Background: Addition of neoadjuvant immune checkpoint inhibition to standard-of-care interventions for locally advanced oral cancer could improve clinical outcome. Methods: In this study, 16 evaluable patients with stage III/IV oral cancer were treated with one dose of 480 mg nivolumab 3 weeks prior to surgery. Primary objectives were safety, feasibility, and suitability of programmed death receptor ligand-1 positron emission tomography (PD-L1 PET) as a biomarker for response. Imaging included ¹⁸F-BMS-986192 (PD-L1) PET and ¹⁸F-fluorodeoxyglucose (FDG) PET before and after nivolumab treatment. Secondary objectives included clinical and pathological response, and immune profiling of peripheral blood mononuclear cells (PBMCs) for response prediction. Baseline tumor biopsies and postnivolumab resection specimens were evaluated by histopathology. Results: Grade III or higher adverse events were not observed and treatment was not delayed in relation to nivolumab administration and other study procedures. Six patients (38%) had a pathological response, of whom three (19%) had a major (≥90%) pathological response (MPR). Tumor PD-L1 PET uptake (quantified using standard uptake value) was not statistically different in patients with or without MPR (median 5.3 vs 3.4). All major responders showed a significantly postnivolumab decreased signal on FDG PET. PBMC immune phenotyping showed higher levels of CD8⁺ T cell activation in MPR patients, evidenced by higher baseline expression levels of PD-1, TIGIT, IFNγ and lower levels of PD-L1. Conclusion: Together these data support that neoadjuvant treatment of advanced-stage oral cancers with nivolumab was safe and induced an MPR in a promising 19% of patients. Response was associated with decreased FDG PET uptake as well as activation status of peripheral T cell populations.

Eagle syndrome is a bone disease where elongation of the styloid process leads to throat and neck pain, and in severe cases neurovascular symptoms such as syncope and neuralgia. The pathophysiology of Eagle syndrome is poorly understood with various theories having been proposed how this elongation is caused. To better understand the pathophysiology, we performed an work-up in 6 patients presenting with Eagle syndrome. Patients mainly presented with pain on turning the neck (100%), foreign body sensation (67%), tension in the neck (67%) and dysphagia (50%). The typical length of the styloid process ranges from 25 to 30 millimeters, [¹⁸F]NaF (sodium fluoride) PET/CT showed elongated styloid processes of 52.1 ± 15.6 mm (mean ± SD with increased turnover at the base of one the styloid processes. The removed styloid processes were further examined by histology, micro-CT, quantitative backscatter electron imaging (qBEI), Fourier transform infrared spectroscopy (FTIR) and circularly polarized light (CPL) imaging. Histology revealed one case of a fractured styloid process healing through callus formation and one case of pseudarthrosis. Bone mineral density and mineralization measured in the micro-CT and qBEI analysis and was similar in the styloid processes compared to cortical bone samples derived from the mandibular bone of separate patients. Circular polarized light microscopy showed collagen orientation comparable to cortical bone with a distinct separation of collagen structure between the mineralized structure and the surrounding soft tissue with FTIR analysis demonstrating a typical composition of bone. This altogether suggests that the elongated styloid processes in Eagle syndrome are mature bone, capable of endochondral repair, possibly growing from the base of the process through endochondral ossification and not a form of secondary calcification of the stylohyoid ligament as previously postulated.

Objective: Head and neck cancer care is highly complex, and multidisciplinary team meetings (MDTs) are vital for improved outcomes. In the Netherlands, head and neck cancer care is practiced in eight high-volume head and neck oncologic centers (HNOC) and six affiliated hospitals preferred partner (PP) centers. Patients treated in the PP are presented and discussed in the HNOC. To evaluate the importance of these mandatory and decisive steps in decision making, we have assessed the changes in treatment.Materials and methods: Retrospective evaluation of head and neck cancer patients referred between January 2011 and October 2018 for a MDT evaluation to the HNOC was conducted. The differences in MDT recommendation were classified with regards to major and minor changes.Results: Management recommendation(MR) changed after 113 of 515 MDT discussions within the PP (487 patients; 22%), of which 86 cases (16%) were major changes. In 67 cases (59.3%), escalation of management was recommended, while in 43 cases (38.1%) de-escalation was recommended.Conclusion: There was a high rate of change of MRs, when comparing the PP recommendations with the HNOC recommendations. Since patient and tumor characteristics seem unable to predict these changes, we recommend all patients be seen for a clinical presentation, revision of diagnostics, and MDT discussion in a high volume HNOC.

The main goal of surgery for oral squamous cell carcinoma (OSCC) is to obtain adequate resection margins as inadequate margins are associated with a worse prognosis and treatment intensification. However, reported rates of inadequate resections vary from 30%-85%. Clinical auditing is an upcoming tool to improve margin status. This study investigates resection margins after OSCC surgery and differences in hospital results, disease-free, and overall survival for <1 and ≤5 mm cut-offs. This Dutch nationwide registry-based cohort study includes all patients who underwent surgery for first primary OSCC between 2018 and 2021. Resection margins were categorised as 5 mm. Hospital variation was visualised in funnel plots and corrected for case-mix and treatment variables. Two-year overall and disease-free survival were determined. A total of 2,085 patients from 14 hospitals could be included for analysis. Nationally, margins <1 mm were present in 16.4% which varied from 6.5%-31.6% at hospital level. For margins ≤5 mm, the national average was 61.3%, with hospital outcomes ranging from 50.0%-78.6%. Significant outliers remained after correction for case-mix and treatment variables. Two year overall and disease-free survival was worse in the <1 mm group. Obtaining negative or adequate margins during the resection of invasive OSCC is challenging. Significant hospital differences in resection margin outcomes remained after correction for case-mix characteristics. By identifying best practices in OSCC, surgical and survival outcomes can be improved.

The topic of the unknown primary tumour in head and neck cancer (CUP) has been extensively studied. The increasing incidence of Human papillomavirus (HPV) related oropharyngeal squamous cell carcinoma (OPSCC) as well as the emerging role of transoral robotic surgery (TORS) has led to revision and evolution of diagnostic and treatment paradigms. The concept of tongue base mucosectomy (TBM) has gained its place in the diagnostic pathway. The most recent considerations are described herein with regard to recent literature. An algorithm for patients with CUP is proposed with an emphasis on the role of transoral surgery.

Objectives: Robotic transoral mucosectomy of the base of tongue was introduced as a diagnostic procedure in patients treated for head and neck cancer with unknown primary (CUP), increasing the identification rate of the primary tumour. For the treatment of CUP, a considerable percentage of patients require adjuvant (chemo)radiation. The aim of this study was to investigate swallowing outcomes among CUP patients after TORS and adjuvant treatment.Subjects and Methods: A systematic review was carried out on studies investigating the impact of TORS and adjuvant treatment on swallowing‐related outcomes among CUP patients In addition, a cross‐sectional study was carried out on swallowing problems (measured using the SWAL‐QOL questionnaire) among CUP patients in routine care who visited the outpatient clinic 1–5 years after TORS and adjuvant treatment.Results: The systematic review (6 studies; n = 98) showed that most patients returned to a full oral diet. The cross‐sectional study (n = 12) showed that all patients were able to return to a full oral diet, nevertheless, 50% reported swallowing problems in daily life (SWAL‐QOL total score ≥14).Conclusion: Although after TORS and adjuvant treatment for CUP a full oral diet can be resumed, patients still experience problems with eating and drinking in daily life.