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Background/aim: The aim of this scoping review was to summarise the current evidence for peer-to-peer support and its impact on quality of life (QoL) in head and neck cancer (HNC). Methods: Five search engines were used—PubMed, CINAHL, APA PyscInfo, Web of Science and HaNDLE-on-QoL—to look for publications between 1981 and 2020. Adapted PICO (population, intervention, comparator and outcome) and Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) methodology was used. Results: Of the 1408 papers identified, 10 met the inclusion criteria: five qualitative, two cross-sectional, one case-control, one cohort and one quasi-experimental design. There were four common themes: patient experience of peer-to-peer support, delivery of peer-to-peer support, engagement with peer-to-peer support and impact on QoL. Conclusion: This review highlights the paucity of evidence with regard to QoL and peer-to-peer support in HNC. It provides a summary of the literature and identifies considerations for clinical practice and future research. [ABSTRACT FROM AUTHOR]

Background: Using radiation therapy (RT) to treat head and neck (H&N) cancers requires precise targeting of the tumor to avoid damaging the surrounding healthy organs. Immobilisation masks and planning target volume margins are used to attempt to mitigate patient motion during treatment, however patient motion can still occur. Patient motion during RT can lead to decreased treatment effectiveness and a higher chance of treatment related side effects. Tracking tumor motion would enable motion compensation during RT, leading to more accurate dose delivery. Purpose: The purpose of this paper is to develop a method to detect and segment the tumor in kV images acquired during RT. Unlike previous tumor segmentation methods for kV images, in this paper, a process for generating realistic and synthetic CT deformations was developed to augment the training data and make the segmentation method robust to patient motion. Detecting the tumor in 2D kV images is a necessary step toward 3D tracking of the tumor position during treatment. Method: In this paper, a conditional generative adversarial network (cGAN) is presented that can detect and segment the gross tumor volume (GTV) in kV images acquired during H&N RT. Retrospective data from 15 H&N cancer patients obtained from the Cancer Imaging Archive were used to train and test patient‐specific cGANs. The training data consisted of digitally reconstructed radiographs (DRRs) generated from each patient's planning CT and contoured GTV. Training data was augmented by using synthetically deformed CTs to generate additional DRRs (in total 39 600 DRRs per patient or 25 200 DRRs for nasopharyngeal patients) containing realistic patient motion. The method for deforming the CTs was a novel deformation method based on simulating head rotation and internal tumor motion. The testing dataset consisted of 1080 DRRs for each patient, obtained by deforming the planning CT and GTV at different magnitudes to the training data. The accuracy of the generated segmentations was evaluated by measuring the segmentation centroid error, Dice similarity coefficient (DSC) and mean surface distance (MSD). This paper evaluated the hypothesis that when patient motion occurs, using a cGAN to segment the GTV would create a more accurate segmentation than no‐tracking segmentations from the original contoured GTV, the current standard‐of‐care. This hypothesis was tested using the 1‐tailed Mann‐Whitney U‐test. Results: The magnitude of our cGAN segmentation centroid error was (mean ± standard deviation) 1.1 ± 0.8 mm and the DSC and MSD values were 0.90 ± 0.03 and 1.6 ± 0.5 mm, respectively. Our cGAN segmentation method reduced the segmentation centroid error (p < 0.001), and MSD (p = 0.031) when compared to the no‐tracking segmentation, but did not significantly increase the DSC (p = 0.294). Conclusions: The accuracy of our cGAN segmentation method demonstrates the feasibility of this method for H&N cancer patients during RT. Accurate tumor segmentation of H&N tumors would allow for intrafraction monitoring methods to compensate for tumor motion during treatment, ensuring more accurate dose delivery and enabling better H&N cancer patient outcomes. [ABSTRACT FROM AUTHOR]

This paper proposes a metal artifact reduction method of using MV-CBCT images to correct metal artifacts in kV-CT images, especially for the complex metal artifacts caused by multi-metal interaction of patients with head and neck tumors. The different tissue regions are segmented in the MV-CBCT images to obtain template images and the metal region is segmented in the kV-CT images. Forward projection is performed to get sinogram of the template images, kV-CT images and metal region images. Artifact images can be reconstructed through those sonograms. Corrected images is generated by subtracting the artifact images from the original kV-CT images. After the first correction, the template images are generated again and brought into the previous step for iteration to get better correction result. CT data set of 7 patients are used in this study, compared with linear interpolation metal artifact (LIMAR) and normalized metal artifact reduction method, mean relative error of CT value is reduced by 50.5% and 63.3%, noise is reduced by 56.2% and 58.9%. The Identifiability Score of the tooth, upper/lower jaw, tongue, lips, masseter muscle and cavity in the corrected images by the proposed method have significantly improved (P < 0.05) than original images. The artifacts correction method proposed in this paper can effectively remove the metal artifacts in the images and greatly improve the CT value accuracy, especially in the case of multi-metal and complex metal implantation. [ABSTRACT FROM AUTHOR]

Recent studies have indicated that preoperative biliary drainage (PBD) should not be routinely performed in all patients suffering from obstructive jaundice before pancreatic surgery. The severity of jaundice that mandates PBD has yet to be defined. The evaluated paper examines the impact of PBD on intra-operative, and post-operative outcomes in patients initially presenting with severe obstructive jaundice (bilirubin ≥250 μmol/L). In this key paper evaluation, the impact of PBD versus a direct surgery (DS) approach is discussed. The arguments for and against each approach are considered with regards to drainage associated morbidity and mortality, resection rates, survival and the impact of chemotherapy and malnutrition. Concentrating on resectable head of pancreas tumors, this mini-review aims to scrutinize the authors' recommendations, alongside those of prominent papers in the field. [ABSTRACT FROM AUTHOR]

Objective. Accurate segmentation of head and neck (H&N) tumors is critical in radiotherapy. However, the existing methods lack effective strategies to integrate local and global information, strong semantic information and context information, and spatial and channel features, which are effective clues to improve the accuracy of tumor segmentation. In this paper, we propose a novel method called dual modules convolution transformer network (DMCT-Net) for H&N tumor segmentation in the fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) images. Approach. The DMCT-Net consists of the convolution transformer block (CTB), the squeeze and excitation (SE) pool module, and the multi-attention fusion (MAF) module. First, the CTB is designed to capture the remote dependency and local multi-scale receptive field information by using the standard convolution, the dilated convolution, and the transformer operation. Second, to extract feature information from different angles, we construct the SE pool module, which not only extracts strong semantic features and context features simultaneously but also uses the SE normalization to adaptively fuse features and adjust feature distribution. Third, the MAF module is proposed to combine the global context information, channel information, and voxel-wise local spatial information. Besides, we adopt the up-sampling auxiliary paths to supplement the multi-scale information. Main results. The experimental results show that the method has better or more competitive segmentation performance than several advanced methods on three datasets. The best segmentation metric scores are as follows: DSC of 0.781, HD95 of 3.044, precision of 0.798, and sensitivity of 0.857. Comparative experiments based on bimodal and single modal indicate that bimodal input provides more sufficient and effective information for improving tumor segmentation performance. Ablation experiments verify the effectiveness and significance of each module. Significance. We propose a new network for 3D H&N tumor segmentation in FDG-PET/CT images, which achieves high accuracy. [ABSTRACT FROM AUTHOR]

Background: Head and neck tumors (HNT) are tumors of the paranasal sinuses, the salivary glands and the upper aerodigestive tract. RIN1 is a Ras effector protein regulating epithelial cell properties and has been implicated in a number of cancers. Method: The aim of this study was to investigate the expression of RIN1 in head and neck tumors. RIN1 expression was assessed using quantitative real-time PCR (qRT-PCR) and immunohistochemical staining on archival head and neck tissue samples between 2014 and 2020. Results: RIN1 expression was low in tissue samples as compared with the normal head and neck tissues. High and low RIN1 levels were compared with ages ≤40, >40 in the head and neck tumors of p-value 0.02. There was a significant difference with p-values of 0.001 when poor and well-moderate malignant tumors were compared. Conclusion: Our data suggests that RIN1may play an important role in head and neck tumor progression and that its expression may provide baseline data to facilitate identification of new molecular targeted therapeutics. [ABSTRACT FROM AUTHOR]

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Objectives: The aim of this systematic review was to estimate the osteoradionecrosis rate in patients with head and neck cancer due to teeth extraction performed before radiotherapy and to identify possible risk factors. Material and Methods: PRISMA protocol was used to evaluate and present the results. PubMed, Scopus and Web of Science were used as search engines: English full‐length papers of clinical studies, in peer‐reviewed journals, were investigated. Cumulative meta‐analysis was performed with a random effects model (PROSPERO registration code: CRD42018079986). Results: Among 2,020 records screened, 8 were included in this review. Sixteen of 494 patients who underwent tooth extraction before radiotherapy developed osteoradionecrosis, with an osteoradionecrosis incidence of 2.2% (95% Confidence of Interval = 0.6–3.9, p <.185, I2 = 3,044%). All cases were reported in the mandible. No other clinical risk factor for osteoradionecrosis was detected. Conclusions: Even if it is generally recommended to remove oral foci before radiotherapy, this systematic review confirmed that teeth extractions before radiotherapy represent a risk factor for osteoradionecrosis; the considerable amount of missing data prevented us from identifying other possible risk factors for osteoradionecrosis onset. Major efforts should be done to perform sounder methodological clinical investigations. [ABSTRACT FROM AUTHOR]

Salivary gland malignancies (SGMs) account for less than 5% of new diagnoses in head and neck tumors. If feasible, surgery is the preferred treatment modality. Nevertheless, some malignancies have a tendency of recurrence, with possible distant metastasis. Alternative treatment strategies, such as primary radiation or chemotherapeutics, often present low response rates. As a result, there is an unmet need for novel therapeutic approaches. Nowadays, target-based therapies (e.g., small inhibitors and immunotherapy) are used by the medical oncologist for possible treatment of advanced SGMs. Based on recent published trials, some novel treatments may provide additional disease control for some patients. However, sample sizes are small, the general findings are unsatisfactory, and a lot of uncertainties remain to be elucidated. Nevertheless, research shows that patients do not benefit from blind administration of systemic treatments and therefore a more personalized approach is highly needed. The aim of this review paper is to summarize the most recent advances in the biological understanding and molecular pathways of salivary gland cancers, the association of these pathways with the current treatments used and their implications for more personalized targeted-based therapies. [ABSTRACT FROM AUTHOR]

Purpose: Patients with head and neck cancer (HNC) describe eating as more than a physical activity for nutrition and calories. After treatment for HNC, patients report a changed social experience around food, with eating and drinking in front of family and friends depicted as a challenge. However, there is limited research exploring how patients with HNC adapt and cope with social eating difficulties. This study aims to explore patients' experiences and perceptions of social eating and drinking following treatment for HNC.Methods: A qualitative research design using semi-structured interviews was employed to understand the experiences of social eating of patients living with and beyond HNC. Reflexive thematic analysis was used to inductively develop key themes from the data.Results: Fourteen interviews were conducted with patients, and two key themes were identified: (1) "Social eating became a conscious process" and (2) "Strategies to maximise social eating participation". To maximise social eating enjoyment, patients attempted to minimise the attention on their eating function and the fuss created around food. Patients with HNC established psychological and cognitive adaptations to manage expectations and promote positive participation in social eating.Conclusion: This paper identifies key barriers limiting or diminishing social eating for patients with HNC; including being self-conscious, lack of understanding from others and functional issues with eating and drinking. This research highlights the need to raise awareness of social eating challenges and for the social dimensions of eating to be addressed through family-centred, supportive holistic interventions implemented early in the patient's cancer journey. [ABSTRACT FROM AUTHOR]

Objectives: Electrochemotherapy uses electric fields to facilitate the influx of chemotherapy into cancer cells, producing a targeted effect. For head and neck cancer, it is mainly used for palliation of non-skin-origin metastases. It is used infrequently in the UK. This paper presents our experience and a UK survey to identify its frequency of use. Methods: Between 2016 and 2019, a prospective database was created and reviewed. Only patients with non-skin-origin metastatic head and neck cancer, with no other palliative options, were included. Survival length, complications and symptomatic benefit were assessed. The survey was conducted via e-mail. Results: Five patients were included: three with squamous cell carcinoma, one with esthesioneuroblastoma and one with hepatocellular carcinoma. Survival ranged from 1 month to over 20 months. Minor complications were seen. Only 15 out of 69 UK head and neck multidisciplinary teams offer electrochemotherapy. Conclusion: Electrochemotherapy is a well-tolerated adjunct to standard palliation of metastatic head and neck cancer, and is offered by a limited number of UK multidisciplinary teams. [ABSTRACT FROM AUTHOR]

Background: Head and neck cancers (HNC) are strongly associated with malnutrition. This systematic review aimed to investigate the optimal frequency of individualised nutrition counselling (INC) pre‐, peri‐ and post‐treatment for patients with HNC. Methods: Pubmed, EMBASE, Cinahl and Scopus were searched from inception through to April 2020 to identify randomised controlled trials (RCTs) that focused on the INC frequency for adult patients with HNC (Registration no. 178868). The outcomes assessed were nutritional status, dietary intake, weight change, treatment interruptions, unplanned hospital admissions, quality of life, complications and morbidity. Certainty of evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation (GRADE). Results: Four RCTs were identified with five papers (n = 500 total participants). The certainty of evidence was 'high' for nutritional status and quality of life, 'moderate' for treatment interruptions and unplanned hospital admissions, and 'low' for percentage weight change, complications/morbidity and dietary intake. Compared to control groups, there were consistent improvements for nutritional status, quality of life, treatment interruptions, unplanned hospital admissions, dietary intake, percentage weight change and morbidity when weekly INC was provided peri‐treatment and fortnightly INC was provided post‐treatment. No statistical significance was found for treatment interruptions, dietary intake and weight change when INC was provided fortnightly peri‐treatment only. There were no RCTs in the current review that offered INC pre‐treatment. Conclusions: This systematic review shows beneficial effects with weekly INC peri‐treatment and fortnightly INC post‐treatment for patients with HNC in all outcomes studied. Future research should focus on models of care to address the optimal frequency of pre‐treatment INC as well as the duration of post‐treatment INC. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this systematic review was to incorporate the information published on metastatic lesions in the in the oral and maxillofacial region into a comprehensive analysis of their demographic, clinical, and imaginological features and survival rate. Materials and methods: An electronic search was undertaken in the subsequent databases: PubMed, Web of Science, Scopus, EMBASE, and LILACS. All papers included were case reports or case series. Absolute and relative frequencies were obtained by descriptive analysis. Overall survival was defined by the Kaplan–Meier method. Results: This systematic review identified 217 studies from 33 countries, comprising 348 cases. Male individuals were more affected (n = 199/57.68%) in the 5th to 7th decades of life. The most usual primary site was the lung in men (n = 49/14.08%) and the breast in women (n = 40/11.49%). Jawbones were affected in 183 cases (53.19%), with the posterior mandible (n = 96/66.66%) representing the preferred site. In soft tissues, the gingiva (n = 80/23.25%) was more affected. Clinical presentation was a nodular mass with or without ulceration (n = 280/85.89%). Imaginological examinations revealed radiolucent/hypodense lesions (n = 115/59.28%). The mean survival time was eight months. Conclusion: Despite the rare occurrence of metastatic lesions in the oral and maxillofacial region, the current systematic review offers substantial data that could assist clinicians and surgeons. [ABSTRACT FROM AUTHOR]

By focusing on metabolic and morphological tissue properties respectively, FluoroDeoxyGlucose (FDG)-Positron Emission Tomography (PET) and Computed Tomography (CT) modalities include complementary and synergistic information for cancerous lesion delineation and characterization (e.g. for outcome prediction), in addition to usual clinical variables. This is especially true in Head and Neck Cancer (HNC). The goal of the HEad and neCK TumOR segmentation and outcome prediction (HECKTOR) challenge was to develop and compare modern image analysis methods to best extract and leverage this information automatically. We present here the post-analysis of HECKTOR 2nd edition, at the 24th International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2021. The scope of the challenge was substantially expanded compared to the first edition, by providing a larger population (adding patients from a new clinical center) and proposing an additional task to the challengers, namely the prediction of Progression-Free Survival (PFS). To this end, the participants were given access to a training set of 224 cases from 5 different centers, each with a pre-treatment FDG-PET/CT scan and clinical variables. Their methods were subsequently evaluated on a held-out test set of 101 cases from two centers. For the segmentation task (Task 1), the ranking was based on a Borda counting of their ranks according to two metrics: mean Dice Similarity Coefficient (DSC) and median Hausdorff Distance at 95th percentile (HD95). For the PFS prediction task, challengers could use the tumor contours provided by experts (Task 3) or rely on their own (Task 2). The ranking was obtained according to the Concordance index (C-index) calculated on the predicted risk scores. A total of 103 teams registered for the challenge, for a total of 448 submissions and 29 papers. The best method in the segmentation task obtained an average DSC of 0.759, and the best predictions of PFS obtained a C-index of 0.717 (without relying on the provided contours) and 0.698 (using the expert contours). An interesting finding was that best PFS predictions were reached by relying on DL approaches (with or without explicit tumor segmentation, 4 out of the 5 best ranked) compared to standard radiomics methods using handcrafted features extracted from delineated tumors, and by exploiting alternative tumor contours (automated and/or larger volumes encompassing surrounding tissues) rather than relying on the expert contours. This second edition of the challenge confirmed the promising performance of fully automated primary tumor delineation in PET/CT images of HNC patients, although there is still a margin for improvement in some difficult cases. For the first time, the prediction of outcome was also addressed and the best methods reached relatively good performance (C-index above 0.7). Both results constitute another step forward toward large-scale outcome prediction studies in HNC. [Display omitted] • The paper describes the second edition of the HECKTOR challenge. • New data (total of 325 cases from 6 centers). • Fully novel task for outcome prediction in synergy with the tumor segmentation task. • Strong participation and high performance (DSC > 0.77, C-index > 0.71). • Various post-challenge analyses, e.g. ranking robustness, ensembling, influence of tumor size on performance. [ABSTRACT FROM AUTHOR]

Objectives: The number of citations an article receives is an important indication of its impact. The main objectives of this investigation provide readers with a practical guide in evaluating head and neck oncology literature and determine the characteristics of trends in ORL. Methods: This was a retrospective bibliometric analysis that did not involve human participant. The Thomson Reuters Web of Science was searched to determine the citations of all published HNO articles. Most cited 300 article analyzed and a total of 100 articles were included in our investigation under the topic search "Head AND NECK AND (cancer OR carcinoma OR oncology)." Articles include malignancies other than head and neck are excluded. The top 100 cited articles were selected and analyzed by 2 independent investigators. Country, Institution, First Author, Journal name, study design, cites per year information gathered and analyzed. Results: The journal with the highest number of top 100 cited articles was New England Journal Of Medicine with 19 paper, followed by The Journal of Clinical Oncology(17) and Cancer Research (12). The top article on the list (Radiotherapy plus cetuximab for squamous cell carcinoma of the head and neck-NEJM) has 2243 citations. A statistically significant association was found between the journal impact factor and the number of top 100 cited articles (P <.05). The United States had the highest number of articles (63). John Hopkins is differed from other institutions with 15 contributing articles. Conclusion: Our analysis provides an insight into the citation frequency of top cited articles published in HNO to help recognize the quality of the works, discoveries and the trends steering the study of HNO. This is also a modern reading list for young HNO scientist. [ABSTRACT FROM AUTHOR]

Objective. Head and neck (H&N) cancers are among the most prevalent types of cancer worldwide, and [18F]F-FDG PET/CT is widely used for H&N cancer management. Recently, the diffusion model has demonstrated remarkable performance in various image-generation tasks. In this work, we proposed a 3D diffusion model to accurately perform H&N tumor segmentation from 3D PET and CT volumes. Approach. The 3D diffusion model was developed considering the 3D nature of PET and CT images acquired. During the reverse process, the model utilized a 3D UNet structure and took the concatenation of 3D PET, CT, and Gaussian noise volumes as the network input to generate the tumor mask. Experiments based on the HECKTOR challenge dataset were conducted to evaluate the effectiveness of the proposed diffusion model. Several state-of-the-art techniques based on U-Net and Transformer structures were adopted as the reference methods. Benefits of employing both PET and CT as the network input, as well as further extending the diffusion model from 2D to 3D, were investigated based on various quantitative metrics and qualitative results. Main results. Results showed that the proposed 3D diffusion model could generate more accurate segmentation results compared with other methods (mean Dice of 0.739 compared to less than 0.726 for other methods). Compared to the diffusion model in 2D form, the proposed 3D model yielded superior results (mean Dice of 0.739 compared to 0.669). Our experiments also highlighted the advantage of utilizing dual-modality PET and CT data over only single-modality data for H&N tumor segmentation (with mean Dice less than 0.570). Significance. This work demonstrated the effectiveness of the proposed 3D diffusion model in generating more accurate H&N tumor segmentation masks compared to the other reference methods. [ABSTRACT FROM AUTHOR]

Purpose: Effective radiation therapy requires accurate segmentation of head and neck cancer, one of the most common types of cancer. With the advancement of deep learning, people have come up with various methods that use positron emission tomography-computed tomography to get complementary information. However, these approaches are computationally expensive because of the separation of feature extraction and fusion functions and do not make use of the high sensitivity of PET. We propose a new deep learning-based approach to alleviate these challenges. Methods: We proposed a tumor region attention module that fully exploits the high sensitivity of PET and designed a network that learns the correlation between the PET and CT features using squeeze-and-excitation normalization (SE Norm) without separating the feature extraction and fusion functions. In addition, we introduce multi-scale context fusion, which exploits contextual information from different scales. Results: The HECKTOR challenge 2021 dataset was used for training and testing. The proposed model outperformed the state-of-the-art models for medical image segmentation; in particular, the dice similarity coefficient increased by 8.78% compared to U-net. Conclusion: The proposed network segmented the complex shape of the tumor better than the state-of-the-art medical image segmentation methods, accurately distinguishing between tumor and non-tumor regions. [ABSTRACT FROM AUTHOR]

Recent studies have highlighted neurons and their associated Schwann cells (SCs) as key regulators of cancer development. However, the mode of their interaction with tumor cells or other components of the tumor microenvironment (TME) remains elusive. We established an SC-related 43-gene set as a surrogate for peripheral nerves in the TME. Head and neck squamous cell carcinoma (HNSCC) from The Cancer Genome Atlas (TCGA) were classified into low, intermediate and high SC score groups based on the expression of this gene set. Perineural invasion (PNI) and TGF-β signaling were hallmarks of SChigh tumors, whereas SClow tumors were enriched for HPV16-positive OPSCC and higher PI3K-MTOR activity. The latter activity was partially explained by a higher frequency of PTEN mutation and PIK3CA copy number gain. The inverse association between PI3K-MTOR activity and peripheral nerve abundance was context-dependent and influenced by the TP53 mutation status. An in silico drug screening approach highlighted the potential vulnerabilities of HNSCC with variable SC scores and predicted a higher sensitivity of SClow tumors to DNA topoisomerase inhibitors. In conclusion, we have established a tool for assessing peripheral nerve abundance in the TME and provided new clinical and biological insights into their regulation. This knowledge may pave the way for new therapeutic strategies and impart proof of concept in appropriate preclinical models. [ABSTRACT FROM AUTHOR]

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors of the head and neck, and its incidence is the highest all around the world. Intensive radiotherapy using computer-aided diagnosis is the best technique for the treatment of NPC. The key step of radiotherapy is the delineation of the target areas and organs at risk, that is, tumor images segmentation. We proposed the segmentation method of NPC image based on multi-scale cascaded fully convolutional network. It used cascaded network and multi-scale feature for a coarse-to-fine segmentation to improve the segmentation effect. In coarse segmentation, image blocks and data augmentation were used to compensate for the shortage of training samples. In fine segmentation, Atrous Spatial Pyramid Pooling (ASPP) was used to increase the receptive field and image feature transfer, which was added in the Dense block of DenseNet. In the process of upsampling, the features of multiple views were fused to reduce false positive samples. Additionally, in order to improve the class imbalance problem, Focal Loss was used to weight the loss function of tumor voxel distance because it could reduce the weight of background category samples. The cascaded network can alleviate the problem of gradient disappearance and obtain a smoother boundary. The experimental results were quantitatively analyzed by DSC, ASSD and F1_score values, and the results showed that the proposed method was effective for nasopharyngeal carcinoma segmentation compared with other methods in this paper. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the number, reasons and costs of surgical voice restoration related tracheoesophageal valve attendances over 36 months at a head and neck oncology unit. Method: Demographic, medical and valve related details from all patient contacts were recorded, including self-change information, urgent appointment information, modifications required and costs of prostheses. Results: Over 3 years, 99 patients underwent 970 valve changes. The main reasons for changes were central leakage, prophylactic change and self-change at home. Changes were significantly more frequent in the first 12 months (mean, 42 days) compared with longstanding patients (mean, 109.96). Intervals between changes were unpredictable; no predictive factors reached statistical significance. Mean expenditure on valves was £966.63 per week (including value added tax and in-house customisation). Conclusion: Valve lifespan is comparable with outcomes in similar units despite more pre-emptive and patient-led changes and more comprehensive data inclusion. Investigation into how patient satisfaction and costs relate to valve selection and units' service delivery models is needed. [ABSTRACT FROM AUTHOR]

Objective. Accurate and reproducible tumor delineation on positron emission tomography (PET) images is required to validate predictive and prognostic models based on PET radiomic features. Manual segmentation of tumors is time-consuming whereas semi-automatic methods are easily implementable and inexpensive. This study assessed the reliability of semi-automatic segmentation methods over manual segmentation for tumor delineation in head and neck squamous cell carcinoma (HNSCC) PET images. Approach. We employed manual and six semi-automatic segmentation methods (just enough interaction (JEI), watershed, grow from seeds (GfS), flood filling (FF), 30% SUVmax and 40%SUVmax threshold) using 3D slicer software to extract 128 radiomic features from FDG-PET images of 100 HNSCC patients independently by three operators. We assessed the distributional properties of all features and considered 92 log-transformed features for subsequent analysis. For each paired comparison of a feature, we fitted a separate linear mixed effect model using the method (two levels; manual versus one semi-automatic method) as a fixed effect and the subject and the operator as the random effects. We estimated different statistics—the intraclass correlation coefficient agreement (aICC), limits of agreement (LoA), total deviation index (TDI), coverage probability (CP) and coefficient of individual agreement (CIA)—to evaluate the agreement between the manual and semi-automatic methods. Main results. Accounting for all statistics across 92 features, the JEI method consistently demonstrated acceptable agreement with the manual method, with median values of aICC = 0.86, TDI = 0.94, CP = 0.66, and CIA = 0.91. Significance. This study demonstrated that JEI method is a reliable semi-automatic method for tumor delineation on HNSCC PET images. [ABSTRACT FROM AUTHOR]

Background: This investigation sought to cross validate the predictors of tongue pressure recovery in elderly patients' post-treatment for head and neck tumors, leveraging advanced machine learning techniques. Methods: By employing logistic regression, support vector regression, random forest, and extreme gradient boosting, the study analyzed an array of variables including patient demographics, surgery types, dental health status, and age, drawn from comprehensive medical records and direct tongue pressure assessments. Results: Among the models, logistic regression emerged as the most effective, demonstrating an accuracy of 0.630 [95% confidence interval (CI): 0.370–0.778], F1 score of 0.688 [95% confidence interval (CI): 0.435–0.853], precision of 0.611 [95% confidence interval (CI): 0.313–0.801], recall of 0.786 [95% confidence interval (CI): 0.413–0.938] and an area under the receiver operating characteristic curve of 0.626 [95% confidence interval (CI): 0.409–0.806]. This model distinctly highlighted the significance of glossectomy (p = 0.039), the presence of functional teeth (p = 0.043), and the patient's age (p = 0.044) as pivotal factors influencing tongue pressure, setting the threshold for statistical significance at p < 0.05. Conclusions: The analysis underscored the critical role of glossectomy, the presence of functional natural teeth, and age as determinants of tongue pressure in logistics regression, with the presence of natural teeth and the tumor site located in the tongue consistently emerging as the key predictors across all computational models employed in this study. [ABSTRACT FROM AUTHOR]

Purpose: This study aims to minimize monitor units (MUs) of intensity-modulated treatments in the Monaco treatment planning system while preserving plan quality by optimizing the "Minimum Segment Width" (MSW) and "Fluence Smoothing" parameters. Materials and Methods: We retrospectively analyzed 30 prostate, 30 gynecological, 15 breast cancer, 10 head and neck tumor, 11 radiosurgery, and 10 hypo-fractionated plans. Original prostate plans employed "Fluence Smoothing" = Off and were reoptimized with Low, Medium, and High settings. The remaining pathologies initially used MSW = 0.5 cm and were reoptimized with MSW = 1.0 cm. Plan quality, including total MU, delivery time, and dosimetric constraints, was statistically analyzed with a paired t-test. Results: Prostate plans exhibited the highest MU variation when changing "Fluence Smoothing" from Off to High (average ΔMU = -5.1%; P < 0.001). However, a High setting may increase overall MU when MSW = 0.5 cm. Gynecological plans changed substantially when MSW increased from 0.5 cm to 1.0 cm (average ΔMU = -29%; P < 0.001). Organs at risk sparing and planning target volumes remained within 1.2% differences. Replanning other pathologies with MSW = 1.0 cm affected breast and head and neck tumor plans (average ΔMU = -168.38, average Δt = -11.74 s, and average ΔMU = -256.56, average Δt = -15.05 s, respectively; all with P < 0.004). Radiosurgery and hypofractioned highly modulated plans did not yield statistically significant results. Conclusions: In breast, pelvis, head and neck, and prostate plans, starting with MSW = 1.0 cm optimally reduces MU and treatment time without compromising plan quality. MSW has a greater impact on MU than the "Fluence Smoothing" parameter. Plans with high modulation might present divergent behavior, requiring a case-specific analysis with MSW values higher than 0.5 cm. [ABSTRACT FROM AUTHOR]

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN+ fibroblasts and SPP1+ macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8+ T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma. Head and neck squamous cell carcinoma (HNSCC) is characterised with high heterogeneity and unfavourable prognosis. Here, the authors perform single cell transcriptomics to investigate the tumour microenvironment features of HNSCC initiation, progression, lymph node metastasis and recurrence. [ABSTRACT FROM AUTHOR]

Background: Our initial clinical study using simple diffusion kurtosis imaging (SDI), which simultaneously produces a diffusion kurtosis image (DKI) and an apparent diffusion coefficient map, confirmed the usefulness of SDI for tumor diagnosis. However, the obtained DKI had noticeable variability in the mean kurtosis (MK) values, which is inherent to SDI. We aimed to improve this variability in SDI by preprocessing with three different filters (Gaussian [G], median [M], and nonlocal mean) of the diffusion-weighted images used for SDI. Methods: The usefulness of filter parameters for diagnosis was examined in basic and clinical studies involving 13 patients with head and neck tumors. Results: The filter parameters, which did not change the median MK value, but reduced the variability and significantly homogenized the MK values in tumor and normal tissues in both basic and clinical studies, were identified. In the receiver operating characteristic curve analysis for distinguishing tumors from normal tissues using MK values, the area under curve values significantly improved from 0.627 without filters to 0.641 with G (σ = 0.5) and 0.638 with M (radius = 0.5). Conclusions: Thus, image pretreatment with G and M for SDI was shown to be useful for improving tumor diagnosis in clinical practice. [ABSTRACT FROM AUTHOR]

Advances in radiotherapy (RT) techniques, including intensity-modulated RT and image-guided RT, have allowed hypofractionation, increasing the fraction size over the conventional dose of 1.8-2.0 Gy. Hypofractionation offers advantages such as shorter treatment times, improved compliance, and under specific conditions, particularly in tumors with a low a/ß ratio, higher efficacy. It was initially explored for use in RT for prostate cancer and adjuvant RT for breast cancer, and its application has been extended to various other malignancies. Hypofractionated RT (HFRT) may also be effective in patients who are unable to undergo conventional treatment owing to poor performance status, comorbidities, or old age. The treatment of brain tumors with HFRT is relatively common because brain stereotactic radiosurgery has been performed for over two decades. However, re-irradiation of recurrent lesions and treatment of elderly or frail patients are areas under investigation. HFRT for head and neck cancer has not been widely used because of concerns regarding late toxicity. Thus, we aimed to provide a comprehensive summary of the current evidence for HFRT for brain tumors and head and neck cancer and to offer practical recommendations to clinicians faced with the challenge of choosing new treatment options. [ABSTRACT FROM AUTHOR]

Simple Summary: Next-generation sequencing of head and neck squamous cell carcinoma has revealed multiple new gene mutations, while simultaneously confirming the role of others in head and neck cancer tumorigenesis. The ever-expanding number of actionable druggable targets has fuelled a plethora of clinical trials assessing various pharmacotherapeutics in the management of this group of cancers. This review paper summarizes the state of play of molecular therapies used in head and neck oncology with particular focus dedicated to current FDA-approved drugs and emerging therapies undergoing advanced clinical trials. Head and neck cancer affects nearly 750,000 patients, with more than 300,000 deaths annually. Advances in first line surgical treatment have improved survival rates marginally particularly in developed countries, however survival rates for aggressive locally advanced head and neck cancer are still poor. Recurrent and metastatic disease remains a significant problem for patients and the health system. As our knowledge of the genomic landscape of the head and neck cancers continues to expand, there are promising developments occurring in molecular therapies available for advanced or recalcitrant disease. The concept of precision medicine is underpinned by our ability to accurately sequence tumour samples to best understand individual patient genomic variations and to tailor targeted therapy for them based on such molecular profiling. Not only is their purported response to therapy a factor of their genomic variation, but so is their inclusion in biomarker-driven personalised medicine therapeutic trials. With the ever-expanding number of molecular druggable targets explored through advances in next generation sequencing, the number of clinical trials assessing these targets has significantly increased over recent years. Although some trials are focussed on first-line therapeutic approaches, a greater majority are focussed on locally advanced, recurrent or metastatic disease. Similarly, although single agent monotherapy has been found effective in some cases, it is the combination of drugs targeting different signalling pathways that seem to be more beneficial to patients. This paper outlines current and emerging molecular therapies for head and neck cancer, and updates readers on outcomes of the most pertinent clinical trials in this area while also summarising ongoing efforts to bring more molecular therapies into clinical practice. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to review the clinical profile, management, and outcome of solid tumors in the head-and-neck region in children at our institute. Methods: We retrospectively reviewed children with head-and-neck solid tumors who were treated jointly under the departments of Pediatric Surgery and Otorhinolaryngology at our institute between 2016 and 2019. Results: In the study period, 10 children (6 males, 4 females) with a median age of 9.5 years (range 5 days–16 years) were treated by our unit. The patients had four tumors arising from the parotid, 2 from nose/naso-pharynx, 1 each from the tongue, submandibular gland, para-pharyngeal space, and infratemporal fossa. A majority (90%) of the patients underwent complete surgical excision of the tumor, preserving the loco-regional neurovascular structures to minimize postoperative morbidity. Malignant lesions were seen in 4 patients (2 rhabdomyosarcoma, 1 primitive neuro-ectodermal tumor, 1 mucoepidermoid carcinoma) and 6 patients had benign pathology (3 pleomorphic adenoma, 2 mature teratoma, 1 schwanomma). Additional therapy with chemotherapy and local radiotherapy was required in 3 out of 4 patients with malignant pathology. The median follow-up duration is 15 months. At last follow-up, all patients are alive and 9 out of 10 patients (90%) are disease-free. Conclusion: Our experience highlights rare and difficult tumors in the head-and-neck region in children. These tumors are not commonly managed by the pediatric surgeon in routine practice. The paper outlines the multi-modality management of these tumors, which is essential for an optimal outcome. [ABSTRACT FROM AUTHOR]

Objective: To report intensive care unit admission outcomes for head and neck cancer patients. Methods: A retrospective, observational cohort analysis of all Australian and New Zealander head and neck cancer patient intensive care unit admissions from January 2000 to June 2016, including data from 192 intensive care units. Results: There were 10 721 head and neck cancer patients, with a median age of 64 years (71.6 per cent male). Of admissions, 76.4 per cent were in public hospitals, 96.9 per cent were post-operative and 43.6 per cent required mechanical ventilation. Annual head and neck cancer admissions increased from 2000 to 2015 (from 348 to 1132 patients), but the overall proportion of intensive care unit admissions remained constant. In-hospital mortality was 2.7 per cent, and intensive care unit mortality was 0.7 per cent. The in-hospital mortality risk decreased three-fold (p < 0.001). Conclusion: Head and neck cancer patients had low mortality in the intensive care unit and in hospital. Risk of dying decreased despite more intensive care unit admissions. This is the first large-scale cohort study quantifying intensive care unit utilisation by head and neck cancer patients. It informs future work investigating alternatives to the intensive care unit for these patients. [ABSTRACT FROM AUTHOR]

Introduction: Meningiomas are the most common benign tumor of the central nervous system, accounting for 53.3% and 37.6% of all central nervous system tumors (1). The World Health Organization (WHO) Grade I meningiomas account for 80.5% of all meningiomas and are considered benign meningiomas; the WHO Grade II meningiomas account for 17.7% of all meningiomas and exhibit more aggressive behavior. Methods: In the period 2015-2022, a retrospective single-center study at the clinic of neurosurgery at the Clinical Center University of Sarajevo was conducted, which included patients with a pathohistological finding of WHO Grade I or II meningioma. Depending on the pathohistological grade of the tumor, patients were divided into two groups: Grade I and Grade II patients. Patients were examined clinically and radiologically. Clinical data collected included in the study: Gender, age, number of symptoms before surgery, whether patients were symptomatic or asymptomatic, pre-operative Eastern Cooperative Oncology Group,and Karnopsky performance scale. Pre-operative contrast magnetic resonance imaging of the head measured tumor volume, temporal muscle thickness (TMT), sagittal midline shift, and surrounding cerebral edema. Results: A total of 80 patients were enrolled in the study, 68 with WHO Grade I and 12 with WHO Grade II meningiomas. We found that patients with Grade I meningioma were younger and that the mean thickness of the temporal muscle was statistically thicker than in patients with Grade II. Increasing TMT was significantly and positively associated with Grade I tumors and negatively associated with Grade II tumors (p = 0.032). Conclusion: This study demonstrates that TMT can serve as a radiologic pre-operative indicator of meningioma grade and provide valuable guidance to neurosurgeons in surgical planning. Further studies are needed to validate these results. [ABSTRACT FROM AUTHOR]

Background and objectives Tumor size has been identified as a critical prognostic factor after pancreatic adenocarcinoma resection; however, this is still up for debate. The authors aimed to investigate the relationship between size and the results of pancreatic cancer resection. Patients and methods The studied subjects were divided into two groups as follows: group A: included 69 patients with pancreatic head/uncinate process tumor ≤3cm in size (maximum tumor diameter), subjected to elective pancreaticoduodenectomy, group B: included 87 patients with pancreatic head/uncinate process tumor >3cm in size (maximum tumor diameter), subjected to elective pancreaticoduodenectomy. From January 1, 2016 to December 31, 2021, at Menoufia University's National Liver Institute, we looked at the clinical, radiological, histological, and survival characteristics of tiny pancreatic cancer tumors (tumors ≤3 cm) in comparison to tumors above 3cm in size following pancreaticoduodenectomy. Calculations were made of overall cancer-specific survivals. Key factors were assessed for relevance in survival prediction using a Cox proportional hazards model. Results Among the tumors measured, 44.2% were ≤3cm in size 55.8% tumor were greater than 3cm in size. Larger tumors were associated with worse symptoms, higher Ca19.9, more progressive TNM stages, longer operative time, more blood transfusion, higher grade, more vascular invasion, more involved surgical margin, and more lymph node invasion. Our study compared data of 1-year survival rates of 79.1% and 50% as seen with ≤3cm tumor size and with above 3cm tumor size, respectively, also 2-year survival rates of 40.3% and 19.2% were seen with ≤3 cm tumor size and with above 3 cm tumor size, respectively, the result being statistically significant (P<0.001). Pancreatic ductal adenocarcinoma size above 3cm was associated with a worse prognosis together with histologic grading, vascular invasion, involved surgical margin, longer waiting list time, and progressive T stages. Conclusions Our findings suggest that early pancreatic ductal adenocarcinoma detection can have clinical benefits, which has positive implications for future screening strategies. Pancreatic ductal adenocarcinoma size above 3 cm is an independent predictive factor for poor prognosis after surgical resection and is associated with more aggressive tumor biology. Future trials are required to evaluate the survival benefit of neoadjuvant therapy in this subset of patients. [ABSTRACT FROM AUTHOR]

The purpose of this study was to review the diagnostic accuracy of MRI in detecting perineural spreading (PNS) of head and neck tumors using histopathological or surgical evidence from the afflicted nerve as the reference standard. Previous studies in the English language published in the last 30 years were searched from PubMed and Embase databases. We included studies that used magnetic resonance imaging (MRI) (with and without contrast enhancement) to detect PNS, as well as the histological or surgical confirmation of PNS, and that reported the exact numbers of patients required for assessing diagnostic accuracy. The outcome measures were sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Heterogeneity was assessed with the Higgins inconsistency test (I2). P-values smaller than 0.05 were considered statistically significant. A total of 11 retrospective studies were found, reporting 319 nerve samples from 245 patients. Meta-analytic estimates and their 95% confidence intervals were as follows: sensitivity 0.85 (0.70–0.95), specificity 0.85 (0.80–0.89), PPV 0.86 (0.70–0.94), and NPV 0.85 (0.71–0.93). We found statistically significant heterogeneity for sensitivity (I2 = 72%, p = 0.003) and PPV (I2 = 70%, p = 0.038), but not for NPV (I2 = 65%, p = 0.119) or specificity (I2 = 12%, p = 0.842). The most frequent MRI features of PNS were nerve enlargement and enhancement. Squamous cell carcinoma and adenoid cystic carcinoma were the most common tumor types, and the facial and trigeminal nerves were the most commonly affected nerves in PNS. Only a few studies provided examples of false MRI diagnoses. MRI demonstrated high diagnostic accuracy in depicting PNS of cranial nerves, yet this statement was based on scarce and heterogeneous evidence. [ABSTRACT FROM AUTHOR]

Ewing's sarcoma of bone is a rare malignant round cell tumor of the head and neck. The jaw, particularly the mandible, accounts for 3% of occurrences in the head and neck area. These tumors have been reported more frequently in men than in women, and they are usually between 5- and 20-year-old. It is difficult for clinicians and pathologists to make a diagnosis based solely on clinical and microscopic findings. Immunohistochemistry presents a plausible tool that can help the pathologist to arrive at a confirmatory diagnosis. This jaw tumor has the best prognosis when detected and treated early in the disease course, so the importance of timely, and accurate diagnosis cannot be overemphasized. The highlighting feature of this case report of an 18-year-old male that was primary detected by immunohistochemically as Ewing's sarcoma and is localized to the impacted left mandibular molars. [ABSTRACT FROM AUTHOR]

High mortality in head and neck squamous cell carcinoma (HNSCC) is due to recurrence, metastasis, and radiochemotherapy (RCT) resistance. These phenomena are related to the tumor cell subpopulation undergoing partial epithelial to mesenchymal transition (pEMT). Repeated transforming growth factor-beta (TGF-beta-1) treatment via the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway induces pEMT in SCC-25 HNSCC cells, and activates and stabilizes the pro-EMT transcription factor Slug. We investigated the growth inhibitory, cisplatin-sensitizing, and pro-apoptotic effects of p38 MAPK inhibition in cisplatin-resistant (SCC-25) and -sensitive (UPCI-SCC090) HNSCC cell lines, using two specific p38 MAPK inhibitors, SB202190 and ralimetinib. Cell viability was measured by MTT assay; cell cycle distribution and cell death were evaluated by flow cytometry; p38 MAPK phosphorylation, Slug protein stabilization, and p38 MAPK downstream targets were investigated by Western blot. p-p38 inhibitors achieved sustained phosphorylation of p38 MAPK (Thr180/Tyr182) and inhibition of its function, which resulted in decreased phosphorylation (Thr69/71) of the downstream target pATF2 in pEMT cells. Subsequently, the p-p38 inhibition resulted in reduced Slug protein levels. In accordance, p-p38 inhibition led to sensitization of pEMT cells to cisplatin-induced cell death; moreover, p-p38 inhibitor treatment cycles significantly decreased the viability of cisplatin-surviving cells. In conclusion, clinically relevant p38 inhibitors might be effective for RCT-resistant pEMT cells in HNSCC patients. [ABSTRACT FROM AUTHOR]

• Proposed an improved spatial attention method based on multi-modal data, which can make full use of the differences and complementarities between different modal data. • We analyze and discuss the influence of different weighting factors assigned to each modality on the fusion results. • In the encoding stage, each channel extracts feature information separately, and then performs fusion in the decoding stage to realize information complementarity • Special internal structure design can highlight the tumor region location information and suppress the non-tumor region location information and prevent model degradation effectively. • Experimental results show that our method improves the segmentation accuracy and has good generalization. Background and Objective: Achieving accurate and automated tumor segmentation plays an important role in both clinical practice and radiomics research. Segmentation in medicine is now often performed manually by experts, which is a laborious, expensive and error-prone task. Manual annotation relies heavily on the experience and knowledge of these experts. In addition, there is much intra- and interobserver variation. Therefore, it is of great significance to develop a method that can automatically segment tumor target regions. Methods: In this paper, we propose a deep learning segmentation method based on multimodal positron emission tomography-computed tomography (PET-CT), which combines the high sensitivity of PET and the precise anatomical information of CT. We design an improved spatial attention network(ISA-Net) to increase the accuracy of PET or CT in detecting tumors, which uses multi-scale convolution operation to extract feature information and can highlight the tumor region location information and suppress the non-tumor region location information. In addition, our network uses dual-channel inputs in the coding stage and fuses them in the decoding stage, which can take advantage of the differences and complementarities between PET and CT. Results: We validated the proposed ISA-Net method on two clinical datasets, a soft tissue sarcoma(STS) and a head and neck tumor(HECKTOR) dataset, and compared with other attention methods for tumor segmentation. The DSC score of 0.8378 on STS dataset and 0.8076 on HECKTOR dataset show that ISA-Net method achieves better segmentation performance and has better generalization. Conclusions: The method proposed in this paper is based on multi-modal medical image tumor segmentation, which can effectively utilize the difference and complementarity of different modes. The method can also be applied to other multi-modal data or single-modal data by proper adjustment. [ABSTRACT FROM AUTHOR]

• The paper describes the first challenge on head and neck tumor segmentation in PET/CT. • Training (n = 201 , 4 centers) and test sets (n = 53 , 1 unseen center) amount to 254 cases. • All ground truth segmentations underwent cleaning to ensure quality and homogeneity. • The winning team obtained a DSC of 0.759, showing a larg improvement over the baseline. • Additional post-challenge analyses (e.g. false positives analysis, ranking stability). [Display omitted] This paper relates the post-analysis of the first edition of the HEad and neCK TumOR (HECKTOR) challenge. This challenge was held as a satellite event of the 23rd International Conference on Medical Image Computing and Computer-Assisted Intervention (MICCAI) 2020, and was the first of its kind focusing on lesion segmentation in combined FDG-PET and CT image modalities. The challenge's task is the automatic segmentation of the Gross Tumor Volume (GTV) of Head and Neck (H&N) oropharyngeal primary tumors in FDG-PET/CT images. To this end, the participants were given a training set of 201 cases from four different centers and their methods were tested on a held-out set of 53 cases from a fifth center. The methods were ranked according to the Dice Score Coefficient (DSC) averaged across all test cases. An additional inter-observer agreement study was organized to assess the difficulty of the task from a human perspective. 64 teams registered to the challenge, among which 10 provided a paper detailing their approach. The best method obtained an average DSC of 0.7591, showing a large improvement over our proposed baseline method and the inter-observer agreement, associated with DSCs of 0.6610 and 0.61, respectively. The automatic methods proved to successfully leverage the wealth of metabolic and structural properties of combined PET and CT modalities, significantly outperforming human inter-observer agreement level, semi-automatic thresholding based on PET images as well as other single modality-based methods. This promising performance is one step forward towards large-scale radiomics studies in H&N cancer, obviating the need for error-prone and time-consuming manual delineation of GTVs. [ABSTRACT FROM AUTHOR]

Objective. Head and neck (H&N) cancers are prevalent globally, and early and accurate detection is absolutely crucial for timely and effective treatment. However, the segmentation of H&N tumors is challenging due to the similar density of the tumors and surrounding tissues in CT images. While positron emission computed tomography (PET) images provide information about the metabolic activity of the tissue and can distinguish between lesion regions and normal tissue. But they are limited by their low spatial resolution. To fully leverage the complementary information from PET and CT images, we propose a novel and innovative multi-modal tumor segmentation method specifically designed for H&N tumor segmentation. Approach. The proposed novel and innovative multi-modal tumor segmentation network (LSAM) consists of two key learning modules, namely L2-Norm self-attention and latent space feature interaction, which exploit the high sensitivity of PET images and the anatomical information of CT images. These two advanced modules contribute to a powerful 3D segmentation network based on a U-shaped structure. The well-designed segmentation method can integrate complementary features from different modalities at multiple scales, thereby improving the feature interaction between modalities. Main results. We evaluated the proposed method on the public HECKTOR PET-CT dataset, and the experimental results demonstrate that the proposed method convincingly outperforms existing H&N tumor segmentation methods in terms of key evaluation metrics, including DSC (0.8457), Jaccard (0.7756), RVD (0.0938), and HD95 (11.75). Significance. The innovative Self-Attention mechanism based on L2-Norm offers scalability and is effective in reducing the impact of outliers on the performance of the model. And the novel method for multi-scale feature interaction based on Latent Space utilizes the learning process in the encoder phase to achieve the best complementary effects among different modalities. [ABSTRACT FROM AUTHOR]

This study aimed to evaluate the optimal extent of lymphadenectomy in patients with nonfunctioning pancreatic neuroendocrine neoplasms. We retrospectively analyzed the clinicopathological data of patients with nonfunctioning pancreatic neuroendocrine neoplasms who underwent surgical resection. We investigated the frequency of metastases at each lymph node station according to tumor location and analyzed the factors contributing to poor overall survival (OS) and disease-free survival (DFS). Overall, data of 84 patients were analyzed. Among patients with pancreatic head tumors, metastases at stations 8, 13, and 17 were found in one (3.1%), four (12.5%), and three (9.3%) patients, respectively. However, none of the other stations showed metastases. For pancreatic body and tail tumors, metastases only at station 11 were found in two (5.1%) patients. Additionally, multivariate DFS and OS analyses showed that lymph node metastasis was the only independent prognostic factor. In conclusion, lymph node metastasis near the primary tumor was the only independent factor of poor prognosis in patients with nonfunctioning pancreatic neuroendocrine neoplasms after undergoing curative surgery. Peri-pancreatic lymphadenectomy might be recommended for nonfunctioning pancreatic neuroendocrine neoplasms. [ABSTRACT FROM AUTHOR]

Background: Optimum management of the N0 neck is unresolved in parotid salivary gland cancer. Sentinel node biopsy (SNB) can reliably detect microscopic lymph node metastasis and its´ clinical use is increasing for head and neck tumors. The object of this study was to establish whether the technique is applicable to detect distribution of sentinel nodes for parotid tumors. Materials and Methods: Prosepective observational study in 30 patients with benign or low‐grade T1‐T2N0 malignant tumors in the parotid gland planned for surgical treatment. Distribution of SN was detected with a preoperative ultrasound‐guided peritumoral injection with a technetium‐99 (Tc‐99 m) laballed tracer followed by a SPECT–CT and intraoperative measurement in the neck and parotidal tissue. In patients with cytologically suspected malignant tumor or highly unclerar cytology, SNB was also performed. Results: Sentinel nodes (SNs) were detected in 26/30 cases. Out of these, 7 presented with only one SN, whereas multiple sentinel nodes where detected in 19 cases. No SNs were found in neck level 1. SN was detected in level 5 independent of tumor location within the parotid gland. An intraparotidal distribution of SNs was more frequent in larger tumors. Conclusions: The use of SN‐technique in the planning of surgical treatment of parotid tumors seems feasible. It may be of clinical value for patients with parotid cancer to enable a more accurate staging and to detect occult metastasis in the SNs within the parotid as well as in the neck, enabaling the possibility to surgically remove all positive SNs at primary surgery and with reduced surgical morbidity. [ABSTRACT FROM AUTHOR]

Background: FLASH radiotherapy (RT) is a novel method for delivering ionizing radiation, which has been shown in preclinical studies to have a normal tissue sparing effect and to maintain anticancer efficacy as compared to conventional RT. Treatment of head and neck tumors with conventional RT is commonly associated with severe toxicity, hence the normal tissue sparing effect of FLASH RT potentially makes it especially advantageous for treating oral tumors. In this work, the objective was to study the adverse effects of dogs with spontaneous oral tumors treated with FLASH RT. Methods: Privately-owned dogs with macroscopic malignant tumors of the oral cavity were treated with a single fraction of ≥30Gy electron FLASH RT and subsequently followed for 12 months. A modified conventional linear accelerator was used to deliver the FLASH RT. Results: Eleven dogs were enrolled in this prospective study. High grade adverse effects were common, especially if bone was included in the treatment field. Four out of six dogs, who had bone in their treatment field and lived at least 5 months after RT, developed osteoradionecrosis at 3-12 months post treatment. The treatment was overall effective with 8/11 complete clinical responses and 3/11 partial responses. Conclusion: This study shows that single-fraction high dose FLASH RT was generally effective in this mixed group of malignant oral tumors, but the risk of osteoradionecrosis is a serious clinical concern. It is possible that the risk of osteonecrosis can be mitigated through fractionation and improved dose conformity, which needs to be addressed before moving forward with clinical trials in human cancer patients. [ABSTRACT FROM AUTHOR]

Simple Summary: The conventional methods that seek to predict clinical treatment response are based on the number of circulating tumor cells (CTCs) present in liquid biopsies or genetic profiling of extracted CTCs. This paper presents a novel process by which CTCs can be extracted from blood samples taken from head and neck cancer patients and then expanded ex vivo to form organoids that can be tested with a panel of anti-cancer treatments. The resulting drug sensitivity profiles derived from cisplatin treatment of organoids were subsequently found to correlate with clinical treatment response to cisplatin in patients. CTCs extracted from liquid biopsies for ex vivo expansion negates the need for complicated and potentially risky biopsies of tumor material, thereby supporting the application of this procedure for checkups and treatment monitoring. The advanced-stage head and neck cancer (HNC) patients respond poorly to platinum-based treatments. Thus, a reliable pretreatment method for evaluating platinum treatment response would improve therapeutic efficiency and outcomes. This study describes a novel strategy to predict clinical drug responses in HNC patients by using eSelect, a lab-developed biomimetic cell culture system, which enables us to perform ex vivo expansion and drug sensitivity profiling of circulating tumor cells (CTCs). Forty liquid biopsies were collected from HNC patients, and the CTCs were expanded ex vivo using the eSelect system within four weeks. Immunofluorescence staining confirmed that the CTC-derived organoids were positive for EpCAM and negative for CD45. Two illustrative cases present the potential of this strategy for evaluating treatment response. The statistical analysis confirmed that drug sensitivity in CTC-derived organoids was associated with a clinical response. The multivariant logistic regression model predicted that the treatment accuracy of chemotherapy responses achieved 93.75%, and the area under the curves (AUCs) of prediction models was 0.8841 in the whole dataset and 0.9167 in cisplatin specific dataset. In summary, cisplatin sensitivity profiles of patient-derived CTCs expanded ex vivo correlate with a clinical response to cisplatin treatment, and this can potentially underpin predictive assays to guide HNC treatments. [ABSTRACT FROM AUTHOR]

Simple Summary: Daily adaptive proton therapy will allow the unique properties of protons to be fully exploited. Cone-beam CT (CBCT) is the primary imaging modality considered for daily adaptation due to its low cost, compactness, and thus wide availability. However, there are proton therapy centers equipped with CT-on-rails or considering the installation of such scanners for the so-called "near-treatment-position" imaging. Our study addresses the critical question, whether CT-on-rails is a suitable modality for daily adaptive proton therapy. Although high precision accuracies have been claimed for CT-on-rails, no quantitative study of the adaptation efficacy with increased treatment execution uncertainties has ever been performed. In this paper, we demonstrate that the expected uncertainties will not affect the dosimetric efficacy of the adaptation based on in-room CT for head and neck cancers, and thus CT-on-rails applied to "near-treatment-position" imaging is a suitable modality for online adaptive proton therapy. Purpose: To compare the efficacy of CT-on-rails versus in-room CBCT for daily adaptive proton therapy. Methods: We analyzed a cohort of ten head-and-neck patients with daily CBCT and corresponding virtual CT images. The necessity of moving the patient after a CT scan is the most significant difference in the adaptation workflow, leading to an increased treatment execution uncertainty σ. It is a combination of the isocenter-matching σi and random patient movements induced by the couch motion σm. The former is assumed to never exceed 1 mm. For the latter, we studied three different scenarios with σm = 1, 2, and 3 mm. Accordingly, to mimic the adaptation workflow with CT-on-rails, we introduced random offsets after Monte-Carlo-based adaptation but before delivery of the adapted plan. Results: There were no significant differences in accumulated dose-volume histograms and dose distributions for σm = 1 and 2 mm. Offsets with σm = 3 mm resulted in underdosage to CTV and hot spots of considerable volume. Conclusion: Since σm typically does not exceed 2 mm for in-room CT, there is no clinically significant dosimetric difference between the two modalities for online adaptive therapy of head-and-neck patients. Therefore, in-room CT-on-rails can be considered a good alternative to CBCT for adaptive proton therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Human microbiome research is rapidly expanding, including a variety of clinical medicine and public health disciplines. Commensal microbiome has a significant impact on shaping homeostasis of the organism, as well as the development of pathological states. A number of studies indicate that changes in the human microbiome could determine an oncogenic effect by, among other things, inducing chronic inflammatory response, instigating cellular antiapoptotic signals or modulation of anticancer immunity. The presence of pathogenic species also contributes to the exacerbation of the complications of the treatment applied, such as radiation-induced oral mucositis, which is the most common side effect of the treatment. A better understanding of the interplay between oral microbiome and head and neck cancers might provide an important step towards a more effective treatment for this highly malignant tumor. The following review is a complex revision of the up-to-date research on the oral microbiome and its impact on the development of head and neck cancer and radiation-induced oral mucositis. Head and neck carcinoma is one of the most common human malignancy types and it ranks as the sixth most common cancer worldwide. Nowadays, a great potential of microbiome research is observed in oncology—investigating the effect of oral microbiome in oncogenesis, occurrence of treatment side effects and response to anticancer therapies. The microbiome is a unique collection of microorganisms and their genetic material, interactions and products residing within the mucous membranes. The aim of this paper is to summarize current research on the oral microbiome and its impact on the development of head and neck cancer and radiation-induced oral mucositis. Human microbiome might determine an oncogenic effect by, among other things, inducing chronic inflammatory response, instigating cellular antiapoptotic signals, modulation of anticancer immunity or influencing xenobiotic metabolism. Influence of oral microbiome on radiation-induced oral mucositis is expressed by the production of additional inflammatory cytokines and facilitates progression and aggravation of mucositis. Exacerbated acute radiation reaction and bacterial superinfections lead to the deterioration of the patient's condition and worsening of the quality of life. Simultaneously, positive effects of probiotics on the course of radiation-induced oral mucositis have been observed. Understanding the impact on the emerging acute radiation reaction on the composition of the microflora can be helpful in developing a multifactorial model to forecast the course of radiation-induced oral mucositis. Investigating these processes will allow us to create optimized and personalized preventive measures and treatment aimed at their formation mechanism. Further studies are needed to better establish the structure of the oral microbiome as well as the dynamics of its changes before and after therapy. It will help to expand the understanding of the biological function of commensal and pathogenic oral microbiota in HNC carcinogenesis and the development of radiation-induced oral mucositis. [ABSTRACT FROM AUTHOR]

Purpose: The association of NUCB-2/Nesfatin-1 with nasopharyngeal carcinoma (NPC) remains unclear. We clarified the role of NUCB-2/Nesfatin-1 in the development, progression and diagnosis of NPC. Materials and methods: In nasopharyngeal carcinoma cell lines (5-8 F, 6-10B, CNE1, CNE2 and NP69), western blotting, MTT, EdU and other techniques were performed to investigate the role of NUCB-2 in nasopharyngeal carcinoma. 70 tissue samples (39 NPC and 31 rhinitis) and 140 serum samples (including NPC, rhinitis, other head and neck tumors and healthy control) were included to explore the expression of NUCB-2 and its metabolite Nesfatin-1 in tissues or serum of patients with nasopharyngeal carcinoma. Results: NUCB-2 level in NPC tissue was higher than that in rhinitis tissue (P < 0.05). Suppression of NUCB-2 in the NPC cell line CNE2 inhibited proliferation and clone formation of the cells; on the contrary, improvement of NUCB-2 in the NPC cell line CNE1 promoted cell propagation and clone development. An elevated serum level of NUCB-2 in NPC patients was detected, compared to that in patients with other head and neck tumors, rhinitis or healthy donors. Determination of nesfatin-1 combined with EA-IgA, VCA-IgA and Rta-IgG in serum samples for NPC diagnosis reached a sensitivity of 93.6% and a specificity of 94.5%, while the positive and negative predictive value of this diagnostic model was 89.8% and 96.6%, and the accuracy yielded 94.2%. Conclusion: This study revealed that NUCB-2 could enhance proliferation of NPC cells and NUCB-2/nesfatin-1 has the potential to be a serological marker to aid early diagnosis of nasopharyngeal carcinoma. [ABSTRACT FROM AUTHOR]

We analyzed transcriptional data from 104 HPV+ (Human papillomavirus) HNSCC (head and neck squamous cell carcinoma) tumors together with two publicly available sources to identify highly robust transcriptional programs (modules) which could be detected consistently despite heterogeneous sequencing and quantification methodologies. Among 22 modules identified, we found a single module that naturally subclassifies HPV+ HNSCC tumors based on a bimodal pattern of gene expression, clusters all atypical features of HPV+ HNSCC biology into a single subclass, and predicts patient outcome in four independent cohorts. The subclass-defining gene set was strongly correlated with Nuclear factor kappa B (NF-κB) target expression. Tumors with high expression of this NF-κB module were rarely associated with activating PIK3CA alterations or viral integration, and also expressed higher levels of HPHPV E2 and had decreased APOBEC mutagenesis. Alternatively, they harbored inactivating alterations of key regulators of NF-κB, TNF receptor associated factor 3 (TRAF3), and cylindromatosis (CYLD), as well as retinoblastoma protein (RB1). HPV+ HNSCC cells in culture with experimental depletion of TRAF3 or CYLD displayed increased expression of the subclass-defining genes, as well as robust radio-sensitization, thus recapitulating both the tumor transcriptional state and improved treatment response observed in patient data. Across all gene sets investigated, methylation to expression correlations were the strongest for the subclass-defining, NF-κB-related genes. Increased tumor-infiltrating CD4+ T cells and increased Estrogen receptors alpha (ERa) expression were identified in NF-κB active tumors. Based on the relatively high rates of cure in HPV+ HNSCC, deintensification of therapy to reduce treatment-related morbidity is being studied at many institutions. Tumor subclassification based on oncogenic subtypes may help guide the selection of therapeutic intensity or modality for patients with HPV+ HNSCC. [ABSTRACT FROM AUTHOR]

Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignancy typically originating from the abdominal or pelvic cavity. DSRCT presenting as a primary head and neck tumor has rarely been described in the literature. We present three cases of DSRCT arising in the head and neck to further characterize its clinicopathological features. All three patients were male and aged 36, 30 and 17 years. The involved sites included the orbit (1 case) and submandibular gland (2 cases). The tumors ranged in size from 2.4 to 3.5 cm (mean, 2.1 cm). Histologically, all tumors showed irregular-shaped, variable-sized nests of small round cells deposited in an abundant desmoplastic stroma. Tumor cells contained scant amounts of eosinophilic cytoplasm and small hyperchromatic nuclei with inconspicuous nucleoli. Immunohistochemically, the tumors were positive for keratin (AE1/AE3) (3/3), desmin (3/3), vimentin (2/2), NSE (1/1) and EMA (1/1). Fluorescence in situ hybridization (FISH) analysis demonstrated the presence of EWSR1 and WT1 rearrangements in all three cases. All patients received surgery and adjuvant chemotherapy and/or radiotherapy. There was no evidence of recurrence and metastasis in two patients, and the third suffered lung metastasis. DSRCT arising in the head and neck represents an extremely rare condition. It is easily mistaken as poorly differentiated carcinoma due to similar morphology and expression of epithelial markers. Immunohistochemistry assay in conjunction with molecular detection of EWSR1::WT1 fusion will be helpful for arriving at an accurate diagnosis to avoid misdiagnosis and inappropriate treatment. [ABSTRACT FROM AUTHOR]

Animal experiments are often used to determine effects of drugs and other biological conditions on cancer progression, but poor accuracy and reproducibility of established tumor measurement methods make results unreliable. In orthotopic mouse models of head and neck cancer, tumor volumes approximated from caliper measurements are conventionally used to compare groups, but geometrical challenges make the procedure imprecise. To address this, we developed software to better measure these tumors by automated analysis of cone-beam computed tomography (CBCT) scans. This allows for analyses of tumor shape and growth dynamics that would otherwise be too inaccurate to provide biological insight. Monitoring tumor growth by calipers and imaging in parallel, we find that caliper measurements of small tumors are weakly correlated with actual tumor volume and highly susceptible to experimenter bias. The method presented provides a unique window to sources of error in a foundational aspect of preclinical head and neck cancer research and a valuable tool to mitigate them. [ABSTRACT FROM AUTHOR]

Introduction: Salivary gland tumors (SGT) represent 6 to 8 percent of head and neck tumors. The cytologic diagnosis of SGT is performed by fine-needle aspiration cytology (FNAC) with variable sensitivity and specificity. The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) categorizes the cytological results and provides the risk of malignancy (ROM). The aim of our study was to evaluate the cytological findings with the definitive pathological findings to assess the sensitivity, specificity, and diagnostic accuracy of FNAC in SGT according to MSRSGC classification. Method: An observational, retrospective, single-center study was carried out at a tertiary referral hospital over a period of 10 years. Patients that underwent FNAC for major SGT and that have undergone surgery to remove the tumor were included. A histopathological follow-up was performed on the surgically excised lesions. Results from the FNAC were categorized into one of the six MSRSGC categories. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy of FNAC for determining benign and malignant cases were calculated. Results: A total of 417 cases were analyzed. The cytological prediction of ROM was 10% in nondiagnostic, 12.12% in non-neoplastic, 3.58% in neoplasm benign group, 60% in AUS and SUMP groups, and 100% in suspicious and malignant group. The statistical analysis of sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy for determining benign cases was 99%, 55%, 94%, 93%, and 94%, respectively, and for determining malignant neoplasm was 54%, 99%, 93%, 94%, and 94%, respectively. Conclusion: In our hands, MSRSGC is highly sensitive for benign tumors and highly specific for malignant tumors. The low sensitivity to differentiate malignant from benign cases makes it necessary to apply an adequate anamnesis, physical examination, and imaging tests to consider surgical treatment in most cases. [ABSTRACT FROM AUTHOR]