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Purpose: Treatment for head and neck cancer (HNC), such as surgery and chemoradiotherapy, can reduce oral function and affect quality of life (QoL). However, whether HNC treatment affects QoL via the decline of oral function remains unclear. This study aimed to investigate the relationship among cancer treatment, QoL, and actual oral function in HNC survivors., Methods: A total of 100 HNC survivors who had completed definitive treatment for HNC at least 6 months prior to enrollment were enrolled in this cross-sectional study. QoL was evaluated using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 summary score. Oral diadochokinesis (ODK), tongue pressure, moisture level on the mucosal surface, and mouth opening were measured. Information on age, sex, tumor site, tumor stage, history of HNC treatment, height, body weight, and lifestyle were collected from medical records. Structural equation modeling (SEM) was conducted to analyze the indirect/direct associations among HNC treatment, QoL, and oral function., Results: In total, 100 HNC survivors (58 males and 42 females; age range, 30-81 years, median, 67 years) were analyzed. Overall, 63 patients (63.0%) were diagnosed as oral cancer, 66 (66.0%) developed advanced cancer (stage 3/4), and 58 (58.0%) underwent reconstruction surgery in 100 HNC survivors. The SEM results supported the hypothesized structural model (root mean square error of approximation = 0.044, comparative fit index = 0.990, Tucker-Lewis index = 0.986). Surgery with neck dissection and reconstruction for advanced cancer had indirect effects on lower QoL via ODK and mouth opening., Conclusion: HNC treatment is indirectly associated with QoL via oral function in HNC survivors., Competing Interests: Declarations. Ethics approval: All procedures performed in studies involving human participants were conducted in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the ethics committee of Okayama University Hospital (No. 1810–034). Consent to participate: Informed consent was obtained from all individual participants included in this study. Consent to publish: All participants also provided informed consent regarding the publication of their data. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: For patients with locally advanced head and neck squamous cell carcinoma (HNSCC), combined programmed death receptor-1 inhibitor and chemotherapy improved response rate to neoadjuvant therapy. However, treatment response varies among patients. There is no tool to predict pathologic complete response (pCR) with high accuracy for now. To develop a tool based on radiomics features of MRI to predict pCR to neoadjuvant chemoimmunotherapy (NACI) may provide valuable assistance in treatment regimen determination for HNSCC., Methods: From January 2021 to April 2024, a total of 172 patients with HNSCC from three medical center, who received NACI followed by surgery, were included and allocated into a training set (n=84), an internal validation set (n=37) and an external validation set (n=51). Radiomics features were extracted from intratumoral and different peritumoral areas, and radiomics signature (Rad-score) for each area was constructed. A radiomics-clinical nomogram was developed based on Rad-scores and clinicopathological characteristics, tested in the validation sets, and compared with clinical nomogram and combined positive score (CPS) in predicting pCR., Results: The radiomics-clinical nomogram, incorporating peritumoral Rad-score, intratumoral Rad-score and CPS, achieved the highest accuracy with areas under the receiver operating characteristic curve of 0.904 (95% CI, 0.835 to 0.972) in the training cohort, 0.860 (95% CI, 0.722 to 0.998) in the internal validation cohort, and 0.849 (95% CI, 0.739 to 0.959) in the external validation cohort, respectively, which outperformed the clinical nomogram and CPS in predict pCR to NACI for HNSCC., Conclusion: A nomogram developed based on intratumoral and peritumoral MRI radiomics features outperformed CPS, a widely employed biomarker, in predict pCR to NACI for HNSCC, which would provide incremental value in treatment regimen determination., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Oropharyngeal mucositis is a common complication of anticancer therapy. This study aimed to determine the effectiveness and safety of intralesional corticosteroid therapy (ICT) in the management of persistent mucositis., Methods: A retrospective chart review of patients who underwent ICT in the oral cavity to manage oral mucositis managed with basic oral care and preventive modalities and persisting at least 6 weeks after head and neck radiation or chemoradiation therapy completion between November 2017 and September 2023 was performed. Bio-demographic data, cancer and anticancer therapy characteristics, medical history, and mucositis-related variables were extracted from electronic medical records., Results: Among the 34 participants, 22 (64.7%) were male. Twenty (58.8%) participants received radiotherapy; the rest received chemoradiation therapy. Before the ICT, the median mucositis lesion surface area was 225 mm 2 (range 9-2025 mm 2 ), and 22 (64.7%) patients had grade III mucositis. Post-intervention, the median size was reduced to 0 mm 2 (range 0-1600 mm 2 ). Clinically effective response (≥ 75% size and symptom reduction) was observed in 28 (82.4%) participants over a median of 26 days (7-60 days). Within this cohort, complete healing of the lesion was seen in 18 (64.3%) subjects. Overall, 25 (73.5%) participants experienced a downgradation in the mucositis stage. Local complications from injections were found in two (5.7%) participants. A correlation was found between clinically effective relief and absence of trismus (p = .03) and smaller pre-procedure surface area (p = .009)., Conclusion: The ICT represents a viable option in managing non-healing, persistent radiation, and chemoradiation-induced oral mucositis. The modality was well tolerated and had no systemic complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: An uncommon cancer, lymphoepithelioma-like carcinoma (LELC) resembles undifferentiated nasopharyngeal carcinoma (NPC) histologically. The aim is mainly to introduce the diagnosis and treatment of LELC and compare it with NPC in our descriptive study., Methods: A total of 278 patients with NPC and 157 patients with head and neck LELC had their medical records examined in this study. The propensity score matching (PSM) approach was employed to attain a 1:1 match between the LELC and NPC groups. Kaplan-Meier analysis was performed for overall survival (OS) of LELC and NPC. To determine their predictive values for OS, univariate and multivariate Cox regression analyses with significant survival differences (p < 0.05) were carried out., Results: Similar to NPC, 107 (68.2%) LELC cases had Epstein-Barr virus (EBV) infection. LELC of the parotid glands was present in nearly 46.5% of patients with head and neck LELC. Most patients were treated with surgery with neck dissection. After PSM, LELC had similar 5-year OS rates to NPC (81.6% vs. 79.0%). LELC was less prone to distant metastasis compared to NPC. Age, T stage, N stage, and distant metastases were found to be substantially correlated with the outcome of LELC, according to the multivariate Cox regression analysis (p < 0.05)., Conclusions: EBV infection in the head and neck has been associated with LELC and NPC. When compared to NPC, LELC is more likely to arise in the salivary glands and has a lower incidence of distant metastasis. Surgery with neck dissection is the primary treatment for LELC., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background/aim: Locally advanced squamous cell carcinoma of the head and neck (L/A SCCHN) is typically treated with surgery or chemoradiation therapy (CRT), whereas salvage surgery is considered for residual disease post-CRT. However, salvage surgery after radiation therapy presents challenges due to tissue fibrosis. Planned neck dissection (ND) combined with CRT, as well as positron emission tomography after CRT, have been proposed strategies, but no definitive consensus has been reached. Therefore, this study aimed to investigate the utility of "upfront ND" performed prior to CRT to enhance local control and reduce complications., Patients and Methods: We retrospectively reviewed 121 patients who underwent primary CRT for oropharyngeal, hypopharyngeal, or laryngeal cancer at Tokyo Medical University Hospital from January 2015 to September 2021. Patients without cervical lymph node metastasis or with unresectable nodes were excluded. All patients underwent pre-treatment imaging and staging. CRT consisted of intensity-modulated radiation therapy (IMRT) and cisplatin-based chemotherapy. Selective ND or modified radical neck dissection was performed based on lymph node involvement., Results: Overall, 35 patients underwent upfront ND, whereas 54 did not. The upfront ND group exhibited significantly better 2-year locoregional recurrence-free survival than the group without upfront ND (93.7% vs. 71.0%). No significant differences were noted in adverse events between groups., Conclusion: The findings highlight upfront ND before CRT as a viable option for locally advanced head and neck cancer, particularly beneficial in cases with extranodal extension. This approach enhances local control and may reduce the need for salvage surgery, thus improving patient outcomes., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: Burkitt lymphoma (BL) is an aggressive form of non-Hodgkin lymphoma with the sporadic subtype being predominant in North America. The clinical presentations and outcomes of pediatric BL within the head and neck were assessed using both an institutional case series and the Surveillance, Epidemiology, and End Results (SEER) Cancer database., Methods: The electronic medical record at our quaternary children's hospital was queried over a 22-year period (2000-2022) for BL patients with head and neck manifestations. Demographics, clinical presentation, staging, treatment, and outcomes data were collected and analyzed. A corresponding review of the SEER database from 1975 to 2022 was also performed., Results: Our institutional case series identified 48 sporadic BL patients with a mean age of 8.7 years, the majority of whom were male (79 %) and white (74 %). The most common primary sites were the cervical lymph nodes (38 %) and (or) palatine tonsils (23 %). Thirty-five patients (73 %) were treated initially for a presumed inflammatory or infectious process before undergoing malignancy work-up, which did not significantly delay time to diagnosis (31.5 vs. 38.8 days, p = 0.27). The SEER database analysis identified 78 cases, 43.5 % of whom were 5-9 years of age, with a similar male (66 %) and Caucasian (76.9 %) predominance. Cervical lymph nodes were also the most common subsite (67 %), followed by the palatine tonsils (13 %). Remission rates were similar, 93.7 % and 94.8 %, respectively, in both the institutional and SEER database cohorts., Conclusion: Unilateral cervical lymphadenopathy and asymmetric tonsillar hypertrophy are the most common presentations in sporadic BL in the head and neck. Clinical presentation in patients with BL is often similar to common, insidious pediatric otolaryngology symptoms and a majority of patients initially undergo treatment for presumed infectious or inflammatory disease. Although overall BL disease-free survival is high even for disseminated BL, the prognosis is better for local/regional disease, and minimizing time to diagnosis and treatment should remain a priority., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Despite its prevalence in adults, head and neck squamous cell carcinoma (HNSCC) is considered a rare entity in pediatrics where lymphomas, neural tumors, and soft tissue sarcomas predominate in the head and neck. Given the association of squamous cell carcinoma with the human papillomavirus, a risk factor that may be present from birth, and the difficulties in staging this disease for prognostication in children, it is important to revisit nationally collected data for prevalence and outcomes assessments., Objective: To examine a publicly available national database to describe the incidence, pathology, treatment, and survival of pediatric HNSCC. To review the available literature regarding management, outcomes, and risk factors for this disease process., Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor database was queried to identify pediatric subjects ages 0 to 19 diagnosed HNSCC between 1973 and 2019., Results: Two-hundred ninety-two cases were identified. Subjects were 62.7 % male (n = 183) and the average age was 15.4 years (range 2-19, median 16). Subjects were 65.8 % white (n = 192), 22.9 % black (n = 67), 8.9 % Asian/Pacific Islander (n = 26), 1 % American Indian (n = 3), and 1.4 % unknown (n = 4). The most common primary sites were nasopharynx (45.9 %), oral cavity (30.5 %), larynx (8.6 %), salivary gland (4.1 %), nasal cavity & paranasal sinus (3.4 %), and lip (2.7 %). There was no statistically significant difference between primary subsite and age, race, histologic grade, or extent of disease. The 5-year overall survival was 83.6 %., Discussion: Head and neck squamous cell carcinoma is more likely to present in older children and is more prevalent in White populations. The nasopharynx is the most common subsite involved, which differs from adult populations in which non-nasopharyngeal subsites including the larynx, oral cavity, and oropharynx are most frequently affected., Conclusion: Head and neck squamous cell carcinoma is rare in pediatric patients but should not be overlooked by physicians in the differential diagnosis, particularly in teenagers. Further study is needed to determine whether this represents a unique entity or can be staged and treated according to adult guidelines., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to disclose., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Areas Covered: Here we describe novel agents, their mechanism(s) of action, preclinical results, and ongoing clinical trials in HNSCC., Expert Opinion: Established therapeutic targets in HNSCC include EGFR (cetuximab) and PD-1 (pembrolizumab and nivolumab). Despite the detection of many other possible targets in HNSCC cell lines and patient tumors, no other therapies have successfully advanced to date. Identification of predictive biomarkers may guide the use of targeted agents and combination therapies. Clinical trials supported by strong preclinical data in relevant models are more likely to advance treatment options.

Introduction: Minimal important change estimates (MIC) are useful for interpreting results of clinical research with quality of life (QoL) as an endpoint. For the European Organisation for Research and Treatment of Cancer head and neck cancer module, the EORTC QLQ-HN43, no such thresholds are established., Methods: Head and neck cancer patients under active treatment (n = 503) from 15 countries completed the EORTC QLQ-HN43 three times (t1: before treatment, t2: three months after t1, t3: six months after t1). A subgroup completed a Subjective Significance Questionnaire (SSQ), indicating experienced change from the previous time point in four QoL domains. QoL was assumed to deteriorate after t1 and improve again until t3. The MIC was established using the average of mean differences in SSQ groups (MIC mean ) and estimates based on logistic regressions (MIC predict ). Additionally, minimal detectable changes (MDC) were computed using 0.5 standard deviation and standard error of the mean., Results: For swallowing, speech, dry mouth, and global QoL, the MIC for deterioration were 13, 14, 26, and 10 respectively. The MIC for improvement were 8 (swallowing), 6 (dry mouth), and 5 (global QoL); no MIC for speech improvement can be presented because of insufficient correlation between change score and anchor. The MDC estimates for deterioration were 15, 14, 15, and 11. For improvement, the MDC estimates were 13, 14, 14, and 11., Conclusions: Our results underline that no single MIC or MDC can be applied to all EORTC QLQ-HN43 scales, and that the MIC for deterioration seems larger than those for improvement., Competing Interests: Declaration of Competing Interest Authors declare they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Oncological therapy can trigger various complications and side effects in certain tissues, such as the oral cavity, inducing a direct or indirect impact on basic functions and the patient's quality of life. The aim of the study is to determine the prevalence of chronic oral complications of oncological treatments in patients with head and neck cancer and assess their possible relationship with risk indicators associated with the patient, the tumor, and the treatment., Material and Methods: A retrospective, single-center, observational pilot cohort study was designed at the Dental Hospital of the University of Barcelona, involving patients with head and neck cancer who underwent surgery, non-surgical oncological therapy (radiotherapy/chemotherapy/immunotherapy), or combined therapy. Medical histories were analyzed, and data related to demographics, toxic, hygienic, and dietary habits, systemic and oral health status, characteristics of cancer and its treatment, and registered chronic oral complications were collected. The results were expressed in descriptive measures (means, standard deviations, counts, prevalence, and 95% confidence intervals), and for statistical associations, parametric and non-parametric tests were used., Results: The overall prevalence of chronic oral complications was 92.57%. Dental disease (81.14%), periodontal disease (65.14%), and hyposalivation/xerostomia (62.86%) showed the highest prevalence. Advanced age, certain cancer locations, advanced cancer stages, and oncological therapy including radiotherapy were significantly associated with the presence and number of complications., Conclusions: The elevated noticed prevalence necessitates rigorous monitoring and preventive care. The combination of risk factors can significantly contribute to oral complications. Understanding these factors services dentists establish protocols for preventing, diagnosing, and treating oncology patients.

The introduction of immune checkpoint inhibitors (ICIs) to oncological care has transformed the management of various malignancies, including head and neck squamous cell carcinoma (HNSCC), offering improved outcomes. The first-line treatment of recurrent and malignant HNSCC for many years was combined platinum, 5-fluorouracil, and cetuximab. Recently, the ICI pembrolizumab was approved as a first-line treatment, with or without chemotherapy, based on tumor and immune cell percentage of programmed-death ligand 1 (PD-L1). Multiple head and neck (HN) cancer trials have subsequently explored immunotherapies in combination with surgery, chemotherapy, and/or radiation. Immunotherapy regimens may be personalized by tumor biomarker, including PD-L1 content, tumor mutational burden, and microsatellite instability. However, further clinical trials are needed to refine biomarker-driven protocols and standardize pathological methods to guide combined regimen timing, sequencing, and deescalation. Gaps remain for protocols using immunotherapy to reverse oral premalignant lesions, particularly high-risk leukoplakias. A phase II nonrandomized controlled trial, using the ICI nivolumab, showed a 2-y cancer-free survival of 73%, although larger trials are needed. Guidelines are also needed to standardize the role of dental evaluation and care before, during, and after immunotherapy, specifically in regard to oral immune-related adverse events and their impact on cancer recurrence. Standardized diagnostic and oral care coordination strategies to close these gaps are needed to ensure continued success of HN cancer immunotherapy., Competing Interests: Declaration of Conflicting InterestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Guilherme Rabinowits reported serving as a consultant for Replimune, Sanofi, Merck, Exelixis, and Boston Gene outside the submitted work. Dr. Villa reported receiving grants from PCCA and Mureva and serving as a consultant for Lipella Pharmaceuticals, K Pharmaceuticals, Merck, and Afyx Therapeutics outside the submitted work. No other disclosures were reported.

Importance: The eighth edition tumor, node, metastasis (TNM) staging for head and neck cutaneous squamous cell carcinoma (HNcSCC) is a poor predictor of survival in patients with lymph node metastases, possibly due to the inclusion of extranodal extension (ENE)., Objective: To identify the key determinants of prognosis in patients with nodal metastatic HNcSCC and analyze the association of ENE with TNM stage and investigate for prognostic heterogeneity in ENE-positive disease., Design, Setting, and Participants: This retrospective, multicenter cohort study was conducted at 4 Australian tertiary referral centers using prospectively collected data in patients treated between 1980 and 2017 with a median (IQR) follow-up of 3.2 (3.9) years. The study population included 1309 consecutive patients with HNcSCC that was metastatic to parotid and/or cervical nodes. After excluding cases with perioperative mortality, missing data, or follow-up, the final study population included 1151 patients., Exposure: Curative intent surgery ± adjuvant radiotherapy., Main Outcomes and Measures: Differences in locoregional control (LRC), disease-specific survival (DSS), and overall survival were determined using Cox regression analysis., Results: Among 1151 patients, 976 (84.8%) were male and 175 (15.2%) female, with a median age of 73.3 years (range, 18-100 years). On multivariable analysis, immunosuppression (hazard ratio [HR], 2.48; 95% CI, 1.64-3.74), perineural invasion (HR, 1.69; 95% CI, 1.25-2.30), ENE (HR, 1.53; 95% CI, 0.95-2.44), size (>3-6 cm vs ≤3 cm [HR, 1.41; 95% CI, 1.03-1.93]; >6 cm vs ≤3 cm [HR, 5.01; 95% CI, 2.98-8.42]), and number of nodal metastases (3-4 vs 1-2 [HR, 1.54; 95% CI, 1.01-2.34]; ≥5 vs 1-2 [HR, 2.86; 95% CI, 1.99-4.11]) were associated with DSS. Similar results were found for LRC and overall survival. More than 90% of the population was categorized as TNM stage IV, with 32% attributable to ENE. In the ENE-positive subset (n = 860), DSS ranged from 8% to 88% based on stratification using other clinicopathological factors., Conclusions and Relevance: The study results suggest that immunosuppression, perineural invasion, ENE, and size and number of nodal metastases are associated with reduced survival and LRC in HNcSCC with nodal metastases. The inclusion of ENE in HNcSCC staging needs to be reassessed, as it ascribes excessive importance to ENE and upstages most patients to TNM stage IV, despite many having a high chance of cure.

Introduction: Frailty is a recognized condition associated with poorer outcomes in patients with head and neck cancer (HNC). The objective of this study was to ascertain the prognostic significance of various frailty metrics on short-term treatment toxicity in patients with HNC undergoing curative-intent therapy., Materials and Methods: A systematic review was performed searching multiple databases. An inverse-variation, random-effects model was used to perform the meta-analysis to evaluate the prognostic significance of various frailty metrics on short-term treatment-related toxicity in this population., Results: A total of 292,560 patients with HNC originating from 36 observational studies were analyzed. The most frequently reported frailty metrics were the modified frailty index (mFI), Geriatric 8 questionnaire (G8), Adjusted Clinical Groups (ACG), Groningen Frailty Indicator (GFI), and comprehensive geriatric assessment (CGA). The overall prevalence of frailty using any metric in all included studies was 7.5 %. The combined odds ratio (OR) for short-term treatment toxicity using the mFI was 2.60 (95 % CI of 1.81-3.72), G8 2.69 (95 % CI 1.37-5.28), ACG 3.43 (95 %CI 2.52-4.67), GFI 2.71 (95 % CI 1.11-6.62), and CGA 3.36 (95 % CI 1.18-9.53). The association of frailty with short-term treatment toxicity using various frailty metrics was more pronounced in patients with upfront surgery (OR 3.00, 95 %CI of 2.35-3.81) compared to definitive (chemo)radiotherapy 2.64 (95 % CI 1.04-6.68)., Discussion: Various frailty metrics exists in the HNC literature, with the most common being the mFI, G8, ACG, GFI, and CGA. Patients with HNC and frailty are more than twice as likely to suffer a short-term treatment-related toxicity when undergoing curative-intent HNC treatment than patients without frailty. This effect is more pronounced in patients undergoing upfront surgery., Competing Interests: Declaration of Competing Interest None of the authors have conflicts of interest to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Pharyngocutaneous fistula is a critical complication of head and neck cancer reconstruction and it is often difficult to manage. We herein report two cases of pharyngocutaneous fistulas that developed after oropharyngeal reconstruction and were successfully treated with negative pressure wound therapy with instillation and dwell time (NPWTi-d), an advanced form of traditional NPWT. NPWTi-d may be a useful nonsurgical treatment for pharyngocutaneous fistula. Laryngoscope, 134:4573-4576, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

Objectives: This scoping review sought to evaluate the current literature regarding the following outcomes in relation to rurality: stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes of head and neck cancer (HNC)., Data Sources: A literature search was performed using PubMed (MEDLINE), Science Direct, EMBASE, SCOPUS, and Web of Science databases., Review Methods: A 20-year study cutoff from the initial search was used to increase the comparability of the studies regarding population and standards of clinical care. These searches were designed to capture all primary studies reporting HNC incidence, presenting characteristics, treatments, and treatment outcomes. Two reviewers independently screened abstracts, selected articles for exclusion, extracted data, and appraised studies. Critical appraisal was done according to the Joanna Briggs Institute Quality Assessment Tool for Cohort Studies., Findings: Twenty eligible original articles were included. Stage at diagnosis, clinical characteristics, treatment characteristics, and survival outcomes were measured. Our review indicates that although this relationship is unclear, there may be variations in treatment choice for laryngeal cancer based on geographic location and rural residency status. The studies assessing HNC outcomes related to stage at diagnosis, clinical characteristics, treatment characteristics, and overall survival demonstrated conflicting findings, indicating a need for further research examining HNC outcomes with a focus on rurality as the main exposure., Conclusions: The relationship between HNC and rural-urban status remains unclear. More studies are needed, along with a consistent metric for measuring rurality and recruitment of comparable populations from both rural and urban areas. Laryngoscope, 134:4441-4457, 2024., (© 2024 The American Laryngological, Rhinological and Otological Society, Inc.)

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., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: This meta-analysis aims to evaluate the efficacy and safety of antiprogressive disease (PD)-(L)1-based neoadjuvant therapy in head and neck squamous cell carcinoma (HNSCC) patients and identify potential prognostic biomarkers., Data Sources: Databases were systematically searched for prospective clinical trials evaluating the efficacy and safety of anti-PD-(L)1-based neoadjuvant therapy for HNSCC before January 12, 2024., Review Methods: We estimated the efficacy and safety of neoadjuvant immune checkpoint inhibitors. Subgroup and sensitivity analyses were further performed., Results: A total of 570 patients from 20 studies were included. The pooled major pathological response (MPR), pathological complete response (pCR), and partial pathological response (PPR) rates were 30.7%, 15.3%, and 68.2%, respectively. Surgical complications, surgical delayed rate, all grade treatment-related adverse effects (TRAEs) and ≥Grade 3 TRAEs were 0.6%, 0.3%, 82.6%, and 9.7%, respectively. Best MPR or pCR rate was detected in patients receiving neoadjuvant anti-PD-(L)1 therapy + radiotherapy (with MPR rate of 75.5% and pCR rate of 51.1%) and neoadjuvant anti-PD-(L)1 therapy + chemotherapy groups (with MPR rate of 57.5% and pCR rate of 26.7%). No differences were detected in subgroups stratified by neoadjuvant treatment cycles, human papillomavirus (HPV) status, and tumor location. Patients with baseline Combined Positive Score (CPS) ≥ 20 have higher MPR and pCR rates compared to patients with CPS < 20. High Tumor Cell Proportion Score was also associated with MPR and pCR. Objective response rate is a strong predictor of MPR (odds ratio [OR] = 7.78, 95% confidence interval [CI] = 3.20%-18.91%) and pCR (OR = 3.24, 95% CI = 1.40%-7.48%)., Conclusion: Anti-PD-(L)1-based neoadjuvant therapy was effective and safe for HNSCC patients., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Head and neck cancer treatment often leads to trismus, a condition characterized by limited mouth opening. Exercise-based therapy is the most common intervention but there are no clear guidelines as to the optimal exercise regimen. Restorabite™ is a portable and force-regulated trismus device designed to enhance exercise adherence. This study explores the adherence to exercises using Restorabite™ in head and neck cancer patients with trismus and identifies facilitators and barriers to exercise therapy., Materials and Methods: Mixed-methods, prospective cohort study undertaken at a quaternary oncology hospital, in Sydney Australia involving participants diagnosed with head and neck cancer diagnosed with trismus (maximal incisal opening under 35 mm). Patients underwent a 10-week individualized trismus program using Restorabite™ with weekly speech pathology reviews. Exercise adherence was tracked through categorized descriptors. Data were collected prospectively at baseline, during 10 weeks of therapy with Restorabite™, and at 6- and 12-month post-trismus exercise. Participants described facilitators of trismus therapy, and barriers to completing the prescribed exercises. Clinical documentation of these responses was then analyzed using content analysis., Results: One-hundred and thirty-five participants were recruited. During the intervention 69% (n = 93) exercised as recommended, 24% (n = 32) exercised less, and 7% (n = 10) exercised more than recommended. At 6 months post-intervention, 55.5% (n = 75) exercised as recommended, 38.5% (n = 52) exercised less, and 4% (n = 6) exercised more. At 12 months, 36% (n = 49) exercised as recommended, 48% (n = 62) exercised less, and 11% (n = 15) exercised more. MIO increased from a mean of 18.6 mm at baseline, to 30.1 mm at the end of the 10-week intervention. This was maintained at 6 and 12 months (31.7 and 32.1 mm, respectively). Adherence to the exercise program was associated with greater improvement in maximum interincisal opening (p < 0.001). Facilitators of adherence included intrinsic motivation, device portability, perceived functional change, and external support tools. Barriers included cancer treatment toxicities, competing priorities, and health challenges. Positive outcomes included functional improvements, while negative outcomes included increased pain., Conclusions: Seventy-six percent of patients prescribed Restorabite™ performed trismus exercises at or more than the recommended frequency. Facilitators and barriers identified provide insights into factors influencing adherence. Future research should involve comparative studies that compare the adherence and effectiveness of different exercise programs., (© 2024 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Objectives: Head and neck squamous cell carcinoma (HNSCC) is a complex malignancy that requires a multidisciplinary tumor board approach for individual treatment planning. In recent years, artificial intelligence tools have emerged to assist healthcare professionals in making informed treatment decisions. This study investigates the application of the newly published LLM Claude 3 Opus compared to the currently most advanced LLM ChatGPT 4.0 for the diagnosis and therapy planning of primary HNSCC. The results were compared to that of a conventional multidisciplinary tumor board; (2) Materials and Methods: We conducted a study in March 2024 on 50 consecutive primary head and neck cancer cases. The diagnostics and MDT recommendations were compared to the Claude 3 Opus and ChatGPT 4.0 recommendations for each patient and rated by two independent reviewers for the following parameters: clinical recommendation, explanation, and summarization in addition to the Artificial Intelligence Performance Instrument (AIPI); (3) Results: In this study, Claude 3 achieved better scores for the diagnostic workup of patients than ChatGPT 4.0 and provided treatment recommendations involving surgery, chemotherapy, and radiation therapy. In terms of clinical recommendations, explanation and summarization Claude 3 scored similar to ChatGPT 4.0, listing treatment recommendations which were congruent with the MDT, but failed to cite the source of the information; (4) Conclusion: This study is the first analysis of Claude 3 for primary head and neck cancer cases and demonstrates a superior performance in the diagnosis of HNSCC than ChatGPT 4.0 and similar results for therapy recommendations. This marks the advent of a newly launched advanced AI model that may be superior to ChatGPT 4.0 for the assessment of primary head and neck cancer cases and may assist in the clinical diagnostic and MDT setting., (© 2024. The Author(s).)

Purpose: To evaluate the diagnostic performance (DP) of the high-resolution contrast computed tomography (HR-contrast-CT) based Neck-Persistency-Net in distinguishing vital from non-vital persistent cervical lymph nodes (pcLNs) in patients with advanced head and neck squamous cell carcinoma (HNSCC) following primary concurrent chemoradiotherapy (CRT) with [18F]-fluorodeoxyglucose positron emission tomography and high-resolution contrast-enhanced computed tomography ([18F]FDG-PET-CT). Furthermore, the Neck-Persistency-Net's potential to justify omitting post-CRT neck dissection (ND) without risking treatment delays or preventing unnecessary surgery was explored., Methods: All HNSCC patients undergoing primary CRT followed by post-CRT-ND for pcLNs recorded in the institutional HNSCC registry were analyzed. The Neck-Persistency-Net DP was explored for three scenarios: balanced performance (BalPerf), optimized sensitivity (OptSens), and optimized specificity (OptSpec). Histopathology of post-CRT-ND served as a reference., Results: Among 68 included patients, 11 were female and 32 had vital pcLNs. The Neck-Persistency-Net demonstrated good DP with an area under the curve of 0.82. For BalPerf, both sensitivity and specificity were 78%; for OptSens (90%), specificity was 62%; for OptSpec (95%), sensitivity was 54%. Limiting post-CRT-ND to negative results would have delayed treatment in 27%, 40%, and 7% for BalPerf, OptSens and OptSpec, respectively, versus 23% for [18F]FDG-PET-CT. Conversely, restricting post-CRT-ND to positive results would have prevented unnecessary post-CRT-ND in 78%, 60%, and 95% for BalPerf, OptSens and OptSpec, respectively, versus 55% for [18F]FDG-PET-CT., Conclusion: The DP of the Neck-Persistency-Net was comparable to [18F]-FDG-PET-CT. Depending on the chosen decision boundary, the potential to justify the omission of post-CRT-ND without risking treatment delays in false negative findings or reliably prevent unnecessary surgery in false positive findings outperforms the [18F]-FDG-PET-CT., (© 2024. The Author(s).)

Objectives: This study aimed to compare the efficacy of chemoradiotherapy (CRT) with radiotherapy (RT) alone for elderly patients (≥ 65 years) with stage IV inoperable head and neck cancer (IV-HNC)., Methods: Elderly patients diagnosed with inoperable IV-HNC from 2010 to 2015 were identified using the SEER database. Then, we performed a 1:1 propensity-score matched (PSM) analysis to reduce treatment selection bias, and the prognostic role of CRT was investigated using Kaplan-Meier analysis, log-rank test, and Cox proportional hazard models. The main outcome was overall survival (OS), and the secondary outcome was cancer-specific survival (CSS)., Results: A total of 3318 patients were enrolled, of whom 601 received RT alone and 2717 received CRT. Through PSM, 526 patients were successfully matched, and balances between the two treatment groups were reached. In the matched dataset, multivariable Cox analysis revealed that CRT was associated with better OS (HR = 0.580, P < 0.001) and CSS (HR = 0.586, P < 0.001). Meanwhile, subgroups of patients with IV-HNC (younger age, male sex, being married, black race, grade I-II, oral cavity site, T3-T4 stage, N0-N1 stage, M1 stage) were inclined to benefit more from CRT treatment. Furthermore, the survival benefit of CRT was more pronounced in patients aged 65 to 80 years, but was absent in patients aged 80 years or older., Conclusions: This study indicated that CRT resulted in better survival than RT alone in elderly patients with inoperable IV-HNC, especially for those subpopulations that benefit more from CRT treatment., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: The multimodal treatments for pediatric head and neck (H&N) malignancies can have significant long-term functional consequences for growing patients. This systematic review aims to analyze the current knowledge of functional outcomes for pediatric H&N cancer survivors., Data Sources: PubMed, Embase, Web of Science., Review Methods: Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed, and 1356 papers were reviewed by 3 team members with conflict resolution by a senior member., Results: Fourteen studies were included. Nine of 14 (64%) papers reported issues with swallowing, characterized as either dysphagia, odynophagia, oropharyngeal fibrosis, esophageal stenosis, xerostomia, trismus, or general issues with the throat and mouth. Six of 14 papers noted nutritional and feeding deficiencies, and 5 of 14 additionally noted issues with speech and voice changes. Four of 14 (29%) reported hearing impairments and/or loss. A majority of papers (9/14) reported long-term functional characteristics as a secondary outcome. Three of 14 (21%) reported a quality of life (QoL) measure. Heterogeneity in methodology and reporting precluded analysis of any relationship between treatment type and functional outcomes. Recommendations include integration of objective measures of feeding support and swallowing, as well as regular measurements of function and QoL parameters during treatment to better understand the evolution of QoL and function throughout care., Conclusion: Relatively few studies focus on functional outcomes following the treatment of pediatric H&N cancer. Swallowing difficulty is the most frequently reported deficit, but objective data is rarely reported. Standardization of functional outcome assessment could improve the quality of evidence for pediatric patients treated for H&N cancer., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Head and neck cancer (HNC) patients often have dysphagia following surgical and/or chemoradiation treatment, which can lead to reduced quality of life. Some patients suffer from decreased tongue strength and mobility that may cause discomfort and difficulty with swallowing. Our group has developed a patented genioglossus muscle strength trainer (GMST) to increase tongue protrusive force that has been used in patients with sleep apnea. We hypothesized that the GMST device would increase tongue strength in the HNC population., Methods: We conducted an IRB approved, non-randomized, interventional clinical trial of HNC patients with dysphagia to determine the effect of GMST on tongue strength. Our secondary objective was to assess dysphagia quality of life, as determined by questionnaires. Genioglossus muscle strength measurements (measured in Newtons, N) and dysphagia quality of life scores (SWAL-QoL questionnaire) were obtained from enrolled patients at baseline and following 4 weeks of intervention. Treatment was at-home GMST exercise regimen 3 times daily, 5 days per week. Compliance was assessed via review of training logs. Two-sided paired t -tests at significance level α = .05 were performed to assess difference in mean GG muscle strength pre- and post-treatment., Results: Out of 10 patients initially enrolled, 7 patients completed the trial. Eighty-six percent were male and the average age was 60. About 5 patients had surgery plus adjuvant radiation and 2 patients had primary radiation. All patients had baseline dysphagia as determined by patient complaint and/or objective measurement (prior modified barium swallow). No adverse events were reported. We observed a statistically significant increase in genioglossus muscle strength (mean change: 4.0 N, 95% CI 1.1-6.9, P  = .015) after 4 weeks of treatment. Patients reported reduced swallowing burden and feeling of stigma around eating based on SWAL-QoL results., Conclusions: Our data suggest that protrusive tongue-training exercises utilizing a novel tongue trainer device is well-tolerated and increases genioglossus muscle strength in treated HNC patients complaining of dysphagia. Patient-reported outcomes based on the SWAL-QoL survey indicate improvements in quality-of-life post-treatment, although our results are limited by small sample size. Larger studies are needed to see if this device could have clinically meaningful results for this difficult-to-treat patient population., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: The schedule of cisplatin concurrent with definitive radiation for squamous carcinoma of the head and neck remains controversial. Most institutions deliver either a high-dose "bolus" schedule once every 3 weeks or a low-dose weekly schedule. We compared these 2 schedules via a simplified network meta-analysis with a common comparator., Methods and Materials: We performed a PRISMA-concordant systematic review to identify randomized controlled trials comparing cisplatin with cetuximab for nonmetastatic, locoregionally advanced squamous carcinoma of the head and neck treated with definitive radiation. Trials incorporating primary surgery or induction therapy were excluded. Patient survival times were extracted on a per-event basis from the published curves using a digitizer and validated against published point estimates and hazard ratios (HRs). Survival was compared using random effects Cox regression under a frequentist framework. Toxicity and secondary endpoints were analyzed qualitatively. The Cochrane method assessed the risk of bias. The analysis plan was preregistered with the Open Science Foundation., Results: Five randomized trials were identified, including 1678 patients. There was no statistical difference in overall survival between weekly and bolus regimens (HR, 0.90; 95% CI, 0.53-1.52, P = .345). This Cox model suggested that for the average patient in the cohort, the absolute difference in 5-year overall survival between weekly and bolus regimens was +1.2% (95% CI, -6.1%-+5.9%, P = .345). Secondary endpoints and toxicity were not obviously different by regimen, qualitatively., Conclusions: The cetuximab trials provide indirect data suggesting that the differences between cisplatin schedules are subtle., Competing Interests: Disclosures Matthew C. Ward reports receiving grant support from Varian Medical Systems, Naveris, Inc, consulting honoraria from Exact Sciences, and participating in an ad board for Bayer Pharmaceuticals with publishing royalties from Demos Medical Publishing. All was paid to his institution and none was related to the subject of this manuscript. The remaining authors declare no conflicts of interest., (Copyright © 2024 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.)

Background: Patients with head and neck squamous cell carcinoma (HNSCC) face several physical, emotional, and psychological challenges throughout treatment. Cisplatin-based chemoradiotherapy (CRT) is an effective but toxic treatment, with an increased risk for toxicities in patients with low skeletal muscle mass (SMM). Consequently, these patients are anticipated to experience greater treatment-related difficulties. We aimed to explore the experiences of patients with HNSCC and low SMM regarding cisplatin-based CRT., Methods: A descriptive qualitative study was conducted, interviewing seven patients 3 months after CRT using a topic guide. Thematic analysis of semi-structured interviews was conducted, to create a multi-dimensional understanding of patients' experiences during and after cisplatin-based CRT., Results: Prior to CRT themes included pre-treatment information, expectations towards treatment and trial, psychosocial circumstances, and supporting network. During CRT themes included toxicities, psychosocial impact, and supporting network. After CRT themes included reflection on period during CRT, psychosocial circumstances, informal support from networks and healthcare workers, and ongoing toxicities., Conclusion: Most patients experience cisplatin-based CRT as a life-changing and distressing life event but cope through various strategies and supporting networks. Tailored counseling, ideally with on-demand consultations, is recommended. No differences were noted in patients' perceptions of their cisplatin regimen., (© 2024. The Author(s).)

This simulation-based study presented a novel hybrid RF antenna array designed for neck cancer treatment within a 7T MRI system. The proposed design aimed to provide microwave hyperthermia to release 19F-labeled anticancer drugs from thermosensitive liposomes, facilitating drug concentration monitoring through 19F imaging and enabling 1H anatomical imaging and MR thermometry for temperature control. The design featured a bidirectional microstrip for generating the magnetic |B1|-fields required for 1H and 19F MR imaging, along with a patch antenna for localized RF heating. The bidirectional microstrip was operated at 300 MHz and 280 MHz through the placement of excitation ports at the ends of the antenna and an asymmetric structure along the antenna. Additionally, a patch antenna was positioned at the center. Based on this setup, an array of six antennas was designed. Simulation results using a tissue-mimicking simulation model confirmed the intensity and uniformity of |B1|-fields for both 19F and 1H nuclei, demonstrating the suitability of the design for clinical imaging. RF heating from the patch antennas was effectively localized at the center of the cancer model. In simulations with a human model, average |B1|-fields were 0.21 μT for 19F and 0.12 μT for 1H, with normalized-absolute-average-deviation values of 81.75% and 87.74%, respectively. Hyperthermia treatment was applied at 120 W for 600 s, achieving an average temperature of 40.22°C in the cancer model with a perfusion rate of 1 ml/min/kg. This study demonstrated the potential of a hybrid antenna array for integrating 1H MR, 19F drug monitoring, and hyperthermia., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hernandez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Head and neck small-cell carcinoma (HNSmCC) is a rare and aggressive cancer with a high tendency for distant metastasis. It is treated with multimodal treatment involving chemotherapy. Occasionally, surgery is performed for the management of locoregional HNSmCC. However, the benefits of surgery in this context have not yet been elucidated. Therefore, in this study, we aimed to investigate whether surgery could improve the survival of patients with HNSmCC., Patients and Methods: We obtained data from patients with locoregional HNSmCC treated with chemoradiation therapy (CRT) from the Surveillance, Epidemiology, and End Results database. Patients who did and did not undergo surgery were matched using propensity scores. The overall survival (OS) and disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios (HRs) were calculated using the Cox proportional hazard model., Results: The 5-year OS rates of the patients who did and did not undergo surgery were 57.2% and 50.6%, respectively (P = 0.689); the corresponding 5-year DSS rates were 61.0% and 57.5% (P = 0.769). The adjusted HRs for surgery were 0.85 (95% confidence interval [CI]: 0.54-1.33) for OS and 0.87 (95% CI: 0.51-1.49) for DSS., Conclusion: The addition of surgery to CRT did not improve the survival of patients with locoregional HNSmCC., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hosokawa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Substantial studies reveal that tertiary lymphoid structure (TLS) correlate with prognosis and immunotherapy response in various types of cancers. However, the predictive value of TLS, the specific immune cell subtype within TLS and their anti-tumor mechanisms remain unclear., Methods: Based on 23 TLS-related genes (TLSRGs), we utilized bioinformatics methods to construct a scoring system, named TLSscore. By integrating RNA and single-cell sequencing data, we assessed the utility of TLSscore in head and neck squamous cell carcinoma (HNSCC). Flow cytometric sorting was used to isolate specific T cells subtypes, in vivo and in vitro experiments were conducted to demonstrate its anti-tumor effects., Results: The TLSscore model was constructed and specific TLSscore-genes were found to consistently align with the spatial location of TLS. TLSscore has proven to be a robust predictive model for predicting survival prognosis, immune cell infiltration, somatic mutation and immunotherapy response. Notably, a specific PD1 + CXCL13 + CD8 + T cell subtype was identified within TLS. Both in vivo and in vitro experiments demonstrated that PD1 + CXCL13 + CD8 + T cell might represent a functional cell subtype exerting anti-tumor effects during the process of immune surveillance., Conclusions: Our study presents a predictive model for TLS, which can evaluate its presence and predicts survival prognosis and immunotherapy response in HNSSC patients. Additionally, we identify a specific subtype of T cells that might elucidate the mechanism of TLS function in anti-tumor activities. This T cell subtype holds the potential to be a prognostic marker and a target for adoptive cell therapy (ACT) in the future., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wu, Cao, Ren, Wu, Liu, Li, Xu, Chen, Wang, Chen, Kuang, Xia, Li, Wang, Li, Li, Li and Lan.)

Objectives: To describe longitudinal oral health symptom patterns of patients receiving concurrent chemotherapy and radiation therapy for head and neck cancer (HNC) and examine associations between phenotypic characteristics, including human papillomavirus (HPV) status and oral health symptoms., Sample & Setting: A pilot retrospective longitudinal chart review (N = 270) of patients with HNC at a northeastern U.S. regional cancer institute., Methods & Variables: HPV status and oral health symptoms (pain, mucositis, taste alteration, xerostomia, dysphagia, and candidiasis) were examined during treatment (six weeks) and survivorship (three months). Latent transition analysis was conducted across each time point., Results: The latent transition analysis revealed classes with moderate to high symptom expression persisted into survivorship. The HPV-negative phenotype had higher symptom expression across treatment and survivorship., Implications for Nursing: Patients with HPV-negative HNC may require early intervention, while considering social determinants of health to attenuate symptom expression and improve outcomes.

Some special therapeutic responses may appear during immunotherapy, such as hyperprogression, pseudoprogression and so on. Dissociated response of immunotherapy has been clinically reported in recent years mainly in lung cancer and kidney cancer. Since there were poor prognosis and simple treatment of advanced head and neck cancer, the application of immunotherapy in head and neck cancer has risen in recent years. But the dissociated response of immunotherapy in head and neck cancer is rarely reported. We reported two series of cases of advanced head and neck cancer that showed dissociated response after immunotherapy, tumor progression was assessed by imaging methods such as PET-CT, enhanced CT and enhanced MR, and reviewed the literature related to dissociated response in immunotherapy. We propose that the dissociated response of immunotherapy may affect the treatment strategy of advanced head and neck cancer, but more clinical analyses and researches are needed to confirm it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jiang, Li and Li.)

Objective: To summarize the treatment strategies and clinical experiences of 5 cases of giant plexiform neurofibromas (PNF) involving the head, face, and neck., Methods: Between April 2021 and May 2023, 5 patients with giant PNFs involving the head, face, and neck were treated, including 1 male and 4 females, aged 6-54 years (mean, 22.4 years). All tumors showed progressive enlargement, involving multiple regions such as the maxillofacial area, ear, and neck, significantly impacting facial appearance. Among them, 3 cases involved tumor infiltration into deep tissues, affecting development, while 4 cases were accompanied by hearing loss. Imaging studies revealed that all 5 tumors predominantly exhibited an invasive growth pattern, in which 2 and 1 also presenting superficial and displacing pattern, respectively. The surgical procedure followed a step-by-step precision treatment strategy based on aesthetic units, rather than simply aiming for maximal tumor resection in a single operation. Routine preoperative embolization of the tumor-feeding vessels was performed to reduce bleeding risk, followed by tumor resection combined with reconstructive surgery., Results: All 5 patients underwent 1-3 preoperative embolization procedures, with no intraoperative hemorrhagic complications reported. Four patients required intraoperative blood transfusion. A total of 10 surgical procedures were performed across the 5 patients. One patient experienced early postoperative flap margin necrosis due to ligation for hemostasis; however, the incisions in the remaining patients healed without complications. All patients were followed up for a period ranging from 6 to 36 months, with a mean follow-up duration of 21.6 months. No significant tumor recurrence was observed during the follow-up period., Conclusion: For patients with giant PNF involving the head, face, and neck, precision treatment strategy can effectively control surgical risks and improve the standard of aesthetic reconstruction. This approach enhances overall treatment outcomes by minimizing complications and optimizing functional and cosmetic results.

Background: The infection rate among patients with head-and-neck cancer (HNC) undergoing chemoradiotherapy (CRT) is approximately 19%, with sepsis-related death ranging from 3-9%. A previous study at our institute found a 12% sepsis-related death rate in HNC patients during CRT. The objective of this study is to investigate the utilization of sepsis surveillance and early intervention in reducing the occurrence of sepsis-related deaths in locally advanced HNC patients receiving CRT., Methods: This retrospective analysis examined 54 patients with locally advanced HNC undergoing CRT who underwent sepsis surveillance between January 2018 and December 2021. The study recorded the utilization of oral and intravenous antibiotics, G-CSF, early admissions and their reasons, and the incidence of early mortality. Data analysis was conducted using SPSS v.24 software., Results: Twenty-one (38.9%) patients were prescribed oral antibiotics, and 14 (25.9%) received G-CSF on an outpatient basis. Twenty-nine (54%) patients required hospital admission. Among the admitted patients, 28 (96%) received intravenous antibiotics, and G-CSF was administered in 18 (62%) patients. In 8 cases, antibiotic treatment was intensified due to persistent fever and deteriorating neutropenia. The median time for receiving antibiotics and G-CSF after starting CRT was 5th week (range: 3-8 weeks). Five patients required readmission. Only one patient succumbed to sepsis. Among the 54 patients, 48 (89%) completed the scheduled RT, while 14 (25.9%) received all 6 cycles of chemotherapy., Conclusion: Sepsis surveillance and the prompt use of antibiotics and G-CSF, along with early hospitalization, when necessary, reduces the occurrence of sepsis-related early deaths in HNC patients undergoing CRT., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Organoids have been successfully used in several areas of cancer research and large living biobanks of patient-derived organoids (PDOs) have been developed from various malignancies. The characteristics of the original tumour tissue such as mutation signatures, phenotype and genetic diversity are well preserved in organoids, thus showing promising results for the use of this model in translational research. In this study, we aim to assess whether we can generate PDOs from head and neck squamous cell carcinoma (HNSCC) samples and whether PDOs can be used to predict treatment sensitivity in HNSCC patients as well as to explore potential biomarkers., Methods and Analysis: This is a prospective observational study at a single centre (Guy's and St Thomas' NHS Foundation Trust) to generate PDOs from patients' samples to assess treatment response and to correlate with patients' treatment outcomes. Patients will be included if they are diagnosed with HNSCC undergoing curative treatment (primary surgery or radiotherapy) or presenting with recurrent or metastatic cancers and they will be categorised into three groups (cohort 1: primary surgery, cohort 2: primary radiotherapy and cohort 3: recurrent/metastatic disease). Research tumour samples will be collected and processed into PDOs and chemosensitivity/radiosensitivity will be assessed using established methods. Moreover, blood and other biological samples (eg, saliva) will be collected at different time intervals during treatment and will be processed in the laboratory for plasma and peripheral blood mononuclear cell (PBMC) isolation. Plasma and saliva will be used for circulating tumour DNA analysis and PBMC will be stored for assessment of the peripheral immune characteristics of the patients as well as to perform co-culture experiments with PDOs. SOTO study (correlation of the treatment Sensitivity of patient-derived Organoids with Treatment Outcomes in patients with head and neck cancer) uses the collaboration of several specialties in head and neck cancer and has the potential to explore multiple areas of research with the aim of offering a valid and effective approach to personalised medicine for cancer patients., Ethics and Dissemination: This study was approved by North West-Greater Manchester South Research Ethics Committee (REC Ref: 22/NW/0023) on 21 March 2022. An informed consent will be obtained from all participants prior to inclusion in the study. Results will be disseminated via peer-reviewed publications and presentations at international conferences., Trial Registration Number: NCT05400239., Competing Interests: Competing interests: AK received fees for consulting, advisory, speaker’s roles and/or research funding from PUMA BioTechnology, AstraZeneca, Merck, MSD, Bristol-Myers Squibb, and Avvinity Therapeutics., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Purpose: The impact of therapeutic embolization as a stand-alone treatment of head and neck paragangliomas considered surgically high-risk remains insufficiently understood. The aim of this study was to investigate the procedural risks and long-term volumetric development in head and neck paragangliomas with high surgical risk following therapeutic endovascular embolization as a stand-alone treatment., Materials and Methods: A retrospective database review of patients who underwent endovascular embolization as primary treatment for head and neck paragangliomas lacking appropriate curative treatment options at our institution (from January 2000 to February 2023) was conducted. Tumor volumetric analyses were performed before embolization and during follow-up. To assess the changes in tumor volume over time, the measurements were performed after embolization, first at 6 months and then on a yearly basis up to 6 years (mean follow-up time was 33.7 ± 24.4 months). Subgroup analyses were conducted for vagal and jugular/jugulotympanic paragangliomas., Results: A total of 32 head and neck paragangliomas in 28 patients (mean age, 56.1 years ± 16.5 [standard deviation]; 18 female) with therapeutic embolization as stand-alone treatment were evaluated, of which 11 were vagal paragangliomas, 15 jugular/jugulotympanic paragangliomas, and 6 carotid body tumors. After a mean follow-up duration of 33.7 ± 24.4 months, tumor control was achieved in 75%, with significant median tumor volume reduction at 6 months ( P = .02, n = 21). Vagal paragangliomas responded the most to embolization with a significantly decreased median volume from 22.32 cm 3 to 19.09 cm 3 ( P = .008, n = 8). Transient complications occurred in 3.4%., Conclusions: Therapeutic embolization as a stand-alone treatment offers a low-risk control of tumor growth in surgically high-risk lesions, with a significant reduction in tumor volume after treatment. Among the different subtypes, vagal paragangliomas exhibited the strongest and longest regression of the tumor volume., (© 2024 by American Journal of Neuroradiology.)

Background: Chemoradiotherapy (CRT) with high-dose cisplatin (CDDP) is the standard treatment for locally advanced head and neck squamous cell carcinoma (HNSCC). Although dosing is based on body surface area (BSA), some patients experience CDDP-related adverse events (AEs). We aimed to evaluate the impact of relative CDDP dose to skeletal muscle mass (SMM) on chemotherapy-associated AEs in patients with HNSCC undergoing CRT with high-dose CDDP., Materials and Methods: We retrospectively analyzed data of patients who underwent CRT with high-dose CDDP (80-100 mg/m2, triweekly) between 2010 and 2023. SMM was measured as the cross-sectional muscle area at the third cervical vertebra (C3-SMM) using computed tomography; the skeletal muscle index (SMI) was defined as SMM normalized by squared height. The CDDP index was defined as the prescribed CDDP dose divided by SMI. CDDP-related AEs were assessed during the first cycle using Common Terminology Criteria for Adverse Events v5.0., Results: Overall, 306 patients were identified. The CDDP index cutoff value best associated with grade ≥ 3 AEs was 10.312. Grade ≥ 3 hematological toxicities exhibited stronger association with high CDDP index value than with low CDDP index value (26.9% vs 16.3%, P = .033). Multivariate analysis revealed that high CDDP index value and creatinine clearance < 70 mL/minute were predictive factors for grade ≥ 3 AEs (odds ratio [OR] 2.55, P = .008; OR 3.68, P = .002, respectively)., Conclusion: The CDDP index based on C3-SMM was an independent predictive factor for grade ≥ 3 CDDP-related AEs. C3-SMM is potentially more useful than BSA for determining the optimal CDDP dose in patients with HNSCC., (© The Author(s) 2024. Published by Oxford University Press.)

Head and neck cancer (HNC) is the sixth most common cancer in the world, and its incidence is increasing year by year. Due to the late-stage diagnosis and poor prognosis of HNC, as well as the limitations of traditional treatment methods, it is urgent to improve early detection rates and explore alternative treatment approaches. Graphene-based nanomaterials (GBNs) have been widely applied in biomedical fields due to their high surface area, excellent photothermal properties, and high loading capacity. This literature review introduces the functionalization and biocompatibility of GBNs, followed by a focus on their applications in the diagnosis and treatment of HNC. This includes their potential as bioimaging or biosensing platforms for diagnosis and monitoring, as well as their research progress in chemotherapy drug delivery, phototherapy, and gene transfection. The tremendous potential of GBNs as a platform for combination therapies is emphasized. Finally, in this literature review, we briefly discuss the toxicity and limitations of GBNs in the current research and provide an outlook on their future clinical applications in the diagnosis and treatment of HNC., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

CD8 + tumor-infiltrating lymphocytes (TILs) are increasingly used in oncology as a prognostic and predictive tool to guide patient management. This review summarizes current literature on CD8 + TILs in head and neck squamous cell carcinoma (SCC). Published meta-analyses and clinical trials evaluating CD8 + TILs were analyzed. Consistent positive associations between elevated CD8 + TILs and overall survival have been observed across head and neck sites. CD8 + TILs have been found to predict response to treatment, most commonly immunotherapy, but also chemoradiation. Numerous trials have shown that increased CD8 + TIL frequencies in pretreatment biopsies could identify patients likely to respond to neoadjuvant therapies. CD8 + TIL infiltration has also been elevated in responders both during and after treatment. However, wider adoption of CD8 + TIL quantification as a biomarker has been limited by the need for clinical validation and universal measurement guidelines for head and neck SCC, as there are for other malignancies. Measurement variability includes which tumor compartment is sampled, how TILs are quantified, and which cutoffs are clinically relevant. For several head and neck SCC, measurement of CD8 + TILs in the central or intratumoral compartment, followed by the stromal compartment, has been most consistently associated with survival. Future studies are needed to evaluate subpopulations of CD8 + TILs and biomarker-based treatment selection.

Objective: To evaluate better dose distribution with three-dimensional radiation therapy, and to compare it with multi-segmented treatment planning techniques in patients with head and neck cancer., Method: The prospective study was conducted at the Baghdad Centre for Radiation Therapy and Nuclear Medicine, Baghdad, Iraq, and comprised data of 50 patients with head and neck cancerous tumours from June 2021 to February 2022. There were 35 (70%) females and 15(30%) males. The mean age was 47.31 ± 3.95 years (range 19 - 69 years The patients had undergone computed tomography simulation. The images were exported to Monaco 5.1 for contouring by the radiation oncologist. The data was then imported to XiO planning system. Each plan was repeated twice; once with three-dimensional conformal radiation therapy and the other with field-in-field technique. Data was analysed using SPSS 24., Results: There were 50 patients whose data was analysed. The results showed significant differences between three-dimensional conformal radiation therapy and field-in-field techniques for dose coverage at 90% and 95% volumes (p<0.05). There was a significant difference between the two techniques for 2Gy dose (p<0.05), but the difference was not significant for 5Gy dose (p>0.05)., Conclusions: The field-in-field treatment planning technique was found to be more effective than the threedimensional conformal radiation therapy technique.

Objective: In order to better understand the condition and provide the groundwork for early detection and treatment of plasmacytomas, it is important to examine the clinical characteristics, therapeutic options, and effectiveness of plasmacytomas that are initially identified with head and neck symptoms. Methods: Retrospective analysis, evaluation, and discussion of the clinical data of 7 patients with plasmacytoma initially diagnosed with head and neck symptoms and admitted to the Affiliated Hospital of Qingdao University during the period of June 2013 to November 2022 was done in combination with pertinent literature. Results: All seven patients were diagnosed with plasmacytoma by histopathology, with lesions located in the nasopharyngeal oropharynx in 4 cases, nasal sinuses in 2 cases, and ventricular zone in 1 case. Clinical manifestations and imaging were atypical, with localized manifestations, of which 2 cases were accompanied by multiple skeletal lesions throughout the body, and 4 cases had lymph node metastasis. Surgery was preferred for all patients, and individualized treatment was recommended after surgery. Of the 7 patients, 3 patients underwent surgery and chemotherapy, 2 patients underwent surgery and radiotherapy and chemotherapy, 1 patient underwent surgery and radiotherapy, and 1 case was treated with surgery only. The follow-up period was 3-60 months, with a 100% follow-up rate. 5 cases were alive and 2 cases died of multiple myeloma after 4-5 years Conclusion: Plasmacytomas first diagnosed with head and neck symptoms are rare, and extramedullary plasmacytomas have a better prognosis, while more advanced multiple myeloma has a poorer prognosis; Therefore, enhancing the quality of survival as well as the duration of survival for patients with plasmacytomas requires early diagnosis and individualized treatment., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Background: Recurrent squamous cell carcinoma (SCC) of the head and neck (SCCHN) remains a formidable clinical challenge despite available treatments. The phosphatidylinositol 3-kinase (PI3K) pathway has been identified as a potential therapeutic target, and alpelisib, a selective PI3Kα inhibitor, has demonstrated efficacy in certain malignancies. Combining this targeted therapy with immunotherapy has been suggested in previous studies as a promising strategy to bolster the immune response against cancer., Cases: A 69-year-old woman with locoregional recurrence of PIK3CA-mutated SCC of the left maxilla and cervical nodal metastases. Several chemotherapeutic regimens, including cisplatin, docetaxel, 5FU, chemoradiotherapy, and mono-immunotherapy, resulted in disease progression. Alpelisib combined with pembrolizumab led to a sustained response for 9 months. A 58-year-old man with recurrent metastatic PIK3CA-mutated SCC of the oropharynx, involving the left lung, hilar, and mediastinal lymph nodes. Despite prior palliative radiation and platinum-based chemotherapy with pembrolizumab and cetuximab, treatment with alpelisib and nivolumab resulted in a partial response. Severe hyperglycemia and rash led to treatment discontinuation., Conclusion: Our findings highlight the potential of this innovative therapeutic combination, suggesting a need for further investigations in this setting., (© 2024 The Author(s). Cancer Reports published by Wiley Periodicals LLC.)

Introduction: Head and neck cancer (HNC), primarily head and neck squamous cell carcinomas, originates from the squamous epithelium in areas like the oral cavity, lip, larynx, and oropharynx. With high morbidity impacting critical functions, combined treatments like surgery, radiation, and chemotherapy often fall short in advanced stages, highlighting the need for innovative therapies., Areas Covered: This review critically evaluates interleukin (IL) gene therapy for treating HNC. The discussion extends to key ILs in HNC, various gene therapy techniques and delivery methods. We particularly focus on the application of IL-2 , IL-12 , and IL-24 gene therapies, examining their mechanisms and outcomes in preclinical studies and clinical trials. The final sections address IL gene therapy challenges in HNC, exploring solutions and critically assessing future therapeutic directions., Expert Opinion: Despite advancements in genomic and immunotherapy, significant challenges in HNC treatment persist, primarily due to the immunosuppressive nature of the tumor microenvironment and the adverse effects of current therapies. The therapeutic efficacy of IL gene therapy hinges on overcoming these hurdles through refined delivery methods that ensure targeted, tumor-specific gene expression. Future strategies should focus on refining gene delivery methods and combining IL gene therapy with other treatments to optimize efficacy and minimize toxicity.

This article examines disparities in head and neck cancer across the cancer care continuum. It provides a public health lens to understand multilevel determinants of health behavior and the importance of social determinants of health. This article reviews the evidence base showing profound differences in incidence, treatment, and survival for patients with head and neck cancer by race, ethnicity, socioeconomic status, and geography. Continued research is needed to understand and address disparities for patients with head and neck cancer., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The use of immunotherapy in head and neck squamous cell carcinoma (HNSCC)has increased treatment options for patients who may not be candidates for traditional cytotoxic chemotherapy. Recent studies have resulted in the approval of immunotherapy in the first and second line setting for recurrent/metastatic disease. Various combinations of immunotherapy with targeted therapies, monoclonal antibodies, or human papilloma virus vaccines are also being studied in recurrent/metastatic disease. Currently, programmed death-ligand 1 status is the main marker utilized to assess potential response to immunotherapy. Studies are focused on identifying additional markers, which may help better predict response to immunotherapy for HNSCC patients., Competing Interests: Disclosure D. Fishman has no disclosures. J. Choe has served on a scientific expert panel for Merck Sharpe & Dohme and as an advisory board member for Coherus Biosciences, Exelixis, Eisai, Regeneron-Sanofi, and receives institutional research funding from Genmab A/S, Merck Sharpe & Dohme, ALX Oncology, Coherus Biosciences, Rakuten, and Genentech/Roche., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures The authors have no conflicts of interest to disclose.

Background: Head and neck cancers (HNC) present diagnostic challenges due to multifocal disease manifestations, posing difficulties in distinguishing between metastatic disease and second primary malignancies (SPM). This complexity underscores the need for advanced diagnostic approaches. Emerging technologies, such as next-generation sequencing (NGS) and molecular classifier assays, show promise in providing precise insights into the diverse etiologies of HNC., Method: In this article, we employed NGS and molecular classifier assays to delve into three distinct clinical cases. The objective was to showcase the instrumental role of these technologies in facilitating accurate diagnoses and differentiating between metastatic disease and SPM in HNC cases., Results: The results of this series highlight the effectiveness of NGS and molecular classifier assays in enhancing diagnostic accuracy for HNC and contributing to the precise differentiation of disease etiologies. The utilization of these advanced technologies proved instrumental in avoiding unnecessary interventions and paved the way for more targeted and effective treatment strategies., Conclusion: Our findings underscore the necessity of incorporating advanced molecular testing technologies into the diagnostic and therapeutic approaches for HNC, thereby championing a more nuanced and effective approach to managing these complex cases., (© 2024 Wiley Periodicals LLC.)