Treatment Recommendations Research Articles

A Therapeutic Proposal for Mini-Puberty in Male Infants with Hypogonadotropic Hypogonadism: A Retrospective Case Series.

Background: Male patients with congenital hypogonadotropic hypogonadism (CHH) have impaired postnatal activation of the hypothalamic-pituitary-gonadal axis that occurs during mini-puberty. The aim of this study was to report our experience using gonadotropin replacement therapy for mini-puberty in male infants with CHH and to establish treatment recommendations. Methods: The patients included in this retrospective case series (n = 9) were diagnosed in the postnatal period due to micropenis, with two being accompanied by cryptorchidism and four with other associated hormonal deficits. All patients started treatment with gonadotropins early after diagnosis, between 2 weeks and 5 months of age, with a schedule of discontinuous injections with subcutaneous human chorionic gonadotropin (62.5-500 IU) two times per week and recombinant follicle-stimulating hormone-alpha (37.5-75 IU) three times per week. Results: The data from our study show an early response, ranging from almost undetectable levels of testosterone at diagnosis to elevated levels after starting treatment, as well as a positive clinical response with increases in testicular volume and penis size in all cases without requiring complementary treatment with testosterone esters and without adverse effects. Conclusions: Our results show that gonadotropin replacement therapy is a well-tolerated and effective treatment for testicular and penile problems in male patients with CHH.

Neuropsychological morbidity in the First Seizure Clinic: Prominent mood symptoms and memory issues in epilepsy.

To examine the neuropsychological morbidity across the spectrum of patients presenting to a First Seizure Clinic, and test the hypothesis that cognitive and psychological compromise is especially prominent in those diagnosed with epilepsy. A sample of 201 patients referred to the Austin Hospital First Seizure Clinic (FSC) underwent cognitive screening via telephone and psychological screening via online questionnaire, all prior to their diagnostic evaluation (and any attendant treatment recommendation) at the FSC. Rates of cognitive (i.e., scores <10th percentile) and psychological impairment (using established clinical cut scores) were compared against 35 demographically matched controls. Cognitive differences were explored between the most frequently encountered patient subgroups (epilepsy, n = 48; first unprovoked seizure, n = 24; acute symptomatic seizure, n = 24; syncope, n = 35) via a multivariate analysis of variance, with diagnostic labels applied retrospectively after a period of follow-up. People with epilepsy were most likely to show cognitive impairments, particularly in learning and memory, with performances worse than all other FSC groups (F [3127] = 2.44, p = 0.03). Clinically significant depressive symptoms were similarly prevalent in all patient groups, with one in three at risk for Major Depressive Disorder. Elevated anxiety symptoms were common across patient groups; however, not significantly different to controls. Cognitive impairment in epilepsy and mood problems in all FSC groups are detectable via remote screening as early as the first seizure. Learning and memory difficulties are particularly prevalent in new-onset epilepsy and may lend diagnostic information when paired with clinical factors. This study explored cognitive and psychological differences between various patient groups attending an Australian First Seizure Clinic. We found that learning and memory abilities were poorer in people with epilepsy than other patient groups including those with non-epileptic seizures, and seizure-mimics (fainting episodes). Therefore, along with standard epilepsy investigations, memory performances could help to predict which patients have epilepsy versus a non-epileptic condition after a first suspected seizure. Further, approximately one in three from each patient group showed high symptoms of depression and anxiety. The findings highlight the importance of evaluating cognition and mood in people with first seizures.

Consensus Recommendations from the 2024 Lymphoma Research Foundation Workshop on Treatment Selection and Sequencing in CLL or SLL

Over the past decade, treatment recommendations for patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) have shifted from traditional chemoimmunotherapy to targeted therapies. Multiple new therapies are commercially available, and in many cases a lack of randomized clinical trial data makes selection of the optimal treatment for each patient challenging. Additionally, many patients continue to receive chemoimmunotherapy in the US, suggesting a gap between guidelines and real-world practice. The Lymphoma Research Foundation convened a workshop comprised of a panel of CLL/SLL experts in the US to develop consensus recommendations for selection and sequencing of therapies for patients with CLL/SLL in the US. Herein, the recommendations are compiled for use as a practical clinical guide for treating providers caring for patients with CLL/SLL, which complement existing guidelines by providing a nuanced discussion relating how our panel of CLL/SLL experts in the US care for patients in a real-world environment.

The role of bariatric surgery in the treatment of urinary incontinence in obese women

Obesity has become an epidemic in recent decades, affecting millions of people worldwide. Many studies proved a cause between obesity and urinary incontinence in women. Lifestyle modifications, low-calorie diet, and weight loss surgery can improve symptoms of urinary incontinence in obese patients. Studying the effect of bariatric surgery on urinary incontinence symptoms has shown positive results in the short term period. However, there is data on worsening due to regaining weight in the long term period. Contradictory study search findings emphasize the need for further research and development of new clinical recommendations for effective treatment of urinary incontinence in women with obesity.

UK guidelines for the management of bone sarcomas.

This document is an update of the British Sarcoma Group guidelines (2016) and provides a reference standard for the clinical care of UK patients with primary malignant bone tumours (PMBT) and giant cell tumours (GCTB) of bone. The guidelines recommend treatments that are effective and should be available in the UK, and support decisions about management and service delivery. The document represents a consensus amongst British Sarcoma Group members in 2024. Key recommendations are that bone pain, or a palpable mass should always lead to further investigation and that patients with clinical or radiological findings suggestive of a primary bone tumour at any anatomic site should be referred to a specialist centre and managed by an accredited bone sarcoma multidisciplinary team. Treatment recommendations are provided for the major tumour types and for localised, metastatic and recurrent disease. Follow-up schedules are suggested.

Misdiagnosis in breast imaging: a statement paper from European Society Breast Imaging (EUSOBI)-Part 1: The role of common errors in radiology in missed breast cancer and implications of misdiagnosis.

Misdiagnosis in breast imaging can have significant implications for patients, healthcare providers, and the healthcare system as a whole. Some of the potential implications of misdiagnosis in breast imaging include delayed diagnosis or false reassurance, which can result in a delay in treatment and potentially a worse prognosis. Misdiagnosis can also lead to unnecessary procedures, which can cause physical discomfort, anxiety, and emotional distress for patients, as well as increased healthcare costs. All these events can erode patient trust in the healthcare system and in individual healthcare providers. This can have negative implications for patient compliance with screening and treatment recommendations, as well as overall health outcomes. Moreover, misdiagnosis can also result in legal consequences for healthcare providers, including medical malpractice lawsuits and disciplinary action by licensing boards. To minimize the risk of misdiagnosis in breast imaging, it is important for healthcare providers to use appropriate imaging techniques and interpret images accurately and consistently. This requires ongoing training and education for radiologists and other healthcare providers, as well as collaboration and communication among healthcare providers to ensure that patients receive appropriate and timely care. If a misdiagnosis does occur, it is important for healthcare providers to communicate with patients and provide appropriate follow-up care to minimize the potential implications of the misdiagnosis. This may include repeat imaging, additional biopsies or other procedures, and referral to specialists for further evaluation and management. Question What factors most contribute to and what implications stem from misdiagnosis in breast imaging? Findings Ongoing training and education for radiologists and other healthcare providers, as well as interdisciplinary collaboration and communication, is paramount. Clinical relevance Misdiagnosis in breast imaging can have significant implications for patients, healthcare providers, and the entire healthcare system.

Interpretation of the North American Pediatric Aplastic Anemia Consortium's evidence-based treatment recommendations for newly diagnosed pediatric severe aplastic anemia (2024 edition)

Interpretation of the North American Pediatric Aplastic Anemia Consortium's evidence-based treatment recommendations for newly diagnosed pediatric severe aplastic anemia (2024 edition)

2024 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces.

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

2024 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations: Summary From the Basic Life Support; Advanced Life Support; Pediatric Life Support; Neonatal Life Support; Education, Implementation, and Teams; and First Aid Task Forces

This is the eighth annual summary of the International Liaison Committee on Resuscitation International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations; a more comprehensive review was done in 2020. This latest summary addresses the most recent published resuscitation evidence reviewed by the International Liaison Committee on Resuscitation task force science experts. Members from 6 International Liaison Committee on Resuscitation task forces have assessed, discussed, and debated the quality of the evidence, using Grading of Recommendations Assessment, Development, and Evaluation criteria, and their statements include consensus treatment recommendations. Insights into the deliberations of the task forces are provided in the Justification and Evidence-to-Decision Framework Highlights sections. In addition, the task forces list priority knowledge gaps for further research.

Management of acute community-acquired bacterial meningitis : Leading symptoms of impaired consciousness and fever with/without headache

Simultaneous symptoms of impaired consciousness and fever are suspicious for acute bacterial meningitis. This is amedical emergency and prompt action is essential. The clinical workup for suspected bacterial meningitis as well as treatment recommendations and differential diagnosis for the main symptoms of decreased vigilance and fever are described. Evaluation of selective literature using PubMed (U.S. National Library of Medicine®, Bethesda, MD, USA), especially taking into account the AWMF (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften) guideline of community-acquired bacterial meningoencephalitis in adults. Bacterial meningoencephalitis presents with the main symptoms of impaired consciousness, nuchal rigidity, headache and fever, which may, however, be absent in some cases. The diagnosis is confirmed by investigation of the cerebrospinal fluid. Further diagnostics include emergency laboratory tests, blood cultures, microbiological examinations, and cranial computed tomography (CCT). Empirical treatment should be administered promptly. Acute bacterial meningitis must be considered in cases of loss of vigilance and fever, requiring arapid, structured approach in the emergency department.

Sepsis-associated liver injury: Mechanisms and potential therapeutic targets

In this editorial, we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury (SLI) and its treatment. SLI is a serious complication of sepsis, primarily caused by microcirculatory disturbances, the gut-liver axis, and inflammatory responses. Specific treatment recommendations for SLI are lacking. The gut-liver axis represents a potential therapeutic target, with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function. Although immunomodulatory therapies are being explored, anti-tumor necrosis factor agents and interleukin-1 receptor antagonists have not demonstrated significant clinical benefits. Statins may reduce liver inflammation and prevent injury in sepsis, but their clinical application is limited. Reduced D-related human leucocyte antigen expression on monocytes and lymphocytes suggests immune suppression in patients, indicating that corticosteroids could reverse clinical deterioration in severe infections and address adrenal cortical insufficiency. Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results, likely due to inadequate assessment of the immune status of the host. Future research should prioritize the development of personalized immunotherapy tailored to patients’ immune profiles, focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.

2024 American Heart Association and American Red Cross Guidelines for First Aid.

Codeveloped by the American Heart Association and the American Red Cross, these guidelines represent the first comprehensive update of first aid treatment recommendations since 2010. Incorporating the results of structured evidence reviews from the International Liaison Committee on Resuscitation, these guidelines cover first aid treatment for critical and common medical, traumatic, environmental, and toxicological conditions. This update emphasizes the continuous evolution of evidence evaluation and the necessity of adapting educational strategies to local needs and diverse community demographics. Existing guidelines remain relevant unless specifically updated in this publication. Key topics that are new, are substantially revised, or have significant new literature include opioid overdose, bleeding control, open chest wounds, spinal motion restriction, hypothermia, frostbite, presyncope, anaphylaxis, snakebite, oxygen administration, and the use of pulse oximetry in first aid, with the inclusion of pediatric-specific guidance as warranted.

Validity and reliability of the osteoporotic fracture treatment score (OF score) and outcomes across various treatments in osteoporosis vertebral compression fracture patients

BackgroundOsteoporotic vertebral compression fractures (OVF) are prevalent and substantially impact healthcare systems and patients’ quality of life. The osteoporotic fracture treatment score (OF score), developed by the German Society of Orthopedics and Trauma (DGOU), guides surgical decisions, but its reliability and validity are underexplored. This study assessed the OF score’s inter- and intraobserver reliability, validated its treatment recommendations, and investigated intermediate outcomes of different DGOU-recommended surgical strategies for OVF.MethodsA retrospective cohort study was conducted. Inter- and intraobserver reliability of the OF score and its subcomponents were analyzed using clinical and radiographic data. Validity was assessed by comparing the OF score’s recommended treatments with actual treatments received. Outcomes at the final follow-up were back pain visual analog scale, Oswestry Disability Index, EQ-VAS, EQ-5D-5 L, adjacent fracture incidence, local kyphotic angle, and reoperation rates. Patients with at least 1-year follow-up were included.ResultsA total of 157 patients (84.7% female; mean age 74.2 ± 10.5 years) were evaluated. The most frequent osteoporotic fracture (OF) types were OF4 (49.0%) and OF3 (40.8%). The OF score demonstrated good interobserver reliability (ICC = 0.77, 95% CI: 0.65–0.86) and intraobserver reliability (ICC = 0.83, 95% CI: 0.72–0.90). Kappa values for subcomponents ranged from 0.57 to 0.89. Excluding patients with indeterminate recommendations (OF score = 6), 82.9% received treatments concordant with OF score recommendations. Receiver operating characteristic curve analysis showed an area under the curve of 0.77 (95% CI: 0.67–0.86); an OF score cutoff > 6.5 predicted actual treatment with 87.9% sensitivity and 61.0% specificity. All surgical treatments showed comparable improvements in clinical outcomes. However, patients treated with stand-alone cement augmentation (CA) had less local kyphotic angle correction (P = 0.004) and greater postoperative kyphotic progression (P < 0.001) than those undergoing short-segment (SS-PI) or long-segment instrumentation (LS-PI). No significant differences in adjacent fractures or complications were observed.ConclusionsThe OF score is a reliable and valid system with good discriminative ability for surgical decision-making in OVF patients. CA, SS-PI, and LS-PI are viable options with comparable functional outcomes. However, in OF3 or OF4 fractures, caution is advised due to lesser kyphosis correction and greater kyphotic progression with CA compared to SS-PI or LS-PI, as recommended by the DGOU.

HPB SO50 - A comprehensive review of clinical practice guidelines for managing hepatic adenoma

Abstract Background Hepatic adenoma(HCA) are increasingly diagnosed as incidentalomas. Clinical implications and management vary across and within the different types of Hepatic adenomas. Practice guidelines are needed, because of the many variation, diagnostic tools, and conservative and invasive management protocols. Therefore, our aim was to systematically search for available clinical practice guidelines on hepatic adenoma, critically appraise them, and compare management recommendations. Method Systematic literature search was performed by two investigators using appropriate prespecified search terms within the bibliographic databases of MEDLINE, EMBASE, and PubMed. All HCA guidelines published in peer-reviewed, and English language journals were eligible for inclusion. Clinical practice guidelines on HCA were analysed, compared, and critically appraised using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations (PRISMA) 2020 checklist. Results The literature search yielded unique 199 papers, 187 were excluded after screening of title/abstract, and 9 after full-text screening. Guidelines included were: (EASL; 2016, (ACG; 2014), (SBH; 2015),). There were no set standards in the assessment methods for grading and gravity of recommendations between guidelines. Observed differences were: (1) indications for biopsy; (2) advices on contraceptive pills and follow-up; (3) use of an lesion centred approach to HCA; (4) lack of adequate treatment recommendations of HCA in male population ; and (5) approach to HCA depending on subtype varaition on magnetic resonance imaging. Conclusion Recognising differences in recommendations can assist in formulating practice standards and identify needs for research.

Update from d-uo: what can healthcare research contribute to renal cell carcinoma?

Renal cell carcinoma (RCC) accounts for about 13.5% of all urological tumors. Healthcare research analyzes whether treatment recommendations from controlled studies or guidelines are being implemented in routine care. Aprerequisite for the assessment and scientific study of the quality of care in the treatment of urological tumors is standardized documentation. This article illustrates healthcare research in RCC by presenting current data from the prospective of the VERSUS study (VERSorgUngsStudie) by d‑uo (Deutsche Uro-Onkologen). The VERSUS study is anoninterventional, prospective, multicentric study for the documentation and descriptive statistical analysis of the diagnosis, treatment, and aftercare of uro-oncological patients. Of 25,065 patients currently included in the VERSUS study, 1976 have a diagnosis of RCC. Data regarding stage distribution, reason leading to initial diagnosis, distribution of symptomatic vs. asymptomatic patients as well as surgical margins from surgical treatment of RCC are presented. Despite providing interesting results, the VERSUS study remains limited with regard to the depth of the data, since it relies on the same dataset as the German cancer registry. In order to provide more comprehensive healthcare research, organ-related cancer registries like the Urothelial Cancer National Registry (UroNAT) and the Prostate Cancer National Registry (ProNAT) by d‑uo are necessary. These national cancer registries by d‑uo are unique in that they comprise all tumor stages. The Renal Cancer National Registry (ReNAT) by d‑uo is in preparation and will be avaluable contribution to quality assurance of oncological care in Germany.

Abstract 4138494: Remote Blood Pressure Monitoring and Intervention as a better and cost-effective method of Hypertension control compared to Usual care: A Systematic Review

Introduction/Background: Hypertension is a leading cause of morbidity and mortality. Despite treatment recommendations and encouragement of lifestyle changes, the actual rate of blood pressure control is still not at par. Remote intervention methods have been shown to achieve better rates of blood pressure control utilising lesser resources and lower healthcare costs. We conducted a systematic review by qualitatively evaluating the potential impact of remote monitoring and interventions compared to usual care in controlling Hypertension. Research Question: Are remote monitoring techniques and interventions better than usual in-person blood pressure checks for hypertension control? Methods: We did a comprehensive literature search of Pubmed/MEDLINE, Google scholar, Cochrane central Library, PLOS ONE, ScienceDirect and Clinicaltrials.gov to identify eligible randomised control trials and clinical trials published between July 2013 and May 2025. A Risk of Bias assessment was conducted using Cochrane Risk of Bias tools such as ROB-2 for randomised control trials and ROBINS-1 for cohort studies. This study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results: Of the 5,185 records analysed, 10 randomised control trials, 1 cohort study and 1 implementation study satisfied our inclusion criteria. Compared to usual care, remote monitoring methods showed significant difference in systolic blood pressure control at 6-12 months in 9 out of 12 studies, while 3 studies did not show any significant difference. Quality of life, physical health, mental health and drug compliance have also shown a significant positive difference in patients. Remote self monitoring interventions were found to be more cost-effective than usual care. They also reduced the load of patients seeking appointments for hypertension control thereby improving the quality of patient care. Conclusion: The management of clinical hypertension is a challenging entity. Conventional methods of regular in-office blood pressure checks are both tedious and resource consuming. Using remote monitoring methods have shown to significantly improve blood pressure control compared to routine methods. It also eliminates white-coat hypertension during follow-up blood pressure checks which leads to more appropriate interventions. Remote monitoring and intervention for hypertension control is time-effective, cost-effective and improves quality of life.

Diagnosis and Treatment of Renal ANCA Vasculitis: A Summary of the Consensus Document of the Catalan Group for the Study of Glomerular Diseases (GLOMCAT).

The document provides a comprehensive overview of the diagnosis, monitoring, and treatment of anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) with renal involvement, focusing on granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA). It outlines the definitions, clinical presentation, histopathological classification, monitoring strategies, induction and maintenance treatments, as well as special considerations for relapsing, refractory, and frail patients with renal AAV. The document was prepared by the Catalan Group for the Study of Glomerular Diseases (GLOMCAT), which comprises nephrologists with extensive experience in the diagnosis and treatment of AAV patients. Several virtual and face-to-face meetings were held for coordination, section assignments, and content discussion. An exhaustive and systematic search of the literature was carried out, which included, among others, the following databases: PubMed, EMBASE, Cochrane Library, Google Scholar, and ClinicalTrials.gov, as well as the abstract books of national and international congresses. Overall, the document provides a comprehensive guide for clinicians managing patients with renal AAV, offering evidence-based recommendations for diagnosis, monitoring, and treatment across various clinical scenarios.

INNV-22. CEREBELLOPONTINE EPIDERMOID CYST TO SQUAMOUS CELL CARCINOMA: MALIGNANT TRANSFORMATION, LEPTOMENINGEAL CARCINOMATOSIS, AND MANAGEMENT

Abstract BACKGROUND Intracranial epidermoid cysts (EDC) are rare, slow-growing, congenital tumors, that generally follow a benign course. EDCs have a rare potential for transformation to squamous cell carcinoma (SCC). We present a case of a malignant EDC transformation to SCC with leptomeningeal (LM) dissemination. METHODS Case report and review of literature. CASE PRESENTATION A 44-year-old female presented for evaluation of left-sided tinnitus and sensorineural hearing loss, which revealed a left cerebellopontine angle (CPA) tumor. She underwent a subtotal resection at age 47. One year later, she had rapid symptomatic recurrence of the cyst, as well as LM deposits of the right internal acoustic canal bundle, the left trigeminal nerve, and along the lumbar and sacral spine. She underwent repeat resection of the CPA lesion, with pathology now consistent with SCC, with CDKN2A loss. She received focal radiation therapy at the posterior fossa and the lumbar spine. SCC-directed chemotherapy with pembrolizumab and carboplatin followed by 5 cycles of pembrolizumab monotherapy was given as adjuvant therapy, prior to her developing symptomatic LM disease. CONCLUSION Malignant transformation of intracranial EDC is a rare occurrence in these typically benign tumours. Prognosis is especially poor when there is associated LM involvement, with median survival noted to be 10 months. Awareness of this phenomenon amongst clinicians is needed to ensure appropriate surveillance and aggressive treatment if it remains within patient wishes, though there is no consensus on recommendations for treatment. The patient presented has maintained disease stability with LM dissemination for over 10 months and ongoing, with a regimen of chemoradiotherapy informed by therapeutic approach to systemic SCC. To our knowledge, this is the first reported case of EDC to SCC transformation and LM dissemination stabilized with chemoradiotherapy using an immune-checkpoint inhibitor.

CTNI-78. PNOC008: A PILOT TRIAL TESTING THE CLINICAL BENEFIT OF USING MOLECULAR PROFILING TO DETERMINE AN INDIVIDUALIZED TREATMENT PLAN IN CHILDREN AND YOUNG ADULTS WITH NEWLY DIAGNOSED HIGH-GRADE GLIOMA (EXCLUDING DIFFUSE INTRINSIC PONTINE GLIOMA)

Abstract BACKGROUND Despite multiple clinical trials in young patients with newly diagnosed high grade gliomas (HGG), survival remains poor. PNOC008 is a single-arm, multi-center pilot trial, investigating the feasibility, toxicity, and efficacy of a molecularly guided individualized treatment approach following radiotherapy. METHODS Patients aged ≤21 years with newly diagnosed, localized, hemispheric HGG (Stratum A) or non DIPG, diffuse midline glioma (DMG) (Stratum B) were eligible. Comprehensive molecular profiling (targeted gene panel, whole exome, and whole transcriptome sequencing) was performed on primary tumor tissue. The molecular data was reviewed by a dedicated tumor board that recommended an individualized treatment plan combining up to four FDA approved drugs. Patients were followed for toxicity and efficacy. Circulating tumor DNA (ctDNA), imaging, and quality of life (QOL) measures were collected at multiple timepoints. RESULTS Fifty-five HGG patients enrolled between 2018 and 2023 (median age 11 years [range 2-20], n=31 female, n=29 Stratum A), including H3K27-altered (n=17), H3/IDH-wildtype diffuse pediatric-type (n=16), and H3G34-mutant diffuse hemispheric glioma (n=12). In 44 patients that followed the recommended treatment, median overall survival (OS) from time of study enrollment was 26.5 months in Stratum A (lower 95% CI: 18.5) and 23.6 months in Stratum B (lower 95% CI: 16.8), and 30 months in H3G34-mutant patients (n=10, lower 95% CI:24.6) with median follow-up of 34.5 months for all patients (lower 95% CI: 32.2). The treatment recommendations most commonly included alkylator with targeted therapy combinations. The often novel drug combinations were generally well tolerated with grade 3 or 4 treatment-related adverse events being mostly hematologic. Central imaging, ctDNA, and QOL analyses are underway. CONCLUSIONS A personalized treatment approach using comprehensive transcriptomic and genomic analysis is feasible and well tolerated with encouraging survival data in children and young adults with HGG. Further analyses of molecular subgroups and correlatives are ongoing.

Modification and Validation of the System Causability Scale Using AI-Based Therapeutic Recommendations for Urological Cancer Patients: A Basis for the Development of a Prospective Comparative Study.

The integration of artificial intelligence, particularly Large Language Models (LLMs), has the potential to significantly enhance therapeutic decision-making in clinical oncology. Initial studies across various disciplines have demonstrated that LLM-based treatment recommendations can rival those of multidisciplinary tumor boards (MTBs); however, such data are currently lacking for urological cancers. This preparatory study establishes a robust methodological foundation for the forthcoming CONCORDIA trial, including the validation of the System Causability Scale (SCS) and its modified version (mSCS), as well as the selection of LLMs for urological cancer treatment recommendations based on recommendations from ChatGPT-4 and an MTB for 40 urological cancer scenarios. Both scales demonstrated strong validity, reliability (all aggregated Cohen's K > 0.74), and internal consistency (all Cronbach's Alpha > 0.9), with the mSCS showing superior reliability, internal consistency, and clinical applicability (p < 0.01). Two Delphi processes were used to define the LLMs to be tested in the CONCORDIA study (ChatGPT-4 and Claude 3.5 Sonnet) and to establish the acceptable non-inferiority margin for LLM recommendations compared to MTB recommendations. The forthcoming ethics-approved and registered CONCORDIA non-inferiority trial will require 110 urological cancer scenarios, with an mSCS difference threshold of 0.15, a Bonferroni corrected alpha of 0.025, and a beta of 0.1. Blinded mSCS assessments of MTB recommendations will then be compared to those of the LLMs. In summary, this work establishes the necessary prerequisites prior to initiating the CONCORDIA study and validates a modified score with high applicability and reliability for this and future trials.