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Enhancing Patient Blood Management: Evaluating Specimen Collection Techniques from Central Venous Access Devices
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BEE HEARD: Buzzing for Better Patient Experience Through Structured Nurse Communication Using AIDET
No full textNurses\u27 perceptions of the impact of simulation on knowledge and confidence with chimeric antigen receptor T-cell infusion
No full textStrategies to build trustworthiness and increase diversity in colorectal cancer biospecimen research: a multi-phase, multi-site qualitative study.
No full textBACKGROUND: Black, Latino, and American Indian individuals are underrepresented in biospecimen research. Obtaining biospecimens from these populations is particularly relevant for understanding, preventing, and treating colorectal cancer and translating those insights to eliminate persistent racial and ethnic inequities in colorectal cancer. The aim of this qualitative study was to identify information needs and culturally appropriate approaches to biorepository recruitment among Black, Latino, and American Indian patients and community members.
METHODS: We used a multi-phase, multi-site design that included key informant interviews and focus groups with patients and community members in Los Angeles, Boston, and South Dakota. We analyzed interview data using rapid qualitative analysis and focus group data using reflexive thematic analysis.
RESULTS: We interviewed 10 keys informants with expertise in the recruitment of racially and ethnically diverse participants into biospecimen research and facilitated 21 focus groups with a 101 patients and community members who identified as Black, Latino, or American Indian. We generated six themes from our analyses that we organized into a best practices framework for building trustworthiness and increasing diversity in biospecimen research: (1) cultural responsiveness and inclusivity; (2) community-based partnerships; (3) convenience and accessibility; (4) meaningful and compelling purpose; (5) mindful incentives; and (6) trusted messengers and information sharing.
DISCUSSION: Our findings provide insight into the factors that influence Black, Latino, and American Indian individuals\u27 decisions to participate in biorepositories. The best practices framework developed from this study presents actionable strategies researchers can adopt to build trustworthiness and increase diversity in colorectal cancer biospecimen research
Deep-Learning Serial CT Prediction of Survival in Immunotherapy-Treated Non-Small Cell Lung Cancer.
No full textImportance: Reliable early response biomarkers for overall survival (OS) are lacking for patients receiving immune checkpoint inhibitor (ICI) therapy for advanced non-small cell lung cancer (NSCLC). Existing imaging-based measures, such as Response Evaluation Criteria in Solid Tumors (RECIST) and tumor volume change (TVC), have limited predictive value for long-term outcomes, and advanced imaging-based biomarkers may enhance decision-making in clinical practice and clinical trials.
Objective: To develop and validate a fully automated deep-learning imaging-based biomarker using pretherapy and 12-week follow-up computed tomography (CT) scans.
Design, setting, and participants: This prognostic study used retrospectively collected HER data from routine clinical practice (RCP) and clinical trial data from 2013 to 2023. A model using serial CT scans, Serial CT response score (Serial CTRS) was developed using a RCP discovery dataset, validated with 10 US and European institution RCP test datasets, and independently validated on a multinational clinical phase 1 trial of dostarlimab (GARNET). Participants were adults with advanced NSCLC starting ICIs in the period from 2013 to 2021 (RCP discovery), from 2013 to 2022 (RCP test), or from 2017 to 2018 (GARNET).
Interventions: ICI monotherapy or combination therapy in the first-line or later-line setting.
Main outcomes and measures: Cox proportional hazards regression and receiver operating characteristic-area under the curve modeled associations between Serial CTRS and OS.
Results: The study included 1830 patients (RCP discovery, 1171 patients; RCP test, 605 patients; GARNET, 54 patients) with a median (IQR) age of 67 (19-95) years; 1000 participants were male (55%), and 830 were female (45%). Serial CTRS was associated with OS in multivariable analysis controlling for age, sex, programmed death-ligand 1 expression, histologic profile, and tumor volume (hazard ratio [HR] for 10%-point higher probability of 12-month OS, 0.74 [95% CI, 0.70-0.79] for RCP test; 0.45 [95% CI, 0.32-0.65] for GARNET). Serial CTRS outperformed RECIST and TVC in OS risk discrimination, with higher HRs distinguishing low-survival and high-survival groups in RCP test (HR, 6.19; 95% CI, 4.12-9.28) and GARNET (HR, 18.00; 95% CI, 5.40-59.97). Predictive value persisted across programmed death-ligand 1 and RECIST subgroups, including stable disease.
Conclusions and relevance: In this prognostic study of patients with advanced NSCLC receiving ICI treatment, the fully automated biomarker Serial CTRS predicted OS more effectively than resource-intensive RECIST and TVC measurements using the same scans
Drivers of clinical resistance to venetoclax and hypomethylating agents in acute myeloid leukemia and strategies for improving efficacy.
No full textThe B-cell lymphoma 2 (BCL-2) inhibitor venetoclax (VEN) in combination with hypomethylating agents (HMAs) has improved treatment outcomes for acute myeloid leukemia (AML) patients unfit for intensive chemotherapy and is increasingly used in the relapsed/refractory setting. However, primary resistance remains a significant challenge, affecting 20%-35% of treatment-naïve and around 50% of previously treated AML patients. To investigate the mechanisms driving primary resistance to VEN-HMA therapy, we analyzed genetic, transcriptomic, BCL-2 family protein expression, and ex vivo drug sensitivity data from 101 AML patients and correlated these profiles with clinical outcomes to VEN-HMA. Our study found that blasts from refractory patients exhibit an elevated BCL-XL/BCL-2 protein expression ratio, an immature CD34+CD38- phenotype, and frequent TP53 mutations. Consistent with the high ratio of BCL-XL/BCL-2, resistant samples showed increased ex vivo sensitivity to the dual BCL-2/BCL-XL inhibitor navitoclax. In addition, SMAC mimetics were effective in refractory blasts, which correlated with high TNF gene expression in these cells. Ex vivo treatment with the combination of navitoclax and SMAC mimetics further enhanced the eradication of VEN-HMA refractory blasts, although toxicity was also observed in healthy CD34+ cells. In conclusion, our integrative analysis identifies molecular signatures associated with primary VEN-HMA resistance and highlights BCL-2/BCL-XL inhibition and SMAC mimetics as therapeutic strategies to target resistance
Olaparib in Patients With Solid Tumors With
No full textPurpose: The Targeted Agent and Profiling Utilization Registry Study is a phase II basket trial evaluating the antitumor activity of targeted agents in patients with advanced cancer and genomic alterations. Results of four cohorts of patients with ATM-altered tumors treated with olaparib are reported: colorectal cancer (CRC), lung cancer (LC), pancreatic cancer (PC), and other solid tumors (histology-pooled, HP).
Methods: Eligible patients had advanced solid tumors, measurable disease (RECIST), Eastern Cooperative Oncology Group performance status 0-2, adequate organ function, and no standard treatment options. The primary end point was disease control (DC), defined as objective response (OR) or stable disease (SD) of at least 16 weeks duration. For histology-specific cohorts, Simon\u27s two-stage design was based on a null DC rate of 15% versus 35% (power = 0.85; α = .10). For the HP cohort, the hypothesized null DC rate of 15% was rejected if the lower limit of a one-sided 90% CI was \u3e15%. Secondary end points were OR, progression-free survival, overall survival, duration of response or SD, and safety.
Results: Patients with CRC (n = 30), LC (n = 20), PC (n = 28), or other advanced cancers (n = 38) with ATM alterations were enrolled. The DC rates were 23% (one-sided 90% CI, 8 to 100; P = .38), 45% (one-sided 90% CI, 32 to 100; P = .0004), 28% (one-sided 90% CI, 14 to 100; P = .14), and 25% (one-sided 90% CI, 16 to 100), respectively. The null hypothesized 15% DC rate was rejected for the LC and HP cohorts but not the CRC and PC cohorts. Twenty of 116 patients (17%) experienced treatment-related grade 3 adverse events (AE) or serious AEs.
Conclusion: Olaparib met the prespecified criteria to declare a signal of activity in patients with ATM-altered cancer within the LC and HP cohorts but not the CRC or PC cohorts.
Trial registration: ClinicalTrials.gov NCT02693535
Breaking the PROMISE: poor association between brain volume loss and clinical disability worsening over 2 years of follow-up in primary progressive multiple sclerosis.
No full textBACKGROUND: Phase 2 clinical trials in primary progressive multiple sclerosis (PPMS) often use MRI brain volume measures as their primary endpoint. Here, we investigate the longitudinal association between change in MRI outcomes and change in disability over 2 years of follow-up in a large and well-characterised PPMS trial dataset.
METHODS: Using the dataset from PROMISE (n=943, mean age of 58.0 years, mean Expanded Disability Status Scale (EDSS) 5.0, and mean disease duration of 10.5 years at baseline), a phase 3 trial of glatiramer acetate in PPMS, we described the change in MRI and disability measures during follow-up and used multivariable logistic regression models to investigate whether change in four MRI outcomes (grey matter volume, white matter volume, brain fraction and total burden of disease) was associated with seven measures of clinical disability worsening (including the EDSS, Timed 25 Foot Walk, Nine-Hole Peg Test and Paced Auditory Serial Addition Test).
RESULTS: We found only weak and inconsistent associations between change in MRI and physical and cognitive outcome measures over 2 years of follow-up. Change in MRI measures in year 1 of the trial did not predict change in physical nor cognitive disability in year 2.
DISCUSSION: The association of the investigated volumetric MRI measures and clinical disability outcomes was noticeably weak and inconsistent. Our findings question the suitability of brain volume loss and lesion burden accumulation as functionally relevant trial endpoints in PPMS and inform the design and interpretation of clinical trials in PPMS
