bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectroscopic and antibacterial activities of cobalt and nickel nanoparticles: a comparative analysis
Authors: Balogun Sheriff A. , Abolarinwa Tesleem O. , Adesanya Funmilola A. , Ateba Collins N. , Fayemi Omolola E.
Published: June 2024

This study aimed to compare the spectroscopy, morphological, electrocatalytic properties, and antibacterial activities of cobalt nanoparticles (CoNPs) with nickel nanoparticles (NiNPs). Cobalt nanoparticles and NiNPs were prepared via a chemical reduction approach and characterized utilizing transmission electron microscopy (TEM), energy-dispersive X-ray (EDX), and X-ray diffraction (XRD) techniques. The result from XRD and TEM analysis revealed that the synthesized nanoparticles exhibit face-centered cubic with smooth spherical shape, having average particles size of 12 nm (NiNPs) and 18 nm (CoNPs). The electrochemical properties of the nanoparticles were examined via cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) techniques. The CV results showed that GCE-Ni (35.6 μA) has a higher current response compared to GCE-Co (10.5 μA). The EIS analysis revealed that GCE-Ni (1.39 KΩ) has faster electron transport capability compared to GCE-Co (2.99 KΩ) as indicated in their Rct values. The power density of the synthesized nanoparticles was obtained from their "knee" frequency (f°) values, with GCE-Ni (3.16 Hz) having higher f° values compared to GCE-Co (2.00 Hz). The antibacterial activity of the nanoparticles was evaluated against multidrug-resistant Escherichia coli O157, Escherichia coli O177, Salmonella enterica, Staphylococcus aureus, and Vibrio cholerae. The result from the antibacterial study revealed that at low concentrations both CoNPs and NiNPs have significant antibacterial activities against E. coli O157, E. coli O177, S. enterica, S. aureus, and V. cholerae. NiNPs showed better antibacterial activities at low concentrations of 61.5, 61.5, 125, 61.5, and 125 µg/mL compared to CoNPs with minimum inhibitory concentrations of 125, 125, 250, 61.5, and 125 µg/mL against E. coli O157, E. coli O177, S. enterica, S. aureus, and V. cholerae, respectively. These promising antibacterial activities emphasize the potential of CoNPs and NiNPs as effective antibacterial agents, which could aid in the development of novel antibacterial medicines.
An embodied perspective on an augmented reality game in school: pupil's bodily experience toward learning
Authors: Stalheim Odd Rune , Somby Hege Merete
Published: June 2024

There has long been an increased focus on and investment in digital technology in schools to improve the quality of education. While digital tools have gained access to pedagogical spheres, physical activity has been overlooked, as pupils often engage in activities that require minimal bodily movement. In this article, we discuss pupils’ experiences with learning through an augmented reality (AR)-based game application and explain how the application supports embodied learning. Digital tools, including gaming, can supplement traditional activities, motivate children to become physically active and enhance their learning experiences. Integrating technology and physical activity can create a more varied, meaningful, and dynamic school day, positively supporting pupils’ learning processes. The AR game associated with this study facilitated physical activity and learning experiences through a mobile device application. The empirical material for the study includes interviews with pupils participating in an AR game in mathematics. The findings show that participating in an AR game promoted embodied learning and positively impacted pupils’ motivation, engagement and learning processes. More specifically, AR facilitated learners’ engagement in the learning process by fostering their active involvement through physical and social collaboration and by enhancing the pupils’ joy of learning. Additionally, the pupils expressed that they enjoyed the application’s variations and the experiences that followed working collaboratively with the tasks. Moreover, they commonly found the physical and collaborative components of the AR game exciting and academically motivating. Studies on AR games and technology focusing on the opportunities and pedagogical foundations for their use in education are relevant in these precarious times. Indeed, more knowledge is needed on the ways creative and flexible learning processes that transpire within a technological learning environment influence embodied learning, knowledge that is essential for designing teaching and learning in the technical future.
Does a higher hashrate strengthen Bitcoin network security?
Authors: Kim Daehan , Ryu Doojin , Webb Robert I.
Published: June 2024

In the blockchain world, proof-of-work is the dominant protocol mechanism that determines the consensus of the ledger. The hashrate, a measure of the computational power directed toward securing a blockchain through proof-of-work consensus, is a fundamental measure of preventing various attacks. This study tests the causal relationship between the hashrate and the security outcome of the Bitcoin blockchain. We use vector error correction modeling to analyze the endogenous relationships between the hashrate, Bitcoin price, and transaction fee, revealing the need for an additional variable to achieve our aim. Employing a measure summarizing the growth of demand factors in the Bitcoin ecosystem indicates that hashrate fluctuations significantly influence security level changes. This result underscores the importance of the hashrate in ensuring the security of the Bitcoin blockchain.
Can women empowerment boost dietary diversity among children aged 6–23 months in sub-Saharan Africa?
Authors: Aboagye Richard Gyan , Donkoh Irene Esi , Okyere Joshua , Seidu Abdul-Aziz , Ahinkorah Bright Opoku , Yaya Sanni
Published: June 2024

Background

The empowerment of women has implications on the health and dietary needs of children. Using the survey-based women’s empowerment index (SWPER), we examined the association between women’s empowerment and dietary diversity among children aged 6–23 months in sub-Saharan Africa.

Methods

Data from the Demographic and Health Surveys of 21 countries were utilized. Descriptive spatial map was used to present the proportions of dietary diversity among the children. Multilevel binary logistic regression was used to examine the association between SWPER and dietary diversity.

Results

Overall, 22.35% of children aged 6–23 months had adequate minimum dietary diversity (MDD) in sub-Saharan Africa. The countries with the highest proportions of adequate MDD were Angola, Benin, Madagascar, Rwanda, Sierra Leone, and South Africa. South Africa had the highest proportion of MDD (61.00%), while Liberia reported the least (9.12%). Children born to mothers who had high social independence were more likely to have adequate MDD compared to those with low social independence [aOR = 1.31, 95% CI 1.21, 1.41]. In addition, children born to women with medium [aOR = 1.12; 95% CI 1.03, 1.21] and high decision-making [aOR = 1.25, 95% CI 1.14, 1.37] were more likely to receive MDD than those with low decision-making.

Conclusions

Insufficient dietary diversity is evident among children aged 6–23 months in sub-Saharan Africa. MDD in children is influenced by women's empowerment. Policies and interventions promoting women's empowerment can enhance MDD, especially for vulnerable groups in rural and poorer households. It is crucial to leverage media and poverty reduction strategies to improve MDD among children in sub-Saharan African countries.
Genomic and tumor microenvironment dynamics of brain metastases in breast cancer.
Authors: Manogna Dharmini , Wu Sharon , Deshmukh Sachin Kumar , Xiu Joanne , Ehsani Sima , Gopalakrishnan Ragisha , Sandoval-Leon Ana Cristina , Sammons Sarah L , Sledge George W. , Graff Stephanie L.
Published: June 2024

1018

Background: Brain metastases (BM) in breast cancer (BC) have a poor prognosis, with median survival at 7.2-13 months. Interplay between genomic evolution of cancer cells and development of BM is obscure. We sought to identify genomic aberrations associated with BM. Methods: We included 14095 BC samples: 429 BM, 7858 extra-cerebral metastases (ECM) and 5808 primary tumors (PT) were analyzed by next generation sequencing of DNA (NextSeq, 592 genes and NovaSeq, WES) and RNA (NovaSeq, WTS) (Caris Life Sciences, AZ). Tumor mutational burden-high (TMB-H) was defined as ≥10 mt/MB. Cut-off for PD-L1 immunohistochemistry positivity was ≥2 intensity and >5% staining (SP142). Global loss of heterozygosity (gLOH) used a cut-off of ≥ 16%. PAM50 was evaluable for a subset (n=9724, 69%) with WTS data. Statistical significance determined using chi-square and Mann-Whitney U test and adjusted for multiple comparisons (q<0.05). Results: Median age was lower in BM than ECM and PT (55 vs 62 vs 59 years, q<0.05). BM subtype was triple negative (TNBC, 40.1%), HR+/HER2- (30.5%), or HER2+ (29.4%) vs. ECM primarily HR+/HER2- (65.4%) and PT HER2+ (52.5%). BM were Basal-like (35.3%) or HER2-enriched (35.3%), whereas ECM were Luminal B (47.2%) and PT were Basal-like (34.4%) or Luminal B (34.6%). The Table summarizes molecular findings. In HR+/HER2- BC, BM were associated with TMB-H vs. ECM and PT (q<0.05). BM had higher GATA3-mt and ESR1-mt compared to PT (q<0.05). In HER2+ BC, BM had lower PD-L1+ (11.8% vs 39.3%) and higher ESR1-mt than PT. BM had higher ERBB2-amp (93.5% vs 75.2%) and RARA-amp (27.3% vs 6.7%) than PT (q<0.05). TNBC BM had higher proportion of TMB-H tumors but lower PD-L1+ (20.8% vs 50.7%) than PT. BM had increased gLOH than ECM (59.2% vs 36.2%). PIK3CA was lower in BM vs. ECM. In all subtypes, BM, when compared to ECM and PT respectively, were associated with decreased AR+ (HR+/HER2-: 57.7% vs 80.8% vs 85.7%; HER2+: 54.4% vs 77.1% vs 81%; TNBC: 15.1% vs 27.7% vs 23.1%), increased dendritic cell infiltration (HR+/HER2-: 3.2% vs 2.6% vs 2.5%; HER2+: 3.85% vs 2.41% vs 2.36%; TNBC: 3.96% vs 2.89% vs 3.05%) but lower IFN score (HR+/HER2-: -0.56 vs -0.41 vs-0.35; HER2+: -0.53 vs -0.39 vs -0.30; TNBC: -0.55 vs -0.30 vs -0.28). Conclusions: BM in BC are more frequently associated with TNBC and Basal-like BC phenotypes than ECM or PTs. BM have a higher proportion of ESR1-mut than PTs, highlighting a possible association between endocrine resistance and development of BM. BM had lower IFN score and PDL-1 expression highlighting an immunosuppressed tumor microenvironment. [Table: see text]
Imlunestrant, an oral selective estrogen receptor degrader (SERD), in combination with human epidermal growth factor receptor 2 (HER2) directed therapy, with or without abemaciclib, in estrogen receptor (ER) positive, HER2 positive advanced breast cancer (aBC): EMBER phase 1a/1b study.
Authors: Bhave Manali A. , Jhaveri Komal L. , Kaufman Peter A. , Aftimos Philippe Georges , Lombard Janine Margaret , Sideras Kostandinos , Im Seock-Ah , Ma Cynthia X. , Lee Kuo-Ting , Kim Sung-Bae , Li Yujia , Yuen Eunice , Estrem Shawn T. , Nguyen Bastien , Bacchion Francesca , Ismail-Khan Roohi , Beeram Muralidhar , Sohn Joohyuk
Published: June 2024

1027

Background: Imlunestrant is a next-generation, oral SERD designed to deliver continuous ER-target inhibition. In the first-in-human Phase 1a/b EMBER study (NCT04188548), imlunestrant demonstrated favourable safety, PK, and clinical benefit when administered as monotherapy or with targeted therapy in ER+, HER2- aBC. Here we present clinical data of imlunestrant with HER2 targeted therapy, in patients (pts) with ER+, HER2+ aBC enrolled in EMBER. Methods: Pts were randomized to imlunestrant (400mg po daily) + trastuzumab (H), with or without (±) abemaciclib (Part C) or received maintenance treatment with imlunestrant + H + pertuzumab (P) (Part E), at standard doses in 21-day cycles. Key eligibility (Part C): ≥ 2 prior HER2 directed regimens, no prior CDK4/6i or fulvestrant; (Part E): received 1st line induction taxane chemotherapy (any duration) + H + P, without disease progression and ≤1 prior therapy for aBC. Key endpoints included safety, PK, ORR, CBR and PFS. Results: Overall, 45 pts with ER+/HER2+ aBC received the following combinations: imlunestrant + H (n=18), imlunestrant + H + abemaciclib (n=21; 1 pt received 800 mg imlunestrant), and imlunestrant + H + P (n=6). Baseline characteristics, safety, and preliminary efficacy are presented below (Table). Most TEAEs were grade 1-2. Common TEAEs with imlunestrant + H were fatigue (33%) and nausea (28%); with imlunestrant + H + abemaciclib were diarrhea (100%), neutropenia (57%), fatigue (52%) and nausea (48%); and with imlunestrant + H + P were diarrhea (50%) and arthralgia (50%). Imlunestrant PK was consistent with those previously reported with no drug-drug interactions observed with the combinations. From Part C, sequencing of baseline plasma ctDNA samples (n=37) identified prevalent mutations in TP53 (49%), PIK3CA (30%), ESR1 (24%), and GATA3 (14%). Clinical activity of imlunestrant in this ER+/HER2+ population, while based on small numbers, is promising. Conclusions: Imlunestrant in combination with trastuzumab ± abemaciclib or pertuzumab was well tolerated, showed no drug-drug interactions, and demonstrated preliminary antitumor activity in pts with ER+/HER2+ aBC. Clinical trial information: NCT04188548 . [Table: see text]
Immune checkpoint inhibition for the treatment of metastatic breast cancer with high tumor mutational burden: Real world clinical and genomic correlates of response.
Authors: Mai Nicholas , Safonov Anton , Marra Antonio , Chen Yuan , Chandarlapaty Sarat , Razavi Pedram , Plitas George
Published: June 2024

1078

Background: Pembrolizumab has received tumor-agnostic approval for the treatment of unresectable/metastatic solid tumors carrying a tumor mutational burden (TMB) >10 mut/Mb. The registrational KEYNOTE-158 study, however, did not include any patients with metastatic breast cancer (MBC). Here we present a retrospective study of patients with TMB-high MBC treated with immune checkpoint inhibition (ICI) and report real-world efficacy endpoints, including progression free survival as well as clinical and genomic characteristics that may be associated with duration of response. Methods: All patients with MBC treated with an ICI at MSK and with TMB-high tumors (>10 mut/Mb) assessed by tumor-normal targeted sequencing (MSK-IMPACT) were included. Clinicopathological and demographic data were obtained via the MSK Breast Cancer Translational Program. Mutational signatures were determined using the Signature Multivariate Analysis (SigMA) algorithm. Real world progression free survival (PFS) was determined clinically and analyzed using Kaplan-Meier estimates. Univariate and multivariate analyses were performed using Cox-proportional hazards models. Results: Of 688 patients with TMB-high breast cancer at MSKCC, 87 had received ICI-based therapy for estrogen receptor positive (ER+), triple negative breast cancer (TNBC), and HER2+ MBC. Of those, 45 patients were treated with ICI monotherapy (29 ER+, 11 TNBC, 5 HER2), 31 were treated with ICI + chemotherapy (12 ER+, 19 TNBC), and 11 were treated with combinations of ICI and targeted therapy (8 ER+, 1 TNBC, 2 HER2). Median age at time of ICI treatment across all patients was 60. ICI was the median 5th line therapy for all patients (range 1-16). Median PFS of ICI for all patients was 3.17 months (95%CI 2.27-5.5). Multivariable analysis did not show statistically significant differences in PFS based upon treatment regimen (monotherapy vs. chemoIO HR 1.03, 95%CI 0.54-1.96, p= 0.92, monotherapy vs combination IO HR 1.66, 95%CI 0.69-4.02, p=0.26), ER status (ER- vs ER+, HR 1.20, 95%CI 0.63-2.28, p=0.57), or HER2 status (HER2- vs HER2+, HR 1.63, 95%CI 0.51-5.20, p=0.41. However, longer PFS was significantly associated with TMB>30 (HR 0.35, 95%CI 0.13-0.92, p=0.03) and dominant APOBEC signature score (APOBEC- vs APOBEC+, HR 0.49, 95%CI 0.25-0.98, p=0.04). Shorter PFS was significantly associated with later treatment line at the time of ICI exposure (continuous, HR 1.22, 95%CI 1.11-1.36, p=0.0001). Conclusions: In this heavily pretreated real-world cohort, ICI in TMB high MBC shows modest clinical activity. Our analysis suggests that ICI may be more effective in MBC patients that are less heavily pre-treated, have TMB>30, and have a predominantly APOBEC mutational signature. Further translational work is necessary to explore the mechanisms of these findings.
Multicenter retrospective cohort study of the sequential use of the antibody-drug conjugates (ADCs) trastuzumab deruxtecan (T-DXd) and sacituzumab govitecan (SG) in patients with HER2-low metastatic breast cancer (MBC): Updated data and subgroup analyses by age, sites of disease, and use of intervening therapies.
Authors: Huppert Laura Ann , Mahtani Reshma L. , Fisch Samantha Catherine , Dempsey Naomi , Premji Sarah , Taylor Angelina , Jacob Saya , Quintal Laura , Melisko Michelle E. , Chien Amy Jo , Sandoval-Leon Ana Cristina , Carcas Lauren , Ahluwalia Manmeet Singh , Harpalani Natasha , Hoppenworth Jenna , Idossa Dame , Rao Ruta D. , Giridhar Karthik , Rugo Hope S.
Published: June 2024

1083

Background: T-DXd and SG are both FDA-approved treatments for patients (pts) with HER2-low MBC, but little data exists on the sequential use of these ADCs. Methods: In this multicenter retrospective cohort study, we identified pts with HER2-low MBC treated sequentially with both T-DXd and SG in either order, with or without intervening therapies (IntTx), at 5 academic centers between 2020-2023. We previously reported real-world progression free survival (rwPFS) and real-world overall survival (rwOS) by HR-status and ADC sequence order. Here we provide updated rwPFS and rwOS data, as well as new subgroup analyses by age, sites of disease, and use of IntTx between ADCs for HR- and HR+ disease. Results: 84 pts with HER2-low MBC treated with both T-DXd and SG were included, including 56 pts with HR+/HER2-low MBC (66.7%) and 28 pts with HR-/HER2-low MBC (33.3%). Prior to the start of ADC1, median age was 58 yrs and 22 pts were >65 yrs (26.2%), 65 pts (77.4%) had visceral disease, and 14 pts (16.7%) had central nervous system (CNS) disease. 36 pts (42.9%) had an IntTx between ADCs. Table 1 shows updated rwPFS and rwOS data by HR-status and ADC sequence order. For pts with HR+ and HR- MBC, there was no difference in ADC1 rwPFS or ADC2 rwPFS by age ≤65 vs. >65 yr or by presence vs. absence of visceral disease. For pts with HR- MBC, ADC1 rwPFS and rwOS was shorter for pts with CNS disease vs. pts without CNS disease (rwPFS 5.4 mo (n=6) vs. 8.5 mo (n=22), p=0.03; rwOS 11.6 mo vs. 21.1 mo, p<0.01 respectively). For pts with HR+ and HR- MBC, there was no difference in ADC2 rwPFS with or without receipt of IntTx. There was no difference in time to treatment failure for first IntTx vs. ADC2 if no InTx was given. Conclusions: This is one of the largest multicenter cohorts of pts treated with sequential ADCs for HER2-low MBC. Median rwPFS was longer for ADC1 than ADC2 in all subgroups, regardless of HR-status, ADC sequence order, age ≤65 or >65 yr, presence of visceral disease, or use of IntTx. Among pts with HR-/HER2-low MBC, pts with CNS disease had shorter ADC1 rwPFS and rwOS than pts without CNS disease. [Table: see text]
Detection of TROP2: Ushering in a new choice in the treatment of patients with special types of invasive breast cancer.
Authors: Liu Yueping , Li Jinze , Jiang Hanxu , Deng Huiyan , Sun Haoyue , Liu Xudi
Published: June 2024

1106

Background: TROP2 has become an attractive new therapeutic target in breast cancer (BC). TROPiCS-02 trial shows that the sacituzumab govitecan(SG) which is the TROP2 ADC drug can significantly benefit the survival of patients with TNBC and HR+/HER2- BC, and the 2023 ASCO guideline recommends that TROP2 detection is not necessary before the SG treatment. However, less than 5% BC patients of special subtype were included in clinical trials, and the TROP2 expression of them is not yet known. The aim of our study is to compare the expression of TROP2 in different special types of BC, and provide reference for targeted treatment of these patients. Methods: We retrospectively retrieved tissues from 383 patients diagnosed with special type of BC and undergoing surgical resection at our institution from 2018 to 2023. Including metaplastic carcinoma (MBC), mucinous carcinoma (MC), adenoid cystic carcinoma, cribriform carcinoma, carcinoma with apocrine differentiation, neuroendocrine carcinoma and tubular carcinoma. Classify them as TNBC or HR+/HER2- BC. Applying H-score to evaluate the TROP2 expression, H-score<100, 100~200, and 201~300 classified as low, moderate and high expression. Results: Expression of TROP2 is higher in tubular and cribriform carcinoma, while in MBC and MC is significantly lower (χ2=66.756, P<0.001) (Table). Low expression of TROP2 is associated with low clinical staging ( P<0.05), no lymph node metastasis ( P<0.05), and high-grade tumor infiltrating lymphocytes ( P<0.05). Moreover, TROP2 had the lowest expression in MBC, with a median H-score of 45. There are 78.13% (43/55) cases showed H-score<100, with 27.3% (15/55) of cases showing no expression of TROP2 at all. It is worth noting that MBC is highly invasive and has a poor prognosis, but the expression level of TROP2 is very low in mesenchymal cells, while in squamous differentiated tumor tissue, the expression level of TROP2 is high, and the overall H-Score score is low ( P<0.001). Conclusions: This study is the first preliminary study on the TROP2 expression in special types of breast cancer. Although the current ASCO guideline recommends not testing TROP2, but our study shows it is pretty low or even not expressed in MBC and MC. Notably, the lack of expression in the mesenchymal and spindle cell subtypes may be highly indicates that they lack epithelial tumor cells expressing TROP2 as vectors, resulting in the inability to exert the therapeutic effect of ADC, we suggest routine testing of TROP2. [Table: see text]
Overall survival with palbociclib (PAL) plus an aromatase inhibitor (AI) versus AI alone in older patients (pts) with de novo, HR+/HER2− metastatic breast cancer: A SEER-Medicare analysis.
Authors: Brufsky Adam , Sandin Rickard , Stergiopoulos Stella , Chen Connie , Karanth Siddharth , Li Benjamin , Esterberg Lizzi , Makari Doris , Candrilli Sean D. , Goyal Ravi K. , Rugo Hope S.
Published: June 2024

1111

Background: Cyclin-dependent kinase 4/6 inhibitor in combination with endocrine therapy (CDK4/6i) is the current standard of care in first line (1L) treatment for hormone receptor–positive and human epidermal growth factor receptor 2-negative (HR+/HER2–) metastatic breast cancer (mBC). Comparative effectiveness evidence assessing overall survival (OS) outcomes are limited, particularly in older pts. Our primary objective was to compare OS in Medicare pts treated with 1L PAL + AI versus AI alone in the current SEER dataset. Methods: We conducted a retrospective analysis of HR+/HER2–mBC pts using the SEER-Medicare database. Medicare-enrolled pts aged ≥65 years diagnosed with de novo HR+/HER2– mBC between February 1, 2015, and December 31, 2019 were included. Pts were followed from the start of 1L therapy line until death, Medicare disenrollment, enrollment in a health maintenance organization plan, or the end of available study follow-up (December 31, 2020), whichever came first. Stabilized inverse probability of treatment weighting (sIPTW) was the primary method used to balance patient characteristics at baseline, with propensity score matching (PSM) and multivariable CPH regression as sensitivity analyses. Median OS and the hazard ratio (HR) were estimated using the weighted Kaplan-Meier (KM) method and the weighted Cox proportional hazard (CPH) regression model, respectively. Results: Of 779 included pts, 296 received PAL+AI and 483 received AI alone. Median follow-up was 23.9 months for the PAL+AI arm and 18.2 months for the AI alone arm. After sIPTW adjustment, median OS was 37.6 months (95% CI=34.8-42.0) for PAL+AI vs 25.5 months (95% CI=22.0-28.9) for AI alone (HR=0.73, 95% CI=0.59-0.91). Results from the PSM and CPH regression analyses were consistent with the primary analysis. Key patient characteristics are presented (Table). Conclusions: This comparative effectiveness study showed that PAL+AI was associated with significantly prolonged OS vs AI alone in the 1L treatment of older pts with de novo HR+/HER2- mBC treated in US clinical practice using the SEER-Medicare database. Our results add to the body of evidence on the survival benefit of PAL+AI in this population. [Table: see text]
Risk assessment of cardiovascular adverse events with BTK inhibitors in hematological malignancies: Insights from FAERS.
Authors: Faisal Muhammad Salman , Jatwani Karan , Kolli Venkatesh , Soror Noha , Sarangdhar Mayur
Published: June 2024

12145

Background: Burton tyrosine Kinase inhibitors (BTKi) have revolutionized the care of chronic lymphocytic leukemia (CLL) and non-Hodgkin lymphomas (NHL) – including relapsed/refractory mantle cell, ABC diffuse large B cell lymphoma and and lymphoplasmacytic lymphoma. Ibrutinib was the first BTKi to be approved. The newer covalent BTKi include acalabrutinib and zanubrutinib, both of which are approved for frontline and relapsed CLL as well as relapsed NHL. All these agents have cardiovascular adverse events. We aimed to assess the pharmacovigilance (PV), reporting rate, severity, and reaction outcomes of different approved BTKi in the CLL as cancer reported to the United States Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: We analyzed cardiovascular events in 86,370 patients on BTKi. Cardiovascular event reports were submitted to FAERS between 2004-2023 and analyzed using the AERS Mine framework. We compared these incidences within different BTKI. We divided cardiovascular events to three categories: cardiac arrythmia, major coronary or vascular event (MACE) and pericardial complication including effusion or hemorrhage. Our primary composite endpoint was the PV of cardiovascular events caused by BTKI. To mitigate confounding, BTKI were analyzed as mutually exclusive cohorts: Ibrutinib (n = 79,278), acalabrutinib (5200), and zanubrutinib (1354). Two-way ANOVA testing was done to evaluate for statistical significance across the different groups. Results: Across the 86,370 patients on BTKI, we identified 8500 reports of cardiovascular events – ibrutinib (10.15%), acalabrutinib (5.73%), and Zanubrutinib (4.72%). Arrythmia risk was higher with ibrutinib (6.6%) compared to acalabrutinib (3.12%) and zanubrutinib (2.29%). The major difference in the groups was driven by atrial fibrillation (5.1% vs 2.1% vs 1.8%). The MACE rate was 2.79% vs. 2.4% vs. 2%, and pericardial events were 0.72% vs. 0.21% vs. 0.44% in the ibrutinib, acalabrutinib, and zanubrutinib groups, respectively. All the AEs were to have statistical significance (p = 0.011) across all the BTKI as mentioned in table 1. Conclusions: We report the prevalence rate of BTKI-related cardiovascular events in a large cohort of patients. Ibrutinib has demonstrated a higher incidence of toxicity, especially in cardiac arrythmias, while smaller but significant differences exist in other toxicities, including major cardiovascular events and pericardial effusion or hemorrhage. Patient selection and toxicity monitoring are important aspects of the care of these patients, who stay on these therapies for indefinite periods. [Table: see text]
Geriatric assessment in older patients with non-small cell lung cancer: Insights from a cluster-randomized, phase III trial—ENSURE-GA study (NEJ041/CS-Lung001).
Authors: Furuya Naoki , Kanaji Nobuhiro , Yokoo Keiki , Yanagawa Takashi , Yamamoto Hiroshi , Takayama Koichi , Kawase Shigeo , Matsunaga Kazuto , Takeda Kenichi , Nagashima Hiromi , Sakamoto Tomohiro , Hotta Takamasa , Takiguchi Yuichi , Nogawa Hitomi , Nishioka Yasuhiko , Kobayashi Kunihiko , Isobe Takeshi , Tsubata Yukari
Published: June 2024

1502

Background: To determine optimal treatment in older cancer patients, it is recommended to conduct a geriatric assessment (GA) before chemotherapy. The ENSURE-GA study, which focused on patients aged 75 and older with non-small cell lung cancer (NSCLC), reported that the implementation of GA not only enhanced patient satisfaction with regards to communication with their physicians, but also improve the patients’ quality of life. Additionally, we assessed whether GA could improve overall survival and serve as a predictor for severe adverse events. Methods: Patients aged ≥75 with NSCLC who were unable undergo radical treatment were enrolled. All patients underwent a standardized GA before treatment. The participating institutions were cluster-randomized into either intervention group or control group. For the intervention group, GA summaries and recommendations for GA-guided interventions were provided to guide physicians in selecting treatments and interventions. The control group did not provide physicians with GA summaries. Geriatric 8 (G8) and CARG scores were calculated at enrollment, and we investigated whether adverse events during a 3-month follow-up could be predicted. Results: Between 2019 and 2022, 1,021 patients were enrolled from 78 institutions in Japan. No significant differences were observed in patient characteristics or for GA domains between intervention and control groups. Additionally, there were no significant differences seen in 1-year overall survival (20.7m vs 18.8m, p = 0.414), or the incidence of grade 3 or higher adverse events in patients treated with medical treatment (36.8% vs 38.1%, p = 0.732). The ROC curve for G8 regarding the occurrence of grade 3 or higher adverse events in cases receiving cytotoxic chemotherapy yielded an AUC of 0.525, indicating no discriminatory ability. Furthermore, there was no difference in the incidence of adverse events between low-risk and high-risk patients based on the CARG score. Conclusions: The implementation of GA and interventions based on its results enhances patient satisfaction. However, additional studies are needed before incorporating GA into an adverse event prediction system. Developing risk scoring tools specific to cancer types and races may prove useful. Clinical trial information: UMIN0000037590 .
Geographic and racial disparities in bi-specific antibodies trials access for diffuse large B-cell lymphoma.
Authors: Shahzad Moazzam , Khalid Muhammad Fareed , Park Robin , Amin Muhammad Kashif , Anwar Iqra , Jaglal Michael Vishal
Published: June 2024

1525

Background: The trials of bispecific antibodies to treat diffuse large B-cell lymphoma (DLBCL) have increased exponentially. However, there is a geographic limitation to offering these trials and universal access appears to be limited. Here, we investigate the geographical and racial disparities in accessing bispecific antibodies trials for DLBCL. Methods: We searched ClinicalTrials.gov using the terms for DLBCL and bispecific antibodies. A total of 13 out of 51 clinical trials with one or more open sites in the United States (US) were included in this systematic review. 2020 US Census Bureau data was used to obtain data on race and ethnicity. Analysis for this study was performed using SPSS version 26. Results: The majority of the included trials were Phase I (62%) followed by Phase II (23%), and Phase I/II (15%). A total of 885 participants were either enrolled or expected to enroll in these clinical trials. Nine (69%) clinical trials were only open in the US while 4 (31%) clinical trials were open in the US and other countries. The majority of the trials were funded by the pharmaceutical industry 62%. There were 50 unique study sites distributed over 24 states with a 2.4 (1-10) mean number of trials per state and 9.9 (1-39) mean number of sites per trial. Study sites were distributed in 24 different states. Midwestern states had the highest number of trials 28%, followed by Southern 26%, Northeastern 24%, and Western 22%. The highest number of study locations (10) and the highest number of open studies (10) were in California. Twenty-seven states had no open bispecific antibodies trials including three in the Northeast (Maine, Rhode Island, and Vermont), five in the Midwest (Illinois, Indiana, Nebraska, North and South Dakota), eight in the South (Delaware, Virginia, District of Columbia, West Virginia, Mississippi, Arkansas, Louisiana, and Oklahoma), and eleven in the West (Arizona, Colorado, Idaho, New Mexico, Montana, Nevada, Wyoming, Alaska, Hawaii, Oregon, and Washington). Using US Census Bureau data, only 20% of African Americans (AA) (8 349 699 of 41 104 200) lived in a county with a bispecific antibodies trial. There were only five states (21%) with 50% or more of the AA population living in a county with an open bispecific antibodies trial and seven states (29%) with 30-49.9% of their AA county residents. Five states (21%) had less than 10% of the AA population living in a county with an open bispecific antibodies trial. Nine (90%) out of ten states with the highest proportion of AA residents (18.6%-41.4%) have no (five states) or only one clinical trial site (four states). Conclusions: There is significant geographic and racial disparity in accessing bispecific antibodies trials for DLBCL. Strategies should be framed to address the causes of the observed disparities and to improve access to these trials.
Identifying modifiable risk factors to improve immigrant breast cancer screening in the United States.
Authors: Santos Patricia Mae Garcia , Barnes Justin Michael , Boe Lillian A , Shah Kanan , Yabroff Robin , Chino Fumiko
Published: June 2024

1530

Background: Despite marked reductions in breast cancer mortality since 1990, recent data suggest that progress has slowed—owing in part to plateaus in breast cancer screening in underserved populations. Historically low rates of screening coupled with rising breast cancer incidence make immigrants an important population for targeted intervention. Herein, we (1) compare contemporary rates of breast cancer screening among immigrants versus US natives; and (2) identify modifiable risk factors to inform the development of interventions to improve screening among immigrants in the United States. Methods: Using data from the 2019 and 2021 National Health Interview Surveys, screening eligible female participants (ages 40-79 years old) were identified, then classified by immigrant status as defined by nativity (US native vs. foreign-born). Primary outcome was receipt of screening mammogram in the last two years. Logistic regression models examined associations between immigrant status and mammography, with and without adjustments for age, metropolitan residence, overall health status, and survey year. Sequential analysis was then used to assess the degree to which modifiable social risk factors influence the magnitude of the association between immigrant status and mammography. Results: Of 20,090 female participants included in the study, 20% were immigrants. Compared to US natives, immigrants were less likely to have received a mammogram in the last two years (67% vs. 72%, aOR [95%CI], 0.87 [0.78-0.96], p=0.006)—an effect that was most pronounced among immigrant noncitizens (57%; 0.55 [0.47-0.64], p<0.001) but reversed among immigrants with US citizenship (74%; 1.14 [1.01-1.29], p=0.03). Of the factors assessed, having a usual source of care (5.73 [4.77-6.87]) or insurance (4.60 [3.74-5.67]) was associated with the greatest odds of biennial mammography, followed by educational attainment (1.38 [1.19-1.60]) and employment (1.19 [1.09-1.30]; all p<0.001). While having a usual source of care or employment attenuated—but did not eliminate—the association between immigrant status and mammography (0.87 [0.78-0.96], p=0.01 and 0.89 [0.80-0.99], p=0.03, respectively), this finding was not observed upon inclusion of insurance status or education in sequential models (0.97 [0.87-1.09], p=0.6 and 1.09 [0.96-1.21], p=0.13, respectively). With respect to insurance type, Medicare Advantage (4.60 [3.74-5.67]) conferred the largest benefit, followed by private insurance (4.54 [4.00-5.26]), Medicaid (2.63 [2.20-3.14]), and Medicare (4.39 [3.53-5.46]; all p<0.001). Conclusions: Breast cancer screening remains low in noncitizen immigrant populations. Targeted interventions to improve access to health insurance coverage and primary care for noncitizens may be most effective for improving rates of screening mammography among immigrants and thus warrant further investigation.
Unveiling the cost-effectiveness of CDK4/6 inhibitors in treating patients with HR+/HER2- metastatic breast cancer: A closer look at nonmedication expenses.
Authors: Pilehvari Asal , You Wen , Kimmick Gretchen Genevieve , Bonilla Gloribel , Anderson Roger
Published: June 2024

1532

Background: Cyclin-dependent kinase (CDK)4/6 inhibitors have significantly enhanced survival outcomes in postmenopausal patients diagnosed with HR+ MBC. Their integration with endocrine therapy (ET) has become the standard of care in MBC treatment lines. There are limited economic evaluations of these innovative, yet costly, therapies. This study assesses the cost-effectiveness of these drugs using EHR derived data and administrative claims to estimate cost. Methods: We used the nationwide EHR-derived Flatiron Health (FH) de-identified database to identify 3,879 patients receiving 1st line (1L) treatment for HR+ MBC (2,137 received CDK4/6i+ET and 1,742 received ET alone) between Feb 2015 and Nov 2021. SEER-Medicare claims data was used to supplement the missing cost info in the FH database to quantify monthly medication costs, drawing data from Medicare patients continuously enrolled in PARTs A, B, and D between 2015 to 2021 for at least 24 months and specific to therapeutic approaches for MBC and overall healthcare costs. The costs were adjusted by the patient characteristic: age, race, specific ET or CDK4/6i drug, and Medicare dual eligibility. The effectiveness was measured as progression-free duration in months. All costs were adjusted for inflation. The Incremental Cost Effectiveness Ratio (ICER) analysis was conducted to examine the cost-effectiveness of CDK4/6i as compared with ET alone. Results: Average estimated monthly medication costs were $12,524 and $322 for CDK4/6i+ET and ET alone, respectively. On average, CDK4/6i+ET increased the estimated medication costs by $235,564 over the time to first progression and was associated with a gain of 3.2 months of progression-free survival as compared to ET alone, resulting in an ICER of $73,098 per month without progression. At a willingness-to-pay of $65,000 per month without progression, both groups have 50% probability of being considered cost-effective. Notably, the average estimated monthly non-medication costs (total costs-medication costs) for the CDK4/6i+ET group were $2,278 compared to $4,265 for the ET alone group (p<0.001). On average, CDK4/6i+ET decreased the estimated non-medication costs by $ 22,427. For non-medication costs, the ICER drops to $7,178 per month without progression making the CDK4/6i+ET the dominant cost-effective choice over ET alone. Conclusions: Cost-effectiveness of treating HR+ MBC patients is primarily driven by the cost of CDK4/6i drug prices. However, findings highlight significantly lower overall non-medication healthcare costs using CDK4/6i+ET compared to ET alone in 1L treatment. These cost savings, however, are offset by the high medication costs of CDK4/6i. Thus, lowering the market cost of CDK4/6i drugs or targeting those who can benefit the most could shift the balance in favor of a cost-effective benefit from Medicare perspective.
Unveiling the interplay of social factors in cancer survivorship: A comprehensive social determinants of health (SDOH) profile analysis.
Authors: Chen Fangyuan (Chelsea) , Nipp Ryan David , Han Xuesong , Washington Samuel L. , Yabroff Robin , Jiang Changchuan
Published: June 2024

1536

Background: SDOHs contribute to patients’ cancer survivorship outcomes. While studies tend to focus on individual SDOH, understanding the interplay and collective impact of multiple SDOHs is vital for improving patient outcomes and access to care. Our study aims to understand SDOH profiles in cancer survivors and stratify social risks by analyzing relationships between SDOH profiles and health outcomes using a nationally representative dataset. Methods: We conducted an unsupervised clustering analysis using 2013-2018 National Health Interview Survey data, linked to NHIS Mortality Files, to examine 12 social determinants of health (SDOHs) in the general population. 12 SDOH included unmarried status, unemployment, less than high school education, material/psychological/behavioral financial hardship, transportation/food/housing insecurity, delayed care due to other reasons, and low income(less than federal poverty line), and low neighborhood cohesion. K-Modes clustering was used to identify optimal number of cluster. We estimated each cluster’s prevalence in younger (18-64 years) and older (65-79 years) cancer survivors, then used weighted Cox regression to assess the risk of overall (OS)in both age groups, adjusting for demographics. Results: We identified 5 distinct groups based their SDOH profiles, including group A (few SDOH barriers), B (unmarried but no other SDOH barriers), C (unemployed but no other SDOH barriers), D (unmarried, unemployed, occasionally having other SDOH barriers) and E (the highest rate of financial hardship/transportation/food/housing insecurity/low neighborhood cohesion/low income). Notably, group E, compared to all other groups, had the highest rate of racial minorities in both younger and older groups in both younger (71% vs 5-14%) and older populations (74% vs 1-8%). Older survivors in Group C (HR 2.48, 95% CI: 1.02-6.03), Group D (HR 4.09, 95% CI: 1.65-10.14), and Group E (HR 3.88, 95% CI: 1.44-10.46) had significantly lower OS rates compared to those in Group A. For younger survivors, Group D (HR 1.96, 95% CI: 0.97-3.96) and Group E (HR 1.40, 95% CI: 0.67-2.95) were associated with nonsignificant reductions in OS, possibly due to limited sample sizes. Conclusions: SDOHs form distinct clusters, each with profound on cancer survivorship especially among older survivors facing complex social challenges. This necessitates customized health interventions focused on these SDOH profiles, crucial for improving patient outcomes and addressing health disparities.
Trends in the providers’ uptake of advance care planning from 2016 to 2021.
Authors: Wang Nan , Jiang Changchuan , Hu Xin
Published: June 2024

1538

Background: Advance care planning (ACP) facilitates meaningful discussions and preparation for future medical decisions. This person-centered approach has been recognized for its potential to improve care quality and reduce unnecessary aggressive care at the end of life, especially among cancer patients. We examined the trends in ACP visits across specialty groups that may involve cancer care and between rural and urban areas. Methods: We used publicly available data from the Centers for Medicare & Medicaid Services, the Provider Utilization and Payment Data Physician and Other Practitioners Dataset – By Provider and Service files (2016-2021). We included providers in 3 specialty groups that may encounter cancer patients needing ACP: Cancer-Related Specialties, Hospice and Palliative Medicine (HPM), and Midlevel Providers. The primary outcome was billing for any ACP services each year, identified through Healthcare Common Procedure Coding System codes (99497 and 99498). Geographical areas were classified using Rural-Urban Commuting Area codes into metropolitan and non-metropolitan areas. Trends in the percent of providers billing any ACP and average ACP service volumes were described, with Wilcoxon tests used for statistical comparisons. Results: The primary analytic sample consists of 1,280,656 provider-years from 2016 to 2021 (Cancer-Related Specialties: 113,012, HPM: 7,320, and Midlevel: 1,160,324). The percentage of providers billing ACP visits tripled from 1.0% in 2016 to 3.3% in 2021. The highest uptake was among HPM physicians (12.8% to 36.9%) compared to cancer-related specialists and midlevel providers (Table). Average ACP service volume was higher in non-metropolitan areas among Cancer-Related Specialties (53.6 vs. 142.9). However, the average ACP service volume by metropolitan status was similar among HPM (75.0 vs. 66.7, P=0.65) and higher in metropolitan areas among Midlevel providers (70.2 vs. 54.8, P<.001). Conclusions: The proportion of physicians billing ACP codes increased including those in HPM and cancer-related specialties, but adoption remained low. Rural-urban disparities in average ACP service volume among cancer-related specialties might reflect a shortage of specialty-trained HPM physicians to provide ACP services. Particularly noteworthy is the absence of HPM specialty in non-metropolitan areas. A comprehensive strategy involving education, awareness, enhanced training capacity, innovative care models for advanced practice nurses, and increased resources, is needed to promote APC use and patient-centeredness in cancer care.[Table: see text]
Feasibility and satisfaction level of caregivers with telemedicine in childhood cancer: A mixed-methods study.
Authors: Bakhshi Sameer , Ganguly Shuvadeep , Singh Sra Manraj , Sasi Archana , Sharma Shubhangi , Sharma Swetambri
Published: June 2024

1549

Background: Telemedicine has emerged as a crucial solution to addressing health care disparities, especially in countries like India where healthcare disparities are pronounced and specialist care is concentrated in urban areas. Methods: We conducted a mixed-methods study among caregivers of children with cancer who had utilised telemedicine in the past 6 months. Telephonic quantitative interviews collected information on diagnosis, current treatment status, residence and socio-economic parameters. A logistic regression model was created to assess patient and caregiver related factors associated with satisfaction with telemedicine. In-depths interviews were conducted in a sub-set of participants followed by thematic analysis. Results: Caregiver of 465 patients [median (range) age: 8 (0.1-18) years; 70.04% male; 82.54% with haematological malignancy] participated in this study. Patients had a median (range) of 2 (1-30) telemedicine in the past year, with parents being the most common care giver being involved [n=326 (70.10%)]. Telemedicine was reported to be more convenient than in-person visits and helpful in saving time and money by 90.54% (n=421) patients and 88.6% (n=421) patients reported easier follow up and access to care using telemedicine. Difficulty in explaining issues over telephones or emails was the reason for dissatisfaction for 47.53% (n=221) patients, additionally 22.37% (n=104) patients felt they received inadequate attention during telemedicine. Majority of the patients (85.38%, n=397) planned to continue teleconsultation and 88.39% (n=411) would recommend teleconsultation to others. Socioeconomic status of upper and upper-middle class upper and upper-middle socioeconomic status [OR (95%CI): 2.14 (1.38-3.32), p: <0.001; aOR (95%CI): 2.11 (1.35 - 3.31), p: 0.001] was significantly associated with caregiver satisfaction with telemedicine. Qualitative interview showed themes of monetary and time savings with telemedicine, ease of consultations for minor complaints, delay in responsiveness of doctors, language barriers and difficulty in using telemedicine platforms due to low literacy levels. Conclusions: Telemedicine has emerged as a valuable tool for paediatric cancer care offering convenience and accessibility. While most caregivers expressed satisfaction, challenges remain in communication and limited access among caregiver of lower socio-economic strata. Further studies should aim at developing more patient friendly telemedicine platforms.