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Background: Recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is characterized by a complex therapeutic management that needs to be discussed in multidisciplinary tumor boards (MDT). While artificial intelligence (AI) improved significantly to assist healthcare professionals in making informed treatment decisions for primary cases, an application in the even more complex recurrent/metastatic setting has not been evaluated yet. This study also represents the first evaluation of the recently published LLM ChatGPT 4o, compared to ChatGPT 4.0 for providing therapy recommendations. Methods: The therapy recommendations for 100 HNSCC cases generated by each LLM, 50 cases of recurrence and 50 cases of distant metastasis were evaluated by two independent reviewers. The primary outcome measured was the quality of the therapy recommendations measured by the following parameters: clinical recommendation, explanation, and summarization. Results: In this study, ChatGPT 4o and 4.0 provided mostly general answers for surgery, palliative care, or systemic therapy. ChatGPT 4o proved to be 48.5% faster than ChatGPT 4.0. For clinical recommendation, explanation, and summarization both LLMs obtained high scores in terms of performance of therapy recommendations, with no significant differences between both LLMs, but demonstrated to be mostly an assisting tool, requiring validation by an experienced clinician due to a lack of transparency and sometimes recommending treatment modalities that are not part of the current treatment guidelines. Conclusion: This research demonstrates that ChatGPT 4o and 4.0 share a similar performance, while ChatGPT 4o is significantly faster. Since the current versions cannot tailor therapy recommendations, and sometimes recommend incorrect treatment options and lack information on the source material, advanced AI models at the moment can merely assist in the MDT setting for recurrent/metastatic HNSCC. [ABSTRACT FROM AUTHOR]

Simple Summary: We present in this study novel data which demonstrates that the most common type of tumor of the salivary glands may be accurately diagnosed using a specific type of radiological imaging. This may be used to help discriminate this tumor or recurrent versions of it amid various types of benign and malignant tumors. Furthermore, this data suggest that new avenues of minimally invasive therapy may be viable for these tumors and potentially even malignant versions of these tumors and should be examined in further studies. Introduction: Currently, the diagnosis of salivary gland tumors using imaging techniques is unreliable. Methods: In this monocentric retrospective study, we examined patients who received a 68Ga-DOTATOC PET/CT and subsequently underwent a salivary gland tumor resection between 1 January 2010 and 31 December 2021. PET/CT image assessment was compared with somatostatin receptor (SSTR) expression and histology. Results: Thirteen patients (five pleomorphic adenoma (PA) and eight other parotid lesions (OPL)) received a 68Ga-DOTATOC PET/CT. Imaging displayed strong focal tracer uptake in all PA except for one with strong tumor to background discrimination. PA revealed higher SUVmax, SUVmean, liver and blood pool quotients than those of Warthin tumors (WT) and of OPL. In comparison to the contralateral parotid, SUVmax (p = 0.02), SUVmean (p = 0.02), liver quotient (p = 0.03) and blood pool quotient (p = 0.03) were all significantly higher. In contrast, WT and OPL showed in relation to the contralateral parotid no significant differences of SUVmax (WT p = 0.79; OPL p = 0.11), SUVmean (WT p = 1.0; OPL p = 0.08), liver quotient (WT p = 0.5; OPL p = 0.08) and blood pool quotient (WT p = 0.8; OPL p = 0.19). Two PA and one granuloma were not available for examination. In the immunohistochemal analysis, all PA demonstrated the highest intensity of SSTR2 expression (grade 3). Furthermore, PA had a high percentage of cells expressing SSTR2 (20%, 80% and 55%). Conclusions: A strong tracer uptake in PA was shown in 68Ga-DOTATOC PET/CT. This may allow physicians to utilize radioligated somatostatin analogue PET CT/MR imaging to accurately diagnose PA. Additionally, it may be possible in the future to treat the PA with a noninvasive peptide receptor radionuclide therapy or with somatostatin analogues. [ABSTRACT FROM AUTHOR]

Purpose: The use of AI-powered technology, particularly OpenAI's ChatGPT, holds significant potential to reshape healthcare and medical education. Despite existing studies on the performance of ChatGPT in medical licensing examinations across different nations, a comprehensive, multinational analysis using rigorous methodology is currently lacking. Our study sought to address this gap by evaluating the performance of ChatGPT on six different national medical licensing exams and investigating the relationship between test question length and ChatGPT's accuracy. Methods: We manually inputted a total of 1,800 test questions (300 each from US, Italian, French, Spanish, UK, and Indian medical licensing examination) into ChatGPT, and recorded the accuracy of its responses. Results: We found significant variance in ChatGPT's test accuracy across different countries, with the highest accuracy seen in the Italian examination (73% correct answers) and the lowest in the French examination (22% correct answers). Interestingly, question length correlated with ChatGPT's performance in the Italian and French state examinations only. In addition, the study revealed that questions requiring multiple correct answers, as seen in the French examination, posed a greater challenge to ChatGPT. Conclusion: Our findings underscore the need for future research to further delineate ChatGPT's strengths and limitations in medical test-taking across additional countries and to develop guidelines to prevent AI-assisted cheating in medical examinations. [ABSTRACT FROM AUTHOR]

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.

Although small-interfering RNAs (siRNAs) are specific silencers for numerous disease-related genes, their clinical applications still require safe and effective means of delivery into target cells. Highly efficient lipid nanoparticles (LNPs) are developed for siRNA delivery, showcasing the advantages of novel pH-responsive lipoamino xenopeptide (XP) carriers. These sequence-defined XPs are assembled by branched lysine linkages between cationizable polar succinoyl tetraethylene pentamine (Stp) units and apolar lipoamino fatty acids (LAFs) at various ratios into bundle or U-shape topologies. Formulation of siRNA-LNPs using LAF 4 -Stp 1 XPs as ionizable compounds led to robust cellular uptake, high endosomal escape, and successful in vitro gene silencing activity at an extremely low (150 picogram) siRNA dose. Of significance is the functional in vivo endothelium tropism of siRNA-LNPs with bundle LAF 4 -Stp 1 XP after intravenous injection into mice, demonstrated by superior knockdown of liver sinusoidal endothelial cell (LSEC)-derived factor VIII (FVIII) and moderate silencing of hepatocyte-derived FVII compared to DLin-MC3-DMA-based LNPs. Optimizing lipid composition following click-modification of siRNA-LNPs with ligand c(RGDfK) efficiently silenced vascular endothelial growth factor receptor-2 (VEGFR-2) in tumor endothelial cells (TECs). The findings shed light on the role of ionizable XPs in the LNP in vivo cell-type functional targeting, laying the groundwork for future therapeutic applications., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)