tbuckley/cabot-search huggingface dataset:
Association of Memorial Sloan Kettering-Frailty Index with the postoperative intensive and specialized advanced care units admission among older adults with cancer.
Authors: Timothy J Donoghue, Amy L. Tin, Armin Shahrokni
Journal: Journal of Clinical Oncology (2021)

e18606 Background: Understanding factors associated with poor surgical outcomes of older adults with cancer is necessary in identifying high risk patients and finding ways to mitigate poor outcomes following surgery. In this study, we evaluated whether frailty is associated with intensive postoperative healthcare utilization for this vulnerable population. Methods: This was a single hospital, retrospective cohort study, using the Memorial Sloan Kettering Frailty Index (MSK-FI) to define frailty, with higher MSK-FI corresponding to increased frailty. Multivariable logistic regression with random intercept models were used to assess the association between frailty and 30-day postoperative Intensive Care Unit (ICU) admission, and Specialized Advanced Care Unit (SACU) admission, separately. Covariates included surgical department, age, sex, surgical stress score, preoperative albumin level, and whether patients took a Beers criteria medication prior to surgery. Results: We identified 4417 patients over the age of 65 undergoing elective surgery between January 2015 and December 2018 at our institution and had a length of stay of at least one day. A quarter of patients had an MSK-FI score of 3 or greater. Among our patients, 3.8% (95% CI 3.2%, 4.4%), and 5.4% (95% CI 4.8%, 6.1%) were admitted to the ICU, and the SACU, respectively. We found evidence of an association between greater frailty and increased risk of ICU admission (OR per one-point increase in MSK-FI 1.44; 95% CI 1.31, 1.59; p-value &lt; 0.001), and SACU admission (OR per one point increase in MSK-FI 1.46; 95% CI 1.33, 1.60; p-value &lt; 0.001). For example, for a patient with an MSK-FI score of 2, the predicted risk of ICU admission is 2.2% and SACU admission is 1.1%, compared to 4.5% and 2.2%, respectively, for a patient with an MSK-FI score of 4, when all continuous covariates are set to the mean and the categorical covariates are set to the mode. Conclusions: Frailty based on the MSK-FI is associated with intensive postoperative care utilization in this population of older adults with cancer. Future studies should assess the impact of this information on surgery decision making for this vulnerable population.
HGG-16. DISSECTING THE EFFECT OF ATM DELETION ON RADIOSENSITIVITY IN DIFFUSE MIDLINE GLIOMAS WITH H3K27M MUTATION
Authors: Maria Guerra Garcia, Katherine Deland, Lixia Luo, Yan Ma, Nerissa Williams, Connor Stewart, David Kirsch, Zachary Reitman
Journal: Neuro-Oncology (2021)

Abstract Diffuse midline gliomas (DMGs) are responsible for a large proportion of childhood brain tumor deaths. Currently, radiation therapy is thought to be one of the most effective treatment options, but more than 90% of children still die within 2 years of diagnosis. DMGs are defined by somatic histone 3 K27M (H3K27M) mutations that have been shown to promote the G0/G1 to S cell cycle transition. The majority of DMGs also contain loss-of-function mutations in TP53. Prior research demonstrated that orthotopic xenograft and primary mouse models of non-H3K27M-mutated gliomas with inactivation of p53 are preferentially radiosensitized by inactivation of Ataxia Telangiectasia Mutated (ATM), a kinase that mediates DNA repair in response to DNA damage caused by radiation. The high frequency of mutations that deregulate p53 in DMGs raises the possibility that H3K27M-mutant DMGs may also be radiosensitized by ATM inhibition, representing a unique therapeutic opportunity. Here, we hypothesize that H3K27M-mutant DMGs that have loss of function of p53 will be radiosensitized by loss of ATM. To test this hypothesis, we used the RCAS-TVA viral gene delivery system to generate genetically-faithful primary mouse models of H3K27M-mutant DMG with p53 deletion, and we used Cre recombinase to delete Atm in the tumor cells of these mice and generated littermate controls that retained Atm. Mice were imaged weekly via luciferase-based bioluminescence to track tumor development and irradiated with three daily fractions of 10 Gy after tumor detection. We subsequently quantified the survival of mice without neurological decline following irradiation. In separate cohorts, we collected primary tumors after irradiation to verify H3K27M expression and to assess cell cycle arrest and mechanisms of cell death. These studies will elucidate mechanisms by which ATM inactivation can radiosensitize H3K27M-mutant DMGs with nonfunctioning p53, which will guide the design of clinical trials testing ATM inhibitors in DMG patients.
Circulation of tumor cells to destroy correlations in immune system of colorectal cancer patients.
Authors: Anastasia O. Sitkovskaya, Elena Yu. Zlatnik, Oleg I. Kit, Inna A. Novikova, Elena S. Bondarenko, Yuriy A. Gevorkyan, Natalya V. Soldatkina, Vladimir E. Kolesnikov, Maksim K. Aleksandrovich, Andrey V. Dashkov, Sergey I. Poluektov, Dmitry O. Kaymakchi, Ellada A. Mirzoyan, Vladislav K. Pavlov, Maksim A. Vereshchak, Oksana V. Katelnitskaya, Dmitriy A. Savchenko, Roman E. Tolmakh
Journal: Journal of Clinical Oncology (2021)

e15508 Background: The most important stages of metastatic cascade are extravasation and invasion of malignant cells and their surviving in blood. The vast majority of circulating tumor cells (CTC) is destroyed by immune cells. The role of immune system which is able to play not only antitumor but also prooncogenic role is manifested both on local and systemic levels. We studied correlations between lymphocyte subsets` content in blood and in tumor of colorectal cancer patients (II, III, IV stages) with and without CTC. Methods: 60 colorectal cancer patients with II (n = 20), III (n = 20) and IV (n = 20) stages underwent surgery without previous chemotherapy. CTC were measured in blood by CellSearchSystem™ (JanssenDiagnostics, LLC), cell-mediated immunity was assessed in blood by flow cytometry (BD Canto II) and in tissue after surgery by immunohistochemistry; some markers of proliferation and epithelial-mesenchimal transition (EMT) in tumor cells (Ki-67, E- and N-cadherins) were also studied. Criteria of CTC-positive and CTC-negative samples were &gt; 3 and ≤3 respectively. Correlative analysis was performed between the data of the patients with and without CTC in each stage, r was counted. Results: In CTC-positive patients with all the stages the number of strong and moderate correlations between system immunologic factors involving CD8+ appeared to be fewer than in CTC-negative ones (7 vs 19). On the contrary, the number of correlations with T regs in CTC-positive was increased: 5 vs 3 in CTC-negative patients. In patients with CTC &gt; 3 fewer correlations were noted between factors of local and systemic immunity than in CTC-negative ones (9 vs 4 in II stage) and total disruption of all the correlations between system immunologic factors and proliferating tumor cells in III and IV stages was established. Some pathologic correlations appeared in CTC-positive patients like moderate direct one between activated T-lymphocytes` amount and Ki-67+ tumor cells. The number of correlations between intratumoral lymphocytes and tumor cells expressing proliferation and EMT markers in CTC-positive patients was decreased in comparison with CTC-negative ones (4 vs 10 in II stage, 1 vs 9 in III, 2 vs 9 in IV stage). Conclusions: The presence of CTC in colorectal cancer patients rather than tumor stage is associated with imbalance of their systemic and local immunologic factors. This provides some evidence that disruption of interactions in the immune system is at least partly due to CTC.
Pralsetinib for RET fusion-positive non-small-cell lung cancer (ARROW): a multi-cohort, open-label, phase 1/2 study
Authors: Justin F Gainor, Giuseppe Curigliano, Dong-Wan Kim, Dae Ho Lee, Benjamin Besse, Christina S Baik, Robert C Doebele, Philippe A Cassier, Gilberto Lopes, Daniel S W Tan, Elena Garralda, Luis G Paz-Ares, Byoung Chul Cho, Shirish M Gadgeel, Michael Thomas, Stephen V Liu, Matthew H Taylor, Aaron S Mansfield, Viola W Zhu, Corinne Clifford, Hui Zhang, Michael Palmer, Jennifer Green, Christopher D Turner, Vivek Subbiah
Journal: The Lancet Oncology (2021)
Novel molecular classification of colorectal cancer and correlation with long-term survival.
Authors: Fayaz Hussain Mangi, Tanweer Ahmed Shaikh, Daniel Soria, Jawaid Naeem Qureshi, Ikram Uddin Ujjan, Binafsha Manzoor Syed
Journal: Journal of Clinical Oncology (2021)

e15514 Background: Colorectal cancer (CRC) is a heterogeneous disease, however there is limited information available regarding molecular classification and correlation with long term clinical outcome. Methods: Over the period of 11 years (2008 to 2018) totals 435 patients of colorectal cancer were reported and their tumour blocks and complete set of clinical information was available for 201 patients. Immunohistochemistry was done for ER, PR, HER 2-neu, Ki-67, Bcl-2, E-Cadherin, P53, CEA, EGFR, and VEGF. PDL1, CDX-2 and CK 20. The biological pattern characterized by partitioned clustering method as described using R software. Survival analysis was done by using Kaplan Meier method. Results: There were 201 patients including 54.7% male and females were 45.3 %. Median survival was 28 months. Cluster analysis showed four novel clusters (Table), with major difference based on Ki67, CDX2 and p53. These classes showed difference in median survival, where common class 1 showed higher survival while common cluster 4 showed poor survival. Conclusions: There are at least four distinct molecular classes of colorectal cancer which can be potentially utilized in clinical practice. Pattern of Novel molecular classification of colorectal cancer and correlation with long term survival.[Table: see text]
Real-world trends in biosimilar prescribing among oncology providers, 2019-2021.
Authors: Kelly A. McGlynn, Jacqueline McGarry, Kashyap B. Patel, Natasha Clinton
Journal: Journal of Clinical Oncology (2021)

e18701 Background: The number of approved biosimilars in the United States has increased exponentially in recent years. Within the oncology market, there are currently 14 approved biosimilars, with 11 launched since the start of 2019. The emergence of new oncology biosimilars provides a tool for success in value-based care, and has the potential to lower costs to patients and providers and expand access to care. Methods: Analysis of biosimilar prescribing behavior was performed using 2020 prescription data (Wolters Kluwer, n = 130,836), sales data (IQVIA), and dosage data for patients taking bevacizumab, trastuzumab, rituximab, or an FDA-approved biosimilar for these products (FDA Purple Book), between 2019-2021 (ION Solutions, n = 69,884). Drugs not directly interchangeable with the bevacizumab, trastuzumab or rituximab reference products according to NCCN guidelines were excluded. Results: Biosimilar products are currently available for bevacizumab (2 biosimilars), rituximab (3 biosimilars), and trastuzumab (5 biosimilars). We found that in 2020, 8.2% of new prescriptions for any of these three reference products were for a biosimilar. An analysis of real-world drug administration data revealed that in the 3 months following the 2019 launch of trastuzumab’s first biosimilar (trastuzumab-anns), 7.3% of initiating line 1 patients were prescribed the biosimilar over the reference product. During the same period in 2020, when a total of 5 trastuzumab biosimilars were available, 80.5% of initiating line 1 trastuzumab patients began treatment on a biosimilar, suggesting rapid uptake by providers. However, this differed by product, with the initial uptake for the first rituximab biosimilar (rituximab-pvvr), at only 2.3%. Uptake also occurred within treatment lines, with 11.1% of all patients (bevacizumab: 11.3%, trastuzumab: 14.1%, rituximab: 7.9%) switching from a reference product to a biosimilar during treatment. Uptake was particularly rapid for trastuzumab biosimilars: among patients on trastuzumab at the time of its first biosimilar launch, 18.2% switched to trastuzumab-anns in the first 90 days post-launch. Biosimilars launched at significantly lower prices than their reference products, with cost per prescription at -42.0%, -29.9% and -89.5% relative to the reference product for trastuzumab, rituximab and bevacizumab, respectively. However, biosimilar launches had little impact on reference product pricing, with 2019-2020 year-over-year (YOY) differences in price per prescription close to the YOY averages in previous years (2015-2019) for all three reference products. Conclusions: We conclude that uptake of biosimilars among oncology providers between 2019-2020 was rapid, although the extent of biosimilar prescribing varied among products. Biosimilars offered greatly reduced costs to providers, although reference product prices remained stable despite increased biosimilar competition.
Autologous stem cell transplantation (ASCT) versus whole brain radiation (WBRT) as a consolidation therapy in primary CNS lymphoma (PCNSL): A nationwide analysis.
Authors: Yazan Samhouri, Moaath M Ali, Thejus Thayyil Jayakrishnan, Veli Bakalov, Salman Fazal, Cyrus Khan, Rodney E. Wegner, Seung Tae Lee, John Lister
Journal: Journal of Clinical Oncology (2021)

2062 Background: High dose methotrexate-based regimens remain the most effective treatment against PCNSL but optimal consolidative strategy has yet to be determined. There is lack of high scale clinical trials comparing WBRT versus ASCT as consolidation therapy. Only two phase II randomized clinical trials (PRECIS and IELSG 32) have addressed this question. In this comprehensive national cancer database (NCDB) analysis, we examine the effect of WBRT versus ASCT on survival in PCNSL, we also sought to investigate clinical and socioeconomic predictors of treatment selection Methods: We conducted a retrospective cohort analysis using de-identified data accessed from the NCDB. The NCDB provided records of 16579 patients diagnosed with PCNSL between 2004 and 2016. We excluded patients who tested positive for HIV, and those who started chemotherapy &gt; 120 days or started radiation &gt; 365 days since diagnosis, to account for immortal time bias. Patients were divided into two treatment groups based on consolidation therapy: ASCT and WBRT. Multivariable regression models were used to analyze predictors of treatment selection. To account for variable baseline characteristics, we used propensity score weighting methodology. Survival estimates were calculated using the Kaplan-Meier and Cox proportional hazard regression methods Results: We identified 1620 patients with PCNSL who fulfilled the inclusion criteria. ASCT and WBRT were received by 197 patients and 1423 patients, respectively (Table). On multivariable analysis, increased age decreased the odds of receiving ASCT (OR 0.997, CI: 0.996-0.999, P &lt;.001). Patients live in rural areas (OR 1.174, CI: 1.051-1.312, P=.005), those with higher education (OR 1.089, CI: 1.020-1.163, P=.01), and those who live further from the treating facility (OR 1.001, CI: 1.001-1.001, P&lt;.001) received more ASCT. With a median follow up duration of 27.8 months, adjusted-median OS was 91.4 months and not reached for WBRT and ASCT groups, respectively (log-rank P&lt;.001). Adjusted 3-year OS was 82% and 67% in ASCT and WBRT, respectively (HR: 0.43, CI: 0.29-0.64, P&lt;.001) Conclusions: Consolidation with ASCT had improved OS compared with WBRT. There is a trend toward increased ASCT use and decreased WBRT use over the study period. We found clinical and socioeconomic factors that affected treatment selection.[Table: see text]
AIM2-driven inflammasome activation in heart failure
Authors: Zsófia Onódi, Mihály Ruppert, Dániel Kucsera, Alex Ali Sayour, Viktória E Tóth, Gábor Koncsos, Julianna Novák, Gábor B Brenner, András Makkos, Tamás Baranyai, Zoltán Giricz, Anikó Görbe, Przemyslaw Leszek, Mariann Gyöngyösi, Iván G Horváth, Rainer Schulz, Béla Merkely, Péter Ferdinandy, Tamás Radovits, Zoltán V Varga
Journal: Cardiovascular Research (2021)

Interleukin-1β (IL-1β) is an important pathogenic factor in cardiovascular diseases including chronic heart failure (HF). The CANTOS trial highlighted that inflammasomes as primary sources of IL-1 β are promising new therapeutic targets in cardiovascular diseases. Therefore, we aimed to assess inflammasome activation in failing hearts to identify activation patterns of inflammasome subtypes as sources of IL-1β.
Reply to Andréasson <i>et al.</i>: Multiple Manifestations of Systemic Sclerosis Affect Walk Distance
Authors: Roham T. Zamanian, Ashley Pinckney, Robyn T. Domsic, Thomas Medsger, Lynette Keyes-Elstein, Andrew J. Sweatt, Beverly Welch, Ellen Goldmuntz, Mark R. Nicolls, Lorinda Chung
Journal: American Journal of Respiratory and Critical Care Medicine (2021)
The impact of locally-delivered tacrolimus-releasing microspheres and polyethylene glycol-based islet surface modification on xenogeneic islet survival
Authors: Tiep Tien Nguyen, Cao Dai Phung, Jong Oh Kim, Chul Soon Yong, Jae-Ryong Kim, Simmyung Yook, Jee-Heon Jeong
Journal: Journal of Controlled Release (2021)
Meta analysis of arsenic exposed genes expression profiles to develop a bladder cancer predictor.
Authors: Sonalika Singhal, Nathan A. Ruprecht, Donald Sens, Mary Ann Sens, Sandeep K. Singhal
Journal: Journal of Clinical Oncology (2021)

e16523 Background: IARC classified arsenic (As) as “carcinogenic to humans”, but despite the health consequences, there is no molecular signature available yet to predict when exposure may lead to the disease development. First aim of this study is to investigate the genetic changes due to the exposure to carcinogenic compounds such as As. Secondly, how accurately we can predict the disease association when exposed to toxic compounds. Methods: The entire analysis was performed in-silico fashion and data was collected from the public resources such as NCBI database. Two Asian population datasets exposed As were used to find significantly differently express genes. In addition, four cancer cell lines with exposure of As compounds were used to identify the association with cancer. The human bladder cancer biopsy datasets were used to develop a risk predictive model. As per the requirements, numerous machine learning (ML) approaches such as random forest, hierarchical clustering, were used to find the classification and association between the samples and outcome. Statistical approaches such as T-Test, and ANOVA, applied to find the differentially expressed genes associated with different conditions and logistic regression models applied to develop risk prediction models. Results: We identified a set of 1183 genes which were common between both the populations and were significantly changed in humans exposed to As. A subset of 157 genes associated with As exposure and involved in cancer progression was selected for risk prediction model development. A set of four genes (NKIRAS2, AKTIP, HLA-DQA1 and TBC1D7) shows the highest prediction ability of primary bladder tumor with AUC 0.96 (95% CI: 0.82- 0.99) and reproducibility of 0.75 (0.34-0.93) when applied on different dataset. Conclusions: This study identified a list of genes and bladder cancer predictive models that would be very helpful to forecast the outcomes of As exposed in humans.
Symphony of nanomaterials and immunotherapy based on the cancer–immunity cycle
Authors: Qianqian Li, Zhaoqing Shi, Fan Zhang, Weiwei Zeng, Dunwan Zhu, Lin Mei
Journal: Acta Pharmaceutica Sinica B (2021)

The immune system is involved in the initiation and progression of cancer. Research on cancer and immunity has contributed to the development of several clinically successful immunotherapies. These immunotherapies often act on a single step of the cancer-immunity cycle. In recent years, the discovery of new nanomaterials has dramatically expanded the functions and potential applications of nanomaterials. In addition to acting as drug-delivery platforms, some nanomaterials can induce the immunogenic cell death (ICD) of cancer cells or regulate the profile and strength of the immune response as immunomodulators. Based on their versatility, nanomaterials may serve as an integrated platform for multiple drugs or therapeutic strategies, simultaneously targeting several steps of the cancer-immunity cycle to enhance the outcome of anticancer immune response. To illustrate the critical roles of nanomaterials in cancer immunotherapies based on cancer-immunity cycle, this review will comprehensively describe the crosstalk between the immune system and cancer, and the current applications of nanomaterials, including drug carriers, ICD inducers, and immunomodulators. Moreover, this review will provide a detailed discussion of the knowledge regarding developing combinational cancer immunotherapies based on the cancer-immunity cycle, hoping to maximize the efficacy of these treatments assisted by nanomaterials.
The Women’s Leadership Gap in Diabetes: A Call for Equity and Excellence
Authors: Jessica L. Dunne, Jennifer L. Maizel, Amanda L. Posgai, Mark A. Atkinson, Linda A. DiMeglio
Journal: Diabetes Care (2021)

OBJECTIVE Women are broadly underrepresented in scientific leadership positions and their accomplishments are not provided equal recognition compared with those of men, but the imbalance in the field of diabetes is unknown. Hence, we analyzed multiple aspects of historical and present-day female representation in the diabetes field. RESEARCH DESIGN AND METHODS We quantified gender representation at annual American Diabetes Association (ADA) meetings; editorial board service positions for ADA and the European Association for the Study of Diabetes (EASD) journals; principal investigators for ADA, JDRF, and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases P30 grant funding; and ADA, JDRF, and EASD award recipients. RESULTS There are many women in the field of diabetes: registration for the ADA Scientific Sessions has been 43% female since 2016, and for over five decades, women comprised 83% of ADA Presidents of Health Care and Education. Yet, only 9% of ADA Presidents of Medicine and Science have been women. Women were well represented on editorial boards for journals focused on diabetes education (Diabetes Spectrum, 89% female) and primary care (Clinical Diabetes, 49% female) but not for the more academically targeted Diabetes Care (34% female), Diabetes (21% female), and Diabetologia (30% female). Only one-third of ADA Pathway to Stop Diabetes and JDRF grants have been awarded to women, and females only lead 2 of 18 (11%) of the P30-supported Diabetes Research Centers. Finally, only 2–12% of major ADA, JDRF, and EASD awards were given to women, without significant change over time. CONCLUSIONS Despite increasing recognition of gender imbalance in research and medicine, many disparities in the field of diabetes persist. We call for decreasing barriers for advancement of female investigators and creating environments that promote their retention and equitable recognition for their contributions to the field.