Applications In Oncology Research Articles

Empowering health care consumers & understanding patients' perspectives on AI integration in oncology and surgery: A perspective.

Artificial intelligence (AI) is transforming oncology and surgery by improving diagnostics, personalizing treatments, and enhancing surgical precision. Patients appreciate AI for its potential to provide accurate prognoses and tailored therapies. However, AI's implementation raises ethical concerns, data privacy issues, and the need for transparent communication between patients and health care providers. This study aims to understand patients' perspectives on AI integration in oncology and surgery to foster a balanced and patient-centered approach. The study utilized a comprehensive literature review and analysis of existing research on AI applications in oncology and surgery. The focus was on examining patient perceptions, ethical considerations, and the potential benefits and risks associated with AI integration. Data was collected from peer-reviewed journals, conference proceedings, and expert opinions to provide a broad understanding of the topic. The perspectives of patients was also emphasized to highlight the nuances of their acceptance and concerns regarding AI in their health care. Patients generally perceive AI in oncology and surgery as beneficial, appreciating its potential for more accurate diagnoses, personalized treatment plans, and improved surgical outcomes. They particularly value AI's role in providing timely and precise diagnostics, which can lead to better prognoses and reduced anxiety. However, concerns about data privacy, ethical implications, and the reliability of AI systems were prevalent. Consequently, trust in AI and health care providers was deemed as a crucial factor for patient acceptance. Additionally, the need for transparent communication and ethical safeguards was also highlighted to address these concerns effectively. The integration of AI in oncology and surgeryholds significant promise for enhancing patient care and outcomes. Patients view AI as a valuable tool that can provide accurate prognoses and personalized treatments. However, addressing ethical concerns, ensuring data privacy, and building trust through transparent communication are essential for successful AI integration. Future initiatives should focus on refining AI algorithms, establishing robust ethical guidelines, and enhancing patient education to harmonize technological advancements with patient-centered care principles.

Dissecting the antitumor effects of Scutellaria barbata: Initial insights into the metabolism of scutellarin and luteolin by gut microbiota

The high prevalence of cancer and detrimental side effects associated with many cancer treatments necessitate the search for effective alternative therapies. Natural products are increasingly being recognized and investigated for their potential therapeutic benefits. Scutellaria barbata D. Don (SBD), a plant with potent antitumor properties, has attracted significant interest from oncology researchers. Its primary flavonoid components—scutellarin and luteolin—which have limited oral bioavailability due to poor absorption. This hinders its application for cancer treatment. The gut microbiota, which is considered a metabolic organ, can modulate the biotransformation of compounds, thereby altering their bioavailability and efficacy. In this study, we employed liquid chromatography tandem mass spectrometry (LC-MS/MS 8060) and ion trap-time of flight (LC-MSn-IT-TOF) analysis to investigate the ex vivo metabolism of scutellarin and luteolin by the gut microbiota. Five metabolites and one potential metabolite were identified. We summarized previous studies on their antitumor effects and performed in vitro tumor cell line studies to prove their antitumor activities. The possible key pathway of gut microbiota metabolism in vitro was validated using molecular docking and pure enzyme metabolic experiments. In addition, we explored the antitumor mechanisms of the two components of SBD through network pharmacology, providing a basis for subsequent target identification. These findings expand our understanding of the antitumor mechanisms of SBD. Notably, this study contributes to the existing body of knowledge regarding flavonoid biotransformation by the gut microbiota, highlighting the therapeutic potential of SBD in cancer treatment. Moreover, our results provide a theoretical basis for future in vivo pharmacokinetic studies, aiming to optimize the clinical efficacy of SBD in oncological applications.

Synthetic Modifications of Andrographolide Targeting New Potential Anticancer Drug Candidates: A Comprehensive Overview.

This review collects the synthetic modifications performed on andrographolide, a natural molecule derived from Andrographis paniculata, for oncology applications. Various pharmacomodulations were carried out, and the products were tested on different cancer cell lines. The impact of these modifications was analyzed with the aim of mapping the positions essential for activity to facilitate future research in this field. However, this study makes it clear that, in addition to structural modifications of the molecule, which can result in varying degrees of effectiveness in targeting interactions, the lipophilic capacity of the structures obtained through hemisynthesis is of significant importance.

The Immune System-A Double-Edged Sword for Adenovirus-Based Therapies.

Pathogenic adenovirus (Ad) infections are widespread but typically mild and transient, except in the immunocompromised. As vectors for gene therapy, vaccine, and oncology applications, Ad-based platforms offer advantages, including ease of genetic manipulation, scale of production, and well-established safety profiles, making them attractive tools for therapeutic development. However, the immune system often poses a significant challenge that must be overcome for adenovirus-based therapies to be truly efficacious. Both pre-existing anti-Ad immunity in the population as well as the rapid development of an immune response against engineered adenoviral vectors can have detrimental effects on the downstream impact of an adenovirus-based therapeutic. This review focuses on the different challenges posed, including pre-existing natural immunity and anti-vector immunity induced by a therapeutic, in the context of innate and adaptive immune responses. We summarise different approaches developed with the aim of tackling these problems, as well as their outcomes and potential future applications.

In silico approaches for drug repurposing in oncology: a scoping review.

Introduction: Cancer refers to a group of diseases characterized by the uncontrolled growth and spread of abnormal cells in the body. Due to its complexity, it has been hard to find an ideal medicine to treat all cancer types, although there is an urgent need for it. However, the cost of developing a new drug is high and time-consuming. In this sense, drug repurposing (DR) can hasten drug discovery by giving existing drugs new disease indications. Many computational methods have been applied to achieve DR, but just a few have succeeded. Therefore, this review aims to show in silico DR approaches and the gap between these strategies and their ultimate application in oncology. Methods: The scoping review was conducted according to the Arksey and O'Malley framework and the Joanna Briggs Institute recommendations. Relevant studies were identified through electronic searching of PubMed/MEDLINE, Embase, Scopus, and Web of Science databases, as well as the grey literature. We included peer-reviewed research articles involving in silico strategies applied to drug repurposing in oncology, published between 1 January 2003, and 31 December 2021. Results: We identified 238 studies for inclusion in the review. Most studies revealed that the United States, India, China, South Korea, and Italy are top publishers. Regarding cancer types, breast cancer, lymphomas and leukemias, lung, colorectal, and prostate cancer are the top investigated. Additionally, most studies solely used computational methods, and just a few assessed more complex scientific models. Lastly, molecular modeling, which includes molecular docking and molecular dynamics simulations, was the most frequently used method, followed by signature-, Machine Learning-, and network-based strategies. Discussion: DR is a trending opportunity but still demands extensive testing to ensure its safety and efficacy for the new indications. Finally, implementing DR can be challenging due to various factors, including lack of quality data, patient populations, cost, intellectual property issues, market considerations, and regulatory requirements. Despite all the hurdles, DR remains an exciting strategy for identifying new treatments for numerous diseases, including cancer types, and giving patients faster access to new medications.

18F]F-Poly(ADP-Ribose) Polymerase Inhibitor Radiotracers for Imaging PARP Expression and Their Potential Clinical Applications in Oncology.

Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional "PARP enzyme-inhibitor complex" leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as breast cancer-associated gene (BRCA1/2). Hence, identifying HR-deficiencies by genomic analysis-for instance, BRCA1/2 used in triple-negative breast cancer-should be a part of the selection process for PARP inhibitor therapy. Published data suggest BRCA1/2 germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available BRCA1/2 analysis. In this review, we discuss [18F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.

Metronomic chemotherapy: bridging theory to clinical application in canine and feline oncology.

Veterinary oncology has experienced significant evolution over the last few decades, with chemotherapy being currently applied to several neoplasms with therapeutic success. Traditionally, chemotherapy protocols are based on classic cytostatic drugs under the concept of maximum tolerated dose (MTD), which has been associated with a greater risk of toxicity and resistance. Thus, new therapeutic alternatives have emerged, such as metronomic chemotherapy (MC), introducing a new paradigm in cancer treatment. MC consists of administering low doses of chemotherapy drugs continuously over a long period of time, modulating the tumour microenvironment (TME) due to the combination of cytotoxic, antiangiogenic and immunomodulatory effects. This multi-targeted therapy has been described as a treatment option in several canine and feline cancers since 2007, with positive results already published in the literature, particularly in mammary carcinomas and soft tissue sarcomas in dogs. The aim of this review article is to describe the current knowledge about the use of MC in small animal oncology, with emphasis on its mechanisms of action, the most commonly used drugs and clinical outcome.

Chinese Oncologists' Perspectives on Integrating AI into Clinical Practice: Cross-Sectional Survey Study.

The rapid development of artificial intelligence (AI) has brought significant interest to its potential applications in oncology. Although AI-powered tools are already being implemented in some Chinese hospitals, their integration into clinical practice raises several concerns for Chinese oncologists. This study aims to explore the concerns of Chinese oncologists regarding the integration of AI into clinical practice and to identify the factors influencing these concerns. A total of 228 Chinese oncologists participated in a cross-sectional web-based survey from April to June in 2023 in mainland China. The survey gauged their worries about AI with multiple-choice questions. The survey evaluated their views on the statements of "The impact of AI on the doctor-patient relationship" and "AI will replace doctors." The data were analyzed using descriptive statistics, and variate analyses were used to find correlations between the oncologists' backgrounds and their concerns. The study revealed that the most prominent concerns were the potential for AI to mislead diagnosis and treatment (163/228, 71.5%); an overreliance on AI (162/228, 71%); data and algorithm bias (123/228, 54%); issues with data security and patient privacy (123/228, 54%); and a lag in the adaptation of laws, regulations, and policies in keeping up with AI's development (115/228, 50.4%). Oncologists with a bachelor's degree expressed heightened concerns related to data and algorithm bias (34/49, 69%; P=.03) and the lagging nature of legal, regulatory, and policy issues (32/49, 65%; P=.046). Regarding AI's impact on doctor-patient relationships, 53.1% (121/228) saw a positive impact, whereas 35.5% (81/228) found it difficult to judge, 9.2% (21/228) feared increased disputes, and 2.2% (5/228) believed that there is no impact. Although sex differences were not significant (P=.08), perceptions varied-male oncologists tended to be more positive than female oncologists (74/135, 54.8% vs 47/93, 50%). Oncologists with a bachelor's degree (26/49, 53%; P=.03) and experienced clinicians (≥21 years; 28/56, 50%; P=.054). found it the hardest to judge. Those with IT experience were significantly more positive (25/35, 71%) than those without (96/193, 49.7%; P=.02). Opinions regarding the possibility of AI replacing doctors were diverse, with 23.2% (53/228) strongly disagreeing, 14% (32/228) disagreeing, 29.8% (68/228) being neutral, 16.2% (37/228) agreeing, and 16.7% (38/228) strongly agreeing. There were no significant correlations with demographic and professional factors (all P>.05). Addressing oncologists' concerns about AI requires collaborative efforts from policy makers, developers, health care professionals, and legal experts. Emphasizing transparency, human-centered design, bias mitigation, and education about AI's potential and limitations is crucial. Through close collaboration and a multidisciplinary strategy, AI can be effectively integrated into oncology, balancing benefits with ethical considerations and enhancing patient care.

Tumor Size Is Not Everything: Advancing Radiomics as a Precision Medicine Biomarker in Oncology Drug Development and Clinical Care. A Report of a Multidisciplinary Workshop Coordinated by the RECIST Working Group.

Radiomics, the science of extracting quantifiable data from routine medical images, is a powerful tool that has many potential applications in oncology. The Response Evaluation Criteria in Solid Tumors Working Group (RWG) held a workshop in May 2022, which brought together various stakeholders to discuss the potential role of radiomics in oncology drug development and clinical trials, particularly with respect to response assessment. This article summarizes the results of that workshop, reviewing radiomics for the practicing oncologist and highlighting the work that needs to be done to move forward the incorporation of radiomics into clinical trials.

Artificial intelligence to unlock real-world evidence in clinical oncology: A primer on recent advances.

Real world evidence is crucial to understanding the diffusion of new oncologic therapies, monitoring cancer outcomes, and detecting unexpected toxicities. In practice, real world evidence is challenging to collect rapidly and comprehensively, often requiring expensive and time-consuming manual case-finding and annotation of clinical text. In this Review, we summarise recent developments in the use of artificial intelligence to collect and analyze real world evidence in oncology. We performed a narrative review of the major current trends and recent literature in artificial intelligence applications in oncology. Artificial intelligence (AI) approaches are increasingly used to efficiently phenotype patients and tumors at large scale. These tools also may provide novel biological insights and improve risk prediction through multimodal integration of radiographic, pathological, and genomic datasets. Custom language processing pipelines and large language models hold great promise for clinical prediction and phenotyping. Despite rapid advances, continued progress in computation, generalizability, interpretability, and reliability as well as prospective validation are needed to integrate AI approaches into routine clinical care and real-time monitoring of novel therapies.

EE52 The Burden of Intravenous vs Subcutaneous Oncological Products Application in Honduras

EE52 The Burden of Intravenous vs Subcutaneous Oncological Products Application in Honduras

Insights into Nimbolide molecular crosstalk and its anticancer properties.

Nimbolide, one of the main ingredients constituent of Azadirachta indica (neem) leaf extract, has garnered attention for its potential as an anticancer agent. Its efficacy against various cancers and chemopreventive action has been demonstrated through numerous in vivo and in vitro studies. This updated review aims to comprehensively explore the chemopreventive and anticancer properties of nimbolide, emphasizing its molecular mechanisms of action and potential therapeutic applications in oncology. The review synthesizes evidence from various studies that examine nimbolide's roles in apoptosis induction, anti-proliferation, cell death, metastasis inhibition, angiogenesis suppression, and modulation of carcinogen-metabolizing enzymes. Nimbolide exhibits multifaceted anticancer activities, including the modulation of multiple cell signaling pathways related to inflammation, invasion, survival, growth, metastasis, and angiogenesis. However, its pharmacological development is still in the early stages, mainly due to limited pharmacokinetic and comprehensive long-term toxicological studies. Nimbolide shows promising anticancer and chemopreventive properties, but there is need for systematic preclinical pharmacokinetic and toxicological research. Such studies are essential for establishing safe dosage ranges for first-in-human clinical trials and further advancing nimbolide's development as a therapeutic agent against various cancers. The review highlights the potential of nimbolide in cancer treatment and underscores the importance of rigorous preclinical evaluation to realize its full therapeutic potential.

Pulsed Field Energy in Atrial Fibrillation Ablation: From Physical Principles to Clinical Applications.

Atrial fibrillation, representing the most prevalent sustained cardiac arrhythmia, significantly impacts stroke risk and cardiovascular mortality. Historically managed with antiarrhythmic drugs with limited efficacy, and more recently, catheter ablation, the interventional approach field is still evolving with technological advances. This review highlights pulsed field ablation (PFA), a revolutionary technique gaining prominence in interventional electrophysiology because of its efficacy and safety. PFA employs non-thermal electric fields to create irreversible electroporation, disrupting cell membranes selectively within myocardial tissue, thus preventing the non-selective damage associated with traditional thermal ablation methods like radiofrequency or cryoablation. Clinical studies have consistently shown PFA's ability to achieve pulmonary vein isolation-a cornerstone of AF treatment-rapidly and with minimal complications. Notably, PFA reduces procedure times and has shown a lower incidence of esophageal and phrenic nerve damage, two common concerns with thermal techniques. Emerging from oncological applications, the principles of electroporation provide a unique tissue-selective ablation method that minimizes collateral damage. This review synthesizes findings from foundational animal studies through to recent clinical trials, such as the MANIFEST-PF and ADVENT trials, demonstrating PFA's effectiveness and safety. Future perspectives point towards expanding indications and refinement of techniques that promise to improve AF management outcomes further. PFA represents a paradigm shift in AF ablation, offering a safer, faster, and equally effective alternative to conventional methods. This synthesis of its development and clinical application outlines its potential to become the new standard in AF treatment protocols.

Effect of Project Orbis participation by the Swiss regulator on submission gaps, review times, and drug approval decisions between 2020 and 2022: a comparative analysis

Expedited market access for novel and efficacious drugs is warranted for patients. Since 2020, Swissmedic (The Swiss Agency for Therapeutic Products) has been participating in Project Orbis, a collaborative parallel-review programme launched by the US Food and Drug Administration (FDA) in 2019 to expedite patient access to cancer drugs. This programme allows regulatory agencies to remain independent in their decisions. We aimed to evaluate the effect of the first 2 years of Project Orbis from the Swissmedic perspective. In this comparative analysis, we compared submission gap (time between submission at the FDA and Swissmedic), review time, approval and consensus decision rate, and the approved indications between Swissmedic and the FDA for marketing authorisation applications (MAAs) in oncology submitted to Swissmedic through Project Orbis (Orbis MAAs) or outside of Project Orbis (non-Orbis MAAs) from Jan 1, 2020, to Dec 31, 2021. Swissmedic review time was evaluated with a decision until June 30, 2022. For the decision comparison analysis, non-Orbis oncology MAAs submitted and evaluated from Jan 1, 2009, to Dec 31, 2018 (referred to as the pre-Orbis era) were also considered. Inferential statistics were done using Wilcoxon rank-sum test and the 95% CI for the median was based on binomial distribution. For each hypothesis testing, the significance level was set to 5%. No correction for multiple testing was performed. We analysed the submission gap, review time, and regulatory decision for 31 Orbis MAAs and 41 non-Orbis MAAs during the Orbis era. The median submission gap was 33·0 days (95% CI 19·0-57·0) for Orbis MAAs versus 168·0 days (56·0-351·0) for non-Orbis MAAs (p<0·0001). The median review time at Swissmedic was 235·5 days (198·0-264·0) for Orbis MAAs versus 314·0 days (279·0-354·0) for non-Orbis MAAs (p=0·0002). Approval rates at Swissmedic were consistent between Orbis MAAs (20 [77%] of 26) and non-Orbis MAAs (31 [76%] of 41). The rate of consensus decisions between Swissmedic and the FDA was 21 (81%) of 26 for Orbis MAAs and 31 (76%) of 41 for non-Orbis MAAs. Swissmedic approval rates were lower for indication extensions than for new active substances for Orbis MAAs (13 [72%] of 18 vs seven [88%] of eight) and non-Orbis MAAs (17 [71%] of 24 vs 14 [82%] of 17). Divergent decisions between agencies were predominantly observed for indication extensions (11 [73%] of 15 divergent decisions). During the pre-Orbis era, Swissmedic approved 61 (88%) of 69 MAAs for new active substances. Submission gap and review time for oncology applications at Swissmedic were significantly reduced by participation in Project Orbis, and approval consensus decisions were increased between agencies. These findings suggests that participating in Project Orbis could lead to faster patient access to drugs. None.

Prostate-Specific Membrane Antigen Positron Emission Tomography Oncological Applications beyond Prostate Cancer in Comparison to Other Radiopharmaceuticals.

Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed on the surface of tumor cells in most of the patients affected by prostate adenocarcinoma (PCa). However, PSMA expression has also been demonstrated in the endothelial cells of newly formed vessels of various solid tumors, suggesting a role for PSMA in neoangiogenesis. In this scenario, gallium-68 (68Ga) or fluoro-18 (18F)-labeled PSMA positron emission tomography (PET) may play a role in tumors other than PCa, generally evaluated employing other radiopharmaceuticals targeting different pathways. This review aims to investigate the detection rate of PSMA-PET compared to other radiopharmaceuticals (especially [18F]FDG) in non-prostate tumors to identify patients who may benefit from the use of such a theragnostic agent. We performed a bibliographic search on three different databases until February 2024 using the following terms: "positron emission tomography", "PET", "PET/CT", "Prostate-specific membrane antigen", "PSMA", "non-prostate", "not prostate cancer", "solid tumor", "FDG", "Fluorodeoxyglucose", "FAPi", "FET", "MET", "DOPA", "choline", "FCH", "FES", "DOTATOC", "DOTANOC", and "DOTATATE". Only original articles edited in English with at least 10 patients were included. Out of a total of 120 articles, only 25 original articles comparing PSMA with other radiotracers were included in this study. The main evidence was demonstrated in renal cell carcinoma, where PSMA showed a higher detection rate compared to [18F]FDG PET/CT, with implications for patient management. PSMA PET may also improve the assessment of other entities, such as gliomas, in defining regions of early neoangiogenesis. Further data are needed to evaluate the potential role of PSMA-PET in triple-negative breast cancer as a novel therapeutic vascular target. Finally, unclear applications of PSMA-PET include thyroid and gastrointestinal tumors. The present review shows the potential use of PSMA-labeled PET/CT in solid tumors beyond PCa, underlining its value over other radiopharmaceuticals (mainly [18F]FDG). Prospective clinical trials with larger sample sizes are crucial to further investigate these possible clinical applications.

Canine Mammary Tumors as a Potential Model for Human Breast Cancer in Comparative Oncology.

Clinical and molecular similarities between canine mammary tumors (CMTs) and human breast cancer (HBC) propel scientists to further study their application in comparative oncology as a model for human breast cancer. In total, 64 canine mammary tumors were selected to study the most common markers, which are applicable for human breast cancer treatment, including estrogen and progesterone receptors (ER and PR), human epidermal growth factor (HER2/neu), Ki67, and cyclooxygenase 2 (Cox2). Immunohistochemistry (IHC) was used to assess the protein expression. The Veterinary Nottingham Prognostic Index (Vet-NPI) was also computed. Moreover, univariate and multivariable Cox proportional hazard analyses were applied to estimate hazard ratios (HRs). The results demonstrated that Ki67 was strongly expressed in the triple-negative tumors, and Ki67 protein expression continuously increased over the increase of Cox2 protein expression (p < 0.001). Further analysis revealed a significant difference among canine mammary subtypes and Vet-NPI, in which triple-negative tumors displayed the highest mean score compared to other subtypes (p < 0.001). In addition, the multivariable analysis revealed that the regional mastectomy procedure (adjusted HR = 2.78 (1.14-6.8)), the triple-negative tumors (adjusted HR = 48.08 (7.74-298.8)), strong Ki67 protein expression group (adjusted HR = 7.88 (2.02-30.68)), and strong Cox2 protein expression group (adjusted HR = 29.35 (5.18-166.4)) demonstrated significantly lower disease-free survival rates compared to other corresponding groups. Overall, canine mammary tumors showed strong similarities to human breast cancer in terms of clinical and molecular aspects; therefore, they could be suggested as a model for human breast cancer in comparative oncology.

Current status, challenges and prospects of antifouling materials for oncology applications.

Targeted therapy has become crucial to modern translational science, offering a remedy to conventional drug delivery challenges. Conventional drug delivery systems encountered challenges related to solubility, prolonged release, and inadequate drug penetration at the target region, such as a tumor. Several formulations, such as liposomes, polymers, and dendrimers, have been successful in advancing to clinical trials with the goal of improving the drug's pharmacokinetics and biodistribution. Various stealth coatings, including hydrophilic polymers such as PEG, chitosan, and polyacrylamides, can form a protective layer over nanoparticles, preventing aggregation, opsonization, and immune system detection. As a result, they are classified under the Generally Recognized as Safe (GRAS) category. Serum, a biological sample, has a complex composition. Non-specific adsorption of chemicals onto an electrode can lead to fouling, impacting the sensitivity and accuracy of focused diagnostics and therapies. Various anti-fouling materials and procedures have been developed to minimize the impact of fouling on specific diagnoses and therapies, leading to significant advancements in recent decades. This study provides a detailed analysis of current methodologies using surface modifications that leverage the antifouling properties of polymers, peptides, proteins, and cell membranes for advanced targeted diagnostics and therapy in cancer treatment. In conclusion, we examine the significant obstacles encountered by present technologies and the possible avenues for future study and development.

Abstract PO4-18-05: Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer

Abstract Introduction- Cannabis is world’s oldest cultivated medicinal plant. It has potential applications in oncology, in reducing chronic pain, stimulating appetite, alleviating nausea/vomiting, improving overall well-being as well as its anti-cancer properties. We conducted a phase-1 dose escalation study to determine safety of pre-operative oral cannabis in breast and oral cavity squamous cell carcinoma (OC-SCC) with an intent to explore its anticancer potential in the “pre-operative” window. The primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Methodology- Primary objective was to determine maximum tolerated dose (MTD) and establish dose limiting toxicity (DLT). Secondary objectives were pharmacokinetic profiling and transcriptomic analysis of tumour tissue. Non-metastatic breast and OC-SCC patients planned for curative surgery were consented after thorough medical and mini-psychiatric evaluation with Brief Psychiatry Rating Scale (BPRS). The investigational product (IP) comprised of a capsule containing 2.5mg of tetrahydrocannabinol (THC) and 2.5mg cannabidiol (CBD) in 100 mg monocrotolyn oil extract of dried leaves of C. sativa. The capsules were manufactured in an Ayurvedic GMP facility. The classical 3+3, phase-1 design used modified Fibonacci sequence for dose escalation, starting with 5mg THC+5mg CBD. Patients received IP once a day for 5 days after breakfast with hemodynamic and psychiatric monitoring and underwent the planned surgery on day-6. Pharmacokinetic samples were collected at predefined time-points and plasma levels of THC, 11-OH-THC, 11-COOH-THC and CBD were determined using a validated LC-MS/MS method. Tumour tissue was collected before 1st dose of cannabis and during surgery for biomarker analysis. Results- A total of 12 patients were enrolled (6-breast, 3-buccal mucosa, and 3-tongue cancers). First 3 patients completed the study without DLT at 5+5mg dose. A DLT was observed at dose level-2 (10+10mg) and therefore additional 3 patients were enrolled at the same dose. Two patients out of six at this dose had DLT (anxiety- grade-3 and somnolence- grade-2) necessitating dose de-escalation in the next cohort. At 7.5+7.5mg dose, all 3 patients tolerated the IP(MTD). Ten patients completed the study protocol. Common adverse effects were headache (2/12, grade-1), heavy head (8/12, grade-1), hypotension (2/12, grade-1 and 3), epigastric discomfort (1/12, grade-1), diarrhoea (1/12, grade-1), hyponatremia (1/12, grade-1), hypertension (1/12, grade-2), anxiety (1/12, grade-2). Pharmacokinetics of both CBD and THC was less than dose proportional. At the MTD (7.5+7.5), day-1 and day-5 AUC0-24 [median (range)] for CBD were 21.75 (12.44–41.44) ng/ml−1*h and 24.85 (13.72–35.93) ng/ml−1*h respectively. Similarly, for THC, day 1 and day 5 AUC0-24 were 11.79 (8.06–70.58) ng/ml−1*h and 68.98 (1.78 – 136.17) ng/ml−1*h, respectively. Significant accumulation of both CBD and THC was observed across all doses from day 1 to 5. A high variability in pharmacokinetics was observed for both constituents (CV Cmax = 101.26% and 117.48%; CV AUC0-24 = 102.50% and 112.37% for CBD and THC respectively. The median half-life of CBD and THC was 2.2 (1.6–10.7) and 1.9 (1.6–2.4) h respectively. There was no correlation observed between drug exposure and toxicity. There was no significant change in BPRS score before and after IP. Conclusion- We report the first phase-1 study of cannabis in breast and OC-SCC cancer in pre-operative setting for its anti-cancer potential. Biomarker analysis is awaited. MTD identified will be further explored in phase 2/3 clinical trials in breast, oral cavity, lung and pancreatic cancer with survival endpoints. Citation Format: Rajendra Badwe, Shalaka Joshi, Shiva Thiagarajan, Vikram Gota, Vaibhav Vanmali, Pallavi Daphale, Jayita Deodhar, Rohan Chaubal, Rohini Hawaldar, Jaya Chitra Aadhi, Saurabh Kumar Gupta, Delzaad Deolaliwala, Anil Bhansali, Siddhant Mistry, Satyajeet Singh, Nita Nair, Vani Parmar, Sudeep Gupta. Safety and Feasibility of Administration of an Oral Cannabis Preparation in The Preoperative Period in Breast and Oral Cavity Cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-18-05.

Application of artificial intelligence in the prediction of immunotherapy efficacy in hepatocellular carcinoma: Current status and prospects

Artificial Intelligence (AI) has increased as a potent tool in medicine, with promising oncology applications. The emergence of immunotherapy has transformed the treatment terrain for hepatocellular carcinoma (HCC), offering new hope to patients with this challenging malignancy. This article examines the role and future of AI in forecasting the effectiveness of immunotherapy in HCC. We highlight the potential of AI to revolutionize the prediction of therapy response, thus improving patient selection and clinical outcomes. The article further outlines the challenges and future research directions in this emerging field.

Evolution of the meta-neurosurgeon: A systematic review of the current technical capabilities, limitations, and applications of augmented reality in neurosurgery.

Augmented reality (AR) applications in neurosurgery have expanded over the past decade with the introduction of headset-based platforms. Many studies have focused on either preoperative planning to tailor the approach to the patient's anatomy and pathology or intraoperative surgical navigation, primarily realized as AR navigation through microscope oculars. Additional efforts have been made to validate AR in trainee and patient education and to investigate novel surgical approaches. Our objective was to provide a systematic overview of AR in neurosurgery, provide current limitations of this technology, as well as highlight several applications of AR in neurosurgery. We performed a literature search in PubMed/Medline to identify papers that addressed the use of AR in neurosurgery. The authors screened three hundred and seventy-five papers, and 57 papers were selected, analyzed, and included in this systematic review. AR has made significant inroads in neurosurgery, particularly in neuronavigation. In spinal neurosurgery, this primarily has been used for pedicle screw placement. AR-based neuronavigation also has significant applications in cranial neurosurgery, including neurovascular, neurosurgical oncology, and skull base neurosurgery. Other potential applications include operating room streamlining, trainee and patient education, and telecommunications. AR has already made a significant impact in neurosurgery in the above domains and has the potential to be a paradigm-altering technology. Future development in AR should focus on both validating these applications and extending the role of AR.