preclinical tumour model enables the fabrication of spatially defined tumour microenvironment (TME) mimicking the in-vivo situation. It is challenging to opt a bioink that is biocompatible, with minimum to no cytotoxicity & inflammatory-response. Here, we compare tunicate-derived nanocellulose (NC) against widely used semi-synthetic, gelatin methacrylate (GelMA) biomaterial for best mirroring HNSCC TME via bioprinting technology.

Introduction The development of patient-specific preclinical models to assess therapy response in HNSCC is an ambitious goal ("personalised medicine"). However isolated cells from patient material are affected by isolation/expansion methods and change their properties. This study aims to show whether gene expression profiling can be used to analyse the reliability of the chosen model.

Salivary duct carcinomas (SDC) of the parotid gland are rarely occurring highly malignant tumors. A 65-year-old man presented with a preauricular mass. After surgical treatment and histologic examination, the findings were interpreted as a squamous cell carcinoma (SCC) metastasis of the parotid gland deriving from a cancer of unknown primary DD primary SCC of the parotid gland. Adjuvant platinum-based radiochemotherapy was administered in domo. However, re-staging revealed multiple size-progressive pulmonary round lesions. After resection and histological examination of a pulmonary mass and in synopsis with the primary tumor, the initial diagnosis of SCC was revised to SDC of the parotid gland. With positive HER-2 status, off-label trastuzumab/docetaxel was initiated in an individual healing attempt, during which the pulmonary metastases showed clear progression. Consequently, the patient received immunotherapy with nivolumab according to his negative PD-L1 status. After 57 cycles of nivolumab, the patient presents with partial remission and in good condition. We report, for the first time, a robust response of metastatic SDC to checkpoint inhibition with nivolumab without additional radiotherapy.