OBJECTIVE(S):Minimally invasive procedures are well established for patients with sialolithiasis involving single stones. For patients with multiple sialolithiasis, few data are available regarding the treatment approaches and outcomes with gland-preserving therapies. The aim of this study was to review current treatment concepts and postinterventional outcomes in these patients and to propose a treatment algorithm. STUDY DESIGN:Retrospective study. SETTING:University hospital and tertiary referral center. METHODS:The study was conducted to evaluate therapeutic effectiveness and outcome in patients who presented with multiple sialolithiasis in the major salivary glands between January 2016 and October 2022. All patients received minimally invasive treatment following established treatment algorithms. RESULTS:In 177 patients with multiple sialolithiasis, 556 stones were treated using a minimally invasive treatment regimen, with a mean of 2.55 interventions per patient. Monomodal therapy was carried out in 54.8% of the patients and multimodal therapy in 45.2%. Stone-free and/or symptom-free status was achieved for all patients with stones in the submandibular glands and for 97.6% of those with stones in the parotid glands. Gland preservation was possible in 97.2% of the patients, with no significant differences between the submandibular glands (97.8%) and parotid glands (95.2%; P = .371). CONCLUSION:Multiple sialolithiasis can be treated with high success rates. In nearly half of the patients, a multimodal minimally invasive treatment regimen is needed in order to achieve stone-free and/or symptom-free status and preservation of the gland-both possible in over 97% of cases.

Neoadjuvant therapies incorporating immune checkpoint inhibitors (ICIs) have shown promise in locally advanced head and neck squamous cell carcinoma (HNSCC). However, biomarkers for pathological complete response (pCR) remain undefined. In the CheckRad-CD8 trial (NCT03426657), we performed RNA sequencing on pre- and post-treatment biopsies from 77 locally advanced HNSCC patients treated with induction chemoimmunotherapy. Of these, 42 patients achieved pCR, while 35 had residual disease (RD). Differentially expressed genes (DEGs) and pathways were identified using DESeq2 and gene set enrichment analysis. Tumor immune microenvironment analysis, utilizing eight RNAseq deconvolution methods, assessed 266 gene signatures and 38 curated immunotherapy signatures. Baseline intratumoral CD8+ T-cell density, stromal tumor lymphocyte infiltration, and combined PD-L1 proportion score were associated with pCR. Pretreatment analysis identified 830 DEGs between pCR and RD, with T and B-cell-related pathways enriched in pCR samples. Logistic regression models indicated the significance of T and B cells and IFN-gamma signaling in predicting pCR. Furthermore, a new CheckRad-7-gene signature, with an AUC of 0.902 in the training cohort, effectively predicted pCR and survival, serving as a robust biomarker for prognosis and treatment response in HNSCC.

INTRODUCTION:Anterior tympanic membrane (TM) defects present a surgical challenge due to the lack of support for the graft, resulting in reduced success rates. Established anchoring tympanoplasty (EAT) techniques usually aim to anchor the graft to the anterior rim of the TM. The "cartilaginous bending spring tympanoplasty" (CBST) secures the graft to the TM by supporting it with a U-shaped bending spring cartilage placed underneath in the middle ear. Initial experimental studies have already shown the feasibility of CBST without impeding sound transmission. This prospective clinical study evaluates the outcome of CBST compared to EAT in terms of closure of TM defects and hearing outcome. MATERIALS AND METHODS:This randomized controlled study was conducted at a tertiary referral center from March 22, 2018 to September 17, 2020. Patients were randomized to surgeon and reconstruction technique (EAT vs CBST). Inclusion criteria were chronic otitis media with TM defects that involved at least the anterior part of the TM, subtotal defects, and an intact ossicular chain. Primary objectives were the successful reconstruction of the TM and the hearing outcome. RESULTS:Fifty-five patients (55 ears; CBST n = 26, right ears = 13; EAT n = 28, right ears = 8) with a mean age of 46.1 ± 15.0 years and a mean follow-up of 140.4 ± 86.7 days were included. The TM was successfully reconstructed in 95% of cases in both groups. Hearing improvement was comparable for both groups (improvement of air-bone gap: EAT: 3.0 ± 9.3 dB; CBST: 5.5 ± 6.2 dB; P = .244; Cohen's d = 0.318). CONCLUSION:CBST allows for comparably high success rates of reconstruction of anterior TM defects and the hearing outcome. Accordingly, the U-spring bending cartilage supporting the graft does not adversely affect hearing outcome. Thus, CBST can be considered a useful technique to close anterior defects of the TM effectively.

In aktuellen Forschungsansätzen zur simultanen Radiochemotherapie (RCT) nichtmetastasierter Plattenepithelkarzinome des Kopf-Hals-Bereichs (HNSCC) werden Möglichkeiten zur sicheren Therapiedeintensivierung bei auf humane Papillomviren (HPV-)positiven Oropharynxkarzinomen (OPC) und zur Therapieeskalation bei lokal fortgeschrittenen (LA-)HNSCC untersucht. Nach entsprechender Patientenselektion wurden in Phase-II-Studien zu HPV-positiven OPC gute onkologische Ergebnisse bei reduzierter Toxizität durch teils drastische Dosisreduktionen der Strahlentherapie auf bis zu 30 Gy erzielt. Eine Methode zur Patientenselektion könnten dabei hypoxiesensible Bildgebungsverfahren sein. Bei HPV-negativen LA-HNSCC wurde hingegen sowohl durch die Kombination von Immuncheckpointinhibitoren (ICI) mit definitiver Cisplatin-basierter RCT als auch durch den additiven Einsatz von Xevinapant, dem apoptosefördernden Antagonisten von IAP („inhibitor of apoptosis protein“) in Phase-III-Studien keine Verbesserung der Prognose erreicht. Ein neuer Ansatz mit ersten positiven Studienergebnissen ist die perioperative Immuntherapie mit Pembrolizumab, die in der Phase-III-Studie KEYNOTE-689 in Kombination mit R(C)T zu einer signifikanten Verbesserung des ereignisfreien Überlebens (EFS) bei resektablen LA-HNSCC führte. Auch durch die additive Nivolumab-Therapie zur postoperativen RCT ließ sich in vorläufigen Ergebnissen der NIVOPOSTOP-GORTEC-2018-01-Studie die Prognose verbessern. Zusammenfassend bleibt die platinbasierte RCT das Rückgrat in der primär definitiven und adjuvanten Situation. Während für HPV-positive OPC bisher nur in Studien Strategien zur Therapiedeintensivierung empfohlen werden, könnte Immuncheckpointinhibition in Kombination mit RCT in der perioperativen Therapie von resektablen LA-HNSCC bald zum neuen Behandlungsstandard werden.

Background: Immunological and rheological properties are important factors of the surfactant protein (SP) family, whose impact on tumorigenesis is not yet known, although some SPs have been identified as tumor marker candidates for various malignancies. This study describes the detection of the two surfactant family proteins SP-G and PLUNC in healthy glottis, the presence of SP-G in glottic cancer, and the in vitro tissue regeneration potential of SP-G and PLUNC on epithelial cells. Methods: The expression and distribution of SP-G and PLUNC were investigated immunohistochemically in squamous cell carcinomas of the vocal folds. The expression of both proteins was analyzed by Western blot in micro-dissected healthy vocal fold mucosa from body donors. The hypopharyngeal squamous carcinoma cell line (FaDu) was used as an in vitro model for wound healing experiments with Electric cell–substrate impedance sensing (ECIS). Results: The results show the presence of SP-G and PLUNC in epithelial cells of the healthy vocal folds and the submucosal glands of the vestibular folds. SP-G was detected in squamous cell carcinomas of the vocal folds. SP-G and PLUNC show accelerated wound healing of FaDu cells in vitro. Conclusions: SP-G and PLUNC were first detected in the vocal fold of the human larynx. SP-G shows a distinct presence in glottic carcinoma, whose relevance needs to be determined in future studies. SP-G and PLUNC exhibit a positive influence on the repair mechanisms of epithelial lesions of the glottis. The data presented form the basis for follow-up studies focusing on the impact of SP-G in glottic cancer development and the potentially meaningful clinical effect of SP-G and PLUNC on tissue repair of the human vocal fold.

Purpose:Uveal and conjunctival melanomas are rare ocular malignancies that present significant diagnostic and therapeutic challenges. This study investigates the efficacy of combining hyperthermic treatments with chemotherapeutics, such as cisplatin, docetaxel, and mitoxantrone, to develop more effective therapies for specific melanoma subtypes, aiming to overcome the limitations of traditional approaches. Methods:The study used hyperthermia by exposing melanoma cell lines to temperatures of 42°C, 45°C, and 47°C for 1 hour. Alongside hyperthermia, cytotoxic drugs were applied at different concentrations to assess their combined effects on cell proliferation and viability. Expression of heat shock proteins was evaluated by immunocytochemistry stainings and Western blots. Results:Findings reveal that certain melanoma cell lines exhibited increased proliferation at 42°C without a significant decrease in cell confluence. Conversely, temperatures of 45°C and above significantly impaired cell viability. Comparative statistical analysis suggests synergistic effects when combining mild to elevated hyperthermia with cisplatin and mitoxantrone, and to some extent with docetaxel. Conclusions:This study serves as preliminary work for the inclusion of superparamagnetic iron oxide nanoparticles functionalized with cytotoxic drugs, which may present a promising therapeutic strategy for treating ocular melanomas. Although further research is necessary, this approach has the potential to significantly advance the treatment landscape for these ocular malignancies, offering a targeted, effective, and minimally invasive option for patients.

Head and neck cancer is a common disease and is associated with a poor prognosis. A promising approach to improving patient outcomes is personalized treatment, which uses information from a variety of modalities. However, only little progress has been made due to the lack of large public datasets. We present a multimodal dataset, HANCOCK, that comprises monocentric, real-world data of 763 head and neck cancer patients. Our dataset contains demographical, pathological, and blood data as well as surgery reports and histologic images, that can be explored in a low-dimensional representation. We can show that combining these modalities using machine learning is superior to a single modality and the integration of imaging data using foundation models helps in endpoint prediction. We believe that HANCOCK will not only open new insights into head and neck cancer pathology but also serve as a major source for researching multimodal machine-learning methodologies in precision oncology.

Background: Advance Directives (ADs) play a critical role in ensuring patient autonomy, particularly among patients with Head and Neck Cancer (HNC). However, the factors influencing AD utilization among HNC patients, especially with respect to varying cancer stages and patient care settings, remain understudied. Our study aims to compare the use of AD between patients Free of Recurrence and/or Metastasis (FRM) from HNC with patients with Recurrent and/or Metastatic (RM) HNC. Methods: In this comparative observational study at a tertiary cancer care center, we analyzed the utilization of ADs in two distinct patient cohorts diagnosed with HNC: Recurrent and/or Metastatic (RM, n = 96) and Free of Recurrence and/or Metastasis (FRM, n = 389). Data collection involved examining the frequency, motivations, and modes of AD creation of both cohorts Results: Our comparative analysis revealed a higher presence of ADs in the RM cohort compared to the FRM cohort (58.3% vs. 46.5%, p = 0.038). The type of AD or the reasons against its creation were similar in both groups. Motivations differed notably: 52.4% of the RM cohort was influenced by advice from acquaintances or professionals versus 27.6% in the FRM cohort (p = 0.054, Cramer’s V = 0.223). Concerns about abandonment or over-therapy motivated 23.4% of the FRM cohort, but only 16.7% of the RM group (p = 0.054, Cramer’s V = 0.223). Decisions to defer AD creation were pronounced in the RM group at 67.4% compared to 55.1% in the FRM group. In terms of AD forms, the RM cohort prepared multiple forms significantly more frequently (9.3% vs. 0.7%, p = 0.002*, Cramer’s V = 0.294). Both groups predominantly sought legal (26.5% vs. 22.9%, p = 0.624, phi = 0.034) or other consultation (20.0% vs. 39.6%, p = 0.006*, phi = 0.193) during AD formation, with no significant differences in medical consultation (12.9% vs. 12.5%, p > 0.999, phi < 0.001) preferences. Conclusion: While approximately every other patient with localized disease had an AD, the rate in patients with recurrent and/or metastatic disease was only slightly higher. Related to the drastically worse prognosis of recurrent and/or metastatic disease, effort should be made to encourage these patients to create an AD. This analysis provides evidence that advice from acquaintances or professionals effectively motivated patients with recurrent and/or metastatic disease to consider their end-of-life wishes and document them in the form of an AD or other advance care directives.

Head and neck cancer (HNC) patients experience a variety of post-treatment symptoms that affect their quality of life (QoL). This study aims to assess the most prevalent symptoms and their relationship to cancer stage (UICC I–IV) while identifying areas for targeted intervention. A cross-sectional study was conducted involving 340 HNC patients at the University Hospital Erlangen from January to December 2019. QoL and its domains were assessed using the German version of the University of Washington Quality of Life Questionnaire Version 4 (UW-QoL v.4), with comparisons made between early-stage (UICC I II, n = 180) and advanced-stage (UICC III IV, n = 160) patients. Statistical analysis examined differences in QoL and its individual domains. Advanced-stage patients reported significantly greater impairments in several QoL domains, including swallowing (p = 0.003, η2 = 0.038), saliva production (p < 0.001, η2 = 0.104), and taste (p = 0.009, η2 = 0.030), compared to early-stage patients. Psychological symptoms, such as anxiety and mood disturbances, were prevalent across all stages, but no significant differences were found between early- and advanced-stage patients for pain, speech, mood, or anxiety (p > 0.05). Patient demographics, including age, gender, and comorbidities, were similar between groups. The greater impairments in QoL domains observed in advanced-stage patients are likely due to more intensive treatments, such as multimodal therapy and radiochemotherapy. Advanced-stage HNC patients experience a significantly higher burden of physical symptoms, particularly issues with swallowing, saliva, and taste, necessitating early and targeted interventions. Psychological issues are also prevalent and should be addressed in both early- and advanced-stage patients. Despite non-significant differences in some symptoms, their clinical relevance may still be important, particularly in individual cases. Comprehensive care, including physical and emotional support, is essential to improving long-term QoL for HNC patients. Further research should focus on longitudinal assessments and clinically meaningful thresholds for symptom management.

At the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO), several important studies on radiotherapy for head and neck squamous cell carcinoma (HNSCC) were presented. There were two Chinese phase III trials on treatment escalation for locally advanced nasopharyngeal carcinoma: adjuvant immune checkpoint inhibition with camrelizumab after induction chemotherapy and cisplatin-based chemoradiotherapy (RCT) in the DIPPER trial reached the primary endpoint of improved event-free survival (EFS) but did not improve overall survival (OS). Simultaneous and adjuvant administration of the angiogenesis inhibitor endostar in addition to cisplatin-based RCT for locally advanced nasopharyngeal carcinoma led to a significant improvement in progression-free survival (PFS) and OS. Another major focus was on treatment optimization and deintensification for oropharyngeal cancer (OPC): using intensity-modulated proton therapy (IMPT), a phase III trial demonstrated noninferiority in definitive RCT for OPC compared to photon-based intensity-modulated radiotherapy (IMRT). In adjuvant treatment of human papillomavirus-positive (HPV+) OPC, the long-term results of the E3311 phase II study confirmed that individually deintensified radiotherapy is feasible. Lee et al. showed with the results of a phase II study that HPV+ OPC might be treatable with chemoradiotherapy to a total dose of only 30 Gy if no hypoxia is detected in the 18F‑fluoromisonidazole positron-emission tomography-computed tomography (F-MISO-PET) scan. Both the deintensified treatment of HPV+ OPC as well as additive immune checkpoint and angiogenesis inhibition in chemoradiotherapy of nasopharyngeal carcinoma require further studies before they can be recommended in clinical practice.

Background Meningiomas are among the most common tumors of the central nervous system. 1-2% of all meningiomas occur extracranially. Manifestations in the soft tissues of the neck are very rare and are therefore only described in small case series.

Background Palliative care is an essential component in the treatment of patients with head and neck cancer (HNC). ENT physicians are required to recognize the need for palliative care in a timely manner and to provide the indication for this care. This study determines the need for palliative medical care and compares it with the actual care situation.

Objectives: In this study, long-term survivors of head and neck cancer (HNC) were evaluated regarding their symptom burden and quality of life (QoL). Methods: This prospective study was performed during the regular follow-up consultations at one of Germany’s largest tertiary referral centers for HNC. The assessment included demographic, clinical, and oncological data, as well as the MIDOS(2) and the University of Washington Quality of Life Questionnaire (UW QoL) questionnaires. Patients were subdivided based on their disease stage, that is, early cancer stages (UICC I/II) and advanced cancer stages UICC (III/IV). Results: Between January 1, 2019 and December 31, 2019, 212 HNC patients with a mean follow-up of 46.36 ± 43.64 months were included (120 patients UICC stage I/II (22.5% female, mean age 61.93 ± 12.38 years) versus 92 patients UICC stage III/IV (25.0% female, mean age 63.73 ± 11.74 years)). For all patients evaluated (UICC I/II versus III/IV), the three most common symptoms were tiredness (47.5 vs 60.9%, P = .073, r = .123), anxiety (35.8 vs 32.6%, P = .624, phi = .034) and drowsiness (35.0 vs 44.6%, P = .157, phi = .097). Patients diagnosed with UICC III/IV stages reported loss of appetite significantly more frequently and with a high level of severity (15.0 vs 32.6%, P = .002, phi = .157; 0.23 ± 0.60 vs 0.47 ± 0.78, P = .003, r = .203). The overall symptom burden was low with a severity sum score (min 0-max 30) of 3.04 ± 3.29 versus 3.58 ± 3.38 ( P = .143, r = .100). All patients rated their QoL as good (65.67 ± 20.93 vs 59.56 ± 22.00, P = .043, r = .139). Conclusion: The overall symptom burden of long-term survivors of HNC is encouragingly low. Trial registration: The study was registered in the German Registry for Clinical Studies (application No.: 00017122). Date of registration: 15.08.2019. https://drks.de/search/de/trial/DRKS00017122 .

Abstract Background The significance of different histological spreading patterns of tumor tissue in oral tongue squamous cell carcinoma (TSCC) is well known. Our aim was to construct a numeric parameter on a continuous scale, that is, the modified Polsby–Popper (MPP) score, to describe the aggressiveness of tumor growth and infiltration, with the potential to analyze hematoxylin and eosin‐stained whole slide images (WSIs) in an automated manner. We investigated the application of the MPP score in predicting survival and cervical lymph node metastases as well as in determining patients at risk in the context of different surgical margin scenarios. Methods We developed a semiautomated image analysis pipeline to detect areas belonging to the tumor tissue compartment. Perimeter and area measurements of all detected tissue regions were derived, and a specific mathematical formula was applied to reflect the perimeter/area ratio in a comparable, observer‐independent manner across digitized WSIs. We demonstrated the plausibility of the MPP score by correlating it with well‐established clinicopathologic parameters. We then performed survival analysis to assess the relevance of the MPP score, with an emphasis on different surgical margin scenarios. Machine learning models were developed to assess the relevance of the MPP score in predicting survival and occult cervical nodal metastases. Results The MPP score was associated with unfavorable tumor growth and infiltration patterns, the presence of lymph node metastases, the extracapsular spread of tumor cells, and higher tumor thickness. Higher MPP scores were associated with worse overall survival (OS) and tongue carcinoma‐specific survival (TCSS), both when assessing all pT‐categories and pT1‐pT2 categories only; moreover, higher MPP scores were associated with a significantly worse TCSS in cases where a cancer‐free surgical margin of <5 mm could be achieved on the main surgical specimen. This discriminatory capacity remained constant when examining pT1‐pT2 categories only. Importantly, the MPP score could successfully define cases at risk in terms of metastatic disease in pT1‐pT2 cancer where tumor thickness failed to exhibit a significant predictive value. Machine learning (ML) models incorporating the MPP score could predict the 5‐year TCSS efficiently. Furthermore, we demonstrated that machine learning models that predict occult cervical lymph node involvement can benefit from including the MPP score. Conclusions We introduced an objective, quantifiable, and observer‐independent parameter, the MPP score, representing the aggressiveness of tumor growth and infiltration in TSCC. We showed its prognostic relevance especially in pT1‐pT2 category TSCC, and its possible use in ML models predicting TCSS and occult lymph node metastases.

Hintergrund Palliativmedizinische Versorgung ist ein essenzieller Bestandteil in der Behandlung von Patienten mit Kopf-Hals-Tumoren (HNC). HNO-Ärzte sind gefordert, den Bedarf rechtzeitig zu erkennen und die Indikation für diese Betreuung zu stellen. Die vorliegende Studie bestimmt den Bedarf an palliativmedizinischer Versorgung und vergleicht diesen mit der tatsächlichen Versorgungssituation.

We aimed to validate the prognostic significance of tumor budding (TB) in p16-positive oropharyngeal squamous cell carcinomas (OPSCC). We analyzed digitized H E-stained slides from a multicenter cohort of five large university centers consisting of n = 275 cases of p16-positive OPSCC. We evaluated TB along with other histological parameters (morphology, tumor-stroma-ratio, lymphovascular invasion (LVI), perineural invasion) and calculated survival outcomes using both univariate and multivariate analyses. TB was identified as an independent prognostic parameter, with TB-high cases showing inferior outcomes in univariate (HR: 3.08, 95

Einleitung Kopf-Hals-Karzinome unbekannten Ursprungs (HNCUP) stellen eine diagnostische Herausforderung dar, da bei 2-5% der Patienten mit Kopf-Hals-Tumoren und zervikalen Lymphknotenmetastasen kein Primärtumor gefunden werden kann. Plattenepithelkarzinome bilden dabei mit 53-77% die häufigste Histologie. Die 5-Jahres-Überlebensraten variieren erheblich von 29% bis 82%.