Carotid Sinus Syndrome With Convulsive Syncope in a Patient With Head and Neck Cancer.

This case report provides a comprehensive overview of a unique case of a 64-year-old male patient with head and neck (H&N) cancer who initially presented with compressive convulsive syncope, an initial manifestation of carotid sinus syndrome (CSS). CSS is an autonomic nervous system disease that often manifests as hypotension, dizziness, cerebral ischemia, or syncope, usually in elderly patients. In this case, the patient's laryngeal cancer led to lymphedema and encasement of the bilateral carotid arteries, inducing CSS and resulting in recurrent episodes of hypotension and bradycardia. These symptoms were managed through the administration of atropine and transcutaneous pacemaker placement, suggesting a probable mixed type of CSS. The patient was discharged on long-term theophylline treatment for symptomatic control of bradycardia episodes. Despite the promising outcomes of CSS cases treated with pacemakers, the efficacy is not universal and limitations may arise, particularly in H&N cancer patients. Therefore, the patient was managed with theophylline rather than a pacemaker due to its non-invasiveness and effectiveness in temporarily managing CSS. Although rare, CSS should be considered in patients experiencing convulsive syncope alongside H&N malignancies. As the evidence and consensus regarding CSS treatment in H&N cancer patients are scarce, additional research is necessary to evaluate and compare available options. This abstract concludes by emphasizing the need for further research and case reports to establish a consensus on the optimal management approach for patients affected by CSS due to compression from H&N cancers.

Impact of Treatment Delay in Head and Neck Mucosal Melanoma on Overall Patient Survival.

Objectives Head and neck mucosal melanoma (HNMM) is a rare malignancy with high mortality. This study evaluates the impact of treatment delays on overall survival in HNMM. Design/Setting/Participants A retrospective review of patients with surgically managed HNMM treated with adjuvant radiation was performed from the 2004-2016 National Cancer Database. Main Outcome Measures Durations of diagnosis-to-treatment initiation (DTI), surgery-to-radiotherapy initiation (SRT), duration of radiotherapy (RTD), surgery-to-immunotherapy initiation (SIT), diagnosis-to-treatment end (DTE), and total treatment package (TTP) were calculated. Results A total of 1,011 patients (50.7% female, 90.5% Caucasian) met inclusion criteria. Median DTI, SRT, RTD, SIT, DTE, and TTP were 30, 49, 41, 102, 119, and 87 days, respectively. Only longer DTE was associated with decreased mortality (hazard ratio, 0.720; 95% confidence interval, 0.536-0.965; p = 0.028). Conclusion DTI, SRT, RTD, SIT, and TTP do not significantly affect overall survival in patients with HNMM who undergo surgery and adjuvant radiation. Longer DTE is associated with improved survival in this population. Level of Evidence 4.

Dosimetric evaluation of intensity modulated photon versus proton reirradiation of head and neck cancer.

BACKGROUND: Reirradiation of head and neck cancer (HNC) became more accessible in the last decade, owing to modern irradiation techniques which offer a reduction in treatment related toxicities. The aim of this paper was to comparatively evaluate the dosimetric aspects derived from intensity modulated photon vs. proton treatment planning in reirradiated HNC patients. METHODS: Six recurrent HNC patients were enrolled in this retrospective study. For each patient two treatment plans were created: one IMRT/VMAT and one IMPT plan. The prescribed dose for the second irradiation was between 50 and 70 Gy RBE. The study comparatively analyzed the CTV coverage, doses to organs at risk (OARs) and low doses received by the healthy tissue (other than OAR). RESULTS: Similar CTV coverage was achieved for photon vs proton plans, with the latter presenting better homogeneity in four cases. Maximum dose to CTV was generally higher for photon plans, with differences ranging from 0.3 to 1.9%. For parotid glands and body, the mean dose was lower for proton plans. A notable reduction of low dose to healthy tissue (other than OARs) could be achieved with protons, with an average of 60% and 64% for D10% and Dmean, respectively. CONCLUSION: The dosimetric comparison between photon and proton reirradiation of HNC showed a great need for treatment individualization, concluding that protons should be considered for reirradiation on an individual basis.

Establishing a role for the oral microbiome in infectious complications following major oral cavity cancer surgery.

Surgery forms the backbone of treatment for most locoregional or advanced oral cavity squamous cell carcinoma. Unfortunately, infectious complications (including orocutaneous fistulas) are common following such extensive surgery and can afflict over half of patients. These complications can lead to delays in adjuvant treatment, prolonged hospitalization, reconstructive failure, and decreased quality of life. The frequency and morbidity associated with infectious complications has led to the search for pre-disposing risk factors; and, several have been identified, including both patient (e.g. diabetes) and surgical (e.g. operative time) factors. However, these findings are inconsistently reproduced, and risk factor modification has had a limited impact on rates of infectious complications. This is striking given that the likely contaminant-the oral microbiome-is a well-studied microbial reservoir. Because many oral cavity cancer surgeries involve violation of oral mucosa and the spillage of the oral microbiome into normally sterile areas (e.g. the neck), variance in oral microbiome composition and function could underly differences in infectious complications. The goal of this perspective is to highlight 1) this knowledge gap and 2) opportunities for studies in this domain. The implication of this line of thought is that the identification of oral microbial dysbiosis in patients undergoing surgery for oral cavity cancer could lead to targeted pre-operative therapeutic interventions, decreased infectious complications, and improved patient outcomes.

Molecular pathways and targeted therapies in head and neck cancers pathogenesis.

The substantial heterogeneity exhibited by head and neck cancer (HNC), encompassing diverse cellular origins, anatomical locations, and etiological contributors, combined with the prevalent late-stage diagnosis, poses significant challenges for clinical management. Genomic sequencing endeavors have revealed extensive alterations in key signaling pathways that regulate cellular proliferation and survival. Initiatives to engineer therapies targeting these dysregulated pathways are underway, with several candidate molecules progressing to clinical evaluation phases, including FDA approval for agents like the EGFR-targeting monoclonal antibody cetuximab for K-RAS wild-type, EGFR-mutant HNSCC treatment. Non-coding RNAs (ncRNAs), owing to their enhanced stability in biological fluids and their important roles in intracellular and intercellular signaling within HNC contexts, are now recognized as potent biomarkers for disease management, catalyzing further refined diagnostic and therapeutic strategies, edging closer to the personalized medicine desideratum. Enhanced comprehension of the genomic and immunological landscapes characteristic of HNC is anticipated to facilitate a more rigorous assessment of targeted therapies benefits and limitations, optimize their clinical deployment, and foster innovative advancements in treatment approaches. This review presents an update on the molecular mechanisms and mutational spectrum of HNC driving the oncogenesis of head and neck malignancies and explores their implications for advancing diagnostic methodologies and precision therapeutics.

Nomenclature of the symptoms of head and neck cancer: a systematic scoping review.

Introduction: Evolution of a patient-reported symptom-based risk stratification system to redesign the suspected head and neck cancer (HNC) referral pathway (EVEREST-HN) will use a broad and open approach to the nomenclature and symptomatology. It aims to capture and utilise the patient reported symptoms in a modern way to identify patients' clinical problems more effectively and risk stratify the patient. Method: The review followed the PRISMA checklist for scoping reviews. A search strategy was carried out using Medline, Embase and Web of Science between January 1st 2012 and October 31st 2023. All titles, abstracts and full paper were screened for eligibility, papers were assessed for inclusion using predetermined criteria. Data was extracted pertaining to the aims, type of study, cancer type, numbers of patients included and symptoms, presenting complaints or signs and symptoms. Results: There were 9,331 publications identified in the searches, following title screening 350 abstracts were reviewed for inclusion and 120 were considered for eligibility for the review. 48 publications met the eligibility criteria and were included in the final review. Data from almost 11,000 HNC patients was included. Twenty-one of the publications were from the UK, most were retrospective examination of patient records. Data was extracted and charted according to the anatomical area of the head and neck where the symptoms are subjectively and objectively found, and presented according to lay terms for symptoms, clinical terms for symptoms and the language of objective clinical findings. Discussion: Symptoms of HNC are common presenting complaints, interpreting these along with clinical history, examination and risk factors will inform a clinician's decision to refer as suspected cancer. UK Head and Neck specialists believe a different way of triaging the referrals is needed to assess the clinical risk of an undiagnosed HNC. EVEREST-HN aims to achieve this using the patient history of their symptoms. This review has highlighted issues in terms of what is considered a symptom, a presenting complaint and a clinical finding or sign.

Proton beam therapy and dentofacial development in paediatric cancer patients: A scoping review.

Purpose: It is known that radiation to dentofacial structures during childhood can lead to developmental disturbances. However, this appears to be a relatively subordinated research subject. For this reason, this review aims to establish the current evidence base on the effect of PBT on dentofacial development in paediatric patients treated for cancer in the head and neck region. Materials and methods: A comprehensive search was undertaken to identify both published and unpublished studies or reports. A single reviewer completed initial screening of abstracts; 2 independent reviewers completed secondary screening and data extraction. A narrative synthesis was then conducted. Results: 82 records were screened in total, resulting in 11 included articles. These articles varied in terms of study design and reporting quality. Owing to both poor study reporting and limited patient numbers, it is not possible to determine the effect of cancer diagnosis, chronological age at treatment, radiation dose or treatment modality on the incidence of facial deformation or dental development anomalies. Conclusion: Disturbances in dentofacial development are an under-reported toxicity in paediatric cancer survivors treated with PBT to the head and neck. There is a need for more research on dentofacial toxicity reporting, focused on the impact of treatment age, radiation dose, concurrent therapies, and the subsequent impact on quality of life.

Diverse roles of dendritic cell and regulatory T cell crosstalk in controlling health and disease.

Dendritic cells (DCs) are specialized antigen-presenting cells for lymphocytes, including regulatory T (Treg) cells, a subset of CD4+ T cells expressing CD25 and Foxp3, a transcription factor. Treg cells maintain immunological self-tolerance in mice and humans, and suppress autoimmunity and other various immune responses such as tumor immunity, transplant rejection, allergy, responses to microbes, and inflammation. Treg cell proliferation is controlled by antigen-presenting DCs. On the other hand, Treg cells suppress the function of DCs by restraining DC maturation. Therefore, the interaction between DCs and Treg cells, DC-Treg crosstalk, could contribute to controlling health and disease. We recently found that unique DC-Treg crosstalk plays a role in several conditions. First, Treg cells are expanded in ultraviolet-B (UVB)-exposed skin by interacting with DCs, and the UVB-expanded Treg cells have a healing function. Second, manipulating DC-Treg crosstalk can induce effective acquired immune responses against SARS-CoV2 antigens without adjuvants. Third, Treg cells with a special feature interact with DCs in the tumor microenvironment of human head and neck squamous cell cancer, which may contribute to the prognosis. Understanding the underlying mechanisms of DC-Treg crosstalk may provide a novel strategy to control health and disease.

Carcinoma ex-pleomorphic adenoma of parotid gland presenting as a gigantic cervicofacial mass.

When neglected for a long time, salivary gland pleomorphic adenoma (PA) can attain a considerable size, increasing the patient's morbidity along with the risk of malignant transformation. Very few case reports are available describing PA of the parotid glands presenting as a large cervicofacial mass. We report a case of epithelial myoepithelial carcinoma -a rare subtype of carcinoma ex-PA (Ca-Ex-PA) of non-luminal differentiation, that developed over a long period in a primary PA of the parotid gland and presented as a giant cervicofacial mass.

Efficacy of probiotics in the treatment of oral mucositis in head and neck cancer patients: a systematic review and meta-analysis.

OBJECTIVES: To assess the effect of probiotics in oral mucositis induced by chemotherapy or radiotherapy on patients with head and neck cancer (HNC). METHODS: The PubMed, Embase, Cochrane Library, Clinical trials were screened from January 2010 to April 2024. Randomized clinical trials (RCTs) comparing the efficacy of probiotics in treatment of oral mucositis in HNC were eligible. Outcomes of interest were incidence of oral mucositis and severe oral mucositis. The PROSPERO registration number was 42022384685. The Cochrane risk-of-bias tool (RoB2) was used to assess methodological quality of studies and GRADE criteria (GRADEpro) was applied for rating the certainty of evidence. Meta-analysis was performed by using RevMan 5.4. RESULTS: A total of eight RCTs comprising 691 patients with HNC were included in this meta-analysis. Probiotics administration significantly reduced the incidence of SOM (RR = 0.60, 95%CI: 0.46-0.78, P = 0.0002). However, it showed no distinct advantage in reducing the overall incidence of oral mucositis (RR = 0.88, 95%CI: 0.76-1.02, P = 0.08). Subgroup analysis found more benefit for reducing SOM in multi-bacterial treated group (RR = 0.35, 95%CI: 0.17-0.73, P = 0.005) than mono-bacterial treated group (RR = 0.69, 95%CI: 0.58-0.82, P < 0.0001). In Addition, probiotics could reduce the incidence of SOM in nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (RR = 0.43, 95%CI: 0.26-0.70, P = 0.0006). CONCLUSION: Probiotics reduced the incidence of SOM caused by chemotherapy or radiotherapy for HNC. The multi-bacterial combination therapy was more efficacious than the mono-bacterial therapy. Moreover, probiotics also reduced the incidence of SOM in nasopharyngeal carcinoma. However, the advantage of probiotics had not been established in the overall incidence of OM.

Primary Tumour Detection in Carcinoma of Unknown Primary with Transoral Robotic Surgery (TORS) Tongue Base Mucosectomy: A Meta-analysis.

BACKGROUND: Head and neck carcinoma of unknown primary (CUP) represents a challenging diagnostic process when standard work-up fails to identify the primary tumour site. The aim of this systematic review and meta-analysis was to evaluate the diagnostic utility and complication profile of transoral robotic surgery (TORS) tongue base mucosectomy (TBM) in the management of CUP. PATIENTS AND METHODS: An electronic database search was performed in the EMBASE, MEDLINE, PubMed and Cochrane databases. A meta-analysis of proportions was performed to obtain an estimate of the overall proportion for the detection and complication rates. RESULTS: Nine studies representing 235 patients with CUP who had TORS TBM were included in the final analysis. The overall pooled tumour detection rate was 66.2% [95% confidence interval (CI) 56.1-75.8]. The incidence of tumour detection in human papilloma virus (HPV)-positive cases (81.5%, 95% CI 60.8-96.4) was significantly higher than HPV-negative cases (2.3%, 95% CI 0.00-45.7). Weighted overall complication rate was 11.4% (95% CI 7.2-16.2). The majority were grade I or II (80%) according to the Clavien-Dindo classification. CONCLUSIONS: This meta-analysis suggests TORS to be safe and effective in localising the primary tumour site in patients with CUP. While the current data supports the use of TORS in patients who are HPV positive, larger numbers of HPV-negative cases are required to determine the true diagnostic effect with TORS before any valid conclusions can be inferred in this particular subgroup. Further research should focus on high quality prospective trials with stringent methodological work-up to minimise heterogeneity and allow for more accurate statistical analysis.

Targeting of 3D oral cancer spheroids by αVß6 integrin using near-infrared peptide-conjugated IRDye 680.

BACKGROUND: In the treatment of oral cavity cancer, margin status is one of the most critical prognostic factors. Positive margins are associated with higher local recurrence and lower survival rates. Therefore, the universal goal of oral surgical oncology is to achieve microscopically clear margins. Near-infrared fluorescence guided surgery (FGS) could improve surgical resection using fluorescent probes. αVß6 integrin has shown great potential for cancer targeting due to its overexpression in oral cancers. Red fluorescent contrast agent IRDye 680 coupled with anti-αVß6 peptide (IRDye-A20) represents an asset to improve FGS of oral cancer. This study investigates the potential of IRDye-A20 as a selective imaging agent in 3D three-dimensional tongue cancer cells. METHODS: αVß6 integrin expression was evaluated by RT-qPCR and Western Blotting in 2D HSC-3 human tongue cancer cells and MRC-5 human fibroblasts. Targeting ability of IRDye-A20 was studied in both cell lines by flow cytometry technique. 3D tumor spheroid models, homotypic (HSC-3) and stroma-enriched heterotypic (HSC-3/MRC-5) spheroids were produced by liquid overlay procedure and further characterized using (immuno)histological and fluorescence-based techniques. IRDye-A20 selectivity was evaluated in each type of spheroids and each cell population. RESULTS: αVß6 integrin was overexpressed in 2D HSC-3 cancer cells but not in MRC-5 fibroblasts and consistently, only HSC-3 were labelled with IRDye-A20. Round shaped spheroids with an average diameter of 400 µm were produced with a final ratio of 55%/45% between HSC-3 and MRC-5 cells, respectively. Immunofluorescence experiments demonstrated an uniform expression of αVß6 integrin in homotypic spheroid, while its expression was restricted to cancer cells only in heterotypic spheroid. In stroma-enriched 3D model, Cytokeratin 19 and E-cadherin were expressed only by cancer cells while vimentin and fibronectin were expressed by fibroblasts. Using flow cytometry, we demonstrated that IRDye-A20 labeled the whole homotypic spheroid, while in the heterotypic model all cancer cells were highly fluorescent, with a negligible fluorescence in fibroblasts. CONCLUSIONS: The present study demonstrated an efficient selective targeting of A20FMDV2-conjugated IRDye 680 in 3D tongue cancer cells stroma-enriched spheroids. Thus, IRDye-A20 could be a promising candidate for the future development of the fluorescence-guided surgery of oral cancers.

Matricellular proteins: Potential biomarkers in head and neck cancer.

The extracellular matrix (ECM) is a complex network of diverse multidomain macromolecules, including collagen, proteoglycans, and fibronectin, that significantly contribute to the mechanical properties of tissues. Matricellular proteins (MCPs), as a family of non-structural proteins, play a crucial role in regulating various ECM functions. They exert their biological effects by interacting with matrix proteins, cell surface receptors, cytokines, and proteases. These interactions govern essential cellular processes such as differentiation, proliferation, adhesion, migration as well as multiple signal transduction pathways. Consequently, MCPs are pivotal in maintaining tissue homeostasis while orchestrating intricate molecular mechanisms within the ECM framework. The expression level of MCPs in adult steady-state tissues is significantly low; however, under pathological conditions such as inflammation and cancer, there is a substantial increase in their expression. In recent years, an increasing number of studies have focused on elucidating the role and significance of MCPs in the development and progression of head and neck cancer (HNC). During HNC progression, there is a remarkable upregulation in MCP expression. Through their distinctive structure and function, they actively promote tumor growth, invasion, epithelial-mesenchymal transition, and lymphatic metastasis of HNC cells. Moreover, by binding to integrins and modulating various signaling pathways, they effectively execute their biological functions. Furthermore, MCPs also hold potential as prognostic indicators. Although the star proteins of various MCPs have been extensively investigated, there remains a plethora of MCP family members that necessitate further scrutiny. This article comprehensively examines the functionalities of each MCP and highlights the research advancements in the context of HNC, with an aim to identify novel biomarkers for HNC and propose promising avenues for future investigations.

Concentration of High-Cost Head and Neck Cancer Surgical Patients.

OBJECTIVE: Health care costs are disproportionately concentrated among a small number of patients. We sought to identify variables associated with high-cost patients and high hospital concentration of high-cost patients and to examine associations with short-term outcomes in head and neck cancer (HNCA) surgery. STUDY DESIGN: The Nationwide Inpatient Sample was used to identify 170,577 patients who underwent HNCA surgery in 2001-2011. High-cost patients were defined as patients whose costs of care were in the top decile, and high-concentration hospitals were defined as those whose percentage of high-cost patients was in the top decile. METHODS: Multivariable regression was used to evaluate associations between cost and patient and hospital variables, postoperative complications, and in-hospital mortality. RESULTS: Costs associated with high-cost patients were 4.47-fold greater than the remaining 90% of patients. High-concentration hospitals treated 36% of all high-cost patients. High-cost patients were more likely to be non-white (OR = 2.08 [1.45-2.97]), have oral cavity cancer (OR = 1.21 [1.05-1.39]), advanced comorbidity (OR = 1.53 [1.31-1.77]), Medicaid (OR = 1.93 [1.62-2.31]) or self-pay payor status (OR = 1.72 [1.38-2.14]), income>50th percentile (OR = 1.25 [1.05-1.51]), undergo major procedures (OR = 3.52 [3.07-4.05]) and have non-routine discharge (OR = 7.50 [6.01-9.35]). High-concentration hospitals were more likely to be teaching hospitals (OR = 3.14 [1.64-6.05]) and less likely to be urban (OR = 0.20 [0.04-0.93]). After controlling for all other variables, high-cost patients were associated with an increased odds of mortality (OR = 8.00 [5.89-10.85]) and postoperative complications (OR = 5.88 [5.18-6.68]). High-concentration hospitals were associated with an increased odds of postoperative complications (OR = 1.31 [1.08-1.61]) but were not associated with increased mortality (OR = 0.98 [0.67-1.44]). CONCLUSIONS: High-cost HNCA surgical patients are associated with increased postoperative morbidity and mortality, and are disproportionately concentrated at teaching hospitals. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Evaluation of sodium borocaptate (BSH) and boronophenylalanine (BPA) as boron delivery agents for neutron capture therapy (NCT) of cancer: an update and a guide for the future clinical evaluation of new boron delivery agents for NCT.

Boron neutron capture therapy (BNCT) is a cancer treatment modality based on the nuclear capture and fission reactions that occur when boron-10, a stable isotope, is irradiated with neutrons of the appropriate energy to produce boron-11 in an unstable form, which undergoes instantaneous nuclear fission to produce high-energy, tumoricidal alpha particles. The primary purpose of this review is to provide an update on the first drug used clinically, sodium borocaptate (BSH), by the Japanese neurosurgeon Hiroshi Hatanaka to treat patients with brain tumors and the second drug, boronophenylalanine (BPA), which first was used clinically by the Japanese dermatologist Yutaka Mishima to treat patients with cutaneous melanomas. Subsequently, BPA has become the primary drug used as a boron delivery agent to treat patients with several types of cancers, specifically brain tumors and recurrent tumors of the head and neck region. The focus of this review will be on the initial studies that were carried out to define the pharmacokinetics and pharmacodynamics of BSH and BPA and their biodistribution in tumor and normal tissues following administration to patients with high-grade gliomas and their subsequent clinical use to treat patients with high-grade gliomas. First, we will summarize the studies that were carried out in Japan with BSH and subsequently at our own institution, The Ohio State University, and those of several other groups. Second, we will describe studies carried out in Japan with BPA and then in the United States that have led to its use as the primary drug that is being used clinically for BNCT. Third, although there have been intense efforts to develop new and better boron delivery agents for BNCT, none of these have yet been evaluated clinically. The present report will provide a guide to the future clinical evaluation of new boron delivery agents prior to their clinical use for BNCT.

Modelling systematic anatomical uncertainties of head and neck cancer patients during fractionated radiotherapy treatment.

Head and neck cancer patients experience systematic anatomical changes as well as random day to day anatomical changes during fractionated radiotherapy treatment. Modelling the expected systematic anatomical changes could aid in creating treatment plans which are more robust against such changes. A patient specific (SM) and population average (AM) model are presented which are able to capture the systematic anatomical changes of some head and neck cancer patients over the course of radiotherapy treatment. Inter- patient correspondence aligned all patients to a model space. Intra- patient correspondence between each planning CT scan and on treatment cone beam CT scans was obtained using diffeomorphic deformable image registration. The stationary velocity fields were then used to develop B-Spline based SMs and AMs. The models were evaluated geometrically and dosimetrically. A leave-one-out method was used to compare the training and testing accuracy of the models. Both SMs and AMs were able to capture systematic changes. The average surface distance between the registration propagated contours and the contours generated by the SM was less than 2mm, showing that the SM are able to capture the anatomical changes which a patient experiences during the course of radiotherapy. The testing accuracy was lower than the training accuracy of the SM, suggesting that the model overfits to the limited data available and therefore also captures some of the random day to day changes. For most patients the AMs were a better estimate of the anatomical changes than assuming there were no changes, but the AMs could not capture the variability in the anatomical changes seen in all patients. No difference was seen in the training and testing accuracy of the AMs. These observations were highlighted in both the geometric and dosimetric evaluations and comparisons. The large patient variability highlights the need for more complex, capable population models.

A cross-sectional survey assessing clinicians' perspectives towards redesigning the surveillance model for head and neck cancer: can we do better?

BACKGROUND: Service delivery of post-treatment surveillance in head and neck cancer (HNC) varies across institutions in Australia. To better understand current practices and develop protocols that maximize service capacity or incorporate emerging technologies, especially in under-resourced regional and remote communities, it is important to obtain the perspectives of clinicians that regularly manage patients with HNC. DESIGN: This cross-sectional study utilized an online survey distributed via email to specialists recruited from HNC-associated networks across Australia. The survey captured information on current practices and explored clinician perspectives towards re-designing the current surveillance model to incorporate telehealth or patient-reported outcome measures (PROMs). Quantitative data was analyzed using descriptive statistics while open-ended survey comments were analyzed using a content analysis approach. RESULTS: Forty participants completed the survey (25 surgeons, 9 medical oncologists, 5 radiation oncologists and 1 oral medicine specialist). Most clinicians used either institution-specific guidelines (44%) or National Comprehensive Cancer Network guidelines (39%), with the remaining 17% using surveillance intervals based on patient symptoms. Following treatment, 53% of participants imaged patients only when there was clinical suspicion of recurrence or new symptoms. Planned surveillance imaging was conducted at 6 or 12-monthly intervals based on the HNC subtype. Fifty-seven percent of clinicians were open to redesigning the surveillance model, specifically in low-risk patients who did not require nasoendoscopic examination. Seventy-one percent had concerns regarding the feasibility of telehealth appointments, citing disparities in digital health equity. Additionally, 61% felt PROMs are currently underutilized and were open to incorporating HNC-specific PROMS into surveillance. Open-ended responses indicated that within the current surveillance model, "fragmented service provision" and "administration issues" were significantly impacting on timing of care. CONCLUSION: Surveyed HNC clinicians feel that current post-treatment surveillance can be fragmented and potentially lead to delayed care. They are open to incorporating PROMS to assist in surveillance scheduling, especially in low-risk patients.

Prognostic Value of the 18F-FDG PET/CT and Haematological Parameters in Head and Neck Cancer.

INTRODUCTION: Fluorine 18-fluoro-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) is commonly used for the staging of head and neck cancer. This study aimed to evaluate the correlation between 18F-FDG PET/CT, haematological parameters and prognosis in patients with advanced head and neck cancer. METHODS: This was a single-institutional retrospective study of 83 patients with advanced head and neck squamous cell carcinoma (HNSCC) who underwent 18F-FDG PET/CT imaging before initial treatment between 2014 and 2018. 18F-FDG PET/CT after treatment was performed in 57 patients. The prognostic parameters of the pre- and post-treatment maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV), total lesion glycolysis (TLG) of primary tumours and haematological parameters were analysed to evaluate the association between overall survival (OS) and progression-free survival (PFS). RESULTS: Pre-MTV, pre-TLG and post-SUVmax were significantly associated with poor OS and PFS (p < 0.05). Haematological parameters, including pretreatment neutrophil/lymphocyte ratio and C-reactive protein/albumin ratio, were associated with 18F-FDG PET/CT parameters. In multivariate analysis, post-SUVmax was an independent prognostic factor for OS and PFS. CONCLUSION: A correlation between PET/CT metabolic and haematological parameters was observed. The volume and intensity of 18F-FDG uptake region, in addition to haematological parameters, are feasible markers for predicting the progression of HNSCC in daily practice. Further, post-SUVmax could be an independent parameter for predicting poor survival.

An epidermal growth factor receptor-targeting immunotoxin based on IgG shows potent antitumor activity against head and neck cancer.

The epidermal growth factor receptor (EGFR) is an important target for cancer therapies. Many head and neck cancer (HNC) cells have been reported to overexpress EGFR; therefore, anti-EGFR therapies have been attempted in patients with HNC. However, its clinical efficacy is limited owing to the development of drug resistance. In this study, we developed an EGFR-targeting immunotoxin consisting of a clinically proven anti-EGFR IgG (cetuximab; CTX) and a toxin fragment (LR-LO10) derived from Pseudomonas exotoxin A (PE) using a novel site-specific conjugation technology (peptide-directed photo-crosslinking reaction), as an alternative option. The immunotoxin (CTX-LR-LO10) showed specific binding to EGFR and properties of a typical IgG, such as stability, interactions with receptors of immune cells, and pharmacokinetics, and inhibited protein synthesis via modification of elongation factor-2. Treatment of EGFR-positive HNC cells with the immunotoxin resulted in apoptotic cell death and the inhibition of cell migration and invasion. The efficacy of CTX-LR-LO10 was evaluated in xenograft mouse models, and the immunotoxin exhibited much stronger tumor suppression than CTX or LR-LO10. Transcriptome analyses revealed that the immunotoxins elicited immune responses and altered the expression of genes related to its mechanisms of action. These results support the notion that CTX-LR-LO10 may serve as a new therapeutic agent targeting EGFR-positive cancers.