bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical validation of a multicancer detection blood test by circulating cell-free DNA (cfDNA) methylation sequencing: The THUNDER study.
Authors: Gao Qiang , Zhang Yuzi , Xu Jiayue , Wang Guoqiang , Zhao Jing , Wen Xiaofang , Li Bingsi , Zhang Zhihong , Cai Shangli , Fan Jia , Su Jing 
Published: June 2022

10544 Background: The development of ultra-sensitive genomic and epigenomic assays enables the early detection of multiple cancers in parallel. However, large-scale prospective clinical validation data are rare. Here, we report clinical validation data from the THUNDER (The Unintrusive Detection of EaRly-stage cancers, NCT04820868) study, which evaluates the performance of ELSA-seq among 6 cancer types in lung, colorectum, liver, esophagus, pancreas and ovary, which account for 50% of cancer morbidity and 62% of cancer mortality. Methods: This prospective case-control study consists of four stages: marker discovery, model training, validation, and independent validation. A customized panel covering 161,984 CpG sites was established using public data and in-house data. Cancer patients were pre-specified into the training and validation sets, and healthy controls (HC) were age-matched. Two multi-cancer detection blood test (MCDBT-1 and MCDBT-2) models with different cut-offs were established from the retrospectively collected training set and tested in the validation set. An independent validation set was enrolled prospectively, matched by age, and tested with the locked MCDBT-1/2 models. An interception model was then applied based on the model performance and China cancer incidence data to infer potential positive predictive value (PPV) and clinical utility in real-world practice. Results: In total, the training set consisted of 399 cases and 626 HC; the validation set consisted of 301 cases and 123 HC; and the independent validation set consisted of 505 cases and 505 HC. In the training set, the specificities were 98.9% (95% confidence interval [CI], 97.7%‒99.5%) and 99.7% (98.8%‒100.0%) for MCDBT-1/2 models, respectively. In the independent validation set ( n = 856, the rest to be sequenced and reported), MCDBT-1 and MCDBT-2 yielded sensitivity of 76.2% (72.0%‒80.0%) and 70.2% (65.8%‒74.4%) in 6 cancers with specificity of 96.3% (93.9%‒97.9%) and 99.3% (97.8%‒99.8%), respectively. Stage I‒III sensitivity was 68.5% (63.1%‒73.5%) and 60.8% (55.3%‒66.2%) for MCDBT-1/2 models, respectively. The prediction accuracy of top predicted origin was 79.1% (74.5%‒83.2%) and 83.0% (78.4%‒87.0%) for MCDBT-1/2, respectively. The interception model projected an estimated PPV of 3.1% and 12.4% for MCDBT-1/2 models, respectively. MCDBT-1 could reduce 5-year cancer mortality by 20.3%‒24.6% and reduce late-stage incidence by 51.7%‒61.7%, and MCDBT-2 could reduce 5-year cancer mortality by 15.9%‒19.9% and reduce late-stage incidence by 40.9%‒49.2%. Conclusions: cfDNA methylation-based MCDBT-1/2 models can effectively identify multiple cancers simultaneously at early stages with promising sensitivity, specificity, and accuracy of predicted origin. Their performances are to be further validated in a prospective interventional study (NCT05227534).
Comprehensive immune profiling unravels evolution of spatial distribution and immune repertoire in tumor microenvironment from primary to metastatic triple-negative breast cancer.
Authors: Guo Weihua , Egelston Colt A. , Hutchinson Katherine E. , Giltnane Jennifer M. , Ibarra-Lopez Veronica , Liu Bonnie , Yost Susan Elaine , Schmolze Daniel , Lee Peter P. , Yuan Yuan 
Published: June 2022

1079 Background: Immune checkpoint inhibitors (ICI) have improved PFS and OS in metastatic triple-negative breast cancer (mTNBC), but benefit is limited to PD-L1 positive tumors. Metastatic tumors are notorious for deficient immune cell infiltration and immunosuppressive features that may limit responses to ICI in mTNBC. However, the underlying mechanisms for the weak immunogenicity of the metastatic tumor immune microenvironment (TIME) and related poor ICI responses are still not well understood. The current study was designed to investigate the evolution of the TIME between paired primary and metastatic TNBCs. Methods: Spatial distribution of 37 key immune regulators using the NanoString digital spatial profiling (DSP) platform was analyzed. 452 regions of interests (ROIs) from 33 primary tumors (PT) and 29 metastatic tumors (MT) including 28 paired specimens, were selected based on CD45+ immune hotspots, and the protein expression levels of the key immune regulators were quantified within pan-cytokeratin (panCK) and CD45 masked regions, respectively. In parallel, we examined the clonality of tumor infiltrating B cell receptors by reconstructing the immune repertoire from bulk RNA-seq data. Results: Using the DSP platform, we confirmed reduced immune infiltration (e.g., CD3 and CD20) in both panCK and CD45 masked regions of MT, while CD8A and CD11c (padj = 2.8×10-7 and 2.1×10-6) expression was only observed in panCK masked regions of MT compared with PT. A significant shift in myeloid composition between PT and MT as evidenced by increased CD68 signal (padj = 5.8×10-4) in CD45 masked regions of MT was identified. Within MT, PD-L1 signal was substantially higher (padj = 0.030) in CD45 masked regions only, while PD1 counts were lower (padj = 0.035) in panCK masked regions. This suggests the limited responses to ICI for MT may stem from relatively low expression of activated and targetable T cell subsets in MT islands. In support of the lower CD20 counts in MT, immune repertoire analysis revealed B cell receptor (BCR) repertoire diversity (represented by Gini index) was substantially lower in MT than PT (p = 0.041) suggesting that the ability of B cells to recognize a wide variety of tumor antigens in MT is greatly reduced in contrast to PT. Conclusions: Through comprehensive analysis of the TIME spatial organization within paired PT and MT, a significant reduction in dendritic cell/macrophage ratios (CD11c/CD68), reduced tumor localized T cell activation (CD8, PD1, PD-L1), and reduced B cell diversity (BCR clonality) are key features of the reduced immunogenicity of the metastatic TIME in TNBC. Further work to understand key mechanistic features driving the evolution of these differences in TIME between primary and metastatic tumors are ongoing.
Retrospective study to estimate the prevalence of HER2-low breast cancer (BC) and describe its clinicopathological characteristics.
Authors: Viale Giuseppe , Niikura Naoki , Tokunaga Eriko , Aleynikova Olga , Hayashi Naoki , Sohn Joohyuk , O'Brien Ciara , Higgins Gavin , Varghese Della , James Gareth D , Moh Akira , Scotto Nana 
Published: June 2022

1087 Background: Approximately 50% of BCs traditionally categorized as HER2 negative (HER2-neg) express low levels of HER2 (IHC 1+ or IHC 2+/ISH-; Miglietta, NPJ Breast Cancer 2021). HER2-targeted therapies for HER2-low metastatic BC (mBC) are under investigation (eg, T-DXd in the phase 3 DESTINY-Breast04 study; NCT03734029), but HER2 assays currently used to select patients (pts) for approved anti-HER2 therapies are optimized for high HER2 expression and are not validated for HER2-low detection. A recent study found relatively poor agreement (<70% interrater agreement) in evaluation of IHC scores of 0 and 1+ using current HER2 assays (Fernandez, JAMA Oncol 2022). Our objectives were to assess the prevalence of HER2-low among HER2-neg based on rescored HER2 IHC slides after training on low-end expression scoring and to describe pt characteristics of HER2-low vs HER2 IHC 0 mBC. Preliminary results are reported for 233 of 1000 planned pts. Methods: This multicenter, retrospective study (NCT04807595) included pts with confirmed HER2-neg unresectable/mBC diagnosed between 2015 and 2017. Local laboratories, blinded to historical HER2 scores, rescored HER2 IHC-stained slides. HER2 was assessed using Ventana 4B5 and other assays. BCs were categorized as HER2-low or HER2 IHC 0. The prevalence of HER2-low BC among pts originally scored as HER2-neg was measured. Demographics (eg, age, country, race) and clinicopathological characteristics were examined via medical charts/electronic health records. Concordance between historical HER2 scores and rescores was assessed. Results: HER2 rescores were obtained for 233 pts (mean age, 54 y). HER2-low prevalence was 63.2% overall and numerically greater in hormone receptor (HR)–positive vs HR-negative subgroups (66.1% vs 54.8%; Table). No notable differences in prevalence were seen among different HER2 assays or in demographic/baseline disease characteristics between the HER2-low and HER2 IHC 0 groups. Concordance rate between historical and rescored slides for HER2-status classification was 82.3%. The presentation will include an expanded data set (≈400 pts) with additional results. Conclusions: Data on HER2-low prevalence in BC is limited. Preliminary data from this study of mBC samples suggest a somewhat higher prevalence estimate (≈63%) than a previous study of primary BC samples (≈50%). Concordance was 82%; ongoing analyses with updated data will clarify the concordance between rescored and historical HER2 slides. These data can support development of best practices for identifying pts with HER2-low expression who may benefit from HER2-targeted therapies. Clinical trial information: NCT04807595. [Table: see text]
Eribulin mesylate versus eribulin plus anlotinib in patients with advanced or metastatic breast cancer: Results of a phase II study.
Authors: Liu Liping , Hu Zhe-Yu , Xie Ning , Yang Xiaohong , Xiao Huawu , Li Jing , Tian Can , Wu Hui , Lu Jun , Gao Jianxiang , Hu Xuming , Cao Min , Shui Zhengrong , Liu Bingliang , Ouyang Quchang 
Published: June 2022

1094 Background: Eribulin mesylate is a structurally simplified, synthetic, macrocyclic ketone analogue of Halichondrin B. We investigated the efficacy and safety of eribulin monotherapy versus eribulin plus the oral anti-angiogenesis inhibitor anlotinib in patients with advanced or metastatic breast cancer. Methods: This Phase II study included adult Chinese patients with locally advanced or metastatic breast cancer previously treated with at least two chemotherapy regimens, including both anthracycline- and taxane-based therapy (NCT05206656). Patients were randomized (1:1) to receive eribulin (1.4 mg/m2, intravenously, on days 1−8), alone or in combination with anlotinib (12 mg orally once daily), in 21-day cycles. The primary endpoint was investigator-assessed disease control rate (DCR), per RECIST version 1.1. Key secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and safety. Results: Between February 12, 2020, and July 22, 2021, 56 patients were randomized to eribulin (n=32) or eribulin plus anlotinib (n=24) (Table). Sites of metastasis were: bone (60.7%), lung (52.7%), liver (53.6%), lymph nodes (73.2%) and soft tissue (7.1%). Among all patients, the DCR was 66.7% versus 100% (treatment difference, 33.3%; P=0.007), the ORR was 37.0% versus 38.9%, and the median PFS was 3.7 months versus 9.7 months (adjusted hazard ratio, 0.20; 95% CI, 0.04 to 0.91; P=0.04) for patients receiving eribulin versus eribulin plus anlotinib, respectively. Among 36 (64.3%) patients with triple-negative breast cancer, the DCR was 55.6% versus 72.2% (treatment difference, 16.7%; P=0.300) and the median PFS was 3.6 months versus 9.7 months (log rank P=0.030) with eribulin alone versus eribulin plus anlotinib, respectively. The most frequent grade 3-4 adverse events in the eribulin and eribulin plus anlotinib groups were decreased neutrophil count (25.0% [n=8] vs. 29.2% [n=7]) elevated transaminase (6.3% [n=2] vs. 0.0%) and decreased thrombocyte count (3.1% [n=1] vs. 0.0%), respectively. Conclusions: Eribulin plus anlotinib was associated with a significantly better DCR, ORR and PFS than eribulin monotherapy in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Clinical trial information: NCT05206656. [Table: see text]
Quality and content of online cancer information: An analysis of NCI-designated cancer center YouTube videos.
Authors: Kim Luke , Trejo Evelin , Idossa Dame , Duma Narjust , Velazquez Manana Ana I. 
Published: June 2022

11041 Background: The internet and social media have become a common source of medical information. Previous analyses have found that YouTube videos disseminate biased cancer related information of low to moderate quality. We analyzed online information disseminated by NCI-designated Cancer Centers (CC) through their YouTube pages. Methods: We searched CC websites and online search engines to identify CC-specific YouTube pages. Our sample included each CC’s top 20 most-viewed videos uploaded during 2019, which were < 5 minutes long, and available in English or Spanish. We examined video content themes and speaker demographics. For patient education videos, we evaluated content understandability and quality of information using validated measures [i.e., Patient Education Materials Assessment Tool (PEMAT) and DISCERN]. Data was summarized using descriptive statistics. Results: A total of 31 of 64 clinical NCI-designated CC had dedicated YouTube pages. Only 6 (19%) CC had videos in languages other than English. A total of 402 videos were examined for content themes and demographic characteristics. 43% focused on patient education (n = 175), 36% research (n = 139), 24% survivorship (n = 95), and 13% clinical trials (n = 52). 32% (n = 119) of speakers were doctors and 18% (n = 65) patients. Perceived speakers’ ethnicity was 57% White (n = 229), followed by Asian (15%, n = 60), Black or African American (8%, n = 32), and Latinx (4%, n = 16). Perceived gender of speakers was 49% women (n = 197) and 51% men (n = 203). Most videos were understandable (91%, n = 159), but only 21% (n = 36) provided high quality information. Videos discussing treatments lacked discussion of risks, alternate options, and effects on quality of life. Conclusions: Most patient education videos uploaded to NCI-designated CC YouTube pages have low to moderate quality information and limited ethnic diversity of speakers. With ongoing trends of increasing misinformation spreading through social media, CC have an opportunity to create and disseminate high-quality, reliable, and comprehensive educational videos that meet the informational needs of patients with cancer and their caregivers.[Table: see text]
Female representation in oncology leadership in Africa: Analysis of trends in the African organization for cancer research and training in cancer (AORTIC).
Authors: Mutebi Miriam Claire , Aryeetey Naa Adorkor , Carson Laura M. , Alemu Haimanot Kasahun , Vanderpuye Verna D. , Hammad Nazik 
Published: June 2022

11052 Background: Board membership in oncology organizations and invitation to speak at major oncology conferences is an established indicator of gender disparities in oncology leadership. Recent studies note an upward trend in female board membership and female speakers at oncology conferences in European and American contexts. However, little is known about trends of female representation in board membership and at oncology conferences in Africa. AORTIC is the premier African cancer organization and hosts a biennial conference, during which its council members are elected for a two-year term. The conference hosts over 1000 participants and is highly regarded internationally. As the largest gathering of African oncologists, the conference presents a unique opportunity for insight into workforce disparities and trends. This study presents an analysis of female council membership and speaker participation at the 2015, 2017, 2019 and 2021 AORTIC conferences. Methods: AORTIC conference programmes and AORTIC elections for council membership in 2015, 2017, 2019 and 2021 were analyzed for gender representation. Speakers were divided into categories including keynote speakers, facilitators, session speakers, panelists, and oral abstract presenters. For each AORTIC session, data was collected on speaker name, gender, and affiliated country. Participants who presented multiple times were counted multiple times, as their role often varied between sessions. Personal data and country affiliation was determined through online biographies of speakers and/or visual confirmation of professional photographs. A simple descriptive analysis of the data and trends is presented here. Results: Since 2015, the proportion of female speakers and council members at AORTIC has increased. In 2015, females accounted for 44% of speakers, in contrast to 55% in 2021. In 2021, females made up over 50% of all speaker categories except keynote. The proportion of female council members also increased, from 42% in 2015 to 69% in 2021. Trends in geographic representation of speakers were also analyzed for gender, revealing an increase in female speakers residing in Africa. (Table) Conclusions: The proportion of female speakers and council members at Africa’s largest cancer conference has increased significantly since 2015. Female speaker participation was higher than in North America and Europe in 2017 and surpassed 50 % in 2021. In addition, female council membership in AORTIC has surpassed 50%, up to 69% in 2021. These trends suggest a rise in female leadership in cancer research and training on the continent, indicating that strengthening local platforms in LMIC may be associated with improved gender assimilation. [Table: see text]
Gender and early career faculty disparities in hematology and medical oncology board review lectures series.
Authors: Al-Kraimeen Leen Mohammad , Syaj Sebawe , Akhdar Marah , Abushukair Hassan Mohammed , Mohty Razan , Al Hadidi Samer 
Published: June 2022

11060 Background: Studies show that women and early career faculty members have less access to career development opportunities and leadership positions. These disparities slow the process of change and may affect leadership roles, promotions, and career advancements in academic medicine. Here, we provide the first analysis of speakers’ gender and early faculty disparities in hematology and medical oncology board review series. Methods: We performed a cross-sectional analysis of speakers at all major hematology and/or oncology board review series meetings, which were held in the United States between January 2017 and December 2021. Six major board review series were involved: Baylor/M.D. Anderson Cancer Center, the Brigham and Dana-Farber, George Washington School of Medicine and Health Sciences, Memorial Sloan Kettering Cancer Center, Seattle Cancer Care Alliance, and the American Society of Hematology. Details of the lectures were acquired via accessing brochures available on the institutions’ official websites. Data on board certification and maintenance of certificate (MOC) were obtained from the American Board of Internal Medicine (ABIM) website. We extracted the number of publications from the PubMed website (MEDLINE). Results: Our analysis included 1224 board review lectures presented by 386 speakers. Of which, 315 (81.6%) were American Board of Internal Medicine (ABIM) certified, and MOC was active in 56.1% of speakers. Females accounted for 37.7% of all speakers, with a representation of less than 50% in 5 out of 6 board review series. The least proportion of female participation was among lectures discussing malignant hematology topics (24.8%), followed by solid tumors (38.9%), and benign hematology topics (44.1%). Faculty members with more than 15 years of experience since initial certification presented more than half of the lectures. The median time from initial hematology or medical oncology certification to lecture presentation was 12.5 years and 14 years, respectively, which varied significantly among different series (p < 0.001). Speakers’ median number of publications was 84. We also investigated how frequently the same speaker gave lectures. Thirteen male speakers conducted more than or equal to 10 lectures across all board review series, compared to only two female speakers who did the same. An upward trend of improvement in females participation was found at all board review conference meetings across the years. Conclusions: Our data suggest that women and early career faculty members are underrepresented in hematology and oncology board review series. Therefore, efforts should be made to ensure equal participation of them in such important activities needed to advance academic careers.
GALLANT: A phase 2 study using metronomic gemcitabine, doxorubicin, nivolumab, and docetaxel as second/third-line therapy for advanced sarcoma (NCT04535713).
Authors: Adnan Noufil , Sekhon Simranjit , Chawla Sant P. , Kim Ted T. , Chua-Alcala Victoria S. , Fernando Mitchel , Ahari Amir , Feske William , Quon Doris V. , Gordon Erlinda Maria 
Published: June 2022

11518 Background: In our experience, combinatorial therapy with lower doses of doxorubicin, gemcitabine, and docetaxel has been effective with a manageable toxicity profile in patients with advanced soft tissue sarcomas. Hypothesis: The addition of nivolumab will have synergistic effects and improve treatment outcomes. Methods: Primary objective: To assess progression-free survival; Secondary objectives: (1) To evaluate best overall response during treatment period confirmed in a 6-week follow-up, (2) PFS rate at 6 and 9 months, (3) Overall survival rate at 6, 12 months, and (4) Incidence of treatment-related adverse events (TRAEs). Inclusion criteria: Previously treated male and female subjects, > 18 years of age, pathologically confirmed diagnosis of locally advanced, unresectable, or metastatic sarcoma, measurable disease by RECIST v1.1, and acceptable hematologic and organ functions. Exclusion Criteria: History of autoimmune disorder. Treatment schedule: Metronomic doses of gemcitabine (600 mg/m2 max:1000 mg), doxorubicin (18 mg/m2; max: 32 mg), docetaxel (25 mg/m2; max:42 mg) on Day 1 and Day 8, and nivolumab (240 mg) on Day 1 only. Repeat treatment cycles may be given every three weeks if toxicity grade is <1. Results: This is an Interim Report on the modified Intent-to-treat population (n = 43). This population completed at least one treatment cycle and had a follow-up CT or MRI scan at week 6. The most common histological subtypes in this group include leiomyosarcoma (n = 15), pleomorphic sarcoma (n = 4), synovial sarcoma (n = 4), liposarcoma (n = 3), osteosarcoma (n = 3) and other (n = 10). Best Overall Response = 2 CR (surgical CR), 6 PR, 30 SD, 5 PD. The disease control rate (CR+PR+SD) was 88.4%. Median PFS was > 4.6 (range: 1-27) months; 4 month PFS rate 60%. Median OS 6.2 months, with 4-month OS 74%. Historically, the median PFS on preceding lines of therapy was 2 (range: 1-14) months. There were no unexpected side effects noted in this study. The most common grade 3/4 TRAEs include Fatigue (n = 13), Nausea (n = 9), Neutropenia (n = 8), thrombocytopenia (n = 6), Anemia (n = 6). Conclusions: The GALLANT protocol using metronomic Gemcitabine, Doxorubicin (Adriamycin), Nivolumab, and Docetaxel (Taxotere) (1) is an effective regimen as second/third-line therapy for advanced sarcoma with no unexpected side effects, and (2) may have synergistic activity when this metronomic chemotherapy is combined with an immune checkpoint inhibitor. Clinical trial information: NCT04535713.