Asymptomatic High-risk Patients Research Articles

Imaging of Multiple Myeloma: Present and Future.

Multiple myeloma (MM) is the second most common adult hematologic malignancy, and early intervention increases survival in asymptomatic high-risk patients. Imaging is crucial for the diagnosis and follow-up of MM, as the detection of bone and bone marrow lesions often dictates the decision to start treatment. Low-dose whole-body computed tomography (CT) is the modality of choice for the initial assessment, and dual-energy CT is a developing technique with the potential for detecting non-lytic marrow infiltration and evaluating the response to treatment. Magnetic resonance imaging (MRI) is more sensitive and specific than 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) for the detection of small focal lesions and diffuse marrow infiltration. However, FDG-PET/CT is recommended as the modality of choice for follow-up. Recently, diffusion-weighted MRI has become a new technique for the quantitative assessment of disease burden and therapy response. Although not widespread, we address current proposals for structured reporting to promote standardization and diminish variations. This review provides an up-to-date overview of MM imaging, indications, advantages, limitations, and recommended reporting of each technique. We also cover the main differential diagnosis and pitfalls and discuss the ongoing controversies and future directions, such as PET-MRI and artificial intelligence.

Improving the screening process for obstructive sleep apnea in the primary care setting.

There is a high prevalence of obstructive sleep apnea (OSA) in the primary care setting that is underdiagnosed and underreported in 75-80% of the population. If untreated, OSA has implications for long-term cardiovascular, cerebrovascular, and metabolic health. At a primary care clinic in New Jersey, patients at high risk for OSA were not being routinely screened for the condition. This project intended to address the administration of the STOP-Bang Questionnaire among asymptomatic high-risk patient populations with hypertension and/or obesity. In addition to determining each participant's level of risk for OSA, and in turn, facilitating referrals and diagnostic testing per a provider's discretion. The STOP-Bang Questionnaire, a validated screening tool for OSA, was implemented in a primary care practice to measure levels of risk for OSA among eligible participants. A total of 32 out of the 100 patients assessed were identified as high risk for OSA. After screening, 36 participants were referred for confirmatory testing. The STOP-Bang Questionnaire, a validated screening tool for OSA, is recommended for all asymptomatic high-risk patients, specifically for those with obesity and/or hypertension, at least annually. The use of a screening tool evaluates a level of risk, promotes detection of disease in the primary stages, delays disease progression, and improves treatment initiatives.

Breast Digital Tomosynthesis versus Contrast-Enhanced Mammography: Comparison of Diagnostic Application and Radiation Dose in a Screening Setting.

This study aims to evaluate the Average Glandular Dose (AGD) and diagnostic performance of CEM versus Digital Mammography (DM) as well as versus DM plus one-view Digital Breast Tomosynthesis (DBT), which were performed in the same patients at short intervals of time. A preventive screening examination in high-risk asymptomatic patients between 2020 and 2022 was performed with two-view Digital Mammography (DM) projections (Cranio Caudal and Medio Lateral) plus one Digital Breast Tomosynthesis (DBT) projection (mediolateral oblique, MLO) in a single session examination. For all patients in whom we found a suspicious lesion by using DM + DBT, we performed (within two weeks) a CEM examination. AGD and compression force were compared between the diagnostic methods. All lesions identified by DM + DBT were biopsied; then, we assessed whether lesions found by DBT were also highlighted by DM alone and/or by CEM. We enrolled 49 patients with 49 lesions in the study. The median AGD was lower for DM alone than for CEM (3.41 mGy vs. 4.24 mGy, p = 0.015). The AGD for CEM was significantly lower than for the DM plus one single projection DBT protocol (4.24 mGy vs. 5.55 mGy, p < 0.001). We did not find a statistically significant difference in the median compression force between the CEM and DM + DBT. DM + DBT allows the identification of one more invasive neoplasm one in situ lesion and two high-risk lesions, compared to DM alone. The CEM, compared to DM + DBT, failed to identify only one of the high-risk lesions. According to these results, CEM could be used in the screening of asymptomatic high-risk patients.

Tumor Marker in Early Detection of Malignancies in Type 2 Diabetes: A Case Series Analysis

Abstract The association between type 2 diabetes mellitus (T2DM) and malignancy has gained significant attention, with a heightened susceptibility to specific cancers. We present a comprehensive case series, documenting four distinctive cases illustrating the critical role of tumor markers in early cancer detection among patients with T2DM. Our findings emphasize the significance of vigilant surveillance and comprehensive patient care in the timely diagnosis and management of malignancies. The cases highlight the utility of tumor markers, particularly carbohydrate antigen 19-9, in the identification of pancreatic adenocarcinoma, lung cancer, and prostate cancer. These markers facilitated early interventions and subsequent tailored treatments, resulting in improved patient outcomes and extended survival. In addition, we underscore the challenges encountered in clinical practice, emphasizing the need for effective patient education and engagement in decision-making processes regarding their health. Although not currently recommended as routine screening tools, the potential lifesaving impact of tumor marker screenings in asymptomatic high-risk patients with T2DM warrants further consideration and research. This case series serves to underscore the critical role of tumor markers in uncovering potential malignancies at early stages, ultimately improving patient outcomes and quality of life.

Abstract P3-03-28: Clinicopathological Risk Factors of Brain Metastasis in Breast Cancer Patients: A Systematic Review and Meta-analysis

Abstract BACKGROUND: Breast cancer brain metastasis (BCBM) has an incidence rate of 5.1% among Breast Cancer (BC) patients. In BCBM, cancerous cells come from a primary tumor that implant and grow in the brain leading to potentially lethal neurologic symptoms and signs. With more clinical options and therapeutics strategies becoming available, a multi-disciplinary approach for treatment is needed in order to best meet BCBM patients’ needs, however, systematic guidelines for the screening of high-risk asymptomatic patients are still lacking and the BCBM diagnoses are performed only after symptoms manifestation. Therefore, understanding the clinical and pathologic drivers of BCBM aids in improving medical interventions by guiding future research directions. This study aims to determine the clinicopathological risk factors of brain metastasis (BM) among BC patients. METHODS: Retrospective cohort studies on the clinicopathological characteristics of BM versus non-BM (NBM) patients were retrieved through reputable search databases. Review Manager version 5.4.1 was used for statistical analyses. In the presence of heterogeneities, a pragmatic approach was undertaken to employ both random-effects (RE) and fixed-effect (FE) meta-analyses. The statistical significance of the pooled effect estimates was examined by the Z-test. Interstudy variations and heterogeneities were estimated using Cochran’s Q-statistic with P &amp;lt; 0.05 indicating a statistically significant heterogeneity. The risk of bias and the quality of studies were assessed at a study level using ROBINS-I tool. RESULTS: A total of four (4) retrospective cohort studies were included in the analyses. Random-effects meta-analyses with i2 &amp;lt; 50% (P &amp;gt; 0.05) had shown significant association (P &amp;lt; 0.05) on the increased incidences of BCBM development for HER2+ expression [OR: 2.43, 95% CI: 1.88 – 3.12, P &amp;lt; 0.00001] and for pre-menopausal status [OR: 1.77, 95% CI: 1.13 – 2.76, P = 0.01]. Fixed-effect meta-analyses had shown significant association (P &amp;lt; 0.05) on the decreased incidence of BCBM development for TNBC disease [OR: 0.66; 95% CI: 0.47 – 0.92; P = 0.02]. The risk of bias was low to moderate in the majority of studies. CONCLUSION: HER2 positivity and pre-menopausal status are risk factors for increased BCBM development while the absence of regional lymph node metastases and ILC findings are less likely to progress to BCBM. Higher T and N categories, higher histological grade, ER negativity, and PR negativity may be associated with higher risks of BCBM while lower T categories, HER2 negativity, and TNBC may likely be associated to less BCBM development. More powerful relevant and upcoming randomized clinical trials with larger sample sizes among BCBM patients versus non-BM patients must be made exploring certainty on the clinicopathological factors contributing to BM among BC patients. Keyword/s: risk factors, breast cancer, brain metastasis Citation Format: Korina Blanca C. Garcia, April Ann A. Lubay. Clinicopathological Risk Factors of Brain Metastasis in Breast Cancer Patients: A Systematic Review and Meta-analysis [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-28.

Transcranial Doppler: A Beginning of a New Era for Stroke Diagnosis

Transcranial Doppler (TCD) is an intracranial neurovascular exam that provides a real-time, rapid, non-invasive ultrasound technique to analyze cerebrovascular function. It uses high-frequency sound waves to assess the blood flow velocity, detect the deficit that causes focal vascular stenosis, and diagnose the embolic signals inside these arteries. Moreover, it can be used to analyze particular vascular territory of physiologic health by measuring cerebral vasoreactivity, cerebral autoregulation, and functional hyperemia. The information obtained from these examinations is increasingly becoming pertinent for therapeutic decision-making. In this study, we are going to focus on a comparative analysis of TCD findings using clinical and other modalities and assess the specificity, sensitivity, and positive and negative predictive value of TCD findings in Asymptomatic and Symptomatic high-risk elderly patients. Furthermore, we will study the clinical usefulness of TCD in evaluating patients with cerebrovascular accidents (CVA).

Transcranial Doppler: A Beginning of a New Era for Stroke Diagnosis

Transcranial Doppler (TCD) is an intracranial neurovascular exam that provides a real-time, rapid, non-invasive ultrasound technique to analyze cerebrovascular function. It uses high-frequency sound waves to assess the blood flow velocity, detect the deficit that causes focal vascular stenosis, and diagnose the embolic signals inside these arteries. Moreover, it can be used to analyze particular vascular territory of physiologic health by measuring cerebral vasoreactivity, cerebral autoregulation, and functional hyperemia. The information obtained from these examinations is increasingly becoming pertinent for therapeutic decision-making. In this study, we are going to focus on a comparative analysis of TCD findings using clinical and other modalities and assess the specificity, sensitivity, and positive and negative predictive value of TCD findings in Asymptomatic and Symptomatic high-risk elderly patients. Furthermore, we will study the clinical usefulness of TCD in evaluating patients with cerebrovascular accidents (CVA).

Mortality risk prediction of the electrocardiogram as an informative indicator of cardiovascular diseases.

The electrocardiogram (ECG) may be the most popular test in the management of cardiovascular disease (CVD). Although wide applications of artificial intelligence (AI)-enabled ECG have been developed, an integrating indicator for CVD risk stratification was not investigated. Since mortality may be the most important global outcome, this study aimed to develop a survival deep learning model (DLM) to establish a critical ECG value and explore the associations with various CVD events. We trained a DLM with 451,950 12-lead resting ECGs obtained from 210,552 patients, for whom 23,592 events occurred. The internal validation set included 27,808 patients with one ECG for each patient. The external validations were performed in a community hospital with 33,047 patients and two transnational data sets with 233,647 and 1631 ECGs. We distinguished the cause of mortality and additionally investigated CVD-related outcomes, including new-onset acute myocardial infarction (AMI), stroke (STK), and heart failure (HF). The DLM achieved C-indices of 0.858/0.836 in internal/external validation sets by using ECG over a 10-year period. The high-mortality-risk group identified by the proposed DLM presented a hazard ratio (HR) of 14.16 (95% confidence interval (CI): 11.33-17.70) compared to the low-risk group in the internal validation and presented a higher risk of cardiovascular (CV) mortality (HR: 18.50, 95% CI: 9.82-34.84), non-CV mortality (HR: 13.68, 95% CI: 10.76-17.38), AMI (HR: 4.01, 95% CI: 2.24-7.17), STK (HR: 2.15, 95% CI: 1.70-2.72), and HF (HR: 6.66, 95% CI: 4.54-9.77), which was consistent in an independent community hospital. The transnational validation also revealed HRs of 4.91 (95% CI: 2.63-9.16) and 2.29 (95% CI: 2.15-2.44) for all-cause mortality in the SaMi-Trop and Clinical Outcomes in Digital Electrocardiography 15% (CODE15) cohorts. The mortality risk by AI-enabled ECG may be applied in passive electronic-health-record-based CVD risk screening, which may identify more asymptomatic and unaware high-risk patients.

Lung Cancer Screening Initiative in Slovakia: Guidelines of screening implementation

Lung cancer (LC) represents a major healthcare issue worldwide. It is the leading cause of cancer-related mortality in Slovakia and European Union. Data from multiple randomized controlled trials have shown significant evidence of a mortality benefit in LC using screening with low-dose computed tomography of the chest (LDCT). Therefore, European healthcare authorities, relevant expert societies, and professional organizations recommend implementing national LC screening (LCS) programs in their member countries. This article outlines the basic methodology, guidelines, and practical aspects of LCS implementation strategies in Slovakia. We describe fundamental principles to identify asymptomatic high-risk patients reduce false positive and false negative results, decrease benign resection rates, and avoid unnecessary invasive procedures. The efficacious utilization of public resources to secure the highest possible quality standards of LDCT plays a crucial role in successfully implementing a nationwide LCS program (Tab. 1, Fig. 4, Ref. 31). Text in PDF www.elis.sk Keywords: lung cancer, screening, early detection, smoking cessation.

280 (PB-104) Poster - Clinicopathologic Risk Factors of Brain Metastasis in Breast Cancer Patients: A Systematic Review and Meta-analysis

Background: Breast cancer brain metastasis (BCBM) has an incidence rate of 5.1% among Breast Cancer (BC) patients. In BCBM, cancerous cells come from a primary tumor that implant and grow in the brain leading to potentially lethal neurologic symptoms and signs. With more clinical options and therapeutics strategies becoming available, a multi-disciplinary approach for treatment is needed in order to best meet BCBM patients’ needs, however, systematic guidelines for the screening of high-risk asymptomatic patients are still lacking and the BCBM diagnoses are performed only after symptoms manifestation.

Interleukin-35 Mitigates ox-LDL-Induced Proatherogenic Effects via Modulating miRNAs Associated with Coronary Artery Disease (CAD).

Recent emergence of miRNAs as important regulators of processes involving lesion formation and regression has highlighted miRNAs as potent therapeutic targets for the treatment of atherosclerosis. Few studies have reported the atheroprotective role of IL-35, a novel immunosuppressive and anti-inflammatory cytokine; however, miRNA-dependent regulation underlying the anti-atherosclerotic potential of IL-35 remains elusive. THP-1 macrophages were incubated with human recombinant IL-35 (rIL-35) either in the presence or absence of ox-LDL. qRT-PCR was conducted to validate the expression levels of previously identified miRNAs including miR-197-5p, miR-4442, miR-324-3p, miR-6879-5p, and miR-6069 that were differentially expressed in peripheral blood mononuclear cells of coronary artery disease (CAD) patients vs. controls. Additionally, bioinformatic analysis was performed to predict miRNA-associated targets and their corresponding functional significance in CAD. Exogenous IL-35 significantly decreased the average area of ox-LDL-stimulated macrophages, indicating the inhibitory effect of IL-35 on lipid-laden foam cell formation. Furthermore, rIL-35 treatment alleviated the ox-LDL-mediated atherogenic effects by modulating the expression levels of aforementioned CAD-associated miRNAs in the cultured macrophages. Moreover, functional enrichment analysis of these miRNA-related targets revealed their role in the molecular processes affecting different stages of atheroslerotic plaque development, such as macrophage polarization, T cell suppression, lipoprotein metabolism, foam cell formation, and iNOS-mediated inflammation. Our observations uncover the novel role of IL-35 as an epigenetic modifier as it influences the expression level of miRNAs implicated in the pathogenesis of atherosclerosis. Thus, IL-35 cytokine therapy-mediated miRNA targeting could be an effective therapeutic strategy against the development of early atheromas in asymptomatic high-risk CAD patients.

Obstructive sleep apnoea and left ventricular diastolic dysfunction among first responders to the 9/11 World Trade Center terrorist attack: a cross-sectional study

ObjectivesObstructive sleep apnoea (OSA) is often linked to cardiovascular disease. A limited number of studies have reported an association between OSA and left ventricular diastolic dysfunction (LVDD). However, prior studies...

Role of Coronary Calcium Score as a Screening Tool for Excluding Significant Coronary Artery Disease in High Risk Asymptomatic Patients

OBJECTIVES: To determine correlation of zero coronary artery calcium score (CACS) with non-significant coronary artery stenosis by using computed tomography coronary angiography (CTCA). METHODOLOGY: 62 patients with suspected coronary artery disease (CAD) underwent CACS test and CTCA from April 2018 to November 2020. Patients were examined with 160 slice multidetector CT and grouped according to their age, gender, CACS, and maximum coronary luminal stenosis. CACS was assessed using Agatston scoring and degree of stenosis was assessed by automatic software and severity was scored according to CAD-RADS. The correlation between these two main variables was calculated using Spearman rank correlation. RESULTS: The 62 patients were divided into four groups according to CACS, using the Agatston Unit (AU). Group 1; 0 AU (41 patients, 66.13%), Group 2; 1-100 AU (13 patients, 20.97%) Group 3; 101-400 AU (4 patients, 6.45%), Group 4; 401-1000 AU (4 patients, 6.45%). In 41 patients with zero calcium score (32 males and 9 females), 38 patients (92.68%) were found to have no coronary artery stenosis, 2 patients (4.87%) had mild coronary artery stenosis and 1 patient (2.43%) had moderate coronary artery stenosis. Total 35 patients presented for screening purpose out of which 25 (71%) had zero calcium score and no significant coronary artery disease. CONCLUSION: In high risk patients, zero calcium score excludes significant coronary artery stenosis (50%), hence coronary calcium score is a good screening tool before subjecting patients to coronary angiography.

Management of adult tuberous sclerosis complex-related angiomyolipoma: A single-center experience.

Tuberous sclerosis complex (TSC) is a rare, multi-system, genetic disease. A significant cause of TSC-related morbidity is potential bleeding from renal angiomyolipoma (AML). To pre-emptively decrease AML bleeding, mTOR inhibitors can be used; however, thresholds for initiating and maintaining everolimus therapy remain uncertain. Recent literature suggests not triggering active treatment of AMLs based on size thresholds alone. We evaluated the appropriateness of initiating everolimus therapy in asymptomatic patients after considering AML size, rate of growth, and other factors. Diagnostic criteria developed by the 2012 International TSC Consensus Group and presence of AML were used as inclusion criteria. Medical and imaging reports of 11/20 TSC patients from a single center were reviewed. Mean age was 40.55 (±16.27) and 11 patients were female. Eight asymptomatic patients at high risk for complications underwent everolimus therapy, of which seven (88%) demonstrated decreased AML size, but multiple side effects were reported. Four high-risk asymptomatic patients did not undergo therapy due to side effect concerns, while four low-risk asymptomatic patients had stable AMLs under active surveillance. Four patients had reduced AMLs through local therapy. Everolimus treatment was effective for managing AML size in most high-risk, asymptomatic patients with tolerable side effects. AML size can remain relatively stable for asymptomatic, low-risk patients despite not receiving intervention(s). Patients with TSC-related AML can be safely managed with mTOR inhibitors like everolimus with shared decision-making, including factors such as bleeding risk, AML growth rate, and number and absolute size of AMLs.

Resting Left Ventricular Global Longitudinal Strain to Identify Silent Myocardial Ischemia in Asymptomatic Patients with Diabetes Mellitus

Screening for silent coronary artery disease in asymptomatic patients with diabetes mellitus (DM) is challenging and controversial. In this context, it seems crucial to identify early markers of coronary artery disease. The aim of this study was to investigate the incremental value of resting left ventricular (LV) global longitudinal strain (GLS) for the prediction of positive results on stress (exercise or dobutamine) transthoracic echocardiography in 273 consecutive asymptomatic high-risk patients with DM. Positive results on stress transthoracic echocardiography were defined as stress-induced LV wall motion abnormalities (new or worsening preexisting abnormalities). Compared with patients with negative stress results, those with positive stress results (n=28 [10%]) more frequently had cardiovascular risk factors, complications of DM, vascular disease, moderate and severe calcification of the aortic valve and mitral annulus, and worse resting LV GLS (-16.7±2.9% vs -19.0±1.9%, P<.001). On multivariable logistic regression analysis, DM duration > 10years, diabetic retinopathy, LV hypertrophy, and impaired LV GLS (odds ratio, 1.39 [95% CI, 1.14-1.70] per percentage increase; odds ratio, 5.16 [95% CI, 1.96-13.59] for LV GLS worse than -18%) were independently associated with positive results on stress transthoracic echocardiography. The area under the curve to predict positive results was 0.74 for LV GLS with a cutoff of -18.0% (sensitivity 68%, specificity 78%). The area under the curve of the multivariable model to predict test results was improved by the addition of LV GLS (P<.001), with a bias-corrected area under the curve after bootstrapping of 0.842 [95% CI, 0.753-0.893]. The present findings show that resting LV GLS is associated with the presence of silent ischemia and could be useful to better identify asymptomatic patients with DM who might benefit from coronary artery disease screening.

Randomized, Phase III Study of Early Intervention with Venetoclax and Obinutuzumab Versus Delayed Therapy with Venetoclax and Obinutuzumab in Newly Diagnosed Asymptomatic High-Risk Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Evolve CLL/SLL Study (SWOG S1925; NCT#04269902)

Randomized, Phase III Study of Early Intervention with Venetoclax and Obinutuzumab Versus Delayed Therapy with Venetoclax and Obinutuzumab in Newly Diagnosed Asymptomatic High-Risk Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL): Evolve CLL/SLL Study (SWOG S1925; NCT#04269902)

A narrative review of plaque and brain imaging biomarkers for stroke risk stratification in patients with atherosclerotic carotid artery disease.

ObjectiveIn this narrative review, we aim to review imaging biomarkers that carry the potential to non-invasively guide stroke risk stratification for treatment optimization.BackgroundCarotid atherosclerosis plays a fundamental part in the occurrence of ischemic stroke. International guidelines select the optimal treatment strategy still mainly based on the presence of clinical symptoms and the degree of stenosis for stroke prevention in patients with atherosclerotic carotid plaques. These guidelines, based on randomized controlled trials that were conducted three decades ago, recommend carotid revascularization in symptomatic patients with high degree of stenosis versus a conservative approach for most asymptomatic patients. Due to optimization of best medical therapy and risk factor control, it is suggested that a subgroup of symptomatic patients is at lower risk of stroke and may not benefit from revascularization, whereas a selective subgroup of high-risk asymptomatic patients would benefit from this procedure.MethodsA literature search was performed for articles published up to December 2020 using PubMed, EMBASE and Scopus. Based on the literature found, change in stenosis degree and volume, plaque echolucency, plaque surface, intraplaque haemorrhage, lipid-rich necrotic core, thin fibrous cap, inflammation, neovascularization, microembolic signals, cerebrovascular reserve, intracranial collaterals, silent brain infarcts, diffusion weighted imaging lesions and white matters lesions have the potential to predict stroke risk.ConclusionsThe applicability of imaging biomarkers needs to be further improved before the potential synergistic prognostic ability of imaging biomarkers can be verified on top of the clinical biomarkers. In the future, the routine and combined assessment of both plaque and brain imaging biomarkers might help to improve optimization of treatment strategies in individual patients with atherosclerotic carotid artery disease.

The Screening and Treatment of Vitamin B12 Deficiency

Vitamin B12 deficiency is now more prevalent than ever. It is a common cause of megaloblastic anemia, neuropsychiatric disorders, and other clinical manifestations. Screening is required in patients with single or multiple risk factors. Measurement of serum methylmalonic acid can be used to confirm deficiency in asymptomatic high-risk patients with low-normal levels of vitamin B12. Oral administration of high-dose vitamin B12 as well as intramuscular administration are effective as corrective therapy. This review briefs about the pharmacokinetics and pharmacodynamics of Vitamin B12, risk factors associated with its deficiency, screening methods and treatment options.

Development of Molecular Magnetic Resonance Imaging Tools for Risk Stratification of Carotid Atherosclerotic Disease Using Dual-Targeted Microparticles of Iron Oxide

Identification of patients with high-risk asymptomatic carotid plaques remains a challenging but crucial step in stroke prevention. Inflammation is the key factor that drives plaque instability. Currently, there is no imaging tool in routine clinical practice to assess the inflammatory status within atherosclerotic plaques. We have developed a molecular magnetic resonance imaging (MRI) tool to quantitatively report the inflammatory activity in atherosclerosis using dual-targeted microparticles of iron oxide (DT-MPIO) against P-selectin and VCAM-1 as a smart MRI probe. A periarterial cuff was used to generate plaques with varying degree of phenotypes, inflammation and risk levels at specific locations along the same single carotid artery in an Apolipoprotein-E-deficient mouse model. Using this platform, we demonstrated that in vivo DT-MPIO-enhanced MRI can (i) target high-risk vulnerable plaques, (ii) differentiate the heterogeneity (i.e. high vs intermediate vs low-risk plaques) within the asymptomatic plaque population and (iii) quantitatively report the inflammatory activity of local plaques in carotid artery. This novel molecular MRI tool may allow characterisation of plaque vulnerability and quantitative reporting of inflammatory status in atherosclerosis. This would permit accurate risk stratification by identifying high-risk asymptomatic individual patients for prophylactic carotid intervention, expediting early stroke prevention and paving the way for personalised management of carotid atherosclerotic disease.

Randomized, phase III study of early intervention with venetoclax and obinutuzumab versus delayed therapy with venetoclax and obinutuzumab in newly diagnosed asymptomatic high-risk patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL): EVOLVE CLL/SLL study (SWOG S1925, NCT#04269902).

TPS7567 Background: Currently, asymptomatic patients with CLL/SLL are observed without treatment until development of symptoms or cytopenias. Historically, early intervention studies with chemoimmunotherapy have not resulted in an overall survival (OS) benefit and have resulted in toxicity. The introduction of targeted therapies, such as venetoclax and obinutuzumab (VO), have provided tolerable/efficacious options for CLL patients. In the CLL14 study, symptomatic CLL patients receiving frontline therapy with VO had longer progression-free survival (PFS) and deeper remissions [more minimal residual disease-undetectable (MRDu)] compared with those receiving chlorambucil and obinutuzumab (Fischer 2019). The CLL-International Prognostic Index (CLL-IPI; Table) is a validated prognostic model to predict which patients are highest risk for a shorter time to first therapy and shorter OS. We aim to use VO as early intervention in asymptomatic, high-risk patients with CLL to potentially lengthen OS and thus alter the natural history of the disease. Methods: On 12/14/20, we activated the S1925 study for adult patients with CLL or SLL, who were diagnosed within 12 months of enrollment. Eligible patients have a CLL-IPI score ≥ 4 (Table) or complex cytogenetics (≥3 cytogenetic abnormalities) and do not meet any criteria for initiation of treatment by the International Working Group for CLL (IWCLL; Hallek 2018) guidelines. Enrolled patients are randomized in a 2:1 manner to early versus delayed (at the time IWCLL indication for treatment is met) therapy with VO. VO is administered for a fixed duration of 12 months as previously described (Fischer 2019). The primary endpoint is OS. We hypothesize that early intervention with VO will improve the rate of 6-year OS from 60% to 80%. This design requires 222 eligible patients for 88% power (2-sided α=0.05) for the primary comparison. To allow for 10% ineligibility, we will enroll 247 patients. Estimated accrual time is 4 years. Secondary endpoints include: rates of response, PFS, and relapse-free survival; safety; time to 2nd CLL-directed therapy; and quality of life (FACT-Leukemia total score). The primary translational objective is to evaluate the prognostic association between OS and peripheral blood MRD status at 15 months after treatment initiation by flow cytometry. Additional exploratory objectives include the association of other clinical outcomes, baseline prognostic factors, and IWCLL-defined response with MRD status at multiple timepoints. Currently, enrollment is open. Clinical trial information: NCT04269902. [Table: see text]