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ABSTRACT Objective Methods Results Conclusions We aimed to investigate the pattern, risk, and treatment of subsequent events after curative‐intent treatment of lip cancer.This retrospective cohort study included 313 patients treated for lip cancer from 2011 to 2021 in a tertiary oncological center.After a median follow‐up time of 29.16 months, 145 (46.32%) patients presented with second primary tumors, 93% of which were skin carcinomas. Locoregional recurrence occurred in 7.9% of cases, with 2.5% with nodal recurrence. The 1‐, 5‐, and 10‐year cumulative second primary tumor probabilities were 32.8%, 60.92%, and 70.92%, respectively. A higher risk was observed in elderly patients and basal cell carcinoma cases located on the cutaneous surface of the upper lip. Regional metastasis but not second primary tumors negatively impacted survival.Our study helps fill a literature gap, structuring specific recommendations regarding evaluations and follow‐up protocols for patients with lip cancer. Since cutaneous second primary tumors were the most common second event, standard skin examination is key. Age and histology were significant predictors for second primary tumors. For cases of locally advanced lip squamous cell carcinoma, standard guidelines for head and neck cancer must be followed. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions Patients with limited distant metastatic disease, also known as oligometastasis, show better survival rates than polymetastatic patients, and may be amenable for curative‐intent treatment. The definition of oligometastasis, however, is unknown, and no quantitative analyses on the cutoff value for oligometastasis have been performed before. This study aims to derive specific threshold values for the number of metastases and affected locations that defines oligometastatic disease in head and neck squamous cell carcinoma.A retrospective cohort study was conducted including all patients diagnosed with distant metastases between 2006 and 2021. For each patient, the number of distant metastases and affected locations was recorded on the basis of the available imaging at the time of diagnosis. Cox regression analyses and a machine‐learning k‐means algorithm were used to determine threshold values.A total of 384 patients untreated for their metastatic foci were analyzed. Most patients (n = 207; 53.9%) had metastasis to one anatomic location, followed by metastases in two anatomic locations (n = 62; 16.1%). The majority of patients had ≥9 metastatic foci (n = 174; 45.3%), followed by one focus (n = 74; 19.3%) and two foci (n = 32; 8.3%). Cox regression and machine‐learning k‐means models showed that although the number of metastases did not predict survival, the number of affected locations did significantly (p < .001), by identifying a threshold of two locations.Contrary to the prevalent dogma, the definition of oligometastasis should not be defined by the number of metastases but rather by the number of affected locations, with a maximum number of affected locations set at two. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) is a deadly form of cancer, affecting areas like the mouth, throat, and larynx. This review explores the complex molecular pathways involved in HNSCC development and progression, focusing on the role of microRNAs (miRNAs)—small molecules that regulate gene expression. We aim to provide a comprehensive overview of how miRNAs influence HNSCC, their potential as diagnostic and prognostic markers, and their use in developing new targeted therapies. We also discuss promising nanotechnology-based approaches for delivering miRNA therapies more effectively. By synthesizing the current knowledge on miRNAs in HNSCC, this research may help identify new biomarkers for early detection and prognosis, as well as novel therapeutic targets. Ultimately, these insights could lead to improved personalized treatments and better outcomes for HNSCC patients. This paper presents a comprehensive comparative analysis of biomarkers for head and neck cancer (HNC), a prevalent but molecularly diverse malignancy. We detail the roles of key proteins and genes in tumourigenesis and progression, emphasizing their diagnostic, prognostic, and therapeutic relevance. Our bioinformatic validation reveals crucial genes such as AURKA, HMGA2, MMP1, PLAU, and SERPINE1, along with microRNAs (miRNA), linked to HNC progression. OncomiRs, including hsa-miR-21-5p, hsa-miR-31-5p, hsa-miR-221-3p, hsa-miR-222-3p, hsa-miR-196a-5p, and hsa-miR-200c-3p, drive tumourigenesis, while tumour-suppressive miRNAs like hsa-miR-375 and hsa-miR-145-5p inhibit it. Notably, hsa-miR-155-3p correlates with survival outcomes in addition to the genes RAI14, S1PR5, OSBPL10, and METTL6, highlighting its prognostic potential. Future directions should focus on leveraging precision medicine, novel therapeutics, and AI integration to advance personalized treatment strategies to optimize patient outcomes in HNC care. [ABSTRACT FROM AUTHOR]

Simple Summary: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with the head and neck region being the most common location. Perineural invasion (PNI), or the invasion of cancer into and around nerves, is a high-risk factor in cSCC associated with poor outcomes. The mechanisms of PNI in cSCC are poorly understood, but recent studies suggest that cross-communication between nerve components and cancer is a contributing factor. A better understanding of the mechanisms that promote PNI may lead to new therapies that improve outcomes in cSCC patients. Background/Objectives: Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, with a lifetime risk of 14–20% that is rising every year. Although prognosis for cSCC is generally good, certain high-risk features of cSCC portend increased rates of nodal and distant metastasis, recurrence, and disease-specific mortality. One such high-risk factor is perineural invasion (PNI), which is broadly defined as the invasion of cancer into and around nerves. Compared to other high-risk factors, PNI presence is associated with the highest risk for locoregional and distant metastasis. Still, the mechanisms underlying the pathogenesis of PNI remain poorly understood. Recent studies suggest the migration and invasion of tumors into nerves is a result of complex molecular crosstalk within the tumor-nerve microenvironment, wherein the milieu of signaling molecules simultaneously promote neuronal growth and tumor cell invasion. Methods: Understanding the molecular and cellular mechanisms that promote PNI will lead to future developments of targeted therapies that may improve locoregional control and survival. Results/Conclusions: In our article, we aim to provide a comprehensive review of recent findings about the pathogenesis of PNI, clinical implications of PNI-positive disease in cSCC, available treatment modalities, and potential future therapeutic targets. [ABSTRACT FROM AUTHOR]

Simple Summary: Oral cancer represents a main public health issue around the world due to the mortality rates associated with it, the lack of effective and potent drugs, the multitude of side effects and the expensive treatments. Until now, no natural alternative therapeutic methods have been found beneficial enough to replace conventional drugs. Thus, bioactive compounds with anticancer properties can represent a necessary alternative through a targeted molecular approach to the multiple pathways involved in carcinogenesis. This review explores how the therapeutic potential of natural compounds can be harnessed and how they can be used as adjuvant therapies for oral cancer treatment. The collected results focused only on plant extracts and biologically active metabolites known for their antioxidant, anti-inflammatory and antitumor potential, which can be described as future chemopreventive agents against oral cancer, alone or in therapeutic combinations. Background: With a significant increase in both incidence and mortality, oral cancer—particularly oral squamous cell carcinoma (OSCC)—is one of the main causes of death in developing countries. Even though there is evidence of advances in surgery, chemotherapy, and radiotherapy, the overall survival rate for patients with OSCC has improved, but by a small percentage. This may be due, on the one hand, to the fact that the disease is diagnosed when it is at a too-advanced stage, when metastases are already present. Methods: This review explores the therapeutic potential of natural herbal products and their use as adjuvant therapies in the treatment of oral cancer from online sources in databases (PubMed, Web of Science, Google Scholar, Research Gate, Scopus, Elsevier). Results: Even if classic therapies are known to be effective, they often produce many serious side effects and can create resistance. Certain natural plant compounds may offer a complementary approach by inducing apoptosis, suppressing tumor growth, and improving chemotherapy effectiveness. The integration of these compounds with conventional treatments to obtain remarkable synergistic effects represents a major point of interest to many authors. This review highlights the study of molecular mechanisms and their efficiency in in vitro and in vivo models, as well as the strategic ways in which drugs can be administered to optimize their use in real contexts. Conclusions: This review may have a significant impact on the oncology community, creating new inspirations for the development of more effective, safer cancer therapies with less toxic potential. [ABSTRACT FROM AUTHOR]

Purpose: To explore the prevalence of synchronous and metachronous tonsillar cancer in patients with base of tongue cancer, as well as identifying potential risk factors linked to these secondary malignancies. We aim to answer the following question: Should bilateral tonsillectomy be recommended to patients diagnosed with base of tongue cancer? Methods: A case-series study was conducted at Aarhus University Hospital, including all patients with histologically confirmed base of tongue squamous cell carcinoma treated between January 2012 and December 2021. Data from electronic patient records, including diagnosis of prior, synchronous or metachronous tonsillar cancer, demographics, and clinical features were analysed. Fisher's exact test was performed to assess factors associated with synchronous and metachronous tonsillar cancer. Results: Among 198 patients with base of tongue cancer, 5.6% had a history of tonsillar cancer, either prior to (4.5%), synchronous (0.5%), or metachronous (0.5%) to the base of tongue diagnosis. The prevalence of synchronous or metachronous tonsillar cancer among patients without previous bilateral tonsillectomy was 1.2%. Patients with tonsillar cancer were older, had heavier smoking histories, and exhibited less frequent P16-overexpression. Conclusion: Our findings deepen understanding of tonsillar cancer in patients with base of tongue cancer. The prevalence of synchronous or metachronous tonsillar cancer was found to be relatively low, suggesting that routine tonsillectomy for all base of tongue cancer patients is not warranted. [ABSTRACT FROM AUTHOR]

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. Highlights: Claude 3 Opus HNSCC Multidisciplinary Tumorboard Artificial Intelligence LLM [ABSTRACT FROM AUTHOR]

Nasal vestibule squamous cell carcinoma (NVSCC) is an exceedingly rare malignancy, often misclassified due to its anatomical location and lack of a standardized definition. This review aims to consolidate current evidence on NVSCC, focusing on epidemiology, risk factors, classification, clinical presentation, treatment modalities, and prognostic factors. The NV anatomy is delineated, emphasizing the need for a clear definition to avoid misclassification. Risk factors include smoking, sunlight exposure, and debated associations with chalk exposure or viral factors. Clinical presentation includes symptoms like nasal obstruction, pain, burning, and bleeding, often misdiagnosed as inflammatory conditions. NVSCC exhibits distinct local spread patterns along cartilaginous surfaces, with the facial and submandibular lymph nodes at higher metastatic risk. Current classifications lack consensus, hindering comparison of outcomes. Treatment varies, with surgery or radiotherapy for early-stage tumors and multimodality approaches for advanced cases. The choice between surgery and radiotherapy is debated, with potential advantages and drawbacks for each. Radiotherapy, especially with Interventional RadioTherapy (IRT, previously known as brachytherapy), is gaining prominence, showing promising outcomes in terms of local control and cosmetic results. Prophylactic neck treatment remains controversial, with indications based on tumor characteristics. Prognostic factors include T classification, tumor size, surgical margins, nodal involvement, and histological features. Long-term survival rates range widely, emphasizing the need for further studies to refine management strategies for this rare malignancy. In conclusion, NVSCC poses diagnostic and therapeutic challenges, warranting multidisciplinary approaches and continued research efforts to optimize patient outcomes. [ABSTRACT FROM AUTHOR]

Background: Oral and laryngeal squamous cell carcinoma (OSCC and LSCC) and papillary thyroid carcinoma (PTC) are common head and neck cancers (HNCs) typically treated surgically. Challenges in tumour delineation often lead to inadequate resection margins in OSCC and LSCC, and missed multifocality in PTC. Fluorescence imaging (FLI) using near-infrared tumour-targeting tracers may improve intraoperative identification of malignancy, facilitating precise excision. This study evaluates six potential FLI targets in OSCC, LSCC and PTC. Materials and methods: Immunohistochemical staining was performed on OSCC (n = 20), LSCC (n = 10) and PTC (n = 10), assessing CEA, c-Met, EpCAM, EGFR, integrin αvβ6 and VEGF-α. Expression was scored (0–12) using the total immunostaining score (TIS) system, and categorized into absent (TIS 0), low (TIS 1–5), moderate (TIS 6–8) or high (TIS 9–12). Results: Integrin αvβ6 showed significant overexpression in OSCC (TIS: 12; p < 0.001) and LSCC (TIS: 8; p = 0.002), with 80% of OSCC and 90% of LSCC exhibiting moderate-high expression. Similarly, EGFR expression was moderate-high in most OSCC (87.5%; TIS: 8) and universally high in LSCC (100%; TIS: 12). In PTC, EGFR and VEGF-α expressions were low-moderate, but significantly higher than in healthy tissue (TIS: 6; p < 0.006). Conclusion: This study highlights integrin αvβ6 and EGFR as viable FLI targets in OSCC and LSCC, especially integrin αvβ6 for tumour margin delineation. In PTC, despite lower expressions, the significant overexpression of VEGF-α, c-MET, and EGFR suggests their potential as FLI targets. Our findings support the development of tumour-targeted FLI tracers to improve surgical precision in HNC. [ABSTRACT FROM AUTHOR]

This article discusses the challenges in managing head neck squamous cell cancer from an unknown primary (HSCCUP) due to a lack of contemporary evidence and evolving understanding of the role of human papillomavirus (HPV) in head and neck cancer. Despite these limitations, various organizations have produced guidelines for managing HSCCUP using different methodologies. The article presents the results of a consensus process involving multiple stakeholders and centers, which led to the publication of consensus statements in the United Kingdom National Multidisciplinary Guidelines. The authors of the document, Vinidh Paleri, John Hardman, Tom Roques, and Ben O'Leary, made significant contributions to the work and have no conflicts of interest to report. The peer review history of the article is available for further reference. [Extracted from the article]

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. [ABSTRACT FROM AUTHOR]

Head and neck cancer (HNC) is the sixth most common type of cancer worldwide, and head and neck squamous cell carcinoma (HNSCC) accounts for 90% of HNC cases. Furthermore, HNSCC accounts for 400,000 cancer-associated deaths worldwide each year. However, at present there is an absence of a versatile biomarker that can be used for diagnosis, prognosis evaluation and as a therapeutic target for HNSCC. In the present study, bioinformatics analysis was used to assess the relationship between hub genes and the clinical features of patients with HNSCC. The findings from the bioinformatics analysis were then verified using clinical samples and in vitro experiments. A total of 51 overlapping genes were identified from the intersection of differentially expressed genes and co-expressed genes. The top 10 hub genes were obtained from a protein-protein interaction network of overlapping genes. Among the hub genes, only secretoglobin family 1A member 1 (SCGB1A1) was significantly associated with both overall and disease-free survival. Specifically, upregulated SCGB1A1 expression levels were associated with prolonged overall and disease-free survival. Moreover, the SCGB1A1 expression levels were negatively correlated with drug sensitivity. Notably, it was demonstrated that SCGB1A1 was involved in tumor immunoreaction by affecting the infiltration of cells and checkpoint regulation of immune cells. Additionally, it was shown that SCGB1A1 regulated multiple key cancer-related signaling pathways, including extracellular matrix receptor interaction, transforming growth factor-β and tumor metabolism signaling pathways. Based on the results of the present study, SCGB1A1 may serve as a novel biomarker for predicting the diagnosis, prognosis and therapeutic effectiveness of certain drugs in patients with HNSCC. Moreover, SCGB1A1 may serve as a potential therapeutic target for the management of HNSCC. [ABSTRACT FROM AUTHOR]

The MD Anderson Dysphagia Inventory (MDADI), a measure of swallowing-related quality of life, has become the preferred patient-reported outcome measure (PROM) in contemporary clinical trials evaluating the experience of human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPVOPSCC) survivors. With many potentially practice-changing studies using the MDADI composite score as either a primary or coprimary endpoint, or as a key secondary endpoint, it is important to understand its psychometric properties as judged by contemporary PROM standards, with a particular focus on its application to contemporary HPVOPSCC populations. In this critical review, we evaluate contemporary HPVOPSCC studies reporting MDADI outcomes, followed by a detailed evaluation of the psychometric properties of the MDADI. Although the focus of this review was the MDADI, the issues discussed are not unique to the MDADI and have broader applicability to the evaluation and assessment of other PROMs currently in use. First, it may be possible to improve administration of the instrument, as related to missing items, scoring, and the number of items required. Second, although in many instances, the MDADI has been intended as a direct or surrogate measure of swallowing physiology, the MDADI composite score captures a broader health-related quality of life construct affected by both swallowing and eating, the latter of which may be affected by a range of nonswallowing treatment-related toxicities. Finally, a clinically meaningful change of 10 in the MDADI composite score, widely accepted and applied to the clinical trial setting, represents an undoubtably clinically relevant difference in unselected head and neck cancer survivors. However, the smallest difference that might be clinically important to a highly functional HPVOPSCC cohort remains uncertain. Understanding the purpose and properties of the MDADI instrument and furthering the sophistication with which we apply it in this population would improve its interpretation in clinical trials. [ABSTRACT FROM AUTHOR]

Recurrent head and neck cancer presents a therapeutic challenge because of cumulative toxicity from initial radiation therapy, limiting reirradiation options. Boron neutron capture therapy (BNCT) offers a promising alternative, selectively delivering a radical dose to tumors while sparing adjacent normal tissue. This study investigates the initial clinical outcomes and prognostic factors associated with BNCT for recurrent squamous cell carcinoma of the head and neck. This retrospective analysis investigated the initial 47 patients treated with BNCT between May 2020 and February 2021 in Japan. All patients had received radiation therapy with a median dose of 70 Gy (range, 44-176) before BNCT. Median tumor size was 11 cm3 (range, 1-117 cm3), with 23% of tumors larger than 30 cm3, and 87% of patients had prior systemic therapy. The most common prescribed dose to the pharyngeal mucosa was 15 Gy-Eq (36%), followed by 18 Gy-Eq (34%). The minimum dose given to tumor was 27.4 Gy-Eq (range, 13.3-45.2). In 23 patients, 18F-fluoro-borono-phenylalanine positron emission tomography was performed within 1 week before BNCT, and the tumor-to-blood 10B ratio was 3.5 (range, 2.0-8.7). Efficacy analysis revealed a 51% complete response rate and a 74% overall response rate. Disease-free survival rates at 1 and 2 years were 34.6% and 26.6%, respectively. Overall survival rates at 1 and 2 years were 86.1% and 66.5%, respectively. Multivariate analysis revealed that, among the patient characteristics, whether the lesion was mucosal had a significant effect on achieving complete response. This study provided valuable insights into the early integration of BNCT into routine clinical practice, highlighting its efficacy and safety. Technical improvements are needed to ensure precise dose administration. Ongoing prospective studies, such as the phase II REBIVAL study, will further elucidate the role of BNCT in recurrent head and neck cancer. [ABSTRACT FROM AUTHOR]

Background: Hypopharyngeal cancer, constituting 3%–5% of head and neck cancers, predominantly presents as squamous cell carcinoma, with a 5‐year overall survival rate of approximately 40%. Treatment modalities for locally advanced cases include chemoradiotherapy; however, the role of upfront neck dissection (UND) remains controversial. This study aimed to investigate the effect of UND on definitive radiotherapy in locally advanced hypopharyngeal carcinoma. Methods: This retrospective analysis included consecutive patients with locally advanced hypopharyngeal squamous cell carcinoma who were treated in our department between January 2007 and June 2023. All patients underwent definitive radiotherapy (dRT) at a total dose of 70 Gy in 35 fractions. The patients were categorized into two groups: dRT (radiotherapy with or without chemotherapy) and UND‐dRT (surgical neck dissection followed by radiotherapy). Univariate Cox models and multivariate analyses were conducted to investigate the independent prognostic factors for overall survival and locoregional control rate. Results: This study included 115 patients, predominantly male (109/115), with a median age of 66 years. Clinical stage and chemotherapy distribution differed significantly between the dRT and UND‐dRT groups. The 3‐year overall survival and locoregional control rates for all patients were 63.8% and was 63.3%, respectively. The UND‐dRT group exhibited a trend toward improved locoregional control, although this difference was not statistically significant. The multivariate analysis revealed that UND was an independent factor significantly associated with improved overall survival and locoregional control. Conclusion: This study provided evidence supporting the effectiveness of UND in conjunction with definitive radiotherapy for locally advanced hypopharyngeal carcinoma. Future research should focus on validating and refining these findings through well‐designed prospective multicenter trials. [ABSTRACT FROM AUTHOR]

Importance: The management of hypopharyngeal squamous cell carcinoma (HPSCC) continues to be one of the most formidable challenges in the realm of head and neck oncology. Objectives: The aim of this meta-analysis was to evaluate the disparity in survival outcomes between upfront surgery and upfront concurrent chemoradiotherapy as the primary treatment modality in patients with HPSCC. Design: Systemic review with meta-analysis. Setting: The meta-analysis was conducted in strict accordance with the PRISMA guideline. A literature search through PubMed, EMBASE, and the Cochrane Library were conducted until January 2023. The adjusted hazard ratio (aHR) with 95% confidence intervals (CIs) of different survival outcomes were extracted and pooled. Participants: Studies that incorporated HPSCC patients without receiving induction chemotherapy. Interventions: Upfront surgery versus upfront concurrent chemoradiotherapy. Main Outcome Measures: Overall survival (OS) and disease-free survival (DFS). Results: Eight studies published between 2015 and 2023, with a pooled patient population of 1619, were included in this meta-analysis. The outcomes reveal that upfront surgery was notably linked with improved OS (aHR 0.66, 95% CI 0.57-0.78) and DFS (aHR 0.75, 95% CI 0.63-0.90). Subgroup analyses were conducted to investigate the impact of the overall stage of the tumor and the extent of surgery on OS. In patients with advanced HPSCC (stages III and IV), upfront surgery remained associated with better OS (aHR 0.65, 95% CI 0.56-0.77). Concerning the extent of surgery, both subgroups exhibited a superior OS outcome associated with upfront surgery (exclusive total laryngopharyngectomy group: aHR 0.54, 95% CI 0.39-0.75; total/partial laryngopharyngectomy group: aHR 0.71, 95% CI 0.59-0.84). Conclusions and Relevance: The results demonstrated that upfront surgery showed better OS and DFS than concurrent chemoradiation and remind the clinicians of the potential reduction in survival outcomes when choosing concurrent chemoradiotherapy as primary treatment. [ABSTRACT FROM AUTHOR]

Super‐enhancers (SEs) have been recognized as key epigenetic regulators underlying cancer stemness and malignant traits by aberrant transcriptional control and promising therapeutic targets against human cancers. However, the SE landscape and their roles during head and neck squamous cell carcinoma (HNSCC) development especially in cancer stem cells (CSCs) maintenance remain underexplored yet. Here, we identify leukemia inhibitory factor (LIF)‐SE as a representative oncogenic SE to activate LIF transcription in HNSCC. LIF secreted from cancer cells and cancer‐associated fibroblasts promotes cancer stemness by driving SOX2 transcription in an autocrine/paracrine manner, respectively. Mechanistically, enhancer elements E1, 2, 4 within LIF‐SE recruit SOX2/SMAD3/BRD4/EP300 to facilitate LIF transcription; LIF activates downstream LIFR‐STAT3 signaling to drive SOX2 transcription, thus forming a previously unknown regulatory feedback loop (LIF‐SE‐LIF/LIFR‐STAT3‐SOX2) to maintain LIF overexpression and CSCs stemness. Clinically, increased LIF abundance in clinical samples correlate with malignant clinicopathological features and patient prognosis; higher LIF concentrations in presurgical plasma dramatically diminish following cancer eradication. Therapeutically, pharmacological targeting LIF‐SE‐LIF/LIFR‐STAT3 significantly impairs tumor growth and reduces CSC subpopulations in xenograft and PDX models. Our findings reveal a hitherto uncharacterized LIF‐SE‐mediated auto‐regulatory loop in regulating HNSCC stemness and highlight LIF as a novel noninvasive biomarker and potential therapeutic target for HNSCC. [ABSTRACT FROM AUTHOR]

Background: The integration of high-risk human papilloma virus (HPV) DNA into the human genome has been implicated in cervical carcinogenesis and head and neck squamous cell cancer. However, its role in lung squamous cell carcinoma is not well understood. In addition, tuberculosis (TB) and lung cancer(LC) share similar clinical symptoms and imaging features, increasing the risk of misdiagnosis. Case Presentation: The patient presented with a 16-month history of hemoptysis, chest pain, and occasional fatigue, without fever, chills, or history of mechanical damage or autoimmune diseases. Examination revealed normal vital signs and laboratory parameters, except for a positive interferon-gamma release assay indicating tuberculosis infection. Bronchoscopic examinations identified congestion and edema of the tracheal wall, along with a tiny lesion in the right wall of the trachea. She had been misdiagnosed with tuberculosis. However, the diagnosis of squamous cell carcinoma was eventually confirmed by endoscopic biopsy. The patient's macrogenomic second-generation sequencing (mNGS) of the bronchoscopic biopsy specimen was positive for HPV-16.The patient's sex partner tested positive for HPV-16 in penile scrapings, indicating HPV transmission through oral sex. Conclusions: This case highlights the potential for HPV infection acquired through oral sex to lead to lung squamous cell carcinoma. It emphasizes the importance of considering HPV-associated malignancies in patients with respiratory symptoms who engage in oral sexual behaviors. [ABSTRACT FROM AUTHOR]

Background: The evidence for adjuvant chemoradiotherapy (CRT) of oral cavity squamous cell carcinoma (OCSCC) with extra-nodal extension (ENE) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. The guidelines further suggest a radiation dose ranging from 6000 to 6600 cGy. In this nationwide study, we sought to evaluate the prognostic significance of adjuvant therapy and the specific radiation dosage in Taiwanese patients with pure OCSCC and ENE. Methods: A retrospective analysis of 1577 OCSCC patients with ENE who underwent resection and received adjuvant CRT or radiotherapy (RT) between January 2011 and December 2020 was conducted. Results: Multivariable analysis revealed that adjuvant RT, more than four pathologically positive nodes, and radiation dosage below 6000 cGy were independent risk factors for unfavorable 5-year disease-specific survival (DSS) and overall survival (OS). Comparing patients who received CRT (n = 1453) to those treated with RT (n = 124) before and after propensity score (PS) matching, the 5-year outcomes were as follows: before PS matching, DSS (54% versus 30%, p < 0.0001), OS (42% versus 18%, p < 0.0001); after PS matching (n = 111 in each group), DSS (52% versus 30%, p = 0.0016), OS (38% versus 21%, p = 0.0019). For patients who underwent CRT, the 5-year outcomes for different radiation dose groups (6600 − 7000 cGy, n = 1155 versus 6000 − 6500 cGy, n = 199) were as follows: before PS matching, DSS (52% versus 54%, p = 0.1904), OS (43% versus 46%, p = 0.1610); after PS matching (n = 199 in each group), DSS (55% versus 54%, p = 0.8374), OS (46.5% versus 46.3%, p = 0.7578). Conclusions: For OCSCC patients with ENE, our study shows CRT improved survivals than RT alone, underscoring the clinical significance of chemotherapy. Patients undergoing CRT with irradiation doses ranging from 6000 to 6500 cGy exhibited comparable survival outcomes to those receiving doses of 6600–7000 cGy. This observation suggests that irradiation doses exceeding the 6600 cGy may not confer the survival advantage in these patients. Further research is needed to confirm our results and explore the optimal irradiation dose for managing these patients. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of the head and neck (HNSCC) is a difficult-to-treat cancer and treatment is challenging due to recurrence or metastasis. Therefore, there is an urgent need to explore more effective targeted therapies to improve the clinical outcomes and survival of HNSCC patients. The nanomedicine is emerging as a promising strategy to achieve maximal anti-tumor effect in cancer therapy. In this review, we summarize some important signaling pathways and present the current and potential roles of various nanomaterial drug-delivery formulations in HNSCC treatment, aiming to understand the pathogenesis of HNSCC and further improve the therapeutic efficacy of nanomaterial HNSCC. This article seeks to highlight the exciting potential of novel nanomaterials for targeted cancer therapy in HNSCC and thus provide motivation for further research in this field. [ABSTRACT FROM AUTHOR]

Background: To compare the diagnostic utility of computed tomography (CT) and ultrasonography (USG) for preoperative determination of metastatic lymph nodes. Methods: Head and neck squamous cell carcinoma (HNSCC) cases planned for neck dissection were included. All underwent preoperative neck USG and CT followed by histopathological evaluation after surgery. Sensitivity, specificity, positive and negative predictive value along with accuracy was calculated for each outcome variable. Efficacy was calculated by comparing these to postoperative histopathology. Both imaging modalities were compared with lymph nodal volume. Results: Eighty-seven lymph nodes were selected from 30 patients. Median volume on CT was 5412.15 mm3 for metastatic and 237.7 mm3 for benign nodes and on ultrasound, 4168.92 mm3 for metastatic and 233.1 mm3 for benign nodes (p < 0.001). Sensitivity, specificity, accuracy, positive predictive value, and negative predictive value for volume on USG were 81.8%, 98.7%, 96.6%, 90%, and 97.4% and on CT were 81.8%, 100%, 97.7%, 100%, and 97.4% respectively. Conclusions: Lymph nodal volume had higher sensitivity and specificity for detection of metastatic cervical lymphadenopathy and individually or in combination should be included as one of the criteria in preoperative assessment of HNSCC. [ABSTRACT FROM AUTHOR]

The article discusses a retrospective cohort study on cutaneous squamous cell carcinoma (CSCC) and the refinement of prognostic stratification using the top eight risk factors identified in a meta-analysis. The study compared the performance of a classification system based on these risk factors with the Brigham and Women's Hospital (BWH) and American Joint Committee on Cancer (AJCC) staging systems. Results showed a stepwise worsening of prognosis with an increase in the number of risk factors, highlighting the importance of considering multiple factors for accurate risk assessment. The study suggests the potential incorporation of molecular biomarkers for further improvement in predicting prognosis for high-risk CSCC cases. [Extracted from the article]

Background: Brain metastasis (BM) is a rare but severe complication of head and neck squamous cell carcinoma (HNSCC), with limited knowledge of molecular characteristics and immunogenicity. Methods: We analyzed 61 cases of HNSCC-BM from three academic institutions (n = 24) and Foundation Medicine Inc (FMI, n = 37). A subset of cases underwent next-generation sequencing, multiple immunofluorescence, and proximity ligation sequencing. Gene enrichment analysis compared alterations in FMI BM samples (n = 37) with local samples (n = 4082). Results: Demographics included: median age of 59 years, 75% male, 55% current/former smokers, 75% oropharyngeal primary, and 67% human papillomavirus (HPV) +. ATM (54%), KMT2A (54%), PTEN (46%), RB1 (46%), and TP53 (46%) were frequently altered in BM samples from academic centers (62% HPV/p16+). Structural rearrangements ranged from 9 to 90 variants by proximity ligation sequencing. BMs had low densities of CD8+, PD-1+, PD-L1+, and FOXP3 + cells, and 92% had PD-L1 combined positive scores < 1%. CDKN2A (40.5%), TP53 (37.8%), and PIK3CA (27.0%) alterations were common in the FMI BMs (51% HPV+). MAP2K2 alterations and HPV + signature were enriched in FMI BMs compared to local tumors (11.8% vs. 6.4%, P = 0.005 and 51.25% vs. 26.11%, P = 0.001 respectively), and pathogenic TSC1 inactivating mutations were enriched in local tumors (67.3% vs. 37.8%, P = 0.008). Median overall survival from BM diagnosis was 9 months (range 0–27). Conclusions: HNSCC patients with BM frequently have oropharyngeal primary sites and are HPV+. Common molecular alterations in BM samples, including targetable PIK3CA and ATM, were identified. MAP2K2 alterations were enriched and densities of immune cells were low, highlighting potential targets for further research and immunotherapy considerations. [ABSTRACT FROM AUTHOR]

Recent strides in understanding the molecular underpinnings of head and neck cancers have sparked considerable interest in identifying precise biomarkers that can enhance prognostication and enable personalized treatment strategies. Immunotherapy has particularly revolutionized the therapeutic landscape for head and neck squamous cell carcinoma, offering new avenues for treatment. This review comprehensively examines the application and limitations of the established and emerging/novel biomarkers for head and neck squamous cell carcinoma. Established biomarkers, including well-characterized genetic mutations, protein expressions, and clinical factors, have been extensively studied and validated in clinical practice. Novel biomarkers identified through molecular analyses, including novel genetic alterations, immune-related markers, and molecular signatures, are currently being investigated and validated in preclinical and clinical settings. Biomarkers hold the potential to deepen our understanding of head and neck squamous cell carcinoma biology and guide therapeutic strategies. The evolving paradigm of predictive biomarkers facilitates the study of individual responses to specific treatments, including targeted therapy and immunotherapy. [ABSTRACT FROM AUTHOR]

Cancer is caused by an accumulation of somatic mutations and copy number alterations (CNAs). Besides mutations, these copy number changes are key characteristics of cancer development. Nonetheless, some tumors show hardly any CNAs, a remarkable phenomenon in oncogenesis. Head and neck squamous cell carcinomas (HNSCCs) arise by either exposure to carcinogens, or infection with the human papillomavirus (HPV). HPV-negative HNSCCs are generally characterized by many CNAs and frequent mutations in CDKN2A, TP53, FAT1, and NOTCH1. Here, we present the hallmarks of the distinct subgroup of HPV-negative HNSCC with no or few CNAs (CNA-quiet) by genetic profiling of 802 oral cavity squamous cell carcinomas (OCSCCs). In total, 73 OCSCC (9.1%) are classified as CNA-quiet and 729 as CNA-other. The CNA-quiet group is characterized by wild-type TP53, frequent CASP8 and HRAS mutations, and a less immunosuppressed tumor immune microenvironment with lower density of regulatory T cells. Patients with CNA-quiet OCSCC are older, more often women, less frequently current smokers, and have a better 5-year overall survival compared to CNA-other OCSCC. This study demonstrates that CNA-quiet OCSCC should be considered as a distinct, clinically relevant subclass. Given the clinical characteristics, the patient group with these tumors will rapidly increase in the aging population. HPV-negative head and neck squamous cell carcinomas (HNSCCs) are generally characterized by many copy number alterations (CNAs) and mutations. Here, the authors characterize a subgroup of HPV-negative HNSCC with no or few CNAs (CNA-quiet) by genomic profiling of 802 oral cavity squamous cell carcinomas. [ABSTRACT FROM AUTHOR]

Introduction: Cetuximab, used to treat head and neck squamous cell carcinoma and metastatic colorectal cancer, can cause severe infusion reactions. Case presentation: We report an 87-year-old East Asian woman with stage IV ileocecal signet ring cell carcinoma who experienced severe allergic reactions to cetuximab despite pre-treatment. A dose escalation method, involving weekly incremental doses with comprehensive pre-treatment and close monitoring, was employed, successfully reducing allergic reactions and allowing safe administration. Conclusion: This approach demonstrates a viable alternative for patients with hypersensitivity to cetuximab, warranting further research for personalized treatment optimization. [ABSTRACT FROM AUTHOR]

Simple Summary: The landscape for medical therapy in head and neck squamous cell carcinoma has considerably evolved in the last few decades. While early-stage disease remains primarily managed with surgery and/or radiation therapy, immunotherapy and antibody-based therapy have been transformative and practice-changing for patients with recurrent and/or metastatic disease. Unfortunately, many patients ultimately develop resistance to these approaches, with limited options for subsequent treatment. A wide breadth of novel therapies has shown promise in preclinical and early-phase clinical settings, many of which are now undergoing translation into the clinical arena. Here, we provide a review of how medical therapy is used in the management of HNSCC, with a specific focus on active clinical trials, to inform the medical oncologist treating patients with this disease. Head and neck squamous cell carcinoma (HNSCC) is a complex cancer requiring a multidisciplinary approach. For patients with locally or regionally advanced disease, surgery and/or radiation are the cornerstones of definitive treatment. Medical therapy plays an important adjunct role in this setting, typically consisting of a platinum-based regimen given as induction, concurrent, or adjuvant treatment. While relapsed/metastatic HNSCC has historically been a difficult-to-treat disease with poor outcomes, options have considerably improved with the incorporation of biologics and immune checkpoint inhibitors. Clinical trials are ongoing to investigate novel approaches, including new and combination immunotherapies, targeted therapies, therapeutic vaccines, antibody–drug conjugates, and cellular therapies. The results thus far have been mixed, highlighting the knowledge gaps that continue to challenge the medical oncologist treating HNSCC. Here, we present the most updated and broad review of the current treatment landscape in both locoregional and metastatic HNSCC and discuss the expansive future medical therapies under investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNC) is a heterogeneous group of malignancies that originate in the upper aerodigestive tract. Sarcopenia, which is a condition characterized by the loss of skeletal muscle mass and function, is a prevalent condition among cancer patients, significantly impacting their overall health and treatment outcomes. This paper provides a comprehensive review of the relationship between HNC and sarcopenia, focusing on the underlying mechanisms, clinical implications, assessment methods, and potential interventions. The aim is to enhance our understanding of the complex interplay between these two conditions and guide the development of personalized therapeutic strategies to improve patient outcomes. Sarcopenia is recognized as a crucial factor impacting the prognosis, treatment responses, and quality of life of HNC patients. This review discusses various mechanisms, including common etiological factors, such as aging, chronic inflammation, and metabolic dysregulation. Cancer-related factors, including tumor locations and treatment modalities, contribute to the development of sarcopenia. The clinical implications of sarcopenia in HNC patients extend beyond reduced muscle strength; it affects overall mobility, reduces quality of life, and increases the risk of falls and fractures. Sarcopenia serves as an independent predictor of postoperative complications, chemotherapy dose-limiting toxicity, and treatment outcomes, which affect therapy planning and perioperative management decisions. Methods to assess sarcopenia in HNC patients encompass various techniques. A sarcopenia assessment offers a potentially efficient and readily available tool for clinical practice. Interventions and management strategies for sarcopenia involve exercise interventions as a cornerstone; however, challenges arise due to patient-specific limitations during cancer treatment. A routine body composition analysis is proposed as a valuable addition to HNC patient management, with ongoing research required to refine preoperative exercise and nutrition programs for improved treatment outcomes and survival. [ABSTRACT FROM AUTHOR]

Introduction: Head and neck squamous cell carcinoma (HNSCC) ranks sixth among cancers in the world, and the 5-year survival rate ranges from 25% to 60%. The risk factors for HNSCC are primarily smoking, alcohol consumption and human papillomavirus (HPV). Data indicate that 15–20% of cancers are caused by infectious agents, 20–30% by smoking and 30–35% by unhealthy lifestyles, diet, lack of physical activity and obesity. Dysbiosis is a microbiome imbalance, which promotes oncogenesis by intensifying inflammatory processes and affecting the host's metabolism. Profiling the microbiome in various types of cancer is currently the subject of research and analysis. However, there is still little information on the correlation of the microbiome with HNSCC and its impact on oncogenesis, the course of the disease and its treatment. Objective: The aim of the study was to prospectively assess risk factors with assessment of the impact of the microbiome on the risk of squamous cell carcinoma of the larynx. The study included a group of 44 patients diagnosed with squamous cell carcinoma of the larynx and 30 patients from the control group. Results: In the control group, bacteria of the normal microbiome dominated—the genus Streptococcus, Gemella, Neisseria and Kingella. In the group of patients with laryngeal cancer, Prevotella, Clostridiales and Stomatobaculum were found significantly more often. Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia odontolytica were also found at a higher percentage in the study group. Analyzing the phylum, Firmicutes dominated in the control group; there were statistically significantly more of them than in patients from the study group. Bacteroides and Bacillota were found significantly more often in patients with laryngeal cancer. Conclusions: The importance of the microbiome in oncology has been confirmed in many studies. Independent risk factors for laryngeal cancer were primarily a lower number of Firmicutes in the microbiome, but also an increased leukocyte level above 6.52 × 103/mm and a decreased total protein level below 6.9 g/dL. Prevotella, Clostridiales, Stomatobaculum, Porphyromonas, Fusobacterium, Lactobacillus, Actinobacteria, Actinomyces and Shaalia were considered to be the bacteria contributing to the development of laryngeal cancer. Streptococcus, Gemella, Neisserie and Kingella were considered to be protective bacteria. Moreover, the study confirmed the significant impact of smoking, alcohol consumption and poor oral hygiene on the development of laryngeal cancer. The microbiome, its identification and manipulation may constitute a breakthrough discovery for improving the diagnosis and oncological therapy of laryngeal cancer, and also of the entire group of HNSCC. Profiling the microbiome may allow for personalized therapy related to its modification. Assessing the microbiome of patients diagnosed with cancer may provide an opportunity to predict treatment response and effectiveness. [ABSTRACT FROM AUTHOR]

Among all cancers occurring in the head and neck region, oral squamous cell carcinoma (OSCC) is the most common oral malignant tumours characterized by its aggressiveness and metastasis. The development of transcriptomics technology has greatly facilitated the diagnosis of various cancers. However, identifying genetic biomarkers is limited by data from a single batch of OSCC samples, and integrating analysis across different platforms remains a great challenge. In this study, we integrated five OSCC transcriptome datasets using an innovative strategy capable of mitigating batch effect, and extracting information from different datasets based on changes in the relative expression of gene pairs. By leveraging a machine learning method, we developed a prediction model including 27 differential gene pairs (DGPs) to discriminate OSCC from control samples, achieving an area under the receiver operating characteristic curve (AUC) of 0.8987 for the training set. Moreover, the model demonstrated commendable performance in four external validation sets, with AUCs of 0.9926, 0.9688, 0.8052 and 0.8565, respectively. Subsequently, a prognostic model was constructed based on six key gene pairs through univariate and multivariate Cox regression analysis. The AUCs of the model at 1‐year and 3‐year overall survival time prediction were 0.717 and 0.779 in an independent dataset. Our result demonstrates the effectiveness of this new method of integrating data and identifying DGPs. Using DGPs can significantly improve the performance of both diagnostic and prognostic models. [ABSTRACT FROM AUTHOR]

Background: Enhancing the prognosis and treatment outcomes of oral cancer relies heavily on its early detection. This study aims to establish a connection between serum and salivary dipeptidyl peptidase-4 (DPP-4) levels and oral squamous cell carcinoma (OSCC), comparing them with oral potentially malignant lesions (OPMLs) and control subjects and validating salivary DPP-4 as a diagnostic marker for the early detection of oral cancer. Methodology: Forty-five systemically healthy individuals were categorized into three groups: Group I consisted of 15 patients diagnosed with OSCC, Group II comprised 15 patients with OPMLs (including leukoplakia and oral lichen planus), and Group III included 15 participants without any oral mucosal lesions. Serum and whole unstimulated salivary samples were collected from all participants to assess DPP-4 levels using an enzyme-linked immunosorbent assay (ELISA) kit. Receiver operating characteristic (ROC) analysis was conducted to determine the area under the curve (AUC), sensitivity, specificity, and diagnostic accuracy of DPP-4. Results: Both serum and salivary DPP-4 levels were highest in the healthy group, followed by OPMLs, and lowest in the OSCC group, with statistically significant differences observed. ROC analysis demonstrated excellent diagnostic accuracy of salivary DPP-4 in distinguishing OSCC from healthy individuals, OPMLs from healthy individuals, and OSCC from OPMLs, with accuracies of 100%, 100%, and 96.67%, respectively. Salivary DPP-4 levels also exhibited a statistically significant correlation with OSCC grades. Conclusions: DPP-4 appears to play a protective, anti-oncogenic role in maintaining oral tissue health. The remarkable diagnostic accuracy of both serum and salivary DPP-4 in discriminating between OSCC, OPMLs, and healthy controls suggests its potential utility as a well-established marker for early oral cancer diagnosis. Salivary DPP-4, being non-invasive, could serve as a convenient chair-side diagnostic tool for the early detection of OSCC. Clinical trial registration: The study was retrospectively registered on clinicaltrial.gov with NCT06087042, date of registration (first posted date): 17/10/2023 [ABSTRACT FROM AUTHOR]

ABSTRACT Objective Materials and Methods Results Conclusions This study aimed to develop and internally validate a prognostic nomogram for predicting nodal recurrence‐free survival (NRFS) in patients with early‐stage oral squamous cell carcinoma (OSCC) with clinically negative neck lymph nodes.The management of early‐stage oral cancer patients with clinically negative neck lymph nodes (cN0) remains controversial, especially concerning the need for elective neck dissection. Data from a single institution spanning 2010 to 2020 were utilized to develop and evaluate the nomogram. The nomogram was constructed using multivariable Cox regression and LASSO regression analyses to identify independent risk factors for lymph node metastasis. Internal validation was performed using bootstrap resampling to assess the nomogram's predictive accuracy.A total of 930 cN0 patients with T1 and T2 stage OSCC were randomly divided into training and validation cohorts (8:2 ratio). Independent risk factors for lymph node metastasis included tumor pathological grade (well: reference, moderate/poor: OR 1.69), cT (cT1: reference, cT2: OR 2.01), history of drinking (never: reference, current/former: OR 1.72), and depth of invasion (0 mm < DOI ≤ 5 mm: reference, 5 mm < DOI ≤ 10 mm: OR 1.31). The nomogram, incorporating these variables, demonstrated good predictive accuracy with a C‐index of 0.67 (95% CI: 0.58–0.76) in the validation set. In both training and validation groups, the nomogram effectively stratified patients into low‐risk and high‐risk groups for occult cervical nodal metastases (p < 0.05).The nomogram enables risk stratification and improved identification of occult cervical nodal metastases in clinically node‐negative OSCC patients by incorporating tumor‐specific and patient‐specific risk factors. [ABSTRACT FROM AUTHOR]

AbstractHypopharyngeal cancer is rare subtype of head and neck cancers with relatively poor prognosis. Current therapeutic modalities lack the potential to provide patients with better clinical outcome and quality of life. This study was conducted on the synthesis of 2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl-4-(2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl)-4-oxobutanoates (3) using biologically important 1,2,4-triazole. The condensation of 3-alkyl(aryl)-4-amino-4,5-dihydro-1H-1,2,4-triazol-5-ones (1) with 4-formyl-2-methoxyphenyl-4-(4-formyl-2-methoxyphenyl)-4-oxobutanoate yielded the biologically active 2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl-4-(2-methoxy-4-((3-alkyl(aryl)-5-oxo-1H-1,2,4-triazol-4(5H)-ylimino)-methyl)-phenyl)-4-oxobutanoates (3). The compounds obtained were analyzed via FT-IR,1H-/13C-NMR spectrometers, elemental analysis, and HRMS spectroscopic techniques. Furthermore, we aimed at investigating the potential of compounds 3a-g against FaDu hypopharyngeal cancer cells. We demonstrated that compounds 3c, 3e, and 3 g had relatively lower IC50 values compared to the remaining tested compounds and more importantly their IC50 values were comparable to 5-FU, which suggests them as important therapeutic agent candidates. These newly synthesized compounds were assessed for their inhibitory activities toward two human carbonic anhydrase isoforms I and II (hCA I and II). Then, molecular docking calculations were made to compare the biological activities of studied molecules against cancer proteins. Compound 3c has a docking score of −7.15 against squamous cell carcinoma protein with ID: 2DO4 and −5.49 docking score against squamous cell carcinoma protein with ID:5PJZ. ADME/T analysis was performed to examine the drug properties of studied molecules. [ABSTRACT FROM AUTHOR]

Background: Evidence has been presented that the tumor protein D52 (TPD52) family plays a critical role in tumor development and progression. As a member of the TPD52 family, the changes in TPD52L2 gene status are instrumental in kinds of cancer development. However, its effects on patient prognosis and immune infiltration in Head and Neck Squamous Carcinoma (HNSCC) are still poorly understood. Methods: The Tumor Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and c-BioPortal database was used to explore the expression pattern, prognostic value, and variation of gene status in HNSCC. The LinkedOmics database was used to obtain the co-expression genes of TPD52L2 and identify the diagnostic value of TPD52L2 in HNSCC. The correlations between TPD52L2 expression and six main types of immune cell infiltrations and immune signatures were explored using Tumor Immune Estimation Resource (TIMER). The correlation between TPD52L2 expression and immune checkpoint genes (ICGs) was analyzed by TCGA database. Immunohistochemistry (IHC) was performed to validate the expression of three ICGs (PDL1, PDL2, EGFR) and TPD52L2 using 5 paired HNSCC and normal head and neck tissues. Polymerase Chain Reaction (PCR) and Western Blot (WB) of HNSCC and normal head and neck cell lines were performed to verify the high level of TPD52L2 mRNA and protein expression. protein expression of TPD52L2 in pan-cancer was also validated using UALCAN. Results: TPD52L2 was overexpressed in tumor tissues, and it predicted worse survival status in HNSCC. ROC analysis suggested that TPD52L2 had a diagnostic value. Multivariate Cox analysis identified TPD52L2 as an independent negative prognostic marker of overall survival. Functional network analysis suggested that TPD52L2 was associated with immune-related signaling pathways, cell migration pathways, and cancer-related pathways. High expression of TPD52L2 was associated with a more mutant frequency of TP53. Notably, we found that the expression of TPD52L2 was closely negatively correlated with the infiltration levels of 15 types of immune cells and positively correlated with several immune markers. PCR, WB experiments, and UALCAN database verified the high level of TPD52L2 mRNA and protein expression. Conclusion: TPD52L2 is upregulated in HNSCC, which is an independent factor for adverse prognosis prediction. It probably plays a role in the negative regulation of immune cell infiltration. TPD52L2 might be a promising prognostic biomarker and therapeutic target in HNSCC. [ABSTRACT FROM AUTHOR]

This paper presents a multifaceted assessment of inhibitors of anti-apoptotic proteins (IAPs) in the context of head and neck squamous cell carcinoma (HNSCC). The article discusses the results of in vitro, in vivo, and clinical studies, highlighting the significance of IAPs in the resistance of cancer cells to apoptosis, which is a key factor hindering effective treatment. The main apoptosis pathways, including the intrinsic and extrinsic pathways, and the role of IAPs in their regulation, are presented. The study's findings suggest that targeting IAPs with novel therapies may offer clinical benefits in the treatment of advanced HNSCC, especially in cases resistant to conventional treatment methods. These conclusions underscore the need for further research to develop more effective and safer therapeutic strategies. [ABSTRACT FROM AUTHOR]

The oral cavity is a frequent site for head and neck cancers, which rank as the sixth most common cancer globally, with a 5-year survival rate slightly over 50%. Current treatments are limited, and resistance to therapy remains a significant clinical obstacle. IsCT1, a membrane-active peptide derived from the venom of the scorpion Opisthacanthus madagascariensis, has shown antitumor effects in various cancer cell lines, including breast cancer and chronic myeloid leukemia. However, its hemolytic action limits its potential therapeutic use. This study aims to assess the antitumor and antiproliferative activities of synthetic peptides derived from IsCT1 (IsCT-P, AC-AFPK-IsCT1, AFPK-IsCT1, AC-KKK-IsCT1, and KKK-IsCT1) in the context of oral squamous cell carcinoma. We evaluated the cytotoxic effects of these peptides on tongue squamous cell carcinoma cells and normal cells, as well as their impact on cell cycle phases, the expression of proliferation markers, modulators of cell death pathways, and mitochondrial potential. Our results indicate that the IsCT1 derivatives IsCT-P and AC-AFPK-IsCT1 possess cytotoxic properties towards squamous cell carcinoma cells, reducing mitochondrial membrane potential and the proliferative index. The treatment of cancer cells with AC-AFPK-IsCT1 led to a positive modulation of pro-apoptotic markers p53 and caspases 3 and 8, a decrease in PCNA and Cyclin D1 expression, and cell cycle arrest in the S phase. Notably, contrary to the parental IsCT1 peptide, AC-AFPK-IsCT1 did not exhibit hemolytic activity or cytotoxicity towards normal cells. Therefore, AC-AFPK-IsCT1 might be a viable therapeutic option for head and neck cancer treatment. [ABSTRACT FROM AUTHOR]

Head and neck squamous cell carcinomas (HNSCC) are among the most common malignancies in men worldwide. Nevertheless, their clinical management is hampered by the limited availability of reliable predictive and prognostic biomarkers. Protein kinase D (PKD) isoforms contribute to major cellular processes. However, their potential role in HNSCC has not been studied systematically, which is the focus of this study. A total of 63 therapy-naive patients with squamous cell carcinoma were consecutively enrolled. Tissue microarray duplicate cores from each case were tested in situ for PKD1, PKD2, and PKD3 expression using immunohistochemistry, and the results were correlated with clinicopathological parameters. We found a high frequency of PKD1/PKD2 positive cases in oropharyngeal and PKD2 positive cases in laryngeal localizations. Only high PKD2 levels were statistically linked to elevated tumor grades, more advanced TNM (3–4) tumor stages, and p16INK4a expression, while elevated PKD3 levels were associated with favorable disease-specific survival. Both PKD2 and PKD3 have been proposed to promote tumor cell proliferation, migration/invasion, and angiogenesis. However, the role of PKD3 was elusive in some cancers. Our findings suggest that testing for PKD isotypes with immunohistochemistry may support the diagnostic estimation of tumor progression and prognosis in HNSCC with a potential therapeutic relevance. [ABSTRACT FROM AUTHOR]

Simple Summary: This research investigates how personal and health-related factors impact the quality of life of head and neck cancer survivors treated with radiotherapy and surgery. By studying 150 patients—60 with nasopharyngeal cancer and 90 with oral cavity cancer—researchers utilized a specific survey to assess the effects of various elements, including cancer type, age, gender, relationship status, education, and employment. Findings revealed that cancer type, treatment history, and employment status significantly influenced quality of life. Patients with nasopharyngeal cancer reported better social and functional outcomes than those with oral cavity cancer. Additionally, unemployment was correlated with lower quality of life, while having a partner and undergoing certain surgeries positively impacted outcomes. These insights can aid research efforts to better support cancer survivors and customize treatment approaches for improved well-being. Objectives: This study aimed to examine the relationship between health-related quality of life (HRQoL) and sociodemographic and clinical variables in survivors of head and neck cancer (HNC) treated with radiotherapy, with or without surgery. Materials and Methods: HRQoL was measured using the functional assessment of cancer therapy—head and neck (FACT-H&N) in a cross-sectional survey involving 150 patients. Of these, 60 had nasopharyngeal cancer (NPC), treated exclusively with radiotherapy, while 90 had oral cavity squamous cell cancer (OSCC), undergoing radical surgery followed by adjuvant radiotherapy. Key variables included cancer type, age, gender, partnership status, education, and employment, with additional clinical variables assessed in patients with OSCC. Statistical analyses included multiple regression, ANOVA, and t-tests to explore relationships between variables and HRQoL. Results: Cancer type, surgical treatment, and employment status emerged as significant independent predictors of HRQoL in HNC patients. Patients with NPC reported better HRQoL on three FACT-H&N subscales—social/family well-being, functional well-being, and additional concerns—compared to patients with OSCC. Unemployed individuals exhibited lower HRQoL on four subscales. In patients with OSCC, partnership status and segmental mandibulectomy were found to predict HRQoL independently. Conclusions: This study concludes that cancer type, surgical intervention, and employment status notably influence HRQoL among HNC patients undergoing radiotherapy. In addition, partnership status is a key factor affecting HRQoL in patients with OSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer-associated cachexia is a serious complication that can arise in patients with head and neck cancer due to both the disease and its treatments. It causes severe weight loss, muscle and fat depletion, and systemic inflammation, which significantly diminish patients' quality of life and survival. This study uses advanced machine learning techniques to improve the prediction and understanding of cachexia. By analyzing detailed imaging and clinical data, the research seeks to identify early signs of cachexia, providing insights that could help shape future management strategies. Our findings suggest that specific imaging biomarkers, particularly pancreatic volume, could play a crucial role in predicting cachexia, potentially leading to improved treatment outcomes for affected patients. Background/Objectives: Cancer-associated cachexia in head and neck squamous cell carcinoma (HNSCC) is challenging to diagnose due to its complex pathophysiology. This study aimed to identify metabolic biomarkers linked to cachexia and survival in HNSCC patients using [18F]FDG-PET/CT imaging and machine learning (ML) techniques. Methods: We retrospectively analyzed 253 HNSCC patients from Vienna General Hospital and the MD Anderson Cancer Center. Automated organ segmentation was employed to quantify metabolic and volumetric data from [18F]FDG-PET/CT scans across 29 tissues and organs. Patients were categorized into low weight loss (LoWL; grades 0–2) and high weight loss (HiWL; grades 3–4) groups, according to the weight loss grading system (WLGS). Machine learning models, combined with Cox regression, were used to identify survival predictors. Shapley additive explanation (SHAP) analysis was conducted to determine the significance of individual features. Results: The HiWL group exhibited increased glucose metabolism in skeletal muscle and adipose tissue (p = 0.01), while the LoWL group showed higher lung metabolism. The one-year survival rate was 84.1% in the LoWL group compared to 69.2% in the HiWL group (p < 0.01). Pancreatic volume emerged as a key biomarker associated with cachexia, with the ML model achieving an AUC of 0.79 (95% CI: 0.77–0.80) and an accuracy of 0.82 (95% CI: 0.81–0.83). Multivariate Cox regression confirmed pancreatic volume as an independent prognostic factor (HR: 0.66, 95% CI: 0.46–0.95; p < 0.05). Conclusions: The integration of metabolic and volumetric data provided a strong predictive model, highlighting pancreatic volume as a key imaging biomarker in the metabolic assessment of cachexia in HNSCC. This finding enhances our understanding and may improve prognostic evaluations and therapeutic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Head and neck squamous cell carcinoma (HNSCC) is a complex and varied cancer that is difficult to treat due to its biological diversity. Single-cell RNA sequencing (scRNAseq) offers a way to study HNSCC by examining individual cells within tumors. This technology helps identify different cell types and their roles in cancer development, diagnosis, and treatment. By understanding how various cells respond to treatments like chemotherapy and immunotherapy, scRNAseq can enhance the study of cancer biology and improve therapeutic outcomes. This review highlights the significant impact of scRNAseq on HNSCC research and its potential to advance the study of other cancers. Background/Objectives: Head and neck squamous cell carcinoma (HNSCC) is a highly heterogeneous and the most common form of head and neck cancer, posing significant challenges for disease management. The objective of this review is to assess the utility of single-cell RNA sequencing (scRNAseq) in addressing these challenges by enabling a detailed characterization of the tumor microenvironment (TME) at the cellular level. Methods: This review compiles and analyzes current strategies that utilize scRNAseq and other single-cell technologies in HNSCC research. Results: For HNSCC etiology, scRNAseq allows for the construction of cellular atlases, characterization of different cell types, and investigation of genes and processes involved in cancer initiation, development, and progression within the TME. In terms of HNSCC diagnosis and prognosis, the resolution offered by scRNAseq enables the identification of cell type-specific signatures, enhancing prognostic models and disease stratifiers for patient outcome assessments. Regarding HNSCC treatment, scRNAseq provides insights into cellular responses to various treatments, including radiotherapy, chemotherapy, and immunotherapy, contributing to a better understanding of treatment efficacy and patient outcomes. Conclusions: This review highlights the contributions of scRNAseq to HNSCC research, addressing its cellular and biological complexity, and emphasizes its potential for advancing research and clinical practice in other cancer types. [ABSTRACT FROM AUTHOR]

Zinc finger E‐box binding homeobox 1 (ZEB1) has been identified as a key factor in cancer cell differentiation and metastasis, and has been well studied in the field of cancer cell biology. ZEB2 has a highly similar conformation to ZEB1, but its role in head and neck squamous cell carcinoma (HNSCC) cells is not fully understood. Here, we separately overexpressed ZEB1 and ZEB2 in C57BL/6 mouse oral cancer (MOC) cells and investigated their cellular characteristics, including E‐cadherin levels, motile properties, chemoresistance, and metastatic ability in immunocompetent mice. Both ZEB1 and ZEB2 overexpression reduced epithelial traits and converted cells to an aggressive phenotype. Surprisingly, ZEB1 overexpression increased the endogenous level of ZEB2 in MOC cells, and vice versa. The molecular mechanisms underlying these findings remain unclear. However, the in vitro anchorage‐independent growth of MOC cells overexpressing ZEB2 was considerably greater than that of MOC cells overexpressing ZEB1. These findings suggest that ZEB2, like ZEB1, has the ability to induce the differentiation of cancer cells into those with highly aggressive traits. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to determine the role of c‐Fos in growth and invasion of oral squamous cell carcinoma (OSCC). Methods: Immunohistochemistry was used to assess c‐Fos expression in 94 OSCC tissues and 30 adjacent normal tissues, the correlation between c‐Fos expression and clinicopathological characteristics was examined, and Kaplan–Meier and Cox analysis were used to investigate the role of c‐Fos in predicting the prognosis of OSCC patients. The effects of c‐Fos on the growth and invasion of OSCC were disclosed by overexpression and knockdown of c‐Fos. Furthermore, based on bioinformatics prediction, the effect of miR‐155‐5p on c‐Fos expression was examined, and dual‐luciferase reporter assay system was used to determine whether miR‐155‐5p regulated the transcriptional activity of c‐Fos in OSCC. Results: c‐Fos was markedly increased in OSCC tissues and cells. c‐Fos upregulation indicates a poor prognosis in OSCC patients, and c‐Fos promotes cell proliferation, migration, and invasion in OSCC. miR‐155‐5p could regulate the expression and the transcriptional activity of c‐Fos by directly targeting the c‐Fos 3′‐UTR. Conclusion: This study demonstrated that c‐Fos contributed to the progression of OSCC and may act as a potential target for OSCC therapy, and a potential prognostic biomarker of OSCC. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the inhibitory effects of STM2457, which is a novel METTL3 (m6A writer) inhibitor, both as a monotherapy and in combination with anlotinib, in the treatment of oral squamous cell carcinoma (OSCC) both in vitro and in vivo. Materials and Methods: The efficacy of STM2457 or STM2457 plus anlotinib was evaluated using two OSCC cell lines by CCK8, transwell, colony formation, would‐healing, sphere formation, cell cycle, apoptosis assays, and nude mice tumor xenograft techniques. The molecular mechanism study was carried out by western blotting, qRT‐PCR, MeRIP‐qPCR, immunofluorescence, and immunohistochemistry. Results: STM2457 combined with anlotinib enhanced inhibition of cellular survival/proliferation and promotion of apoptosis in vitro. Moreover, this combinatorial approach exerted a notable reduction in stemness properties and EMT (epithelial‐mesenchymal transition) features of OSCC cells. Remarkably, in vivo studies validated the efficacy of the combination treatment. Mechanistically, our investigations revealed that the combined action of STM2457 and anlotinib exerted downregulatory effects on EGFR (epidermal growth factor receptor) expression in OSCC cells. Conclusions: The combination of STM2457 and anlotinib targeting EGFR exerted a multiple anti‐tumor effect. In near future, anlotinib combined with STM2457 may provide a novel insight for the treatment of OSCC. [ABSTRACT FROM AUTHOR]

Objective: Immune checkpoint inhibitors (ICI) are recommended as the first‐line therapy for platinum‐refractory head and neck squamous cell carcinoma (HNSCC), a disease with a poor prognosis. However, biomarkers in this situation are rare. The objective was to identify radiomic features‐associated biomarkers to guide the prognosis and treatment opinions in the era of ICI. Methods: A total of 31 platinum‐refractory HNSCC patients were retrospectively enrolled. Of these, 65.5% (20/31) received ICI‐based therapy and 35.5% (11/31) did not. Radiomic features of the primary site at the onset of recurrent metastatic (R/M) status were extracted. Prognostic and predictive radiomic biomarkers were analysed. Results: The median overall survival from R/M status (R/M OS) was 9.6 months. Grey‐level co‐occurrence matrix‐associated texture features were the most important in identifying the patients with or without 9‐month R/M death. A radiomic risk‐stratification model was established and equally separated the patients into high‐, intermittent‐ and lower‐risk groups (1‐year R/M death rate, 100.0% vs. 70.8% vs. 27.1%, p = 0.001). Short‐run high grey‐level emphasis (SRHGE) was more suitable than programmed death ligand 1 (PD‐L1) expression in selecting whether patients received ICI‐based therapy. Conclusions: Radiomic features were effective prognostic and predictive biomarkers. Future studies are warranted. [ABSTRACT FROM AUTHOR]

The major prognostic factor in head-neck squamous cell carcinoma is the status of lymph nodes. Though there are studies addressing the role of neck dissection in organ preservation protocol, a lacuna still exists as far as the question of upfront neck dissection arises. Despite the potential benefits of upfront neck dissection; the benefits have not been well researched and thus its place in management of head-neck cancers undergoing organ preservation protocol is still questionable. We conducted an observational study in 22 patients with T1 − 2N2 − 3a biopsy proven squamous cell carcinoma of hypopharynx, oropharynx and laryngopharynx which were eligible for organ preservation protocol for their primary site. The primary outcome was to calculate their overall survival rate at 5 years. Overall 5 year survival rate was 68.12%, 5-year Disease free survival rate was 77.2%. The time to start for the primary site, after neck dissection however had a significant effect on overall survival. Those who had a delay of 21 days or less had 80.1% survival at 5 years compared to those who started at 30 days (61.3%) and drastically reduced in those who started at 39 days (20.4%). Log-rank test for the effect of nodal status showed a significant difference in terms of 5 year survival between the groups(p =.027). The 5 year survival rates for N2A, N3A and N2B nodal status were 88.8%, 50% ,and 54.5% ,respectively. We strongly favour upfront neck dissections in a subset of head-neck squamous cell carcinoma cases with T1 − 2N2 − 3a eligible for organ preservation regimen. [ABSTRACT FROM AUTHOR]

Background: Laryngeal cancer is a common advanced head and neck cancer. Surgery, radiation, chemotherapy, or a combination of these treatments are used to treat locally advanced laryngeal cancer. Total laryngectomy is generally preferred for T3-4 laryngeal cancers, despite being an invasive procedure. Post-surgical hypocalcemia is a known complication of neck compartment surgeries, and patients who have undergone laryngectomy are at a higher risk of developing hypoparathyroidism, leading to hypocalcemia. This study aims to investigate the prevalence and risk factors of hypocalcemia in individuals following laryngectomy. Method: This retrospective study examined 50 consecutive laryngectomy patients over eight years. Data on demographic characteristics, medical history, surgical details, pre-and post-operative calcium levels, neck dissection laterality, history of radiotherapy were collected. Hypocalcemia was defined as calcium levels < 8.5 mg/dl or corrected calcium < 8.5 mg/dl. Statistical analyses included paired t-tests, Wilcoxon signed-rank tests, and binary logistic regression using R studio. Results: The mean age of participants was 59 years, predominating males (94%) and habitual smokers (94%). Squamous cell carcinoma was the most prevalent (98%) pathological diagnosis, and various surgical techniques were employed. While initial comparisons showed no significant changes in calcium levels pre-and post-operatively, adjusting for albumin levels revealed a significant association. Logistic regression identified neck dissection, low pre-operative calcium, radiotherapy, and total thyroidectomy as significant predictors of post-operative hypocalcemia (p < 0.05). Conclusion: Surgical factors such as neck dissection and total thyroidectomy, alongside albumin levels, significantly impact postoperative hypocalcemia. These findings underscore the need for meticulous monitoring and potential preventive measures to manage calcium imbalance post-laryngectomy. [ABSTRACT FROM AUTHOR]

Oral tongue squamous cell cancer (OTSCC) is one of the most prevalent cancers worldwide and incidence increases with age. An alarming increase in the incidence of OTSCC in the younger age group. This study aimed to explore clinical and histopathological characteristics, survival, and other post-surgical outcomes in patients with OTSCC treated with glossectomy through the Department of Otolaryngology-Head & Neck Surgery at the Ministry of National Guard Health Affairs (MNGHA) within our study period. This is a retrospective study carried out through the collection and analysis of data from medical charts of 56 patients with oral tongue cancer who were treated by glossectomy. Treatment was initiated from January 2010 to December 2021. Patient characteristics, tumor characteristics, treatment modality, failure patterns, and survival rates were collected and analyzed. At diagnosis, 62.5% were tobacco smokers, 46.8% had poor dental hygiene, and 76.8% had ulcerative lesions. Furthermore, 33 cases presented with early-stage clinical disease and 23 cases with advanced stage. The median follow-up was 54 months, 28 patients (50%) were free for 3–5 years. Patients who were free on 5-year follow-up had a significantly higher percentage of negative lymphovascular and perineural invasion (p < 0.05). Additionally, 12 patients (21.4%) had developed recurrence. Mortality in all cases was 30.3, but mortality-related cancer was 19.6%. Locoregional failure remains the main cause of treatment failure in resectable OTSCC. Pathological T-stage, N-stage, LVI, PNI, ECE, and LNR are all considered strong prognostic factors. [ABSTRACT FROM AUTHOR]

Background: Platelet‐derived growth factor A (PDGFA) has been shown to be upregulated in several tumors, contributing to their malignant phenotypes. However, its expression and function in head and neck squamous cell carcinoma (HNSC) are not clearly understood. Thus, we aimed to evaluate this issue using bioinformatic analyses and primary experimental validation. Methods: The expression of PDGFA was analyzed using popular bio‐databases and further validated by RT‐PCR and immunohistochemical staining. Survival analyses were then performed. The association between PDGFA expression levels and immune cell infiltration in the immune microenvironment was assessed. Results: PDGFA has been found to be significantly upregulated in a variety of cancers, including HNSC, and increased PDGFA expression may be an independent prognostic factor associated with immune cell infiltration in HNSC. Conclusion: Overexpression of PDGFA in HNSC is significantly associated with poor prognosis and immune cell infiltration in the tumor microenvironment (TME). PDGFA has potential as a molecular indicator for diagnosis, prognosis, and immune processes in HNSC. [ABSTRACT FROM AUTHOR]

Introduction: Squamous cell carcinoma (SCC) of the head and neck is a great burden globally, which is being tackled through treatment options of surgery, radiation therapy, chemotherapy, or a combination of these, to avoid disease-related mortality. Multidisciplinary tumour boards play a pivotal role in customising and deciding management plan based on clinical aspects. The objective of the study is to determine the concordance of opinion between the treatment plan of a primary physician and board members. Material and methods: This is a retrospective cross-sectional study that includes 137 head and neck carcinoma cases. They were discussed in the multidisciplinary tumour board meeting and were reviewed; all demographics were analysed including the tumour staging and the decisions of the primary physician was compared with those of the board. To check the concordance between primary surgeon plans or after board discussion Kappa agreement test was used. Results: Total of 137 patients were included in the study out of which 63 cases were pre-treatment and 74 cases were post-treatment, i.e., surgically treated cases, with the distribution being 46% and 54%, respectively. Most cases, totaling 120, were SCC, accounting for 80% of the total cases. Among the pre-treatment cases, T4a and N0 were the most common categories, with 29 and 40 cases, respectively. Similarly, in post-treatment cases, the majority fell into the T4a and N1 categories, with 29 and 38 cases, respectively. When comparing the primary surgeon's plan with the tumour board meeting decision, the agreement showed a value of 0.273, indicating a slight level of agreement between the two entities. Conclusion: Our data indicates that the multidisciplinary head and neck tumour board may have influenced the treatment plans of the primary surgeon, in approximately one in two patients (43.06%). [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]