Inform Treatment Decisions Research Articles

MultiSCRIPT-Cycle 1—a pragmatic trial embedded within the Swiss Multiple Sclerosis Cohort (SMSC) on neurofilament light chain monitoring to inform personalized treatment decisions in multiple sclerosis: a study protocol for a randomized clinical trial

BackgroundTreatment decisions for persons with relapsing–remitting multiple sclerosis (RRMS) rely on clinical and radiological disease activity, the benefit-harm profile of drug therapy, and preferences of patients and physicians. However, there is limited evidence to support evidence-based personalized decision-making on how to adapt disease-modifying therapy treatments targeting no evidence of disease activity, while achieving better patient-relevant outcomes, fewer adverse events, and improved care. Serum neurofilament light chain (sNfL) is a sensitive measure of disease activity that captures and prognosticates disease worsening in RRMS. sNfL might therefore be instrumental for a patient-tailored treatment adaptation. We aim to assess whether 6-monthly sNfL monitoring in addition to usual care improves patient-relevant outcomes compared to usual care alone.MethodsPragmatic multicenter, 1:1 randomized, platform trial embedded in the Swiss Multiple Sclerosis Cohort (SMSC). All patients with RRMS in the SMSC for ≥ 1 year are eligible. We plan to include 915 patients with RRMS, randomly allocated to two groups with different care strategies, one of them new (group A) and one of them usual care (group B). In group A, 6-monthly monitoring of sNfL will together with information on relapses, disability, and magnetic resonance imaging (MRI) inform personalized treatment decisions (e.g., escalation or de-escalation) supported by pre-specified algorithms. In group B, patients will receive usual care with their usual 6- or 12-monthly visits. Two primary outcomes will be used: (1) evidence of disease activity (EDA3: occurrence of relapses, disability worsening, or MRI activity) and (2) quality of life (MQoL-54) using 24-month follow-up. The new treatment strategy with sNfL will be considered superior to usual care if either more patients have no EDA3, or their health-related quality of life increases. Data collection will be embedded within the SMSC using established trial-level quality procedures.DiscussionMultiSCRIPT aims to be a platform where research and care are optimally combined to generate evidence to inform personalized decision-making in usual care. This approach aims to foster better personalized treatment and care strategies, at low cost and with rapid translation to clinical practice.Trial registrationClinicalTrials.gov NCT06095271. Registered on October 23, 2023

Exploiting the triple quadrupole mass analyzer for the open detection and tentative identification of synthetic cannabinoid receptor agonists based on common fragmentation pathways

BackgroundThe use of new psychoactive substances (NPS) has emerged as a significant public health concern globally, due to their unknown and unpredictable effects on both physical and mental health. Among them, synthetic cannabinoids receptor agonists (SCRAs) currently stand as the most widely consumed NPS family in Europe. Since the detection of JWH-018 in 2008, the structures of these compounds have evolved to circumvent legislation and/or enhance their effects, consequently increasing the number of reported SCRAs to be monitored. Therefore, new strategies are needed to identify these compounds, whether in seized products or in biological samples. ResultsThis study presents the development of an open method for detecting SCRAs employing a “pseudo-target” screening approach, a strategy previously developed and used in our laboratory for synthetic cathinones identification. The methodology involves monitoring the main product ions and neutral losses derived from 179 SCRAs of the third and fourth generations, based on their fragmentation pathways. This approach allows for the tentative identification of the SCRAs, supported also by the created database. The versatility of the developed methodology is highlighted, extending its utility beyond seizure products or ‘legal highs’, to biological samples. In this sense, it has been successfully applied not only to the detection of SCRAs in research chemicals but also in authentic urine from an anonymous SCRAs consumer, through the identification of a metabolite. SignificanceThis strategy will be particularly useful for the rapid detection of SCRAs in forensic and toxicological laboratories equipped with low-resolution MS/MS instrumentation. This is a valuable tool for the identification and monitoring of SCRAs across various contexts, significantly contributing to public health and forensic security efforts. It is especially beneficial for healthcare providers, enabling them to make informed treatment decisions.

Similarities and differences between European guidelines for the management of postmenopausal osteoporosis

SummaryWe conducted a review of 10 national guidelines from five EU countries to identify similarities or differences in recommendations for the management of patients with osteoporosis. We found general alignment of key recommendations; however, there are notable differences, largely attributed to country-specific approaches to risk assessment and reimbursement conditions.IntroductionThe classification of fracture risk is critical for informing treatment decisions for post-menopausal osteoporosis. The aim of this review was to summarise 10 national guidelines from five European countries, with a focus on identifying similarities or differences in recommendations for the management of patients with osteoporosis.MethodsWe summarised the European Society for Clinical and Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Disease-International Osteoporosis Foundation guidelines and reviewed guidelines from France, Germany, Italy, Spain and the UK.ResultsThe approach to risk assessment differed across the guidelines. In France, and Spain, risk assessment was based on DXA scans and presence of prior fractures, whereas UK, German and Italian guidelines recommended use of a validated risk tool. These differences led to distinct definitions of very high and high-risk patients. Guidelines aligned in recommending antiresorptive and anabolic agents as pharmacologic options for the management of osteoporosis, with sequential treatment recommended. There was agreement that patients at high or very high risk of fracture or with severe osteoporosis should receive anabolic agents first, followed by antiresorptive drugs. Variations were identified in recommendations for follow up of patients on anti-osteoporosis therapies. Reimbursement conditions in each country were a key difference identified.ConclusionsCriteria for risk assessment of fractures differ across European guidelines which may impact treatment and access to anabolic agents. Harmonisation across EU guidelines may help identify patients eligible for treatment and impact treatment uptake. However, country-specific reimbursement and prescribing processes may present a challenge to achieving a consistent approach across Europe.

Predictive models and biomarkers for survival in stage III breast cancer: a review of clinical applications and future directions

Stage III breast cancer, characterized by locally advanced tumors and potential regional lymph node involvement, presents a formidable challenge to both patients and healthcare professionals. Accurate prediction of survival outcomes is crucial for guiding treatment decisions and optimizing patient care. This publication explores the potential clinical utility of predictive tools, encompassing genetic markers, imaging techniques, and clinical parameters, to improve survival outcome predictions in stage III breast cancer. Multimodal approaches, integrating these tools, hold the promise of delivering more precise and personalized predictions. Despite the inherent challenges, such as data standardization and genetic heterogeneity, the future offers opportunities for refinement, driven by precision medicine, artificial intelligence, and global collaboration. The goal is to empower healthcare providers to make informed treatment decisions, ultimately leading to improved survival outcomes and a brighter horizon for individuals facing this challenging disease.

254. QUANTIFYING PERIOPERATIVE RISKS FOR ANTIREFLUX AND HIATUS HERNIA SURGERY: A MULTICENTER COHORT STUDY OF 4301 PATIENTS

Abstract Background Predicting perioperative risks for fundoplication and hiatus hernia repair will inform treatment decision-making, hospital resource allocation, and benchmarking. However, available risk calculators do not account for hernia anatomy or technical aspects of surgery in estimating perioperative risk. Using a comprehensive Australian cohort, we quantified the incidence and determined the independent predictors of intraoperative and postoperative complications associated with antireflux and hiatus hernia surgeries. Additionally, we performed an in-depth analysis to understand the complication profiles associated with each independent risk factor. Methods Retrospective analysis of all elective antireflux and hiatus hernia surgeries in 36 Australian hospitals over 10 years. Hierarchical multivariate logistic regression analyses were performed to determine the independent predictors of intraoperative and postoperative complications accounting for patient, surgical, anatomical, and perioperative factors. Results A total of 4301 surgeries were analyzed. Of these, 1569 (36.5%) were large/giant hernias and 292 (6.8%) were revisional procedures. The incidence rates of intra- and postoperative complications were 12.6% and 13.3%, respectively. The Charlson Comorbidity Index, hernia size, revisional surgery, and baseline anticoagulant usage independently predicted both intraoperative and postoperative complications. These risk factors were associated with their own complication profiles. Finally, using risk matrices, we visualized the cumulative impact of these four risk factors have on the development of intraoperative, overall postoperative, and major postoperative complications. Conclusions This study has improved our understanding of perioperative morbidity associated with antireflux and hiatus hernia surgery. Our findings group patients along a spectrum of perioperative risks that informs care at an individual and institutional level.

127P Clinical utility of circulating tumor DNA (ctDNA) next generation sequencing (NGS) to inform treatment decisions for patients (pts) with advanced solid tumors

127P Clinical utility of circulating tumor DNA (ctDNA) next generation sequencing (NGS) to inform treatment decisions for patients (pts) with advanced solid tumors

Assessing the visual afferent pathway with the multifocal visual evoked potentials in the radiologically isolated syndrome

The early identification of individuals with radiologically isolated syndrome (RIS) who are at an elevated risk of progressing to multiple sclerosis (MS) is essential for making informed treatment decisions. This study aimed to evaluate the predictive potential of multifocal Visual Evoked Potentials (mfVEP) measures in individuals with RIS with respect to their conversion to MS. A prospective observational cohort study was conducted, involving 21 individuals with RIS recruited from a MS center. Baseline assessments, including mfVEP, magnetic resonance imaging (MRI), and clinical examinations, were performed, and participants were longitudinally followed for up to 24 months. The primary outcome measures were the conversion to MS. Over a clinical follow-up period of 24 months, five individuals (5/21) with RIS progressed to MS. MfVEP amplitude responses (interocular and monocular probability analysis) demonstrated abnormal cluster visual field defects in 47.6% of RIS eyes at baseline, whereas multifocal VEP latency analysis showed significant delays in 38.4%. A reduction in interocular amplitude [OR = 0.036, (95% CI 0.003–0.503); P = 0.014], monocular amplitude [OR = 0.083, (95% CI 0.007–0.982); P = 0.048], and a prolonged interocular latency [OR = 0.095, (95% CI 0.009–0.972); P = 0.047] were associated with a higher relative risk of clinical conversion at the 2-year follow-up. Multifocal VEP may serve as a novel and independent risk factor for predicting the conversion to MS in individuals with Radiologically Isolated Syndrome.

Virological impact of HIV drug-resistance testing in children, adolescents, and adults failing first-line ART in Tanzania

BackgroundProspective data on the effectiveness of resistance testing in informing treatment decisions and outcomes in with first-line failure in these settings is limited. This study aimed to assess the virological impact of HIV drug-resistance testing in patients with virological failure in Tanzania. MethodsParticipants were randomly assigned to either the control or the experimental group. In addition to the standard of care, patients in the experimental group had access to genotypic drug-resistance testing, information used during treatment change and were followed up at six-and 12-months to determine virological suppression. ResultsA total of 261 patients with a median age of 32 (14.7–44.7) years were enrolled. In the intention-to-treat analysis, at 6-months, suppression was achieved in 58 (42.3%; 95% CI, 34.1–50.1) experimental group patients versus 51 (41.1%; 95% CI, 32.5–49.8) control group patients, with a p-value of 0.4. At-12 months, suppression was achieved in 110 (80.3%; 95% CI, 73.6–87) experimental patients versus 99 (79.8%; 95% CI, 72.8–86.9) control patients, with a P-value of 0.5. In the per-protocol analysis, at 6-months, suppression was observed in 38.46% (95% CI, 27.6–49.3) experimental patients versus 38.6% (95% CI, 26.0–51.2) control patients, with a P-value of 0.5. At 12-months, suppression was observed in 79.49% (95% CI, 70.5–88.5) of experimental patients versus 75.44% (95% CI, 64.3–86.6) of control patients, with a P-value of 0.3. ConclusionConducting HIV drug-resistance testing, and switch to individualised second-line regimens did not significantly improve virological suppression in patients experiencing first-line ART failure in Tanzania.

CT-based multimodal deep learning for non-invasive overall survival prediction in advanced hepatocellular carcinoma patients treated with immunotherapy

ObjectivesTo develop a deep learning model combining CT scans and clinical information to predict overall survival in advanced hepatocellular carcinoma (HCC).MethodsThis retrospective study included immunotherapy-treated advanced HCC patients from 52 multi-national in-house centers between 2018 and 2022. A multi-modal prognostic model using baseline and the first follow-up CT images and 7 clinical variables was proposed. A convolutional-recurrent neural network (CRNN) was developed to extract spatial-temporal information from automatically selected representative 2D CT slices to provide a radiological score, then fused with a Cox-based clinical score to provide the survival risk. The model’s effectiveness was assessed using a time-dependent area under the receiver operating curve (AUC), and risk group stratification using the log-rank test. Prognostic performances of multi-modal inputs were compared to models of missing modality, and the size-based RECIST criteria.ResultsTwo-hundred seven patients (mean age, 61 years ± 12 [SD], 180 men) were included. The multi-modal CRNN model reached the AUC of 0.777 and 0.704 of 1-year overall survival predictions in the validation and test sets. The model achieved significant risk stratification in validation (hazard ratio [HR] = 3.330, p = 0.008), and test sets (HR = 2.024, p = 0.047) based on the median risk score of the training set. Models with missing modalities (the single-modal imaging-based model and the model incorporating only baseline scans) can still achieve favorable risk stratification performance (all p < 0.05, except for one, p = 0.053). Moreover, results proved the superiority of the deep learning-based model to the RECIST criteria.ConclusionDeep learning analysis of CT scans and clinical data can offer significant prognostic insights for patients with advanced HCC.Critical relevance statementThe established model can help monitor patients’ disease statuses and identify those with poor prognosis at the time of first follow-up, helping clinicians make informed treatment decisions, as well as early and timely interventions.Key PointsAn AI-based prognostic model was developed for advanced HCC using multi-national patients.The model extracts spatial-temporal information from CT scans and integrates it with clinical variables to prognosticate.The model demonstrated superior prognostic ability compared to the conventional size-based RECIST method.Graphical

The Role of Endoscopic Ultrasound in Ampullary Lesion Management.

Ampullary lesions, neoplasms originating in the papilla of Vater, represent a rare yet clinically significant group of tumors with diverse etiologies and management challenges. This comprehensive review aims to elucidate the pivotal role of endoscopic ultrasound (EUS) in the diagnosis, staging, and management of ampullary lesions. This review begins by providing an overview of ampullary lesions, their epidemiology, and associated risk factors. We delve into their clinical presentation, emphasizing the importance of early and accurate diagnosis. Furthermore, we explore the limitations of traditional diagnostic modalities and highlight the growing relevance of EUS in ampullary lesion evaluation. We discuss the superior spatial resolution of EUS in comparison with other imaging methods, and we present an in-depth analysis of EUS-guided sampling and its pivotal role in obtaining histological samples for accurate diagnosis. In addition to diagnosis, we examine the indispensable role of EUS in ampullary lesion staging and its clinical implications. Furthermore, we discuss the potential of EUS in the surveillance and follow-up of ampullary lesions, ensuring timely detection of recurrence and monitoring treatment response in sporadic cases and in the context of familial syndromes, such as familial adenomatous polyposis (FAP). In conclusion, this review underscores the indispensable role of endoscopic ultrasound in the multifaceted approach to ampullary lesion evaluation. EUS not only enhances diagnostic accuracy but also informs treatment decisions and minimally invasive therapeutic interventions. As our understanding of ampullary lesions continues to evolve, EUS remains an invaluable tool for the improvement of patient outcomes and quality of life.

Optimizing treatment sequence for inoperable locally advanced breast cancer: Long-term outcomes of surgery first versus neoadjuvant chemotherapy in a real-world setting.

Locally advanced breast cancer (LABC) is challenging with limited treatment options. This study investigates the feasibility and long-term outcomes of upfront surgery compared to neoadjuvant chemotherapy (NAC) in a real-world cohort. This retrospective study analyzed 243 inoperable LABC patients (excluding T3N1M0) that underwent upfront surgery (n = 187) or NAC (n = 56) in matched groups. Disease-free survival (DFS) and overall survival (OS) are primary outcomes. Secondary outcomes included NAC response rate and subgroup analyses based on age, tumor stage, and treatment response. Survival was estimated using Kaplan-Meier methods with log-rank tests for comparisons. Cox proportional hazards models were used for subgroup analyses. With a median follow-up of 60.9 months, no significant difference emerged in 5-year OS (upfront surgery: 89.6%, NAC: 81.9%, p = .12) or 5-year DFS rates (73.0% vs. 67.1%, p = .24). Subgroup analyses revealed upfront surgery offered significantly better OS for patients under 60 (HR = 0.32; 95% CI: 0.10-0.96; p = .0429) and stage IIIA disease (HR = 0.22; CI: 0.06-0.86; p = .03). Upfront surgery showed a trend towards improved OS for tumors under 5 cm (HR = 0.37; 95% CI: 0.13-1.03; p = .056). Patients with progressive disease (PD) or stable disease (SD) after NAC had significantly worse DFS (HR = 0.27; 95% CI: 0.09-0.79; p = .017) and OS (HR = 0.09; 95% CI: 0.02-0.48; p = .004) compared to responders. Upfront surgery may be viable for LABC patients, particularly younger patients, those with stage IIIA disease, or smaller tumors. NAC response can inform treatment decisions. These findings highlight the need for personalized LABC treatment considering patient characteristics and NAC response.

Efficacy of CalliSpheres® drug-loaded microspheres combined with doxorubicin in hepatocellular carcinoma.

This study compared the efficacy and safety of the transarterial chemoembolization with CalliSpheres® drug-eluting beads loading with doxorubicin (DEB-TACE) versus conventional lipiodol (cTACE) in patients with unresectable hepatocellular carcinoma (HCC). A randomized controlled trial (RCT) was conducted with 144 patients, who were randomly assigned to receive either DEB-TACE with doxorubicin-loaded CalliSpheres® microspheres or cTACE with doxorubicin-lipiodol emulsion. Patients were followed up for 12 months, with assessments at 3 and 12 months posttreatment. The primary endpoint was the clinical response rate (CR), and the secondary endpoints were the overall survival (OS), the progression-free survival (PFS), and the safety profile of the two treatments. The results showed that DEB-TACE was superior to cTACE in terms of CR (50.0% vs 30.6% at 3 months, p = 0.03; 43.1% vs 25.0% at 12 months, p = 0.04), OS (18.2 months vs 14.6 months, p < 0.05), and PFS (7.4 months vs 4.8 months, p < 0.05), and that the safety profile of the two treatments was similar (p > 0.05 for all comparisons). However, the efficacy of DEB-TACE and cTACE varied according to the tumor morphology. DEB-TACE showed better CR rates in patients with nodular tumors, while no significant difference in CR between the two groups in patients with infiltrative tumors. DEB-TACE showed superior efficacy to cTACE in terms of CR, OS, and PFS, particularly in patients with nodular tumors, while maintaining a similar safety profile. These findings suggest that tumor morphology could inform treatment decisions for TACE in HCC patients.

Recent update on cerebral sparganosis: A bibliometric analysis and scientific mapping.

Human sparganosis, a parasitic infection prevalent in Asia, can progress to cerebral sparganosis, a severe condition with significant neurological symptoms. Diagnosis and treatment are challenging due to its clinical similarity to other infections, highlighting the need for improved detection and management strategies. The aim of this study was to observe research trends, key contributors, gaps in the existing knowledge, diagnosis challenges, effective treatment options, and prevention strategies, providing recommendations for future research directions and clinical practice improvements on cerebral sparganosis. A bibliometric analysis was conducted by extracting 139 documents from the Scopus database in June 2024. The retrieved data were analyzed using the R package's Bibliometrix (Biblioshiny) and VOSviewer. Spanning 97 different sources, the research exhibited an annual growth rate of 2.5%. Annual scientific production revealed fluctuating research activity with peaks in 2010 and 2011 and notable citation peaks in 1996 and 2005, indicating pivotal studies that significantly influenced subsequent research. Early studies focused on diagnosis and specific parasites, while recent studies (2010-2024) have increasingly addressed clinical outcomes, treatment strategies, and advanced diagnostic techniques. Trends revealed a shift towards clinical and diagnostic advancements, with recent emphasis on diagnostic imaging, immunoassays, and the relationship between cerebral sparganosis and brain tumors. In conclusion, the studies on cerebral sparganosis underscore the potential for enhancing clinical practice by improving diagnostic accuracy, informing treatment decisions, and implementing targeted screening efforts based on epidemiology and risk factors. Recommendation to further study needs to notify the cerebral sparganosis in high-risk countries with similar socioeconomic and cultural characteristics to endemic regions, including Indonesia.

Cancer Prevention and Treatment on Chinese Social Media: Machine Learning-Based Content Analysis Study.

Nowadays, social media plays a crucial role in disseminating information about cancer prevention and treatment. A growing body of research has focused on assessing access and communication effects of cancer information on social media. However, there remains a limited understanding of the comprehensive presentation of cancer prevention and treatment methods across social media platforms. Furthermore, research comparing the differences between medical social media (MSM) and common social media (CSM) is also lacking. Using big data analytics, this study aims to comprehensively map the characteristics of cancer treatment and prevention information on MSM and CSM. This approach promises to enhance cancer coverage and assist patients in making informed treatment decisions. We collected all posts (N=60,843) from 4 medical WeChat official accounts (accounts with professional medical backgrounds, classified as MSM in this paper) and 5 health and lifestyle WeChat official accounts (accounts with nonprofessional medical backgrounds, classified as CSM in this paper). We applied latent Dirichlet allocation topic modeling to extract cancer-related posts (N=8427) and identified 6 cancer themes separately in CSM and MSM. After manually labeling posts according to our codebook, we used a neural-based method for automated labeling. Specifically, we framed our task as a multilabel task and utilized different pretrained models, such as Bidirectional Encoder Representations from Transformers (BERT) and Global Vectors for Word Representation (GloVe), to learn document-level semantic representations for labeling. We analyzed a total of 4479 articles from MSM and 3948 articles from CSM related to cancer. Among these, 35.52% (2993/8427) contained prevention information and 44.43% (3744/8427) contained treatment information. Themes in CSM were predominantly related to lifestyle, whereas MSM focused more on medical aspects. The most frequently mentioned prevention measures were early screening and testing, healthy diet, and physical exercise. MSM mentioned vaccinations for cancer prevention more frequently compared with CSM. Both types of media provided limited coverage of radiation prevention (including sun protection) and breastfeeding. The most mentioned treatment measures were surgery, chemotherapy, and radiotherapy. Compared with MSM (1137/8427, 13.49%), CSM (2993/8427, 35.52%) focused more on prevention. The information about cancer prevention and treatment on social media revealed a lack of balance. The focus was primarily limited to a few aspects, indicating a need for broader coverage of prevention measures and treatments in social media. Additionally, the study's findings underscored the potential of applying machine learning to content analysis as a promising research approach for mapping key dimensions of cancer information on social media. These findings hold methodological and practical significance for future studies and health promotion.

Efficacy of Ofatumumab and Teriflunomide in Patients With Relapsing MS From Racial/Ethnic Minority Groups: ASCLEPIOS I/II Subgroup Analyses.

Race and ethnicity may influence the efficacy of disease-modifying therapies in patients with multiple sclerosis (MS). Incidence of MS in ethnically diverse groups may be higher; however, these populations are under-represented in MS trials. This post hoc analysis compared the proportion of patients achieving 3-parameter no evidence of disease activity (NEDA-3) with ofatumumab vs teriflunomide in participants with relapsing MS (RMS) enrolled in the ASCLEPIOS I/II trials by race/ethnicity subgroup. ASCLEPIOS I/II were identical, double-blind, double-dummy, active-controlled, multicenter, phase 3 trials. Participants were randomized (1:1) to receive ofatumumab 20 mg every 4 weeks or teriflunomide 14 mg once daily for up to 30 months. Pooled data were used to determine the efficacy/safety of ofatumumab vs teriflunomide in participants who self-identified as non-Hispanic Black, non-Hispanic Asian, Hispanic/Latino, or non-Hispanic White. Participants who did not self-identify into one of these groups were classified as other/unknown. Of the 1,882 participants, 64 (3.4%) self-identified as non-Hispanic Black, 71 (3.8%) as non-Hispanic Asian, 145 (7.7%) as Hispanic/Latino, and 1,538 (81.7%) as non-Hispanic White. Baseline participant demographics/characteristics were largely balanced across subgroups, aside from minor variations in sex, disease duration, and MRI lesions. From months 0 to 24, the proportion of ofatumumab vs teriflunomide-treated patients achieving NEDA-3 (odds ratio [95% CI]) was as follows: non-Hispanic Black, 33.3% vs 3.4% (15.9 [1.67-151.71; p = 0.0162]); non-Hispanic Asian, 42.9% vs 21.9% (3.18 [0.95-10.59; p = 0.06]); Hispanic/Latino, 36.6% vs 18.6% (3.21 [1.32-7.79; p = 0.01]); and non-Hispanic White, 37.4% vs 16.6% (3.57 [2.73-4.67; p < 0.0001]). Rates of AEs were generally similar between treatment groups and across race/ethnicity subgroups; no new or unexpected safety signals were identified. Ofatumumab was associated with greater proportions of NEDA-3 achievement than teriflunomide across race/ethnicity subgroups in the ASCLEPIOS trials. Within each treatment group, the proportion of patients achieving NEDA-3 from months 0 to 24 was similar across the subgroups and overall pooled population. Both ofatumumab and teriflunomide were well tolerated. Future MS trials should include ethnically diverse groups to better inform treatment decisions and improve real-world patient outcomes. ClinicalTrials.gov: NCT02792218 (clinicaltrials.gov/ct2/show/NCT02792218), NCT02792231 (clinicaltrials.gov/ct2/show/NCT02792231). Submission date: June 2, 2016. First enrollment: August 26, 2016. This study provides Class II evidence that among patients aged 18-55 years with RMS, the improvement in NEDA-3 with ofatumumab was comparably better than with teriflunomide among patients self-identified as non-Hispanic Black, non-Hispanic Asian, non-Hispanic White, Hispanic/Latino, and other/unknown.

Age and Functional Outcomes in Patients With Large Ischemic Stroke Receiving Endovascular Thrombectomy

Randomized clinical trials have demonstrated the efficacy and safety of endovascular thrombectomy for acute ischemic stroke with large infarct. Patients older than 80 years with large infarct are commonly encountered in clinical practice but underrepresented in randomized clinical trials. To provide an age-based analysis of functional outcomes in endovascular thrombectomy for acute ischemic strokes with large infarct. This retrospective multicenter cohort study included patients from the German Stroke Registry who received endovascular thrombectomy for acute ischemic stroke with large infarct at 1 of 25 German stroke centers between May 2015 and December 2021. Patients with acute ischemic stroke due to anterior circulation large vessel occlusion and large infarct were included. Large infarct was defined as an Alberta Stroke Program Early Computed Tomography Score of 0 to 5. Patients were subdivided by age to evaluate its association with functional outcomes. Age. Primary outcomes were independent ambulation (90-day modified Rankin Scale score of 0-3) and mortality (90-day modified Rankin Scale score of 6). A total of 408 patients with large infarct were included (217 women [53.2%]; median [IQR] age, 75 [64-83] years). The rate of independent ambulation decreased from 56.4% in patients aged 60 years and younger (44 of 78 patients) to 15.1% in patients older than 80 years (19 of 126 patients) (P < .001), while mortality increased from 15.4% (12 patients) to 64.3% (81 patients) (P < .001). Being older than 80 years was associated with lower rates of independent ambulation (adjusted odds ratio [aOR], 0.44; 95% CI, 0.23-0.82; P = .01) and higher mortality (aOR, 2.75; 95% CI, 1.61-4.72; P < .001). A final modified Thrombolysis in Cerebral Infarction grade of 2b or 3 was associated with higher rates of independent ambulation (aOR, 4.95; 95% CI, 2.14-11.43; P < .001), independent of age and without significant interaction (aOR, 0.69; 95% CI, 0.35-1.34; P = .27). In this cohort study of patients with acute ischemic stroke and large infarct, age was associated with functional outcomes. Patients older than 80 years had poor prognosis with high mortality but with sizeable differences depending on additional baseline and treatment characteristics. While it does not seem justified to apply a fixed upper age limit for endovascular thrombectomy, these results could assist clinicians in making informed treatment decisions in older patients with large ischemic stroke.

Understanding how a personalized risk prediction tool (VALUE-PERSARC) supports informed treatment decisions of soft-tissue sarcomas patients in daily clinical practice – A mixed methods study

IntroductionRisk prediction models (RPM) can help soft-tissue sarcoma(STS) patients and clinicians make informed treatment decisions by providing them with estimates of (disease-free) survival for different treatment options. However, it is unknown how RPMs are used in the clinical encounter to support decision-making. This study aimed to understand how a PERsonalised SARcoma Care (PERSARC) RPM is used to support treatment decisions and which barriers and facilitators influence its use in daily clinical practice. MethodsA convergent mixed-methods design is used to understand how PERSARC is integrated in the clinical encounter in three Dutch sarcoma centers. Data were collected using qualitative interviews with STS patients (n = 15) and clinicians (n = 8), quantitative surveys (n = 50) and audiotaped consultations (n = 30). Qualitative data were analyzed using thematic analysis and integrated with quantitative data through merging guided by the SEIPS model. ResultsPERSARC was generally used to support clinicians’ proposed treatment plan and not to help patients weigh available treatment options. Use of PERSARC in decision-making was hampered by clinician’s doubts about whether there were multiple viable treatment options,the accuracy of risk estimates, and time constraints. On the other hand, use of PERSARC facilitated clinicians to estimate and communicate the expected benefit of adjuvant therapy to patients. ConclusionPERSARC was not used to support informed treatment decision-making in STS patients. Integrating RPMs into clinical consultations requires acknowledgement of their benefits in facilitating clinicians' estimation of the expected benefit of adjuvant therapies and information provision to patients, while also considering concerns regarding RPM quality and treatment options' viability.

Beat-AML 2024 ELN–refined risk stratification for older adults with newly diagnosed AML given lower-intensity therapy

AbstractAlthough the 2022 European LeukemiaNet (ELN) acute myeloid leukemia (AML) risk classification reliably predicts outcomes in younger patients treated with intensive chemotherapy, it is unclear whether it applies to adults ≥60 years treated with lower-intensity treatment (LIT). We aimed to test the prognostic impact of ELN risk in patients with newly diagnosed (ND) AML aged ≥60 years given LIT and to further refine risk stratification for these patients. A total of 595 patients were included: 11% had favorable-, 11% intermediate-, and 78% had adverse-risk AML. ELN risk was prognostic for overall survival (OS) (P < .001) but did not stratify favorable- from intermediate-risk (P = .71). Within adverse-risk AML, the impact of additional molecular abnormalities was further evaluated. Multivariable analysis was performed on a training set (n = 316) and identified IDH2 mutation as an independent favorable prognostic factor, and KRAS, MLL2, and TP53 mutations as unfavorable (P < .05). A “mutation score” was calculated for each combination of these mutations, assigning adverse-risk patients to 2 risk groups: −1 to 0 points (“Beat-AML intermediate”) vs 1+ points (“Beat-AML adverse”). In the final refined risk classification, ELN favorable- and intermediate-risk were combined into a newly defined “Beat-AML favorable-risk” group, in addition to mutation scoring within the ELN adverse-risk group. This approach redefines risk for older patients with ND AML and proposes refined Beat-AML risk groups with improved discrimination for OS (2-year OS, 48% vs 33% vs 11%, respectively; P < .001), providing patients and providers additional information for treatment decision-making.

Patient Perspectives on Social and Identity Factors Affecting Multiple Myeloma Care: Barriers and Opportunities.

Patients living with multiple myeloma (MM) have a substantial disease burden and face multiple barriers to care. Building upon our previous research using mixed methods, this focus group research aimed to identify patients' priorities regarding specific social and identity-related needs, map these prioritized needs to the disease journey, and describe patient-generated ideas to improve patient support. Participants noted that patients with MM need a range of emotional, social, and financial support throughout the disease journey. They identified initial MM diagnosis and treatment adherence as two critical points in the MM journey where patients need the most support and assistance. The findings of this research suggest that overall, patients with MM need comprehensive support, ideally from a multidisciplinary team consisting of health care providers, patient advocates, social workers, and psychologists to help patients understand their disease and treatment options, make informed treatment decisions, adhere to treatment, and ultimately reduce their disease burden and improve outcomes. This research revealed that patients with MM need varying types and levels of support, with the most common needs including information on disease and treatment, connections to financial resources and support systems, assistance with navigating insurance options, and transportation and logistical support for medical appointments.

Assessing the use of the novel tool Claude 3 in comparison to ChatGPT 4.0 as an artificial intelligence tool in the diagnosis and therapy of primary head and neck cancer cases.

Head and neck squamous cell carcinoma (HNSCC) is a complex malignancy that requires a multidisciplinary tumor board approach for individual treatment planning. In recent years, artificial intelligence tools have emerged to assist healthcare professionals in making informed treatment decisions. This study investigates the application of the newly published LLM Claude 3 Opus compared to the currently most advanced LLM ChatGPT 4.0 for the diagnosis and therapy planning of primary HNSCC. The results were compared to that of a conventional multidisciplinary tumor board; (2) Materials and Methods: We conducted a study in March 2024 on 50 consecutive primary head and neck cancer cases. The diagnostics and MDT recommendations were compared to the Claude 3 Opus and ChatGPT 4.0 recommendations for each patient and rated by two independent reviewers for the following parameters: clinical recommendation, explanation, and summarization in addition to the Artificial Intelligence Performance Instrument (AIPI); (3) Results: In this study, Claude 3 achieved better scores for the diagnostic workup of patients than ChatGPT 4.0 and provided treatment recommendations involving surgery, chemotherapy, and radiation therapy. In terms of clinical recommendations, explanation and summarization Claude 3 scored similar to ChatGPT 4.0, listing treatment recommendations which were congruent with the MDT, but failed to cite the source of the information; (4) Conclusion: This study is the first analysis of Claude 3 for primary head and neck cancer cases and demonstrates a superior performance in the diagnosis of HNSCC than ChatGPT 4.0 and similar results for therapy recommendations. This marks the advent of a newly launched advanced AI model that may be superior to ChatGPT 4.0 for the assessment of primary head and neck cancer cases and may assist in the clinical diagnostic and MDT setting.