bluuebunny/crossref_metadata_2025_split huggingface dataset:
Heart rate variability-based prediction of early cardiotoxicity in breast-cancer patients treated with anthracyclines and trastuzumab
Authors: Luna-Alcala Santiago , Espejel-Guzmán Adrián , Lerma Claudia , Leon Paula , Guerra Enrique C. , Fernández Jose Rodrigo Espinosa , Martinez-Dominguez Pavel , Serrano-Roman Javier , Cabello-Ganem Aldo , Aparicio-Ortiz Alexis D. , Keirns Candace , Lerma Abel , Ana-Bayona Maria Jose Santa , Espinola-Zavaleta Nilda 
Published: May 2024

Abstract
Background
Cardiotoxicity is a recognized complication in breast cancer (BC) patients undergoing chemotherapy with anthracyclines with or without trastuzumab. However, the prognostic value of heart rate variability (HRV) indexes for early cardiotoxicity development remains unknown.

Methods
Fifty BC patients underwent TTE assessment before and three months after chemotherapy. HRV indexes were obtained from continuous electrocardiograms in supine position with spontaneous breathing, active standing, and supine position with controlled breathing. The magnitude of change (Δ) between supine-standing and supine-controlled breathing was calculated. Variables were compared using t-test or ANOVA. Cardiotoxicity predictive value was assessed by ROC curve analysis. A p value of < 0.05 was considered significant.

Results
TTE revealed reduced left atrial conduit strain in the cardiotoxicity group. Mean heart rate increased during all maneuvers at follow-up, with no differences in HRV indexes between patients with or without cardiotoxicity. However, a lower Δ in supine-controlled breathing of several HRV indexes predicted early cardiotoxicity identified by echocardiography (e.g. SDNN ≤ -8.44 ms: Sensitivity = 75%, Specificity = 69%).

Conclusions
BC patients treated with chemotherapy maintain cardiac autonomic responses to physiological stimuli after 3 months of chemotherapy. However, a lower Δ during active standing and controlled breathing before chemotherapy may predict early cardiotoxicity.
Broadband spin and angle co-multiplexed waveguide-based metasurface for six-channel crosstalk-free holographic projection
Authors: Liu Zeyang , Gao Hao , Ma Taigao , Ray Vishva , Liu Niu , Zhang Xinliang , Guo L. Jay , Zhang Cheng 
Published: May 2024

AbstractMetasurface-based holograms, or metaholograms, offer unique advantages including enhanced imaging quality, expanded field of view, compact system size, and broad operational bandwidth. Multi-channel metaholograms, capable of switching between multiple projected images based on the properties of illuminating light such as state of polarization and angle of incidence, have emerged as a promising solution for realizing switchable and dynamic holographic displays. Yet, existing designs typically grapple with challenges such as limited multiplexing channels and unwanted crosstalk, which severely constrain their practical use. Here, we present a new type of waveguide-based multi-channel metaholograms, which support six independent and fully crosstalk-free holographic display channels, simultaneously multiplexed by the spin and angle of guided incident light within the glass waveguide. We employ a k-space translation strategy that allows each of the six distinct target images to be selectively translated from evanescent-wave region to the center of propagation-wave region and projected into free space without crosstalk, when the metahologram is under illumination of a guided light with specific spin and azimuthal angle. In addition, by tailoring the encoded target images, we implement a three-channel polarization-independent metahologram and a two-channel full-color (RGB) metahologram. Moreover, the number of multiplexing channels can be further increased by expanding the k-space’s central-period region or combing the k-space translation strategy with other multiplexing techniques such as orbital angular momentum multiplexing. Our work provides a novel approach towards realization of high-performance and compact holographic optical elements with substantial information capacity, opening avenues for applications in AR/VR displays, image encryption, and information storage.
DESTINY-Breast07: Dose-expansion interim analysis of T-DXd monotherapy and T-DXd + pertuzumab in patients with previously untreated HER2+ mBC.
Authors: Andre Fabrice , Hamilton Erika P. , Loi Sherene , Anders Carey K. , Schmid Peter , Stroyakovskiy Daniil , Villanueva Rafael , Pedrini Jose Luiz , Doval Dinesh Chandra , Zurawski Bogdan , Chen Shin-Cheh , Boston Sarice Renee , Konpa Adam , Pierotti Barbara , Fabbri Giulia , Jhaveri Komal L. 
Published: May 2024

1009 Background: Trastuzumab deruxtecan (T-DXd) is approved for adult patients (pts) with HER2+ advanced/metastatic breast cancer (mBC) who received a prior anti-HER2–based regimen. DESTINY-Breast07 is a Phase 1b/2 multicenter, open-label, modular study exploring the safety, tolerability, and antitumor activity of T-DXd alone or in combination with other anticancer agents (NCT04538742). These results are from an interim analysis of the dose-expansion phase assessing T-DXd ± pertuzumab (P) as first-line (1L) treatment in HER2+ mBC. Methods: Pts had locally assessed HER2+ mBC with measurable disease and no or stable brain metastases. A disease-free interval of ≥12 months from (neo)adjuvant therapy was required; no prior therapy for mBC was allowed. Pts were stratified by hormone receptor and disease status (recurrent vs de novo), and PD-L1 expression. Pts received T-DXd 5.4 mg/kg intravenously (IV) every 3 weeks (Q3W) as monotherapy or in combination with P 420 mg IV Q3W, with an 840 mg loading dose. Primary endpoints were safety and tolerability; key secondary endpoints included objective response rate (ORR) and progression-free survival (PFS), per RECIST 1.1 by investigator. Results: Seventy-five pts were treated in the T-DXd module and 50 pts in the T-DXd + P module; median follow up was 19.2 months (range 8.7–29.2) and 20.6 months (range 13.3–26.7), respectively. Median age was 57 years in both modules. As of August 1, 2023, the most common adverse event (AE) was nausea (T-DXd, 70.7% [4.0% Grade 3]; T-DXd + P, 68.0% [0% Grade 3]). Diarrhea was reported in 34.7% (2.7% Grade 3) and 60.0% (6.0% Grade 3) of pts in the T-DXd and T-DXd + P modules, respectively. There were no Grade ≥4 nausea or diarrhea events. Adjudicated drug-related interstitial lung disease (ILD) / pneumonitis was reported in six (8.0%) and five (10.0%) pts in the T-DXd and T-DXd + P modules, respectively (all Grade ≤2). One non-treatment-related AE with outcome of death was reported in the T-DXd module (post-acute COVID-19 syndrome); none with T-DXd + P. The confirmed ORR was 77.3% (80% confidence interval [CI] 70.0, 83.6) with T-DXd and 82.0% (80% CI 73.1, 88.8) with T-DXd + P. PFS rate at 12 months was 77.3% (80% CI 69.0, 83.7) with T-DXd and 89.4% (80% CI 81.9, 93.9) with T-DXd + P. Conclusions: Safety profiles were consistent with the known profiles for T-DXd and P, with no Grade ≥3 ILD events. Early data showed promising efficacy in both modules. The DESTINY-Breast07 study is ongoing; analyses from the Phase 3 DESTINY-Breast09 clinical trial will provide definitive data on TDXd ± P in 1L HER2+ mBC. Clinical trial information: NCT04538742 . [Table: see text]
Testing patterns and prevalence of PIK3CA, AKT1, and PTEN alterations among patients (pts) with HR+/HER2- metastatic breast cancer (mBC) in the US.
Authors: Park Leah , Thompson Samantha L , Roose James , Lu Yichen , Chaki Moumita , Lam Clara , Iorgulescu Bryan 
Published: May 2024

1041 Background: Biomarkers play an essential role to inform treatment decisions in mBC. In hormone receptor positive/HER2 negative (HR+/HER2-) mBC, PIK3CA/AKT1/PTEN alterations are now actionable as pt selection biomarkers with the FDA’s Nov 2023 approval of the pan-AKT inhibitor capivasertib. Here we investigate the testing patterns and prevalence of PIK3CA/AKT1/PTEN alterations in mBC. Methods: This retrospective cohort study used two partially overlapping nationwide de-identified databases: the Flatiron Health electronic health record-derived database (FH DB) to assess next-generation sequencing (NGS) testing rates, and the Flatiron Health-Foundation Medicine clinico-genomic database (FH-FMI CGDB) to assess prevalence among tested. Pts were included if they were ≥18 years old and diagnosed with HR+/HER2- mBC from 1/1/17—6/30/22. Prevalence was assessed using any sample type or timing of testing post-mBC diagnosis and defined as pathogenic/likely pathogenic alterations as captured in FMI NGS testing. All analyses were summarized using descriptive statistics. Results: 8,049 (FH DB) and 2,912 (FH-FMI CGDB) pts were eligible. Overall, 37% of pts with mBC received NGS testing (3,002/8,049). Among pts in FH-FMI CGDB, 98% had PIK3CA tested (2,857/2,912) and 97% also had AKT1/PTEN tested (2,838/2,912) in the metastatic setting. The median time from mBC diagnosis to initial test was 148 days for PIK3CA and 188 days for AKT1/PTEN, and 92-93% of testing occurred after the start of first-line (1L) therapy (Table). 82% of PIK3CA testing was on tissue and 37% on liquid biopsy, with 19% of pts receiving both tissue and liquid biopsy. 77% of AKT1/PTEN testing was on tissue and 28% on liquid biopsy, with 5% of pts receiving both tissue and liquid biopsy. At least one PIK3CA/ AKT1/ PTEN alteration was detected in 55% of the pts (1,557/2857) tested for any of the markers, regardless of sample type. Conclusions: <40% of pts with mBC received NGS testing from 2017-2021, suggesting opportunities for improving pts’ access to testing. Coupled with the high rate of PIK3CA/AKT1/PTEN alterations, NGS testing should be incorporated in routine clinical practice to identify optimal treatments. [Table: see text]
Kinome reprogramming as a therapeutic opportunity in ESR1 fusion driven breast cancer but not in gynecologic cancers.
Authors: Turaga Ravi Chakra , Jagannathan Murali Shivani , Ivan Cristina , Karre Bharath Kumar , Sima Chao , Abera Asfetaw , Radovich Milan , O'Neill Heather 
Published: May 2024

1045 Background: The administration of specific tyrosine-kinase inhibitors in kinase fusion positive cancers has led to significant improvement in clinical outcomes. Gene fusions involving the ESR1 gene, a non-kinase, have been previously reported in breast and gynecologic cancers including ovarian cancer and uterine cancer. However, ERa inhibitors proved to be ineffective in ESR1 fusion positive cases, we have effectively characterized ESR1 fusions and hypothesized a surrogate downstream target as an effective approach to target ESR1 fusion positive breast cancer. Methods: We retrospectively analyzed 216,176 samples submitted for clinical molecular profiling at Caris Life Sciences via Caris MI Tumor Seek (Phoenix, AZ). Gene fusion detection was performed on mRNA isolated from a FFPE tumor sample using the Illumina NovaSeq platform. All ESR1 fusions with ≥ 3 junction reads were identified for manual review and for domain prediction, breakpoints, frame retention and co-occurring alterations by NGS. WES data was also investigated to evaluate co-occurring pathogenic mutations to establish the oncogenicity of gene fusions. Results: ESR1 fusions had the highest frequency in gynecologic and breast cancer. We evaluated ESR1 expression in cases with ESR1 fusions detected and observed higher expression of ESR1 in breast cancer, ovarian cancer (P<0.0001) and uterine cancer (P<0.0001) compared to respective cancer cases as determined by TPM values. The Kaplan-Meier curve also indicated poor prognosis for breast cancer patients with ESR1 fusions (619 days [n=105]) as opposed to patients who did not harbor any ESR1 variants (1396 days [n=755]; P<0.0001). Further, pathway analysis was performed on breast cancer ESR1 fusion positive and negative cases to discern specific downstream markers that might be upregulated. It was observed that RET(p<0.0001), IGF1R(p=0.0001) and FGFR3 (p<0.0001) were upregulated in ESR1 fusion positive breast cancer cases which may be largely determined by the TP53-FOXA1-ER alpha transcriptional axis. However, no significant increase of RET, IGF1R and FGFR3 was observed in gynecologic cancers, owing to high TP53 mutation frequency observed in ovarian cancer (90%) and uterine cancer (82%) compared to breast cancer(19%). Conclusions: We highlight that ESR1 fusions can be reliably detected in patients with breast cancer, ovarian cancer, and endometrial cancers. ESR1 fusions lose the ligand binding domain and cannot be targeted using current estrogen modulators or degraders. We have discovered the upregulation of oncogenic kinase signaling in ESR1 fusion positive breast cancer, but not in gynecologic cancers. Our observations highlight enhanced oncogenic kinase signaling as a surrogate approach with clinically approved kinase inhibitors for targeting ESR1 fusion positive breast cancer cases but not in ovarian and uterine cancers.
Geographic disparities in brachytherapy accessibility for cervical cancer.
Authors: Lee Misuk , Lee Hyo Chun 
Published: May 2024

1577 Background: While brachytherapy stands as a crucial component of the treatment for locally advanced cervical cancer, the issue of geographic disparities in brachytherapy accessibility has become a noteworthy public health concern in South Korea. Moreover, the specific factors contributing to these disparities have not been clearly elucidated. In light of this, we conducted a nationwide ecologic study to comprehensively investigate the socioeconomic factors associated with brachytherapy accessibility. Methods: A total of 2,998 patients newly diagnosed with cervical cancer in 2020 were identified through the Korea Central Cancer Registry (KCCR). Across 17 administrative districts in South Korea, 32 brachytherapy facilities were available. To capture unique socioeconomic factors for each region, including the number of Korean Medicaid (K-Medicaid), Medicare (K-Medicare) beneficiaries, marriage immigrants, registered foreigners, and total residents, data were obtained from the Korean Statistical Information Service (KOSIS). Notably, K-Medicaid and K-Medicare represent governmental medical insurance assistance for patients in poverty and those aged over 65, respectively. The brachytherapy accessibility rate (BAR) was defined as the number of brachytherapy procedures divided by new cervical cancer cases. Additionally, each district's socioeconomic factor was normalized by the number of residents. Univariate and multivariate logistic regression analyses were conducted to explore the relationships between BAR and socioeconomic factors. Results: The capital city and its adjoining metropolitan area accounted for 46.9% of the total brachytherapy facilities, with Seoul having 25% (8 out of 32) and Gyeonggi having 21.9% (7 out of 32). Conversely, three non-metropolitan regions had no brachytherapy facilities. In the multivariate logistic regression analysis, the brachytherapy accessibility rate (BAR) demonstrated an inverse association with both the number of K-Medicare beneficiaries and the total immigrant population (Odds ratios of 0.66 and -2.85, respectively). Conclusions: To the best of our knowledge, this is the inaugural study highlighting the robust associations between older age and foreign residency status with reduced accessibility to brachytherapy. The observed inaccessibility to brachytherapy has the potential to impede the delivery of standard care, consequently leading to a poorer prognosis for vulnerable populations. Future research endeavors and targeted social interventions will be imperative to rectify geographic disparities in brachytherapy accessibility and ensure equitable healthcare outcomes.
Racial disparities in the immunotherapeutic outcomes of patients with non-small cell lung cancer (NSCLC): An in-depth systematic review and meta-analysis.
Authors: Wannaphut Chalothorn , Saowapa Sakditad , Polpichai Natchaya , Wattanachayakul Phuuwadith , Lalitnithi Pakin , Tanariyakul Manasawee , Siladech Pharit 
Published: May 2024

1579 Background: The utilization of immunotherapy has become prevalent in the therapeutic approach to non-small cell lung cancer (NSCLC), owing to its association with enhanced survival outcomes. Nevertheless, a notable gap exists in the available information regarding potential variations in the survival benefits of immunotherapy based on the racial demographics of NSCLC patients. Methods: A systematic search for articles published until January 2023 was performed on PubMed, EMBASE, and Google Scholar databases. Articles that aligned with the research objective were included, while non-English articles, case reports, conference abstracts, studies combining immunotherapy with other cancer therapies, and studies on small-cell lung cancer were excluded. Data required for review and analysis was independently abstracted into separate Excel files by two reviewers. Furthermore, Statistical analyses were performed using the Review Manager software, and the methodological quality evaluation was done using the Newcastle Ottawa Scale. Results: Seven cohort studies were used for review and analysis. A subgroup analysis of data from these studies showed that Black/African American and Asian NSCLC patients receiving immunotherapy had improved overall survival (OS) than White patients (HR: 0.84; 95% CI: 0.75 – 0.95; p = 0.006 and HR: 0.53; 95% CI: 0.30 – 0.93; p = 0.03, respectively). However, the difference in OS is statistically insignificant when Hispanic patients are compared with white patients (HR: 0.68; 95% CI: 0.46 – 1.00; p = 0.05). On the other hand, the subgroup analyses did not demonstrate any significant difference in progression-free survival (PFS) when comparing Black/African American, Asian or Hispanic patients to White patients (HR: 0.93; 95% CI: 0.79 – 1.09; p = 0.35, HR: 0.89; 95% CI: 0.51 – 1.55; p = 0.69, and HR: 1.01; 95% CI: 0.82 – 1.23; p = 0.96, respectively). Conclusions: Among non-small cell lung cancer (NSCLC) patients undergoing immunotherapeutic interventions, it is discerned that Black/African American and Asian individuals exhibit superior overall survival (OS) outcomes compared to their White counterparts. However, it is noteworthy that the observed racial disparity does not appear to exert a discernible influence on the progression-free survival (PFS) of NSCLC patients subjected to immunotherapy.
Pharmacokinetics (PK) and pharmacogenomics (PGx) of ribociclib (ribo) in Black patients with metastatic breast cancer (mBC): The LEANORA study.
Authors: Smith Donald , Schlam Ilana , Peer Cody , Sissung Tristan , Schmidt Keith Thomas , Tan Ming Tony , Chitalia Ami , Bishopric Nanette H. , Steinberg Seth M. , Choo-Wosoba Hyoyoung , Gallagher Christopher , Ashai Nadia , Whitaker Kristen Danielle , Mainor Candace Bavette , Tiwari Shruti Rakesh , Swanson Nicole , Malloy Stacy K , Isaacs Claudine , Figg William Douglas , Swain Sandra M. 
Published: May 2024

1581 Background: Ribo is metabolized by CYP3A and used for the treatment of patients with hormone receptor-positive (HR+)/HER2- mBC. FDA recommends dose reduction if used with CYP3A inhibitors due to a 3.2x increase ribo area-under-the-curve (AUC). It is unknown if modifications are needed in patients who lack enzyme activity (e.g., genetic CYP3A5 poor metabolizers (PM)). CYP3A5varies by genetic ancestry, is known to affect dosing for other drugs (e.g., tacrolimus). CYP3A5, ~85% of people of European ancestry are PM, ~85% of African ancestry are normal or intermediate metabolizers (NM, IM), which may impact ribo exposure and response. 2 percent (41/2066) enrolled in MONALEESA 2, 3, and 7 were Black. Methods: This prospective, multicenter cohort study (NCT04657679) assessed the PK and PGx of ribo (600 mg daily + letrozole/fulvestrant) in self-identified Black women with HR+/HER2- mBC. PK (0.5, 1, 2, 4, and 6 hours after ribo) and PGx studies were performed during cycle 1 via liquid chromatography with tandem mass spectrometry and PharmacoScan (ThermoFisher) microarray, which tests 1,191 genes. Including variants in CYP3A5*3, *6,and *7. Phenotypes assigned: PM (2 variant alleles), intermediate metabolism (IM; 1 variant allele), NM (0 variant alleles). The area under the curve (AUCtau) was compared with the exact Wilcoxon rank-sum test; Fisher’s exact test assessed the AEs and grade 3+ AEs to day 28. Results: 14 completed the trial. CYP3A5 phenotypes were PM (7), IM (6), and NM (1). The primary endpoint, AUCtau, was similar between CYP3A5 PM (39,230 hr*ng/mL; interquartile range [IQR]: 18,745 to 57,566 hr*ng/mL) vs. IM/NM (43,546 hr*ng/mL; IQR: 35,298 to 46,647 hr*ng/mL; p = 0.38). Other PK properties were similar between groups (table). There was a non-statistically significant higher number of AEs and grade 3+ AEs in PMs, when compared to NM/IMs. Study was not powered to assess differences in AEs. Conclusions: This cohort study detected no association between CYP3A5 genotype and ribo exposure. However, PMs may have more AEs relative to IMs/NMs. Future steps include exploring the impact of rare variants, including ~70 variants in CYP3A 4 and 5, on ribo exposure in this population. We will explore the role of clinical and genetic factors on the interindividual variability of ribo. Diverse patient representation in clinical trials is critical to ensure research findings are applicable to all patients. Clinical trial information: NCT04657679 .[Table: see text]