Objective Autosomal dominant variants in the succinate dehydrogenase gene (SDHx) are responsible for similar to 50% of the development of hereditary paragangliomas and pheochromocytomas (PPGLs). Limited research has been conducted on the psychosocial impact of possessing a hereditary tumor syndrome. In this study, the psychological impact of harboring a genetic variant associated with familial paraganglioma syndrome was assessed. Secondary objectives included the analysis of potential variations in quality of life in (pre)symptomatic stage and comparison with the general Dutch population and other hereditary tumor syndromes.Methods The first 100 patients from the Head and Neck PGL Registry in the University Medical Center Utrecht were selected. Psychosocial outcomes were assessed cross-sectionally using 5 validated health-related questionnaires: EuroQol 5D-5L, Cancer Worry Scale, Hospital Anxiety and Depression Scale, Modified Fatigue Impact Scale, and EORTC QLQ-C30.Results No significant differences were observed when stratified for (pre)symptomatic status or genetic variant status. Hereditary PPGLs tended to express greater concern about the development of PPGLs in family members. Complaints in the physical domains were more frequently observed in the sporadic group. The PPGL cohort demonstrated better outcomes when compared to other hereditary tumor syndromes and aligned with the Dutch tariff.Conclusion The psychosocial impact of harboring a PPGL seems to align with the general healthy Dutch population. Clinical care management involving a multidisciplinary approach and comprehensive counseling on PPGLs and their genetic origins, effectively supports patients. Routine psychological support in the care for these patients does not seem imperative and should be offered indicated on a case-by-case basis.

PURPOSE:Deep learning is a promising approach to increase reproducibility and time-efficiency of gross tumor volume (GTV) delineation in head and neck cancer, but model evaluation primarily relies on manual GTV delineations as reference annotation, which are subjective and tend to overestimate tumor volume. This study aimed to validate a deep learning model for laryngeal and hypopharyngeal GTV segmentation with pathology and to compare its performance with clinicians' manual delineations. METHODS AND MATERIALS:A retrospective data set of 193 patients with laryngeal and hypopharyngeal cancer was used to train a deep learning model with clinical GTV delineations as reference. For validation, a data set comprising 18 patients who underwent imaging before total laryngectomy was used, with histopathology-based (n = 16) tumor delineations as ground truth. The performance of the automatic segmentations was compared with that of clinicians' manual delineations, both quantitatively and qualitatively. RESULTS:Median sensitivity (0.90 and 0.91) and largest required clinical target volume margin (6.4 and 6.6 mm) were comparable between automatic and manual GTV delineations. The positive predictive value yielded the only significant difference between automatic and manual GTV delineations, with medians of 0.52 and 0.61, respectively (P = .03). Clinical target volumes derived from automatic and manual GTVs exhibited similar sizes (median of 44.5 and 40.1 mL) and achieved a sensitivity of 1.00 in 13/16 and 14/16 tumors, respectively. Automatic segmentations were considered clinically acceptable in 67% of cases, compared with 63% of manual delineations. CONCLUSIONS:The proposed deep learning model for laryngeal and hypopharyngeal GTV segmentation achieved comparable results with clinicians' manual delineations, showing the potential for more consistency and efficiency in the radiation therapy workflow.

INTRODUCTION:There is a lack of comprehensive and uniform data on head and neck paragangliomas (HNPGLs), and research is challenging due to its rarity and the involvement of multiple medical specialties. To improve current research data collection, we initiated the Head and Neck Paraganglioma Registry (HNPGL Registry). The aim of the HNPGL Registry is to a) collect extensive data on all HNPGL patients through a predefined protocol, b) give insight in the long term outcomes using patient reported outcome measures (PROMs), c) create uniformity in the diagnostic and clinical management of these conditions, and thereby d) help provide content for future (randomized) research. METHODS AND ANALYSIS:The HNPGL Registry is designed as a prospective longitudinal observational registry for data collection on HNPGL patients and carriers of (likely) pathogenic variants causative of HNPGLs. All patients, regardless of the received treatment modality, can be included in the registry after informed consent is obtained. All relevant data regarding the initial presentation, diagnostics, treatment, and follow-up will be collected prospectively in an electronic case report form. In addition a survey containing the EuroQol 5D-5L (EQ-5D-5L), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30), Modified Fatigue Impact Scale (MFIS), Short QUestionnaire to Assess Health-enhancing physical activity (SQUASH), Cancer Worry Scale (CWS) and Hospital Anxiety and Depression Scale (HADS) will be sent periodically. The registry protocol was approved by the Medical Ethical Review Board of the University Medical Center Utrecht. CONCLUSION:The HNPGL Registry data will be used to further establish the optimal management for HNPGL patients and lay the foundation for guideline recommendations and the outline of future research.

BackgroundSinonasal squamous cell carcinoma is known for its rarity and poor prognosis. This study aims to investigate the trends in the incidence of sinonasal squamous cell carcinoma in the Netherlands and to analyze patient characteristics and treatment practices in order to assess their relation with patient outcomes.MethodsIn this prospectively designed population-based cohort study, all patients diagnosed with sinonasal squamous cell carcinoma between 2008 and 2021 in the Netherlands were included. Patients with a squamous cell carcinoma of the nasal vestibule were excluded, leading to a definitive study population of 568 cases.ResultsThe annual incidence rate for the overall population displayed a slight upward trend over the inclusion period with an annual percentage change of 1.6%. The 5-year overall, disease-free, and relative survival were 43.0%, 52.0%, and 47.2%, respectively. Relative survival decreased marginally over the course of the inclusion period.ConclusionSinonasal squamous cell carcinoma is rare with approximately stable incidence rates. There is a limited, non-statistically significant, decrease in survival between 2008 and 2021. Therefore, there is a clear need for innovative treatment approaches to improve outcomes for patients with sinonasal squamous cell carcinoma.

Background and purpose: Individual elective lymph node irradiation instead of elective neck irradiation is a new concept for head-and-neck cancer (HNC) patients developed for the Magnetic Resonance Image guided linear accelerator (MR-linac). To prepare this, the detectability, volume changes and intra-fraction motion of elective lymph nodes on the MR-linac was assessed. Materials and methods: A total of 15 HNC patients underwent diagnostic pre-treatment MRI. Additionally, two MR-linac scans were obtained with a 10-minute time difference in the first week of radiation treatment. Elective lymph node contours inside lymph node levels (Ib-V) were segmented on the pre-treatment MRI and the MR-linac scans and compared on number and maximal transversal diameter. Intra-fraction motion of elective lymph nodes on the MR-linac was estimated using Center of Mass (COM) distances and incremental isotropic expansion of lymph node segmentations. Results: Of all 679 detected lymph nodes on the pre-treatment MRI, eight lymph nodes were not detectable on the first MR-linac scan and 16 new lymph nodes were detected. Lymph node diameters between the pre-treatment MRI scan and the MR-linac scan varied from −0.19 to + 0.13 mm. COM distances varied from 1.2 to 1.7 mm and lymph node contours had to be expanded with 3 mm. Conclusions: Nearly all elective lymph nodes were detectable on the 1.5T MR-linac scan with no major changes in target volumes compared to the pre-treatment MRI. Simulated intra-fraction motion during the MR-linac scans was smaller than the 5-mm margin that will be used in the first elective lymph node radiation treatment.

The Dutch guideline for patients suspected of head and neck paragangliomas (HNPGLs) recommends magnetic resonance imaging (MRI) and/or computed tomography (CT) of the head and neck area. Additionally, it suggests considering additional nuclear imaging. The aim of this study was to evaluate the outcomes of [68Ga]Ga-DOTATOC PET/CT compared to MRI in patients with suspected HNPGLs and carriers of genetic variations. Methods: In this single-center pilot study, retrospective data were obtained from consecutive patients between 2016 and 2023. Both MRI and [68Ga]Ga-DOTATOC PET/CT were performed within 12 months. The primary outcome was the location of HNPGLs. Results: A total of 25 consecutive patients were included, and 7 patients (28.0%, p = 0.5) showed differences between the imaging modalities, of whom 5 patients had unexpected localizations with additional uptake by somatostatin receptors (SSTR) on the [68Ga]Ga-DOTATOC PET/CT. Conclusions: The authors recommend performing baseline imaging with [68Ga]Ga-DOTATOC PET/CT (if available) in variant carriers and using MRI/CT for follow-up according to the regional protocol, thereby shifting the gold standard for baseline imaging from MRI/CT to [68Ga]Ga-DOTATOC PET/CT.

BACKGROUND:Squamous cell carcinoma of the nasal vestibule (SCCNV) is a rare disease, distinctly different in presentation, treatment, and outcome from squamous cell carcinoma (SCC) of the nasal cavity and paranasal sinuses. However, these are often not analyzed separately.METHODS:The Netherlands Cancer Registry (NCR) and pathology reports from the Dutch Nationwide Pathology Databank (PALGA) were used to identify all newly diagnosed SCCNV cases in the Netherlands between 2008 and 2021.RESULTS:A total of 763 patients were included. The yearly incidence rate displayed a significant downward trend with an annual percentage change (APC) of -3.9%. The 5-year overall survival (OS) and disease-free survival were 69.0% and 77.2%, respectively. The 5-year relative survival was 77.9% and improved slightly over the inclusion period. OS for patients who were staged cT3 appeared to be worse than those staged cT4a, calling the applicability of the TNM-classification into question.CONCLUSION:SCC of the nasal vestibule is rare, with declining incidence rates. Introducing a specific topography code for SCCNV is recommended to enhance registration accuracy. The TNM classification seems poorly applicable to SCCNV, suggesting the need to explore alternative staging methods.

The Head and Neck Cancer International Group (HNCIG) has undertaken an international modified Delphi process to reach consensus on the essential data variables to be included in a minimum database for HNC research. Endorsed by 19 research organisations representing 34 countries, these recommendations provide the framework to facilitate and harmonise data collection and sharing for HNC research. These variables have also been incorporated into a ready to use downloadable HNCIG minimum database, available from the HNCIG website.

Sinonasal mucosal melanoma (SNMM) is a rare malignancy, characterised by high (local) recurrence rates and poor survival. Comprehensive understanding of tumour etiology is currently lacking, which complicates adequate tumour treatment. Besides examining trends in incidence, this study aims to assess the association between clinical characteristics, treatment practices and patient outcomes, with the objective of establishing a baseline from which SNMM management can be enhanced. All newly diagnosed SNMM cases in The Netherlands between 2001 and 2021 were included using data from The Netherlands Cancer Registry (NCR). A total of 320 patients were included. The annual incidence rate for the overall population was stable over the inclusion period with an annual percentage change (APC) of only − 0.01

Increased usage of automated tools like deep learning in medical image segmentation has alleviated the bottleneck of manual contouring. This has shifted manual labour to quality assessment (QA) of automated contours which involves detecting errors and correcting them. A potential solution to semi-automated QA is to use deep Bayesian uncertainty to recommend potentially erroneous regions, thus reducing time spent on error detection. Previous work has investigated the correspondence between uncertainty and error, however, no work has been done on improving the “utility” of Bayesian uncertainty maps such that it is only present in inaccurate regions and not in the accurate ones. Our work trains the FlipOut model with the Accuracy-vsUncertainty (AvU) loss which promotes uncertainty to be present only in inaccurate regions. We apply this method on datasets of two radiotherapy body sites, namely CT scans of head and neck and prostate MRs. Uncertainty heatmaps (i.e. predictive entropy) are evaluated using ROC and Precision-Recall curves. Numerical results show that when compared to the Bayesian baseline the proposed method successfully suppresses uncertainty for accurate voxels, with similar presence of uncertainty for inaccurate voxels. Code to reproduce experiments is available on https://github.com/prerakmody/ bayesuncertainty-error-correspondence.

Background/Objectives: Studies have shown that dose to the parotid gland stem cell rich (SCR) regions should be reduced to lower the risk of xerostomia after radiotherapy (RT). This study aimed to assess whether stem cell sparing (SCS)-RT can be adopted in routine clinical practice. Methods: Multiple planning studies were performed to compare SCS-RT with standard (ST)-RT using 30 head and neck cancer patients. Shifts in mean dose to the SCR regions (Dmean,SCR) and other organs at risk and their estimated impact on normal tissue complication probability (NTCP) for side-effects were compared using Wilcoxon signed-rank test. A multicenter study was performed (eight institutions, three patients) to test the generalizability of SCS-RT using the Friedman test. Results: Using photons, Dmean,SCR was reduced with median 4.1/3.5 Gy for ipsilateral/contralateral (p < 0.001). The largest reductions were when the SCR regions overlapped less with target volumes. Subsequently, NTCPs for xerostomia decreased (p < 0.001). Using protons, Dmean,SCR was also reduced (2.2/1.9 Gy for ipsilateral/contralateral, p < 0.002). Nevertheless, SCS-RT did not further decrease NTCPs for xerostomia (p > 0.17). Target coverage and prevention of other side-effects were not compromised. However, increased mean oral cavity dose was observed in some patients. Lastly, in the multicenter study Dmean,SCR could be reduced by slightly adjusting the standard optimization. Contralateral Dmean,SCR reductions differed between centers (p = 0.01), which was attributed to differences in ST-RT plans. Conclusions: Stem cell sparing radiotherapy can be clinically introduced by making small adjustments to the optimization strategy and can reduce the risk of xerostomia.

Background:This study aimed to determine the prognostic value of radiological magnetic resonance imaging (MRI) variables and dynamic contrast enhanced (DCE)-MRI for local control (LC), disease control (DC), and overall survival (OS) in laryngeal and hypopharyngeal cancer patients after radiotherapy. Methods:320 patients treated with radiotherapy were retrospectively included. Pretreatment MRIs were evaluated for the following anatomical tumor characteristics: cartilage invasion, extralaryngeal spread, and involvement of the anterior commissure, pre-epiglottic space, and paralaryngeal space.Pretreatment DCE-MRI was available in 89 patients. The median and 95th percentile of the 60-second area under the contrast-distribution-curve (AUC60median and AUC60p95) were determined in the tumor volume. Results:Univariable log-rank test determined that extralaryngeal spread, tumor volume and T-stage were prognostic for worse LC, DC, and OS. A low AUC60p95 (<31.7 mmol·s/L) and thyroid cartilage invasion were prognostic for worse OS.In multivariable analysis, a Cox proportional hazard model showed that a AUC60p95 ≥ 31.7 mmol·s/L was prognostic for better OS (HR=0.25, P<.001). Tumor volume was prognostic for DC (HR=3.42, P<.001) and OS (HR=3.27, P<.001). No anatomical MRI variables were significantly prognostic for LC, DC, or OS in multivariable analysis when corrected for confounders. Conclusion:Low pretreatment AUC60p95 is prognostic for a worse OS, suggesting that poor tumor perfusion leads to worse survival. Large tumor volume is also prognostic for worse DC and OS. Anatomical MRI parameters are not prognostic for any of the evaluated treatment outcomes when corrected for confounders like age, T-stage, N-stage, and tumor volume.

Background and purpose: Brachytherapy is treatment of choice for early stage nasal vestibule cancer. Over the years improvements were achieved by means of image guided target definition, interstitial implant techniques and also individual mold techniques. The aim of this study was to improve the technique of the implant so that the need for interstitial catheters can be limited by making use of patient individualized 3D-printed applicators. Materials and Methods: In 19 patients 3D-printed applicators were used to deliver pulse dose rate (PDR) brachytherapy. All patients underwent computed tomography (CT) and magnetic resonance imaging (MRI). A pre-plan with tumor delineation and manually optimized catheter positions to achieve tumor coverage was made. Based on the pre-plan a 3D-printed applicator was manufactured. Dose was evaluated by several indices: Conformity Index, Healthy Tissues Conformity Index, Dose Homogeneity Index, Dose non-uniformity ratio, Conformal index and high dose (HD) index. Results: A high target coverage was achieved, with a median V100%CTV CTV of 99.1 % (range, 81.8-100 %) and median CI of 0.99 (range, 0.82-1.00), as well as a median V0.7GyGTV GTV of 100 % (range, 93.0-100 %). The median HD was 0.39 (range, 0.20-0.83). Interstitial catheters were needed in 12 patients. None of the patients developed grade >= II toxicity within the median follow up of 18 months. Conclusions: This study shows that using 3D-printed applicators limits the need for interstitial catheters and also limits the high doses in normal tissue.

Objective: This study aims to determine the added value of a geometrically accurate diffusion -weighted (DW-) MRI sequence on the accuracy of gross tumor volume (GTV) delineations, using pathological tumor delineations as a ground truth. Methods: Sixteen patients with laryngeal or hypopharyngeal carcinoma were included. After total laryngectomy, the specimen was cut into slices. Photographs of these slices were stacked to create a 3D digital specimen reconstruction, which was registered to the in vivo imaging. The pathological tumor (tumorHE) was delineated on the specimen reconstruction. Six observers delineated all tumors twice: once with only anatomical MR imaging, and once (a few weeks later) when DW sequences were also provided. The majority voting delineation of session one (GTVMRI) and session two (GTVDW-MRI), as well as the clinical target volumes (CTVs), were compared to the tumorHE. Results: The mean tumorHE volume was 11.1 cm3, compared to a mean GTVMRI volume of 18.5 cm3 and a mean GTVDW-MRI volume of 15.7 cm3. The median sensitivity (tumor coverage) was comparable between sessions: 0.93 (range: 0.61-0.99) for the GTVMRI and 0.91 (range: 0.53-1.00) for the GTVDW-MRI. The CTV volume also decreased when DWI was available, with a mean CTVMR of 47.1 cm3 and a mean CTVDW-MRI of 41.4 cm3. Complete tumor coverage was achieved in 15 and 14 tumors, respectively. Conclusion: GTV delineations based on anatomical MR imaging tend to overestimate the tumor volume. The availability of the geometrically accurate DW sequence reduces the GTV overestimation and thereby CTV volumes, while maintaining acceptable tumor coverage.

Aim: Interventional radiotherapy (IRT) is being increasingly advocated as the standard treatment for the primary lesion in nasal vestibule squamous cell carcinoma (NV-SCC). The respect of the anatomical planes of the nose tip during implantation has been hypothesized to reduce the classical IRT toxicities on the cartilages, such as septal and even alar perforations. The present work describes a monoinstitutional series of NV-SCC treated with an IRT technique that follows the above principle (anatomical implantation), with a focus on IRT toxicities. Methods: All consecutive patients with nasal vestibule (NV) carcinoma treated between March 2022 and October 2023 with IRT on the primary lesion at Azienda Ospedaliera Universitaria di Sassari and Mater Olbia Hospital were included. Results: A total of 15 patients were treated with IRT following the principles of anatomical implantation. The only treatment-related toxicity observed has been the mechanical damage to the skin from the buttons used to stabilize the plastic tubes. Conclusion: IRT with anatomical implantation allows a high nose preservation rate and very good cosmetic results, which appear to be decisive advantages in comparison with traditional surgery, while confirming comparable effectiveness from an oncological point of view. However, in the present series, we describe typical skin toxicity that may have a negative impact on cosmetic results. We propose a new strategy involving the use of a soft medium such as a sponge to protect the skin from damage.