tbuckley/cabot-search huggingface dataset:
Navigating the new normal: Trendsshaping post-COVID-19 cancer care delivery
Authors: L. Richardson
Journal: Clinical Cancer Research (2020)

In just a few short weeks, COVID-19 transformed cancer care around the world  The crisis has dismantled how careis delivered and forced providers to make difficult decisions about what types of care are essential and can besustained with the resources and staff available  This presentation will provide an overview of the emerging trendsthat are shaping cancer care and how providers are adapting to these new challenges to continue to safely providenecessary care to those who need it most
Interactions between Biomedical Micro‐/Nano‐Motors and the Immune Molecules, Immune Cells, and the Immune System: Challenges and Opportunities
Authors: Dongmei Fu, Zhen Wang, Yingfeng Tu, Fei Peng
Journal: Advanced Healthcare Materials (2021)

Abstract Mobile micro‐ and nano‐motors (MNMs) emerge as revolutionary platforms for biomedical applications, including drug delivery, biosensing, non‐invasive surgery, and cancer therapy. While for applications in biomedical fields and practical clinical translation, the interactions of these untethered tiny machines with the immune system is an essential issue to be considered. This review highlights the recent approaches of surpassing immune barriers to prevent foreign motors from triggering immune responses. In addition to trials focusing on the function preservation of MNMs, examples of versatile MNMs working with the immune components (immune molecules, immune cells and the whole system) to achieve cancer immunotherapy, immunoassay, and detoxification are outlined. The immune interference part provides researchers an idea about what is the limit presented by the immune components. The coworking part suggests ways to bypass or even utilize the limit. With interdisciplinary cooperation of nanoengineering, materials science, and immunology field, the rationally designed functional MNMs are expected to provide novel opportunities for the biomedical field.
Temporally distinct myeloid cell responses mediate damage and repair after cerebrovascular injury
Authors: Panagiotis Mastorakos, Nicole Mihelson, Marie Luby, Scott R. Burks, Kory Johnson, Amie W. Hsia, Jaclyn Witko, Joseph A. Frank, Lawrence Latour, Dorian B. McGavern
Journal: Nature Neuroscience (2021)
Prostate-Only Versus Whole-Pelvic Radiation Therapy in High-Risk and Very High-Risk Prostate Cancer (POP-RT): Outcomes From Phase III Randomized Controlled Trial
Authors: Vedang Murthy, Priyamvada Maitre, Sadhana Kannan, Gitanjali Panigrahi, Rahul Krishnatry, Ganesh Bakshi, Gagan Prakash, Mahendra Pal, Santosh Menon, Reena Phurailatpam, Smruti Mokal, Dipika Chaurasiya, Palak Popat, Nilesh Sable, Archi Agarwal, Venkatesh Rangarajan, Amit Joshi, Vanita Noronha, Kumar Prabhash, Umesh Mahantshetty
Journal: Journal of Clinical Oncology (2021)

We report the clinical outcomes of a randomized trial comparing prophylactic whole-pelvic nodal radiotherapy to prostate-only radiotherapy (PORT) in high-risk prostate cancer.This phase III, single center, randomized controlled trial enrolled eligible patients undergoing radical radiotherapy for node-negative prostate adenocarcinoma, with estimated nodal risk ≥ 20%. Randomization was 1:1 to PORT (68 Gy/25# to prostate) or whole-pelvic radiotherapy (WPRT, 68 Gy/25# to prostate, 50 Gy/25# to pelvic nodes, including common iliac) using computerized stratified block randomization, stratified by Gleason score, type of androgen deprivation, prostate-specific antigen at diagnosis, and prior transurethral resection of the prostate. All patients received image-guided, intensity-modulated radiotherapy and minimum 2 years of androgen deprivation therapy. The primary end point was 5-year biochemical failure-free survival (BFFS), and secondary end points were disease-free survival (DFS) and overall survival (OS).From November 2011 to August 2017, a total of 224 patients were randomly assigned (PORT = 114, WPRT = 110). At a median follow-up of 68 months, 36 biochemical failures (PORT = 25, WPRT = 7) and 24 deaths (PORT = 13, WPRT = 11) were recorded. Five-year BFFS was 95.0% (95% CI, 88.4 to 97.9) with WPRT versus 81.2% (95% CI, 71.6 to 87.8) with PORT, with an unadjusted hazard ratio (HR) of 0.23 (95% CI, 0.10 to 0.52; P < .0001). WPRT also showed higher 5-year DFS (89.5% v 77.2%; HR, 0.40; 95% CI, 0.22 to 0.73; P = .002), but 5-year OS did not appear to differ (92.5% v 90.8%; HR, 0.92; 95% CI, 0.41 to 2.05; P = .83). Distant metastasis-free survival was also higher with WPRT (95.9% v 89.2%; HR, 0.35; 95% CI, 0.15 to 0.82; P = .01). Benefit in BFFS and DFS was maintained across prognostic subgroups.Prophylactic pelvic irradiation for high-risk, locally advanced prostate cancer improved BFFS and DFS as compared with PORT, but OS did not appear to differ.
Durable Effects of iGlarLixi Up to 52 Weeks in Type 2 Diabetes: The LixiLan-G Extension Study
Authors: Lawrence Blonde, Julio Rosenstock, Juan Frias, Andreas L. Birkenfeld, Elisabeth Niemoeller, Elisabeth Souhami, Chen Ji, Stefano Del Prato, Vanita R. Aroda
Journal: Diabetes Care (2021)

OBJECTIVE In the LixiLan-G trial, switching to iGlarLixi, a once-daily titratable fixed-ratio combination of insulin glargine 100 units/mL and the glucagon-like peptide 1 receptor agonist (GLP-1 RA) lixisenatide, improved glucose control in type 2 diabetes uncontrolled with GLP-1 RAs over 26 weeks versus continuing prior GLP-1 RA. A prespecified, 26-week, single-arm extension of LixiLan-G aimed to determine the durability of iGlarLixi efficacy and safety over 52 weeks. RESEARCH DESIGN AND METHODS Participants with type 2 diabetes uncontrolled by GLP-1 RAs (glycated hemoglobin [HbA1c] 7–9% [53–75 mmol/mol]) were initially randomized to switch to iGlarLixi or continue prior GLP-1 RA. Those randomized to iGlarLixi who completed the 26-week primary end point period could continue iGlarLixi open-label treatment over a 26-week extension to assess durability of efficacy and safety. RESULTS Glycemic control achieved with iGlarLixi at week 26 (mean HbA1c 6.7% [50 mmol/mol]) was maintained at week 52 (mean HbA1c 6.7% [50 mmol/mol]; mean ± SD change from baseline at week 52: −1.0 ± 0.9% [11 ± 10 mmol/mol]). Proportions of participants reaching HbA1c &amp;lt;7% (53 mmol/mol) with iGlarLixi were similar at week 26 (62%) and 52 (64%), as were those reaching this target without documented symptomatic (&amp;lt;3.0 mmol/L) hypoglycemia (57% and 58%). Safety of iGlarLixi was similar at weeks 26 and 52, with low rates of documented symptomatic hypoglycemia and gastrointestinal events. CONCLUSIONS The efficacy and safety of iGlarLixi at the end of the 26-week randomized treatment period was maintained over the 26-week extension period in the LixiLan-G trial.
Abstract P346: Modeling Novel Biomarkers with Individual Risk Factors and an “Improved” Bayes Approach are Preferred Strategies for Assessing Predictive Utility of Biomarkers
Authors: Vanessa Xanthakis, Michael J Pencina, Lisa M Sullivan
Journal: Circulation (2012)

Given the rapid growth of new prognostic biomarkers, it is critical to assess their incremental utility for risk prediction while considering standard risk factors. This assessment may be influenced by the approach used to model new biomarkers. We hypothesized that the performance of a putative biomarker is best assessed by adding it to a model that includes standard risk factors as individual variables, as compared to adding it to a composite risk score (based on standard risk factors) estimated from the current study or to a composite risk score from a published study. We also compared 3 approaches of adjusting the prior absolute risk of an event using the information from a new biomarker, when data regarding prior risk are limited, hypothesizing that conditioning the biomarker residuals on prior risk (Improved Bayes approach) or adjusting the intercept of a model that includes the prior risk estimate are superior to the Naïve Bayes approach. Incremental performance was evaluated by comparing measures of improvement in discrimination. Using 1000 simulated datasets, similar incremental performance was observed when a putative biomarker was added to a model with the individual risk factors as compared to adding it to a model with a risk score estimated from the current study. Including a biomarker in a model with a published risk score resulted in an overestimation of its contribution ( Table ).These findings were supported by Framingham Heart Study data predicting incident atrial fibrillation using CRP and BNP.The Improved Bayes approach was a better strategy for updating the prior risk estimate as compared to the Naïve Bayes approach, using information from a new biomarker (Table). Our theoretical and empirical results identified that adding a new biomarker into a multivariable prediction model that includes the individual risk factors is the preferred strategy for assessing the incremental yield of a novel biomarker, and using the Naive Bayes approach (when information on the prior absolute risk of an event is scarce) is suboptimal.
Subtyping CKD Patients by Consensus Clustering: The Chronic Renal Insufficiency Cohort (CRIC) Study
Authors: Zihe Zheng, Sushrut S. Waikar, Insa M. Schmidt, J. Richard Landis, Chi-yuan Hsu, Tariq Shafi, Harold I. Feldman, Amanda H. Anderson, Francis P. Wilson, Jing Chen, Hernan Rincon-Choles, Ana C. Ricardo, Georges Saab, Tamara Isakova, Radhakrishna Kallem, Jeffrey C. Fink, Panduranga S. Rao, Dawei Xie, Wei Yang
Journal: Journal of the American Society of Nephrology (2021)

CKD is a heterogeneous condition with multiple underlying causes, risk factors, and outcomes. Subtyping CKD with multidimensional patient data holds the key to precision medicine. Consensus clustering may reveal CKD subgroups with different risk profiles of adverse outcomes.We used unsupervised consensus clustering on 72 baseline characteristics among 2696 participants in the prospective Chronic Renal Insufficiency Cohort (CRIC) study to identify novel CKD subgroups that best represent the data pattern. Calculation of the standardized difference of each parameter used the cutoff of ±0.3 to show subgroup features. CKD subgroup associations were examined with the clinical end points of kidney failure, the composite outcome of cardiovascular diseases, and death.The algorithm revealed three unique CKD subgroups that best represented patients' baseline characteristics. Patients with relatively favorable levels of bone density and cardiac and kidney function markers, with lower prevalence of diabetes and obesity, and who used fewer medications formed cluster 1 (n=1203). Patients with higher prevalence of diabetes and obesity and who used more medications formed cluster 2 (n=1098). Patients with less favorable levels of bone mineral density, poor cardiac and kidney function markers, and inflammation delineated cluster 3 (n=395). These three subgroups, when linked with future clinical end points, were associated with different risks of CKD progression, cardiovascular disease, and death. Furthermore, patient heterogeneity among predefined subgroups with similar baseline kidney function emerged.Consensus clustering synthesized the patterns of baseline clinical and laboratory measures and revealed distinct CKD subgroups, which were associated with markedly different risks of important clinical outcomes. Further examination of patient subgroups and associated biomarkers may provide next steps toward precision medicine.
Copy number alterations in plasma cell-free DNA from metastatic gastroenteropancreatic neuroendocrine neoplasms.
Authors: Gitta Boons, Timon Vandamme, Willem Lybaert, Geert Roeyen, Tim Rondou, Konstantinos Papadimitriou, Katrien Janssens, Wim Demey, Isabel Dero, Guy Van Camp, Marc Peeters, Ken Op de Beeck
Journal: Journal of Clinical Oncology (2021)

372 Background: Recent studies, including our proof-of-concept study, demonstrated the possibility to detect tumor-derived molecular alterations in cell-free DNA (cfDNA) from plasma of patients with a gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN). More in-depth evaluation of the biomarker potential of cfDNA in GEP-NENs is warranted, since highly sensitive and specific blood-based biomarkers are an important unmet need for this tumor type. The aim of our study was to detect tumor-associated copy number alterations (CNAs) in cfDNA from GEP-NEN patients to molecularly characterize the tumor and to estimate tumor fraction, as a measure of tumor burden, and to evaluate changes in these parameters over time. Methods: Metastatic GEP-NEN patients were included within NETwerk, a multi-institutional network of nine hospitals in Belgium. Clinicopathological data were collected to correlate experimental and clinical findings. Plasma samples were collected from all patients and cfDNA was extracted and subjected to shallow whole-genome sequencing (WGS). Detection of CNAs and estimation of tumor fraction, based on the sequencing data, were performed using the R-based tool ichorCNA. Results: In total, 80 samples of 29 metastatic GEP-NEN patients were analyzed using shallow WGS. All patients had a well-differentiated GEP-NEN of Grade 1/2 and primary sites were pancreas (N = 15), small intestine (N = 9), colon (N = 1), caecum (N = 1), ileocaecal valve (N = 1), pylorus (N = 1) and unknown (N = 1). Median number of samples per patient was two, with a median time between first and last sampling of six months. In 25 cfDNA samples from nine patients (31%), CNAs with tumor fractions higher than 3% could be detected. The primary tumor site of all CNA-positive patients was pancreas, corresponding to 60% of included pancreatic NEN (PNEN) patients. Six of the CNA-positive patients were included at initiation of everolimus treatment. The detected CNA patterns were similar to the copy number profiles of PNENs described in literature, e.g. whole-chromosome gains of chromosomes 5, 7, 9, 12, 13, 14, 19 and 20. CNA profiles were relatively stable over time, although in two patients new alterations did arise. Tumor fractions changed over time, which could be linked to changes in tumor burden, tumor progression and treatment response according to RECIST1.1 criteria and will be further examined, including in additional samples that are being collected. Conclusions: Cell-free DNA of metastatic GEP-NEN patients contains CNAs that correspond to CNA profiles seen in tumor tissue samples. CNAs can be used to quantify the tumor fraction in cfDNA over time, which will be linked to tumor progression in our ongoing study, particularly in the promising subgroup of PNEN patients.
Increasing recruitment into covid-19 trials
Authors: Ara Darzi, Andrew Goddard, Katherine Henderson, Ravi Mahajan, Clare Marx, Neil Mortensen, Alison Pittard
Journal: BMJ (2021)

Since March 2020, UK researchers have established over 70 urgent public health studies to investigate potential treatments, vaccines, and diagnostic tests for covid-19.NHS hospitals have had a vital role in delivering these studies at pace and scale, despite working under extreme pressure.The results are now informing practice worldwide.
SPIN reveals genome-wide landscape of nuclear compartmentalization
Authors: Yuchuan Wang, Yang Zhang, Ruochi Zhang, Tom van Schaik, Liguo Zhang, Takayo Sasaki, Daniel Peric-Hupkes, Yu Chen, David M. Gilbert, Bas van Steensel, Andrew S. Belmont, Jian Ma
Journal: Genome biology (2021)

Abstract We report SPIN, an integrative computational method to reveal genome-wide intranuclear chromosome positioning and nuclear compartmentalization relative to multiple nuclear structures, which are pivotal for modulating genome function. As a proof-of-principle, we use SPIN to integrate nuclear compartment mapping (TSA-seq and DamID) and chromatin interaction data (Hi-C) from K562 cells to identify 10 spatial compartmentalization states genome-wide relative to nuclear speckles, lamina, and putative associations with nucleoli. These SPIN states show novel patterns of genome spatial organization and their relation to other 3D genome features and genome function (transcription and replication timing). SPIN provides critical insights into nuclear spatial and functional compartmentalization.
The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC)
Authors: Ravi Salgia, Rebecca Pharaon, Isa Mambetsariev, Arin Nam, Martin Sattler
Journal: Cell Reports Medicine (2021)

KRAS is a frequent oncogenic driver in solid tumors, including non-small cell lung cancer (NSCLC). It was previously thought to be an "undruggable" target due to the lack of deep binding pockets for specific small-molecule inhibitors. A better understanding of the mechanisms that drive KRAS transformation, improved KRAS-targeted drugs, and immunological approaches that aim at yielding immune responses against KRAS neoantigens have sparked a race for approved therapies. Few treatments are available for KRAS mutant NSCLC patients, and several approaches are being tested in clinicals trials to fill this void. Here, we review promising therapeutics tested for KRAS mutant NSCLC.
The impact of immunotherapy education on GI cancers.
Authors: Kinjal Parikh, Katie Lucero, Charlotte Warren, Emily Sherene Van Laar, Patrick Kugel, Haleh Kadkhoda
Journal: Journal of Clinical Oncology (2021)

479 Background: Gastrointestinal (GI) cancers are a heterogeneous group of cancers with varying underlying pathophysiology and distinct treatment paradigms. Immunotherapy (IO) is unique in each of the subtypes and biomarkers utility varies. With the expansion of IO in each cancer subtypes, education remains essential to optimize patient outcomes through integration of the latest evidence-based data at point of care. Through the partnership between Medscape Oncology and the Society for Immunotherapy of Cancer, 2 educational activities were designed to increase the knowledge and competence of oncologists surrounding the role of IO in patients with advanced GI cancers. Methods: The 2 educational activities included a text based online activity with 3 chapters focused on gastroesophageal cancers, colorectal cancers, and hepatocellular carcinoma (HCC) and a 30-minute online, video discussion with 3 faculty and synchronized slides on HCC. Educational effectiveness was assessed with repeated paired pre/post assessment where learners served as their own controls. A chi-square test was used to identify statistical significance in proportion of correct responses. The first activity launched 11/27/2019 and the second activity launched on 5/8/20. Data were collected and reported through 8/25/2020. Results: A total of 8433 learners, including 1543 oncologists, participated from 11/2019 through 8/2020. Participation in education resulted in significant relative improvements among oncologist learners on IO in GI cancers in (n = 641): 110%: role or eligibility of immune checkpoint inhibitors (ICIs) (p &lt; .001) 38%: clinical trial data of ICIs (p &lt; .001) Subsequent education on unresectable HCC demonstrated a significant relative improvement in both knowledge and competence for oncologist learners (n = 902): 19%: regarding clinical trial data in unresectable HCC (p = .073) 19%; competence identifying role of ICIs in unresectable HCC (p &lt; .05) 59%: competence managing irAEs in unresectable HCC (p &lt; .001). Conclusions: These 2 online CME-certified educational activities resulted in statistically significant gains in oncologist knowledge surrounding the use of IO in advanced GI cancers Follow-up education on HCC demonstrated the value and benefit of multi-modal and sequential activities on improving competence among oncologists caring for patients with unresectable HCC There remains a need for continuous education as more oncologists utilize IO in their practice while the understanding and availability of clinical data continues to expand and evolve in the varying GI cancer subtypes. More than 50% of learners continued to demonstrate a need in understanding the clinical trial data or role of IO in metastatic GI cancers with more than 40% of the learners demonstrating continued need on clinical trial data or role of IO in HCC specifically.
A phase II study of perioperative capecitabine plus oxaliplatin for clinical SS/SE N1-3 M0 gastric cancer (OGSG1601).
Authors: Atsushi Yasuda, Jin Matsuyama, Tetsuji Terazawa, Masahiro Goto, Ryohei Kawabata, Shunji Endo, Motohiro Imano, Shoichiro Fujita, Yusuke Akamaru, Hirokazu Taniguchi, Mitsutoshi Tatsumi, Sang-Woong Lee, Hisato Kawakami, Yukinori Kurokawa, Toshio Shimokawa, Daisuke Sakai, Takeshi Kato, Kazumasa Fujitani, Taroh Satoh
Journal: Journal of Clinical Oncology (2021)

203 Background: D2 gastrectomy followed by adjuvant S-1 is one of the standard therapy for the patients (pts) with stage III gastric cancer (GC) in Japan; however, the outcome is not satisfactory. We examined the efficacy of perioperative capecitabine and oxaliplatin (CapeOx) in pts with clinical SS/SE N1-3 M0 GC. Methods: The eligibility criteria included histopathologically confirmed clinical T3(SS)/T4a(SE) N1-3 M0 GC according to the Japanese Classification of GC (JCGC; 3 rd English Edition). Three cycles of neoadjuvant CapeOx (NAC; capecitabine, 2,000 mg/m 2 for 14 days; oxaliplatin, 130 mg/m 2 on day 1, every 3 weeks) were administered, followed by five cycles of adjuvant CapeOx after D2 gastrectomy. The primary endpoint was the pathological response rate (pRR) according to JCGC ( ≥Grade 1b). Results: Thirty-seven pts were enrolled from April 2016 to May 2017, and fully evaluated for efficacy and toxicity. Thirty-three pts (89.2%) completed the planned three cycles of NAC and underwent gastrectomy, with an R0 resection rate of 78.4% (n = 29) and a pRR of 54.1% (n = 20, p = .058; 90% confidence interval [CI], 39.4–68.2) were demonstrated. The relative dose intensity (RDI) of capecitabine and oxaliplatin were 90.5% and 91.9%, respectively. Among 27 pts who initiated AC, 21 (63.6%) completed the treatment, and the RDI of capecitabine and oxaliplatin were 80.9% and 65.1%, respectively. Grade 3–4 toxicities during NAC included neutropenia (8%), thrombocytopenia (8%), and anorexia (8%) and during AC included neutropenia (37%), diarrhea (4%), and anorexia (4%), but no treatment-related death was reported. The overall survival (OS) rate and relapse free survival (RFS) rate at 3 years was 83.8% (95% CI, 72.7-96.5%) and 73.0% (95% CI, 60.0-88.8%), respectively. Subgroup analyses according to residual tumor after surgery (R status) showed a 3-year OS and RFS rate of 86.2% (95% CI, 74.5-99.7%) and 75.7% (95% CI, 63.0-90.8%) for R0. Conclusions: Perioperative CapeOx showed good feasibility and favorable prognosis with sufficient pathological response, although statistical significance at .058 did not reach the commonly accepted cutoff of .05. The data obtained using this novel approach warrant further investigations. Clinical trial information: 000021641.
Photodynamic Therapy and Medicare Expenditures
Authors: Rachel K. Lim, Martin A. Weinstock
Journal: JAMA Dermatology (2021)

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