tbuckley/cabot-search huggingface dataset:
P85.03 PD-L1 Expression and Efficacy of Immunotherapy in Japanese Patients with NSCLC Harboring MET Exon 14 Skipping Mutation.
Authors: Y. Kato, Y. Watanabe, Y. Yamane, H. Mizutani, F. Kurimoto, G. Yamamoto, K. Akagi, H. Sakai
Journal: Journal of Thoracic Oncology (2021)
The Incidence, Risk Factors, and Outcomes With 5-Fluorouracil–Associated Coronary Vasospasm
Authors: Amna Zafar, Zsofia D. Drobni, Ramya Mosarla, Raza M. Alvi, Matthew Lei, Uvette Y. Lou, Vineet K. Raghu, Sean P. Murphy, Maeve Jones-O’Connor, Sarah Hartmann, Hannah K. Gilman, Colin D. Weekes, John R. Clark, Jeffrey Clark, Lawrence Blaszkowsky, Erica Tavares, Tomas G. Neilan
Journal: JACC CardioOncology (2021)

Coronary vasospasm is a recognized side effect of 5-FU (fluorouracil). There are limited and conflicting data on the incidence, risk factors and prognostic effect of 5-FU associated vasospasm.To assess the incidence, risk factors and prognostic implications of 5-FU coronary vasospasm among patients receiving 5-FU regimens at a single tertiary care center.We conducted a retrospective analysis of all patients who received 5-FU at a single academic center from January 2009 to July 2019. Vasospasm was defined as the occurrence of a typical chest pain syndrome in the presence of 5-FU. The presence of associated electrocardiogram (ECG) changes and/or elevated biomarkers was used to further confirm the diagnosis. Patients with vasospasm were compared to patients treated with 5-FU without vasospasm in a 1:2 ratio. Data regarding demographics, medical history, and follow-up were collected by manual chart review.From approximately 4019 individual patients who received 5-FU from 2009 to 2019 at a single center, 87 (2.16%) developed vasospasm. Patients who developed vasospasm were younger (58±13 vs. 64±13 years, P = 0.001), and were less likely to have any cardiovascular risk factors (70.1% vs. 84.5%, P = 0.007). Patients with vasospasm and patients without vasospasm were otherwise similar in terms of types of cancer, stage of cancer, sex, and race. There was no significant difference in progression-free survival, overall mortality or cancer specific mortality between patients who developed vasospasm versus those who did not.In a large, single-center report of 5-FU associated vasospasm, patients who developed vasospasm were younger, had lower rates of traditional cardiovascular risk factors and had no significant difference in progression-free or overall survival compared to those who did not develop vasospasm.
Rare and Complex Urology: Clinical Overview of ERN eUROGEN
Authors: Loes Oomen, Erik Leijte, Darren E. Shilhan, Michelle Battye, Wout F.J. Feitz, David Waltregny, Frank Van der Aa, Anne-Françoise Spinoit, Wolfgang H. Rösch, Eberhard Schmiedeke, Margit Fisch, Stefanie Märzheuser, Jan-Hendrik Gosemann, Jochen Hubertus, Yazan Rawashdeh, Jorgen Thorup, Yves Heloury, Ernesto Leva, Mariangela Mancini, Pietro Bagolan, Emilio Sacco, Gilvydas Verkauskas, Wout Feitz, Cornelius Sloots, Piotr Czauderna, Maria Mauricio, Gundela Holmdahl, Kate Abrahamsson, Kay Thomas, Linda Cardozo, Christopher Chapple, Vijay Sangar, Tamsin Greenwell, Nick Watkin, Anna Bujons Tur, Jose Lozano Ortega, Maria Begoña Pérez-Valderrama, Jose Gutierrez Baños, Luis Garcia Aparicio, Manuel Lopez, Javier Romero Otero, Pedro Lopez Pereira, Felipe Herranz Amo, Josef Oswald, Valts Abols, Ana Frobe, Maria Judit Molnar, Martine Goergen, Miriam Dalmas, Luca Lovrecic
Journal: European Urology (2021)

In 2017, the European Commission launched 24 European Reference Networks (ERNs). ERN eUROGEN is the network for urorectogenital diseases and complex conditions, and started with 29 full member healthcare providers (HCPs) in 11 countries. It then covered 19 different disease areas distributed over three workstreams (WSs).To provide an overview and identify challenges in data collection at European level of the ERN eUROGEN patient population treated by HCPs in the network.A retrospective cohort study was conducted of the 29 HCPs who were full members between 2013 and 2019.Data were extracted from the original HCP applications and the ERN continuous monitoring system. Patient volumes, new patient numbers, and procedures were compared between different WSs, countries, and HCPs. Discrepancies between monitoring and application data were identified.Between 2013 and 2019, 122 040 patients required long-term care within the 29 HCPs. The volume of patients treated and procedures undertaken per year increased over time. Large discrepancies were found between patient numbers contained in the application forms and those reported in the continuous monitoring system (0-1357% deviation).Patient numbers and procedures increased across ERN eUROGEN HCPs. Reliable data extraction appeared challenging, illustrated by the patient volume discrepancies between application forms and the continuous monitoring data. Improved disease definitions, re-evaluation of affiliated HCPs, and valid data extraction are needed for future improvements.We analysed the patient population with rare urorectogenital diseases or complex conditions within the ERN eUROGEN network between 2013 and 2019. Clinical activity was found to increase, but differences in patient numbers were evident between healthcare providers. In order to acquire valid patient numbers, both improved definitions of diagnostic codes and greater insight into the data-gathering process are required.
P01.02 Trastuzumab Deruxtecan Plus Pembrolizumab in Advanced/Metastatic Breast or Non-Small Cell Lung Cancer: A Phase 1b Study
Authors: H. Borghaei, B. Besse, A. Bardia, J. Mazieres, S. Popat, B. Augustine, A. D'Amelio, D. Barrios, H. Rugo
Journal: Journal of Thoracic Oncology (2021)
MA04.06 Clinical Characteristics and Outcomes in Advanced KRAS Mutant NSCLC – A Multi-Centre Collaboration in Asia (ATORG-005)
Authors: J. Lee, A. Tan, S. Zhou, S. Liu, D. Kim, K. Masuda, U. Batra, H. Hayashi, Y. Goto, S.H. Tan, Y. Wu, D. Tan, M. Ahn
Journal: Journal of Thoracic Oncology (2021)
Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer
Authors: Colt Egelston, Weihua Guo, Susan Yost, Jin Sun Lee, David Rose, Christian Avalos, Jian Ye, Paul Frankel, Daniel Schmolze, James Waisman, Peter Lee, Yuan Yuan
Journal: Journal for ImmunoTherapy of Cancer (2021)

Single-agent pembrolizumab treatment of hormone receptor-positive metastatic breast cancer (MBC) has demonstrated modest clinical responses. Little is known about potential biomarkers or mechanisms of response to immune checkpoint inhibitors (ICIs) in patients with HR+ MBC. The present study presents novel immune correlates of clinical responses to combined treatment with CDK4/6i and ICI. A combined analysis of two independent phase I clinical trials treating patients with HR+ MBC was performed. Patients treated with the combination of the CDK4/6i palbociclib+the ICI pembrolizumab+the aromatase inhibitor (AI) letrozole (palbo+pembro+AI) were compared with patients treated with pembrolizumab+AI (pembro+AI). Peripheral blood mononuclear cells collected at pretreatment, 3 weeks (cycle 2 day 1) and 9 weeks (cycle 4 day 1) were characterized by high-parameter flow cytometry to assess baseline immune subset composition and longitudinal changes in response to therapy. In the peripheral blood, higher pretreatment frequencies of effector memory CD45RA+ CD8+ T cells and effector memory CD4+ T cells were observed in responders to palbo+pembro+AI. In contrast, this was not observed in pembro+AI-treated patients. We further characterized T-cell subsets of effector-like killer cell lectin-like receptor subfamily G member 1 (KLRG1+) ICOS+ CD4+ T cells and KLRG1+ CD45RA+ CD8+ T cells as baseline biomarkers of response. In comparison, pretreatment levels of tumor-infiltrating lymphocyte, tumor mutation burden, tumor programmed death-ligand 1 expression, and overall immune composition did not associate with clinical responses. Over the course of treatment, significant shifts in myeloid cell composition and phenotype were observed in palbo+pembro+AI-treated patients, but not in those treated with pembro+AI. We identified increased fractions of type 1 conventional dendritic cells (cDC1s) within circulating dendritic cells and decreased classical monocytes (cMO) within circulating monocytes only in patients treated with palbociclib. We also demonstrated that in palbociclib-treated patients, cDC1 and cMO displayed increased CD83 and human leukocyte antigen-DR isotype (HLA-DR) expression, respectively, suggesting increased maturation and antigen presentation capacity. Pre-existing circulating effector CD8+ and CD4+ T cells and dynamic modulation of circulating myeloid cell composition denote response to combined pembrolizumab and palbociclib therapy for patients with HR+ MBC. NCT02778685 and NCI02648477.
OA03.03 Datopotamab Deruxtecan (Dato-DXd; DS-1062), a TROP2 ADC, in Patients With Advanced NSCLC: Updated Results of TROPION-PanTumor01 Phase 1 Study
Authors: A. Spira, A. Lisberg, J. Sands, J. Greenberg, P. Phillips, F. Guevara, N. Tajima, Y. Kawasaki, J. Gu, F. Kobayashi, N. Yamamoto, M. Johnson, F. Meric-Bernstam, K. Yoh, E. Garon, R. Heist, T. Shimizu
Journal: Journal of Thoracic Oncology (2021)
P41.01 Disparities in Lung Cancer Screening by Baseline Comorbidities: An Analysis of the Behavioral Risk Factor Surveillance System Survey 2018
Authors: Q. Wang, C. Jiang, H. Xie, Y. Li, Y. Fujiwara, Y. Zhang, T. Kurbanova, N. Theodoropoulos
Journal: Journal of Thoracic Oncology (2021)
Time-Varying mHAP-III Is the Most Accurate Predictor of Survival in Patients with Hepatocellular Carcinoma Undergoing Transarterial Chemoembolization
Authors: Claudia Campani, Alessandro Vitale, Gabriele Dragoni, Umberto Arena, Giacomo Laffi, Umberto Cillo, Edoardo G. Giannini, Francesco Tovoli, Gian Ludovico Rapaccini, Maria Di Marco, Eugenio Caturelli, Marco Zoli, Rodolfo Sacco, Giuseppe Cabibbo, Andrea Mega, Maria Guarino, Antonio Gasbarrini, Gianluca Svegliati-Baroni, Francesco Giuseppe Foschi, Elisabetta Biasini, Alberto Masotto, Gerardo Nardone, Giovanni Raimondo, Francesco Azzaroli, Gianpaolo Vidili, Maurizia Rossana Brunetto, Fabio Farinati, Franco Trevisani, Fabio Marra
Journal: Liver Cancer (2021)

The prognosis of patients undergoing transarterial chemoembolization (TACE) is extremely variable, and a confounding factor is that TACE is often repeated several times. We retrospectively evaluated the accuracy of different prognostic scores and staging systems in estimating overall survival (OS) in patients with hepatocellular carcinoma (HCC).An analysis considering prognostic models as time-varying variables was performed, calculating OS from the time of TACE to the time of the subsequent treatment. Total follow-up time for each patient was therefore split into several observation times accounting for each TACE procedure. Values of the likelihood ratio test (LRT) and Akaike information criterion (AIC) were used to compare different systems. Univariable and multivariable analyses were conducted to identify additional factors predictive of OS. We analyzed 1,610 TACE performed in 1,058 patients recorded in the Italian Liver Cancer database from 2008 through 2016.The median OS of the enrolled patients was 41 months. According to LRT χ2 and AIC values based on the time-varying analysis, mHAP-III achieved the best values (41.72 and 4,625.49, respectively, p < 0.0001), indicating the highest predictive performance compared with all other scores (HAP, mHAP-II, ALBI, and pALBI) and staging systems (MELD, ITALICA, CLIP, MESH, MESIAH, JIS, HKLC, and BCLC). In the multivariable Cox proportional hazards model, mHAP-III maintained an independent effect on OS (hazard ratio 1.31, 95% CI: 1.10-1.55, p < 0.0001). Time-varying age, alcoholic etiology, radiologic response to TACE, and performing ablation or surgery after TACE were additional significant variables resulting from the multivariable model.An innovative time-varying analysis revealed that mHAP-III was the most accurate model in predicting OS in patients with HCC undergoing TACE. Other clinical pre- and post-TACE variables were also found to be relevant for this prediction.
P76.26 Survival Outcomes in Patients Receiving Second Line Osimertinib Post First Line First Generation TKI Alone or in Combination with Chemotherapy
Authors: S. Khaddar, A. Rajpurohit, A. Kapoor, V. Noronha, A. Joshi, V. Patil, N. Menon, S. More, S. Goud, K. Prabhash
Journal: Journal of Thoracic Oncology (2021)
Long-term behavioral and cell-type-specific molecular effects of early life stress are mediated by H3K79me2 dynamics in medium spiny neurons
Authors: Hope Kronman, Angélica Torres-Berrío, Simone Sidoli, Orna Issler, Arthur Godino, Aarthi Ramakrishnan, Philipp Mews, Casey K. Lardner, Eric M. Parise, Deena M. Walker, Yentl Y. van der Zee, Caleb J. Browne, Brittany F. Boyce, Rachael Neve, Benjamin A. Garcia, Li Shen, Catherine J. Peña, Eric J. Nestler
Journal: Nature Neuroscience (2021)
Polypill Plus Aspirin Effective for Cardiovascular Disease Prevention
Authors: Anita Slomski
Journal: JAMA (2021)

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The Open Vein Hypothesis and Postthrombotic Syndrome
Authors: Aaron W. Aday, Joshua A. Beckman
Journal: Circulation (2021)

Postthrombotic syndrome (PTS) is the most common long-term complication of acute lower extremity deep vein thrombosis (DVT), and prospective data suggest that 20% to 50% of individuals develop some manifestation of PTS after DVT. 1 Symptoms of PTS include limb pain, heaviness, fatigue, edema, itching, and venous claudication.After acute DVT, up to 10% of individuals will develop venous ulcers, the most severe manifestation of PTS. 2 It is not surprising that PTS is associated with a poor quality of life and dramatically increased health care costs. 1 The pathophysiology of PTS is incompletely understood.Acute DVT obstructs venous outflow while also causing vein dilation and disrupting normal venous valve function. 3These changes may persist beyond the acute phase and lead to chronic venous insufficiency, inflammation, and venous hypertension, all of which are key to the development of PTS.Patient factors associated with increased risk of PTS include obesity, advanced age, and recurrent ipsilateral DVT. 4,5The extent of DVT, in particular, in the iliofemoral venous segment, is also associated with a heightened risk of PTS. 4,5lthough awareness, detection, and treatment of DVT have dramatically improved in recent decades, effective prevention and treatment of PTS is limited.Graduated compression stockings are often used after acute DVT to reduce soft tissue edema and venous hypertension; however, in a randomized controlled trial, they did not reduce the incidence of PTS compared with placebo stockings. 6A variety of venotonic drugs, such as micronized flavonoid fractions 7 and horse-chestnut seed extract, 8 have shown modest improvements in some PTS symptoms.These drugs have been tested only in small studies with unknown long-term benefits and unclear efficacy in preventing PTS.Given the limits of conservative management for PTS, there is great interest in invasive therapies to prevent the development of PTS after acute DVT.Persistence of thrombus, in particular, in proximal venous segments, worsens venous hypertension and PTS symptoms. 9Furthermore, the presence and extent of residual vein obstruction directly associates with the development of PTS. 10 The open vein hypothesis posits that removing this obstruction through pharmacomechanical means may prevent PTS.This hypothesis has been tested in 2 large randomized controlled trials to date.In the CaVenT study (Catheter-Directed Thrombolysis for Deep Venous Thrombolysis), 209 subjects with acute DVT located from the mid thigh to the common iliac veins were randomly assigned to standard care, including therapeutic anticoagulation and graduated compression stockings, or standard care plus catheterdirected thrombolysis (CDT). 11At 24 months, subjects undergoing CDT were less likely to have developed PTS, and iliofemoral patency rates were higher with CDT. The Open Vein Hypothesis and Postthrombotic SyndromeNot Dead Yet
pH-responsive polymersome-mediated delivery of doxorubicin into tumor sites enhances the therapeutic efficacy and reduces cardiotoxic effects
Authors: Lindomar J.C. Albuquerque, Vladimir Sincari, Alessandro Jäger, Jan Kucka, Jana Humajova, Jan Pankrac, Petr Paral, Tomas Heizer, Olga Janouškova, Irina Davidovich, Yeshayahu Talmon, Pavla Pouckova, Petr Štěpánek, Ludek Sefc, Martin Hruby, Fernando C. Giacomelli, Eliézer Jäger
Journal: Journal of Controlled Release (2021)
Therapeutic strategies in RET gene rearranged non-small cell lung cancer
Authors: Leylah M. Drusbosky, Estelamari Rodriguez, Richa Dawar, Chukwuemeka V. Ikpeazu
Journal: Journal of Hematology & Oncology (2021)

Abstract The recent approvals by the Food and Drug Administration several tumor-agnostic drugs have resulted in a paradigm shift in cancer treatment from an organ/histology-specific strategy to biomarker-guided approaches. RET gene fusions are oncogenic drivers in multiple tumor types and are known to occur in 1–2% of non-squamous NSCLC patients. RET gene fusions give rise to chimeric, cytosolic proteins with constitutively active RET kinase domain. Standard therapeutic regimens provide limited benefit for NSCLC patients with RET fusion-positive tumors, and the outcomes with immunotherapy in the these patients are generally poor. Selpercatinib (LOXO-292) and pralsetinib (BLU-667) are potent and selective inhibitors that target RET alterations, including fusions and mutations, irrespective of the tissue of origin. Recently, the results from the LIBRETTO-001 and ARROW clinical trials demonstrated significant clinical benefits with selpercatinib and pralsetinib respectively, in NSCLC patients with RET gene fusions, with tolerable toxicity profiles. These studies also demonstrated that these RET-TKIs crossed the blood brain barrier with significant activity. As has been observed with other TKIs, the emergence of acquired resistance may limit long-term efficacy of these agents. Therefore, understanding the mechanisms of resistance is necessary for the development of strategies to overcome them.
Assessment of Extractability and Accuracy of Electronic Health Record Data for Joint Implant Registries
Authors: Nicholas J. Giori, John Radin, Alison Callahan, Jason A. Fries, Eni Halilaj, Christopher Ré, Scott L. Delp, Nigam H. Shah, Alex H. S. Harris
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Implant registries provide valuable information on the performance of implants in a real-world setting, yet they have traditionally been expensive to establish and maintain. Electronic health records (EHRs) are widely used and may include the information needed to generate clinically meaningful reports similar to a formal implant registry. <h3>Objectives</h3> To quantify the extractability and accuracy of registry-relevant data from the EHR and to assess the ability of these data to track trends in implant use and the durability of implants (hereafter referred to as implant survivorship), using data stored since 2000 in the EHR of the largest integrated health care system in the United States. <h3>Design, Setting, and Participants</h3> Retrospective cohort study of a large EHR of veterans who had 45 351 total hip arthroplasty procedures in Veterans Health Administration hospitals from 2000 to 2017. Data analysis was performed from January 1, 2000, to December 31, 2017. <h3>Exposures</h3> Total hip arthroplasty. <h3>Main Outcomes and Measures</h3> Number of total hip arthroplasty procedures extracted from the EHR, trends in implant use, and relative survivorship of implants. <h3>Results</h3> A total of 45 351 total hip arthroplasty procedures were identified from 2000 to 2017 with 192 805 implant parts. Data completeness improved over the time. After 2014, 85% of prosthetic heads, 91% of shells, 81% of stems, and 85% of liners used in the Veterans Health Administration health care system were identified by part number. Revision burden and trends in metal vs ceramic prosthetic femoral head use were found to reflect data from the American Joint Replacement Registry. Recalled implants were obvious negative outliers in implant survivorship using Kaplan-Meier curves. <h3>Conclusions and Relevance</h3> Although loss to follow-up remains a challenge that requires additional attention to improve the quantitative nature of calculated implant survivorship, we conclude that data collected during routine clinical care and stored in the EHR of a large health system over 18 years were sufficient to provide clinically meaningful data on trends in implant use and to identify poor implants that were subsequently recalled. This automated approach was low cost and had no reporting burden. This low-cost, low-overhead method to assess implant use and performance within a large health care setting may be useful to internal quality assurance programs and, on a larger scale, to postmarket surveillance of implant performance.