Treatment Options Research Articles

Radiation therapy in functioning and no functioning pituitary neuroendocrine tumor: systematic review of the recent literature after 2011

SummaryNeuroendocrine pituitary tumor, a benign cells proliferation, can cause significant morbidity due to its local invasiveness and secretory properties. Historically, radiotherapy has been employed as a second or third-line treatment option, with studies dating back to the mid-20th century. However, advancements in radiotherapy techniques, such as intensity-modulated radiation therapy (IMRT), stereotactic radiosurgery, and proton therapy, have revolutionized treatment approaches. This review aims to critically evaluate the recent literature (2011–2022) on the use of radiotherapy in both functioning and nonfunctioning neuroendocrine pituitary tumor. We employed the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology to systematically analyze 52 articles, focusing on local and hormonal control, radiotherapy protocols, and treatment-related side effects.

Prevalence and correlates of severe problematic cannabis use: analysis of a population-based survey in Jamaica

BackgroundThere is an increasing demand for the treatment of problematic cannabis use (PCU) in low-income and middle-income countries. Jamaica’s historical inclination towards cannabis use underscores the need for research in addressing this issue.ObjectivesTo determine the prevalence and patterns of cannabis use and assess the sociodemographic factors, psychosocial correlates, knowledge and perceptions associated with severe PCU among Jamaicans using nationally representative data.MethodsThis study involved a secondary data analysis of the last Jamaica National Drug Prevalence Survey. It included 786 participants who used cannabis in the past year and completed the Cannabis Abuse Screening Test (CAST). The CAST has been validated against the Diagnostic and Statistical Manual of Mental Disorders (DSM), with a score ≥ 7 meeting the criteria for severe PCU. CAST scores were dichotomized utilizing these thresholds, and data generated were analyzed with SPSS version 25 using Pearson’s χ2 test and logistic regression.ResultsIn the past year, 53.3% of Jamaicans who smoked cannabis had a score of 7 or higher on the CAST and smoked an average of 62.21 joints per month. Male respondents were twice as likely to have severe PCU as females. Additionally, young, middle, and older adults were respectively 3, 5 and 3 times more likely to report severe PCU compared to adolescent respondents. Participants who started cannabis use at 11 years and under, 12-17 years, and 18-25 years were respectively 5, 7 and 7 times more likely to report severe PCU than those at 26 years and older. Moreover, easy access to cannabis, a high perceived need for treatment, belief in increased national drug use prevalence, and awareness of the National Drug Control and Prevention Agency were associated with increased odds of reporting severe PCU.ConclusionOne out of every two Jamaicans who used cannabis in the past year reported severe PCU and smoked an average of two cannabis joints per day. Early initiation increases the risk of severe PCU. Accordingly, a public health approach involving multiple sectors is needed to provide treatment options.

Clinical Presentations and Treatment Approaches in a Retrospective Analysis of 128 Intracranial Arteriovenous Malformation Cases

Background: Intracranial AVMs are a highly heterogeneous group of lesions that, while not very common, can pose significant risks. The therapeutic management of AVMs is complicated by ambiguous guidelines, particularly regarding which Spetzler–Martin grades should dictate specific treatment options. This study analyzed the clinical presentations and treatment approaches of 128 brain AVM cases managed between 2014 and 2022 at the National Institute of Neurology and Neurovascular Diseases in Bucharest, Romania. Methods: A retrospective analysis was conducted on patient demographics, clinical symptoms, Spetzler–Martin categorization, nidus localization, therapeutic management, and outcomes. Statistical analysis was performed using Python 3.10. Results: In our cohort of patients, the median age was 45 years, with a slight male predominance (67 males, 61 females). At admission, 51.5% presented with elevated blood pressure. The majority of patients had a Spetzler–Martin score of 2 (37.5%), followed by scores of 3 (31.3%) and 1 (20.3%). Treatment strategies included microsurgical resection in 32% of cases, conservative management in 31.2%, Gamma Knife radiosurgery in 22.6%, and endovascular embolization in 13.3%. Notably, open surgery was predominantly chosen for Grade II AVMs. The functional outcomes were favorable, with 69.5% achieving a good recovery score on the Glasgow Outcome Scale. Only four in-hospital deaths occurred, all in patients who underwent open surgery, and no deaths were recorded during the two-year follow-up. Conclusions: AVMs within the same Spetzler–Martin grade display considerable complexity, necessitating personalized treatment strategies. Our findings highlight the limitations of open surgery for Grade I cases but affirm its effectiveness for Grade II AVMs.

Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression

Obesity is a common risk factor in multiple tumor types, including prostate cancer. Obesity has been associated with driving metastasis, therapeutic resistance, and increased mortality. The effect of adipose tissue on the tumor microenvironment is still poorly understood. This review aims to highlight the work conducted in the field of obesity and prostate cancer and bring attention to areas where more research is needed. In this review, we have described key differences between healthy adipose tissues and obese adipose tissues, as they relate to the tumor microenvironment, focusing on mechanisms related to metabolic changes, abnormal adipokine secretion, altered immune cell presence, and heightened oxidative stress as drivers of prostate cancer formation and progression. Interestingly, common treatment options for prostate cancer ignore the adipose tissue located near the site of the tumor. Because of this, we have outlined how excess adipose tissue potentially affects therapeutics’ efficacy, such as androgen deprivation, chemotherapy, and radiation treatment, and identified possible drug targets to increase prostate cancer responsiveness to clinical treatments. Understanding how obesity affects the tumor microenvironment will pave the way for understanding why some prostate cancers become metastatic or treatment-resistant, and why patients experience recurrence.

A Repair Technique for Internal Nasal Valve Collapse Using Lateral Nasal Suspension Sutures

One of the most common reasons a patient would see an otolaryngologist is for nasal obstruction. This article provides an overview of the physical principles related to nasal airflow as well as the critical role that the internal nasal valve plays in regulating airflow resistance. Common treatment options for internal nasal valve obstruction are discussed as well as an in-depth tutorial on an alternate lateral nasal suspension suture technique for internal nasal valve collapse.

The Present Difficulties and Potential Benefits of Dopaminergic Agents in Parkinson's Disease Treatment

Parkinson's disease (PD) is a progressive neurological condition characterized by bradykinesia, rigidity, tremors, and impaired balance, among other motor impairments. The issue arises from dopaminergic neurons located in the spinal column of the brain. This research report examines the therapeutic potential of dopaminergic medications in the management of Parkinson's disease. The central concept of Parkinson's disease (PD) revolves around the notion that dopaminergic pathways exert significant influence over the regulation of movement. The book examines various dopaminergic medications, elucidating their mechanisms of action and the impact they exert on dopamine signaling. Examples of these medications include levodopa, dopamine agonists, and monoamine oxidase-B (MAO-B) inhibitors. Although dopaminergic medicines initially aid in the treatment of Parkinson's disease (PD), prolonged usage of these medications gives rise to several complications. Experiencing dyskinesias and motor fluctuations, characterized by episodes of involuntary movements and behaviors that are undesired, is a significant challenge. This study investigates the underlying causes of these difficulties and explores potential treatment options, including the use of controlled-release formulations and further therapy. The book discusses the non-motor symptoms of Parkinson's disease (PD), as well as the use of dopaminergic medications to treat mood disorders, autonomic dysfunction, and cognitive loss. Dopaminergic medications remain crucial in reducing motor symptoms and enhancing the quality of life for those with Parkinson's disease. Parkinson's disease (PD) is a complex condition with multiple distinct variations. In order to address its existing challenges and explore its potential implications for future Parkinson's disease medications, a comprehensive and effectively coordinated strategy is required.

Influence of Psychological Stress on the Response to Periodontal Treatment: Protocol for a Systematic Review.

The interaction between stress and periodontal treatment is a topic of growing interest. It stands out as a field of research that sheds light on the complexity of oral health in individuals subjected to high levels of emotional stress. This paper aims to provide a protocol for a systematic review to examine the scientific evidence related to the influence of psychological stress on the response to periodontal treatment. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines will be followed, and the study is based on a formulation of PECO (Participants, Exposure, Comparators, and Outcomes) questions. This systematic review will involve a literature search covering studies published from January 2000 to May 2024. It will include searching the PubMed, Web of Science, EBSCOHost, Scopus, and ProQuest databases to identify relevant studies. After selection, data extraction and quality assessment (using the Ottawa-Newcastle Scale) of the included studies will be carried out. The objective is to integrate high-quality evidence on how psychological stress impacts the outcomes of periodontal treatment. Depending on the number and methodological consistency of included studies, the results may be presented by meta-analysis or qualitative synthesis. The current stage of the study consists of selecting studies for the systematic review as outlined by this protocol. The search, screening, and data extraction began in January 2024. The final results are expected by July 2024, with final manuscript submission planned for November 2024. This review will help clarify how psychological factors, such as stress, influence the results of periodontal treatment, providing valuable guidelines for future research and helping clinicians make decisions about the best treatment options for patients. Open Science Framework (OSF) Registries qfs6p; https://osf.io/qfs6p. PRR1-10.2196/56765.

Survival and Treatment Outcomes in Gastric Cancer Patients with Brain Metastases: A Systematic Review and Meta-Analysis

Background: Brain metastases (BM) from gastric cancer (GC) are rare but associated with poor prognosis, significantly impacting patient survival and quality of life. The objective of this systematic review and meta-analysis is to consolidate existing research on BM from GC, evaluate the incidence and clinical outcomes, and explore the effectiveness of treatment options. Methods: A systematic search was conducted across the Medline, Web of Science, and Scopus databases, following PRISMA guidelines. Eighteen high-quality studies, as per the Newcastle–Ottawa Quality Assessment Scale, were included, encompassing 70,237 GC patients, of whom 621 developed BM. Data on progression-free survival (PFS), overall survival (OS), neurological symptoms, and HER2 status were analyzed using a random-effects model. Results: The incidence of BM in GC patients was found to be 2.29% (95% CI: 1.06–3.53%), with the range extending from 0.47% to 7.79% across studies. HER2-positive status was significantly associated with a higher likelihood of developing BM, with an odds ratio of 43.24 (95% CI: 2.05–913.39; p = 0.02), although this finding was based on limited data. The surgical resection of BM was linked to significantly improved survival outcomes, with a mean difference in OS of 12.39 months (95% CI: 2.03–22.75; p = 0.02) compared to non-surgical approaches. Conclusions: The surgical resection of brain metastases in GC patients significantly enhances overall survival, while HER2-positive patients may show a higher risk for developing BM. These findings underscore the importance of tailored therapeutic approaches for GC patients with BM.

Clinical features, treatment options and outcomes in primary cutaneous B-cell lymphomas: a real-world, multicenter, retrospective study.

Primary cutaneous B-cell lymphomas (PCBCLs) are rare cutaneous neoplasms with limited literature regarding treatment options and associated treatment outcomes. This study aimed to investigate and present real-world treatment outcomes in patients with PCBCLs. All patients with PCBCL who were treated in five major referral centers for cutaneous lymphoma in Greece over 10 years were retrospectively included with their baseline characteristics and treatment-associated outcomes collected and analyzed. In total, 235 PCBCL patients, of whom 125 (53.2%) were females, were included. The median age at diagnosis was 60 years (IQR 47-72), and the median follow-up duration was 3 years (IQR 1.3-6.4). The most common subtype was primary cutaneous marginal zone lymphoma (PCMZL) (52.3%), followed by primary cutaneous follicle center lymphoma (PCFCL) (40.9%), and primary cutaneous large B-cell lymphoma, leg type (PCDLBCL, LT) with 16 (6.8%) cases. Complete responses (CRs) were observed in 77.3% after first-line treatment. Both radiotherapy (RT) and surgical excision (SE) achieved superior outcomes, with 88.9% and 89% achieving CR, respectively. Relapses occurred in 22.6% of initial complete responders. The median time to the next treatment (TTNT) for the PCMZL and PCFCL was 349 days. RT and topical/intralesional steroids demonstrated longer TTNT compared to SE (445 and 359 vs. 154 days). For PCMZL and PCFCL, the 1-year progression-free survival (PFS) was 84.2% (75.7-89.9) and 85% (75.1-91.2), and the 5-year PFS was 66.5% (55.2-75.5) and 58.8% (44.4-70.7), respectively. PCBCLs have favorable outcomes. RT demonstrates significantly increased TTNT compared to SE, suggesting RT as the preferable option. After careful evaluation, "watch and wait" may be a reasonable option for asymptomatic patients.

Advances in neoadjuvant therapy for resectable intrahepatic cholangiocarcinoma: An invited commentary

Abstract Intrahepatic cholangiocarcinoma (ICC) poses a significant threat to human health owing to its high malignancy rate and poor prognosis. Surgery is the most effective treatment option for ICC. However, the prognosis remains unfavorable even after surgical resection. Therefore, neoadjuvant therapy has emerged as a potential treatment option for patients with ICC. Neoadjuvant therapy can improve patient prognosis by reducing the tumor size and eliminating tiny lesions that are not visible to the naked eye. Nevertheless, specific treatment options for neoadjuvant therapy are unavailable. This review summarizes the studies on neoadjuvant therapy for ICC in the last decade, including chemotherapy, radiotherapy, interventional therapy, targeted therapy, and immunotherapy, with the aim of providing suggestions for the selection of clinical treatment options for patients with ICC. Current reports suggest that chemotherapy is the most effective neoadjuvant treatment option. However, radiotherapy and interventional therapies require further investigation to obtain conclusive recommendations. Although targeted therapies and immunotherapies have been studied less extensively, several ongoing clinical trials are investigating these promising approaches.

Coexistence of the blaZ gene and selected virulence determinants in multidrug-resistant Staphylococcus aureus: insights from three Nigerian tertiary hospitals.

Infections caused by β-lactamase-producing strains of Staphylococcus aureus have become increasingly difficult to treat due to the expression of multiple virulence factors. This has heightened concerns about managing S. aureus-related infections. This study was conducted to characterize the blaZ gene and selected virulence determinants in β-lactam resistant S. aureus from human sources in three Nigerian tertiary hospitals. Three hundred and sixty samples were collected for the study. S. aureus was isolated and characterized following standard microbiological protocols and nuc gene amplification. Antibiotic susceptibility and minimum inhibitory concentration tests were performed using the disk diffusion method and E-tests, respectively. Biofilm formation and β-lactamase production were assessed using Congo red agar and nitrocefin kits, while the blaZ gene was examined using conventional PCR. Capsular polysaccharide genotyping, accessory gene regulator (agr) detection, Panton-valentine leucocidin (PVL), and PVL proteins were performed using PCR and Western blotting. S. aureus was recovered from 145 samples, 50 (34.5%) of these isolates exhibited multidrug resistance, with MICs ranging from 0.125 to 1.00µg/mL, and showed significant resistance to aminoglycosides, fluoroquinolones, and β-lactams. Of these, 31 strains produced β-lactamases, 30 of which carried the blaZ gene in combination with cap8 (80%) or cap5 (20%). Biofilm formation and PVL gene were observed in 85% of the 20 randomly selected blaZ-positive multidrug-resistant (MDR) strains. The agr2 allele was predominant, found in 70% of the selected MDR strains. No significant difference in the occurrence of the blaZ gene was found among the three clinical sources (p ≤ α0.05). The co-occurrence of the blaZ gene with PVL, capsular polysaccharide genes, and agr alleles is associated with biofilm formation, indicating a high risk of β-lactam-resistant S. aureus infections. Our findings highlight the need for continuous molecular surveillance to enhance infection management, treatment options, and patient outcomes in the study locality. A limitation of this study is the random selection of MDR isolates, which may affect the comprehensiveness of the analyses.

Facial high-pressure injection injury with air in a child.

High-pressure injection injuries are rare injuries and are frequently underestimated due to the limited external damage. Because of their association with occupational activities, these injuries are predominantly seen in hands. Facial involvement in such traumas is extremely rare. The difference in facial anatomy compared to the extremities demands careful consideration of both associated complications and treatment options. A 6-year-old girl with no significant medical history was presented to the Emergency Department with a high-pressure injection injury to her right eye with a high-pressure cleaner. This resulted in injection of air at a pressure of 8bar into the eye. She developed significant subcutaneous emphysema in the facial and neck regions. Additionally, intraorbital and intracranial emphysema were identified without any fractures. Treatment consisted of inpatient observation and antibiotic treatment. The patient was discharged after one day of observation for continued antibiotic treatment at home. Two weeks later, the patient had no residual symptoms and there were no signs of secondary infection. High-pressure injection injuries to the face are rare and demand a different approach compared to the most common high-pressure injection injuries to the extremities. The nature of the injected material is paramount in choosing the appropriate treatment. This case illustrates that a high-pressure injection injury with air in the facial region, leading to extensive emphysema, can be managed conservatively with antibiotic therapy and inpatient observation.

Can We Better Understand, Diagnose, and Treat Ketamine-Induced Uropathy, and Can It Be Reversed? ICI-RS 2024.

Ketamine, a versatile anesthetic, has seen increased recreational use, leading to significant health issues, including ketamine-induced uropathy (KIU). KIU manifests with lower urinary tract symptoms (LUTS) and can involve the upper urinary tract. This study aims to provide a comprehensive overview of KIU, addressing its pathophysiology, diagnostic strategies, and treatment options; and to define/identify future research priorities. During the 2024 meeting of the International Consultation on Incontinence Research Society (ICI-RS) in Bristol, a dedicated Proposal (P) convened to explore KIU. This initiative involved a thorough review of existing literature, expert presentations, and consensus-driven discussions. The methodology ensured a comprehensive exploration of KIU from both clinical and pre-clinical perspectives, leading to actionable research recommendations. Understanding the mechanisms of KIU is crucial for developing effective treatment options targeting specific pathophysiological pathways. Key findings include bladder fibrosis driven by transforming growth factor-β1 (TGF-β1), elevated purinergic responses and upregulated P2X1 purinoceptor expression, decreased barrier function due to increased expression of antiproliferative factor (APF), and functional loss of the bladder through Cav1.2 channel blockade. Research indicates that fibrosis, typically considered irreversible, may be mitigated. However, the exact timing and extent of fibrosis initiation and its impact on long-term outcomes require further research. LUTS typically improve after ketamine cessation but relapse upon resumption, indicating a hypersensitivity mechanism involving elevated serum IgE levels. Advanced stages of KIU do not always correlate with LUTS severity, shedding light on potential systemic effects and the need for evaluating liver enzymes. Furthermore, psychological dependency on ketamine, due to its positive perceptive and mood-altering effects, complicates cessation efforts. Long-term management requires a holistic approach, integrating medical treatments and supportive measures to help patients navigate life with potentially irreversible complications. This comprehensive review spans from fundamental pathology to practical clinical management, addressing both urological and systemic complications, and bridging insights from animal models to human applications. Developing effective treatment strategies necessitates addressing both the physical and psychological aspects of ketamine dependency.

PATH-36. DO GENE EXPRESSION PROFILES BETTER PREDICT OLIGODENDROGLIOMA SURVIVAL?

Abstract The WHO 2021 classification of oligodendroglioma grade 2 (G2) and grade 3 (G3), is separated by histopathology alone and does not universally reflect survival outcome. DNA methylation-based profiling also fails to separate oligodendroglioma grades. Our aim was to define transcriptome-based molecular subgroups that predict survival of oligodendroglioma (IDH-mutant and 1p/19q-codeleted) patients. Clinical and whole-transcriptome data for oligodendroglioma were obtained from TCGA (n=132), CGGA (n=53), and the Exsegen Genomics Research Biobank (n=16) (CTRI/2021/09/036861); while that of control brain samples (n=9) were obtained from CPTAC. Overall survival (OS) was significantly different in TCGA samples between WHO CNS G2 and G3 oligodendrogliomas (log-rank test, p=0.0001); but, not in CGGA (p=0.1833) or Exsegen (p>0.06) samples. Genes with highly variable expression (Median Absolute Deviation, i.e. MAD>1; 1645 genes) across TCGA oligodendroglioma and CPTAC control brain samples were used to exclude 9 oligodendroglioma samples with Pearson’s correlation>0.75 with control brain samples. Consensus clustering (K-means and spectral) of remaining 124 TCGA oligodendroglioma samples identified three significantly different (SigClust, p<0.05) transcriptomic classes using 1347 highly variable genes (MAD>1) in these samples. Principal component analysis (PCA) on expression of 1347 genes in TCGA samples revealed partial overlap of G2 and G3 tumours; but transcriptomic classes with distinct OS could be identified at both extremes of survival. Gene expression signatures for each transcriptomic class were developed using core TCGA samples from each class. For further validation, gene signatures were used to predict the transcriptomic classes of CGGA and Exsegen samples based on highest cosine similarity between sample gene expression and gene signature of each transcriptomic class. OS was significantly different between the transcriptomic classes in TCGA samples and predicted ones in CGGA samples. Transcriptome profiling separated oligodendrogliomas into distinct classes which can predict survival and potentially augment grading and refine prognostication and treatment options.

QLTI-13. A REVIEW OF THE BEST TREATMENT STRATEGY FOR NEUROFIBROMATOSIS TYPE 2 PATIENTS THROUGH A SINGLE-CENTER RETROSPECTIVE STUDY: HOW TO ORCHESTRATE MULTIMODAL TREATMENT OPTIONS

Abstract PURPOSE Neurofibromatosis type 2(NF2) is an autosomal-dominant tumor predisposition syndrome that affects the whole neuro-axis and causes various neurological symptoms decreasing the quality of life throughout the patient’s lifespan. However, due to the diversity of related diseases and the complexity of treatment, there are many cases in which only partial treatments are performed, the timing of the treatment is missed, and inappropriate treatment modality selection is made despite the intervention of many clinicians. Therefore, to increase the overall understanding of the disease, the single-institution experience was analyzed. MATERIALS AND METHODS Between 1998 and 2022, a total of 80 patients who clinically suspected NF2 visited our Brain Tumor Center. After excluding the patients with follow-up loss, the remaining 48 patients were finally analyzed. The patient’s symptoms, diagnosis process, treatment process, and outcomes were analyzed. RESULTS The average age at the time of symptom onset was 31.0(2-63) year-old. Hearing impairment was the major primary symptom(46.8%) among the patients. Five patients(10.9%) had family history of NF2. Thirty-five patients(76.1%) was clinically diagnosed as a NF2 for the bilateral vestibular schwannomas, and 34 patients(73.9%) had intracranial meningiomas, and 37 patients(80.4%) had spinal lesions at the time of diagnosis. Eleven patients were genetically confirmed as NF2. For vestibular schwannomas, 16 patients had surgical resection and 20 patients took gamma-knife surgery as a primary or secondary treatment. For intracranial meningiomas, 16 patients had surgical resection, 13 patients took gamma-knife surgery, and 15 patients took conventional radiation therapy as a primary or secondary treatment. Ventriculo-peritoneal shunt due to increased intracranial pressure was performed in 4 patients(8.7%). For spinal lesions, 16 patients had surgical resection. CONCLUSION NF2 is a disease group requiring a multidisciplinary team approach. The key to treatment is to set and implement a treatment sequence and method tailored to each patient. For this, an overall understanding of the disease and the treatment options is essential.

DISP-08. GBM PATIENTS FACE TTF ACCESS AND INFORMATION INEQUITY THAT MAY IMPACT PATIENT OUTCOMES AND QUALITY-OF-LIFE

Abstract We evaluated the quality and accessibility of healthcare for Glioblastoma (GBM) patients across the United States through an online survey distributed to the OurBrainBank community and partners and promoted on social media. A total of 297 patients or caregivers completed the survey (85% caregivers; 15% GBM patients). Median age at diagnosis was 57, lower than the national average. 78% described having some college education, and 69% reported commercial insurance coverage. Our preliminary findings highlight that 82% of respondents reported that their treating doctor recommended the standard-of-care for GBM consisting of tumor resection, 3-6 weeks of chemo/radiation, and 6 months of chemotherapy and sometimes Tumor-Treating-Fields (TTF), per the Comprehensive- Cancer-Network (2021) guidelines. 40% reported no discussion of TTF as an option. Of those offered TTF, nearly half (46%) received it as part of their initial treatment combined with standard chemotherapy and 36% received it as a subsequent option. For those attempting to access TTF, 29% encountered difficulties, often due to financial constraints linked to insurance denials. These findings illuminate significant concerns regarding dissemination of information on treatment options, as well as access to treatments. Access to these treatments can have a significant influence on survival and quality of life of GBM patients. The substantial number of patients not offered TTF, combined with challenges to accessing treatments due to insurance issues, highlight critical obstacles to engaging in informed and shared decision-making. Compared to the general GBM-affected population, our survey respondents tend to be younger and from urban areas, indicating a possible selection bias in survey participation. This skew could lead to an underrepresentation of the challenges encountered by patients facing additional barriers. We are adopting measures to engage a more diverse participant group, especially from rural communities Ongoing targeted recruitment will further elucidate barriers to patient-centered care in GBM, with the potential for significant improvements in survival and QOL.

EXTH-08. IVOSIDENIB THERAPY FOR IDH-MUTANT WHO GRADE 4 ASTROCYTOMA

Abstract BACKGROUND Isocitrate Dehydrogenase (IDH) is a commonly mutated gene in gliomas, present in approximately 10% of high-grade gliomas. Its oncometabolite, D-2-hydroxyglutarate, has been implicated in promoting gliomagenesis and epileptogenesis. IDH-1 or IDH-2 mutations confer a more favorable prognosis in gliomas than wildtype IDH, leading to the differentiation between IDH-wild type glioblastoma and IDH-mutant WHO Grade 4 astrocytoma. Although IDH-mutant WHO Grade 4 astrocytomas tend to occur in younger patients and show an improved survival, prognosis remains poor and treatment options are limited. Ivosidenib is a small molecule inhibitor of IDH-1 that has shown promise for treating low-grade IDH-mutant glioma. However, little is known about its efficacy in IDH-mutant WHO Grade 4 astrocytoma. METHODS We present a retrospective case of a 38-year-old male with a WHO Grade 4 astrocytoma. Molecular characterization revealed that it was IDH-mutant, MGMTp methylated, and 1p/19q co-deleted. It was treated with ivosidenib at second recurrence. He was originally treated with gross total resection, followed by radiation and 6 cycles of adjuvant temozolomide. At the time of 1st progression (approximately 19 months postoperatively), he was treated with lomustine at 90mg/m2 but progressed after 2 cycles. Here we report the effects of off label use of ivosidenib. RESULTS Radiological surveillance showed interval decrease in tumor size starting two months after initiation of ivosidenib. The patient remained neurologically intact and no adverse effects were observed. A review of the literature revealed only three studies analyzing the effects of ivosidenib in IDH-mutated WHO Grade 4 astrocytomas with varying results. CONCLUSION The INDIGO trial published last year showed evidence of efficacy in using an IDH inhibitor for low-grade gliomas. The role of these drugs in high-grade IDH-mutated gliomas is currently unknown. Further studies are needed to assess their efficacy in overall and progression free survival, specifically in IDH-mutated WHO Grade 4 astrocytoma.

Sarcopenia Is a Prognostic Factor of Adverse Effects and Mortality in Patients With Tumour: A Systematic Review and Meta-Analysis.

The relationship between sarcopenia and the prognosis of patients with tumours who received radio- and/or chemotherapy still needs to be determined. In this study, we aim to investigate the relationship between sarcopenia and adverse effects and mortality in patients with tumours that received radio- and/or chemotherapy, stratified by study design, tumour category, the method sarcopenia assessed, treatment options, study location and among other factors. PubMed, Web of Science and Embase were searched from inception to 15 August 2024, without language restrictions and with a manual search of references for additional articles retrieval. Cohort studies of ≥ 100 patients with tumours that evaluated the association between sarcopenia or muscle mass and the adverse effects or overall survival induced by radio- and/or chemotherapy were included. Thirty-nine studies were included, involving 8966 patients with tumours, including 3383 patients with sarcopenia. The pooled prevalence of sarcopenia in patients with tumours was 0.42 (95% CI 0.36-0.48, p < 0.001) overall. The prevalence of sarcopenia is higher in Oceania patients 0.60 (95% CI 0.28-0.89, p < 0.001), those with reproductive tumour 0.57 (95% CI 0.30-0.83, p < 0.001), and sarcopenia assessed by the lumbar-skeletal muscle index 0.46 (95% CI 0.39-0.53, p < 0.001) than in other subgroups, but not show significant differences in sex. Sarcopenia was associated with an increased risk of adverse effects in patients who received radio- and/or chemotherapy, with a relative risk (RR) of 1.44 (95% CI 1.21-1.71, p < 0.001). Retrospective studies (RR = 1.49; 95% CI 1.24-1.79; p < 0.001), sarcopenia assessed by other methods (RR = 2.98; 95% CI 1.52-5.87; p < 0.001), and patients in Europe (RR = 1.92; 95% CI 1.15-3.22; p = 0.013), received chemoradiotherapy (RR = 1.47; 95% CI 1.23-1.76; p < 0.001), and with head and neck tumours (RR = 1.54; 95% CI 1.17-2.01; p = 0.010) had higher relative risk than other subgroups. Sarcopenia was also associated with reduced overall survival in patients with tumours, with a pooled hazard ratio (HR) of 1.66 (95% CI 1.40-1.96, p < 0.001). Prospective studies (HR = 1.72; 95% CI 0.97-3.07; p = 0.065), sarcopenia assessed by the cervical-skeletal muscle index (HR = 2.66; 95% CI 1.73-4.09; p < 0.001), and patients in Asia (HR = 1.91; 95% CI 1.50-2.42; p < 0.001), received chemoradiotherapy (HR = 1.85; 95% CI 1.46-2.45; p < 0.001) and with head and neck tumours (HR = 2.35; 95% CI 1.88-2.95; p < 0.001) had higher HR than other subgroups. Sarcopenia was associated with a higher risk of adverse effects and mortality in patients with tumours received radio- and/or chemotherapy.

Medical Therapy Alone, Percutaneous Coronary Intervention, or Coronary Artery Bypass Grafting for Treatment of Coronary Artery Disease.

In this review, we describe how the management of coronary artery disease (CAD) has become increasingly complex due to the rapid evolution of pharmacotherapy and procedural techniques. The expanding array of treatment options has driven researchers to investigate the optimal combination of therapies; while the findings offer invaluable insights, the sheer volume and occasional contradictions can foster confusion. Given the diverse spectrum of CAD and its manifestations, a tailored treatment decision is critical for each patient. We hope to demonstrate that by integrating the key messages from clinical trials and prioritizing patient comprehension and preference, healthcare providers can guide their patients toward appropriate treatment options, ultimately leading to enhanced care.

IMMU-62. INVIGORATING EFFECTOR IMMUNE CELLS WITH HIGHLY SELECTIVE IL-2R AGONISTS AND POTENTIAL SYNERGY WITH TUMOR TARGETING THERAPEUTICS FOR TREATMENT OF GLIOBLASTOMAS

Abstract Glioblastoma (GBM) is an aggressive brain tumor with a median overall survival (mOS) of 14 months. Treatment options are limited with no new approved therapies over the past 3 decades and no standard of care for a majority of patients (&amp;gt; 90%) who experience recurrence. GBM has a highly immune suppressive tumor microenvironment (TME) comprising of myeloid derived suppressor cells (MDSCs) and tumor associated macrophages (TAMs) that are capable of suppressing the activity of anti-cancer CD8+ T and NK cells. We have engineered highly selective IL-2 superkines (IL-2SK) that preferentially expand and activate CD8+ T and NK cells with limited effects on immune suppressive regulatory T cells (i.e., Tregs). MDNA11 is an IL-2SK -albumin fusion protein designed to increase half-life and promote tumor accumulation. MDNA223 is a bi-functional anti-PD1-IL-2SK designed to stimulate effector immune cells while preventing immune exhaustion. MDNA11 and MDNA223 extended survival of mice harboring orthotopic GBM tumors with accompanying increase in CD8+ T and NK cells within the TME. When patient-derived GBM tumor explants were treated with MDNA11 and MDNA223 ex vivo, there was clear evidence of activation among resident CD8+ T cells characterized by increased levels of intra-cellular Granzyme B responsible for tumor cell killing. There was also increased release of soluble Fas ligand and granulysin, consistent with an activated anti-tumor immune response within the TME. Ongoing studies include in depth immune profiling to further understand the mechanism of MDNA11 and MDNA223 in GBM as well as to test potential synergy with tumor targeting therapeutics and other treatment modalities capable of eliciting immunogenic cell death.