tbuckley/cabot-search huggingface dataset:
Utility of the 70-gene MammaPrint assay for prediction of benefit from extended letrozole therapy (ELT) in the NRG Oncology/NSABP B-42 trial.
Authors: Priya Rastogi, Hanna Bandos, Peter C. Lucas, Laura van 't Veer, Jia-Perng Jennifer Wei, Charles E. Geyer, Louis Fehrenbacher, Mark Graham, Stephen K. L. Chia, Adam Brufsky, Janice Maria Walshe, Gamini S. Soori, Shaker R. Dakhil, Soonmyung Paik, Sandra M. Swain, Andrea Menicucci, Shiyu Wang, M. William Audeh, Norman Wolmark, Eleftherios P. Mamounas
Journal: Journal of Clinical Oncology (2021)

502 Background: The 70-gene MammaPrint (MP) assay predicts risk of distant recurrence (DR) in hormone-receptor positive early-stage breast cancer and classifies cancers as Low Risk or High Risk. NSABP B-42 evaluated ELT in patients (pts) who had completed 5 yrs of adjuvant endocrine therapy (tx). The primary objective was to determine the utility of MP to identify pts enrolled in NSABP B-42 who are likely to benefit from ELT. Methods: A total of 1,866 pts from B-42 had available MP results. Primary endpoint is DR. Secondary endpoints are disease-free survival (DFS) and breast cancer-free interval (BCFI). For the primary analysis, pts were classified as High Risk (MP-H) (MP score ≤0.000) or Low Risk (MP-L) (MP score &gt; 0.000). Exploratory analyses were performed for MP-L subcategories: MP Ultralow Risk (MP-UL) (MP score &gt; 0.355) and MP-L but not MP-UL (MP-LNUL) (MP score &gt; 0.000, ≤0.355). Likelihood ratio test based on stratified Cox proportional hazards (PH) model was used for treatment by risk group interaction. Stratified log-rank test was used to compare treatment groups. Hazard ratios and 95% CI were computed based on the stratified Cox PH model. Results: Among 1,866 pts, 706 (38%) were MP-H and 1,160 (62%) were MP-L. Of the MP-L, 252 (22%) were MP-UL. There were no significant differences in the distribution of patient and tumor characteristics between the MP group and the rest of the B-42 cohort, except for HER2 status. ELT effect was more pronounced in the MP cohort than in the overall B-42 population. For DR, there was statistically significant ELT benefit in MP-L (HR = 0.43, 95% CI 0.25-0.74, p = 0.002), but not MP-H (HR = 0.65, 0.34-1.24, p = 0.19) (interaction p = 0.38). For DFS, there was statistically significant ELT benefit in MP-L, but not MP-H (interaction p = 0.015). Similar findings were observed for BCFI (interaction p = 0.006). Within subcategories of MP-L, there was statistically significant ELT benefit in MP-LNUL, but not in MP-UL for all three endpoints, however the power in MP-UL was limited due to low number of pts (Table). Clinical trial information: 00382070. Conclusions: Statistically significant ELT benefit was observed for MP-L, but not MP-H. The treatment by risk group interaction was not statistically significant for DR, but it was for DFS and BCFI. The benefit appears to be stronger in MP-LNUL than in MP-UL. NCT: 00382070. Support: U10CA180868, -180822, U24CA196067; Novartis; Agendia.[Table: see text]
グリコーゲンシンターゼキナーゼ-3βはインシュリン様成長因子-1により刺激した心筋肥大の過程に関与する
Authors: Satomi-Kobayashi S, Kawashima S, Sakoda T, Ueyama T, Hirase T, Kawai M, Toh R, Iwai K, Yokoyama M
Journal: Circulation (2004)
REPORT-PFP: a consensus from the International Patellofemoral Research Network to improve REPORTing of quantitative PatelloFemoral Pain studies
Authors: Christian J Barton, Danilo De Oliveira Silva, Sarah Morton, Natalie J Collins, Michael Skovdal Rathleff, Bill Vicenzino, Marienke van Middelkoop, Kay M Crossley, Michael J Callaghan, James Selfe, Sinead Holden, Simon Lack, Erin M Macri, David M Bazett-Jones, Jennifer E Earl-Boehm, Henrik Riel, Christopher M Powers, Irene S Davis, Dylan Morrissey
Journal: British Journal of Sports Medicine (2021)

Patellofemoral pain is a common and often debilitating musculoskeletal condition. Clinical translation and evidence synthesis of patellofemoral pain research are compromised by heterogenous and often inadequately reported study details. This consensus statement and associated checklist provides standards for REPORTing of quantitative PatelloFemoral Pain (REPORT-PFP) research to enhance clinical translation and evidence synthesis, and support clinician engagement with research and data collection. A three-stage Delphi process was initiated at the 2015 International Patellofemoral Research Network (iPFRN) retreat. An initial e-Delphi activity (n=24) generated topics and items, which were refined at the 2017 iPFRN retreat, and voted on prior to and following the 2019 iPFRN retreat (n=51 current and past retreat participants). Voting criteria included 'strongly recommended' (essential), 'recommended' (encouraged) and uncertain/unsure. An item was included in the checklist if ≥70% respondents voted 'recommended'. Items receiving ≥70% votes for 'strongly recommended' were labelled as such. The final REPORT-PFP checklist includes 31 items (11 strongly recommended, 20 recommended), covering (i) demographics (n=2,4); (ii) baseline symptoms and previous treatments (n=3,7); (iii) outcome measures (2,4); (iv) outcomes measure description (n=1,2); (v) clinical trial methodology (0,3) and (vi) reporting study results (n=3,0). The REPORT-PFP checklist is ready to be used by researchers and clinicians. Strong stakeholder engagement from clinical academics during development means consistent application by the international patellofemoral pain research community is likely. Checklist adherence will improve research accessibility for clinicians and enhance future evidence synthesis.
Increased Hemoglobin A1c Time in Range Reduces Adverse Health Outcomes in Older Adults With Diabetes
Authors: Julia C. Prentice, David C. Mohr, Libin Zhang, Donglin Li, Aaron Legler, Richard E. Nelson, Paul R. Conlin
Journal: Diabetes Care (2021)

OBJECTIVE Short- and long-term glycemic variability are risk factors for diabetes complications. However, there are no validated A1C target ranges or measures of A1C stability in older adults. We evaluated the association of a patient-specific A1C variability measure, A1C time in range (A1C TIR), on major adverse outcomes. RESEARCH DESIGN AND METHODS We conducted a retrospective observational study using administrative data from the Department of Veterans Affairs and Medicare from 2004 to 2016. Patients were ≥65 years old, had diabetes, and had at least four A1C tests during a 3-year baseline period. A1C TIR was the percentage of days during the baseline in which A1C was in an individualized target range (6.0–7.0% up to 8.0–9.0%) on the basis of clinical characteristics and predicted life expectancy. Increasing A1C TIR was divided into categories of 20% increments and linked to mortality and cardiovascular disease (CVD) (i.e., myocardial infarction, stroke). RESULTS The study included 402,043 veterans (mean [SD] age 76.9 [5.7] years, 98.8% male). During an average of 5.5 years of follow-up, A1C TIR had a graded relationship with mortality and CVD. Cox proportional hazards models showed that lower A1C TIR was associated with increased mortality (A1C TIR 0 to &amp;lt;20%: hazard ratio [HR] 1.22 [95% CI 1.20–1.25]) and CVD (A1C TIR 0 to &amp;lt;20%: HR 1.14 [95% CI 1.11–1.19]) compared with A1C TIR 80–100%. Competing risk models and shorter follow-up (e.g., 24 months) showed similar results. CONCLUSIONS In older adults with diabetes, maintaining A1C levels within individualized target ranges is associated with lower risk of mortality and CVD.
Study of mirtazapine for agitated behaviours in dementia (SYMBAD): a randomised, double-blind, placebo-controlled trial
Authors: Sube Banerjee, Juliet High, Susan Stirling, Lee Shepstone, Ann Marie Swart, Tanya Telling, Catherine Henderson, Clive Ballard, Peter Bentham, Alistair Burns, Nicolas Farina, Chris Fox, Paul Francis, Robert Howard, Martin Knapp, Iracema Leroi, Gill Livingston, Ramin Nilforooshan, Shirley Nurock, John O'Brien, Annabel Price, Alan J Thomas, Naji Tabet
Journal: The Lancet (2021)

BackgroundAgitation is common in people with dementia and negatively affects the quality of life of both people with dementia and carers. Non-drug patient-centred care is the first-line treatment, but there is a need for other treatment when this care is not effective. Current evidence is sparse on safer and effective alternatives to antipsychotics. We assessed the efficacy and safety of mirtazapine, an antidepressant prescribed for agitation in dementia.MethodsThis parallel-group, double-blind, placebo-controlled trial—the Study of Mirtazapine for Agitated Behaviours in Dementia trial (SYMBAD)—was done in 26 UK centres. Participants had probable or possible Alzheimer's disease, agitation unresponsive to non-drug treatment, and a Cohen-Mansfield Agitation Inventory (CMAI) score of 45 or more. They were randomly assigned (1:1) to receive either mirtazapine (titrated to 45 mg) or placebo. The primary outcome was reduction in CMAI score at 12 weeks. This trial is registered with ClinicalTrials.gov, NCT03031184, and ISRCTN17411897.FindingsBetween Jan 26, 2017, and March 6, 2020, 204 participants were recruited and randomised. Mean CMAI scores at 12 weeks were not significantly different between participants receiving mirtazapine and participants receiving placebo (adjusted mean difference –1·74, 95% CI –7·17 to 3·69; p=0·53). The number of controls with adverse events (65 [64%] of 102 controls) was similar to that in the mirtazapine group (67 [66%] of 102 participants receiving mirtazapine). However, there were more deaths in the mirtazapine group (n=7) by week 16 than in the control group (n=1), with post-hoc analysis suggesting this difference was of marginal statistical significance (p=0·065).InterpretationThis trial found no benefit of mirtazapine compared with placebo, and we observed a potentially higher mortality with use of mirtazapine. The data from this study do not support using mirtazapine as a treatment for agitation in dementia.FundingUK National Institute for Health Research Health Technology Assessment Programme.
An FDA-pooled analysis of frontline combination treatment benefits by risk groups in metastatic renal cell carcinoma (mRCC).
Authors: Daniel Lee, Haley Gittleman, Chana Weinstock, Daniel L. Suzman, Erik Bloomquist, Sundeep Agrawal, Michael Holman Brave, Jamie Renee Brewer, Harpreet Singh, Shenghui Tang, Richard Pazdur, Julia A. Beaver, Amna Ibrahim, Laleh Amiri-Kordestani
Journal: Journal of Clinical Oncology (2021)

4559 Background: The International Metastatic RCC Database Consortium (IMDC) risk model was developed for prognosis of patients with mRCC treated with vascular endothelial growth factor (VEGF)-targeted monotherapy in the first-line setting. Efficacy in trials of anti-VEGF therapy has been generally consistent across risk groups, including for overall survival (OS). For trials of immunotherapy combinations, the small numbers of OS events for the favorable risk group in each trial limited reliable conclusions; however, there was a suggestion of possible differential effects on OS between favorable risk and other risk groups. Methods: We pooled individual patient data (n=3447) from four phase III randomized trials of combinations of immunotherapy + immunotherapy (n=1) or immunotherapy + anti-VEGF therapy (n=3) submitted to the US Food and Drug Administration in support of marketing applications. All trials calculated IMDC risk group for each patient and used a control arm of sunitinib. We combined intermediate and poor prognostic groups (“intermediate/poor”) and compared their OS to that of the favorable risk group using Kaplan-Meier and Cox Proportional Hazards methods. Results: In this pooled analysis, treatment with combination immune checkpoint therapy did not demonstrate an improvement in OS compared to sunitinib in the favorable risk group (HR 0.953; 95% CI: 0.72, 1.27). An improvement in OS was observed in the intermediate/poor risk group (HR 0.696; 95% CI: 0.62, 0.78). Conclusions: Our analysis of OS in patients treated with immunotherapy combinations compared to sunitinib suggests possible differential benefit in the favorable risk compared to the intermediate/poor risk group. These results are not conclusive and considered exploratory due to the relative immaturity of OS in the favorable risk group. Follow-up for survival continues in each study to allow for more definitive results.[Table: see text]
Physical activity guidelines for older people: knowledge gaps and future directions
Authors: Mikel Izquierdo, Gustavo Duque, John E Morley
Journal: The Lancet Healthy Longevity (2021)

Physical function (ie, aerobic capacity, gait speed, and muscle strength) has been proposed as a biomarker of healthy ageing, as it is predictive of adverse health events, disability, and mortality. The role of physical exercise as a therapeutic strategy for prevention of both disease and the associated decline in functional capacity has been emphasised repeatedly. Supervised exercise interventions in hospitalised older people (aged ≥75 years) have been proved to be safe and effective in preventing or attenuating functional and cognitive decline. Unfortunately, few studies have explored the potential role of tailored physical activity guidelines to maximise exercise-related effect on function. Also, exercise has not been fully integrated into primary or geriatric medical practice and is almost absent from the core training of most medical doctors and other health-care providers. Physical trainers should be included in health-care systems to help manage physical exercise programmes for older patients. Taking into consideration current evidence about the benefits of exercise for frail older adults, it is unethical not to prescribe physical exercise for such individuals. To promote healthy and dignified ageing, it is therefore essential to help health-care systems to more efficiently implement evidence-based exercise programmes for frail older adults in all community and care settings.
Can Coronary Artery Calcification on MDCT Predict the Angiographic Coronary Artery Stenosis
Authors: Choi Y.S, Youn H.J, Chung W.S, Jung S.E, Choi Y.W, Lee D.H, Park C.S, Ihm S.H, Oh Y.S, Seung K.B, Kim J.H, Choi K.B
Journal: Circulation (2007)
PD-L1 expression and TOP3A mutation as prognostic factors for adjuvant chemotherapy in triple negative breast cancer.
Authors: Xue Wang, Peng Yuan, Feng Du, Lina Cui, Fangchao Zheng, Jian Yue, Bei Zhang, Jiayu Wang, Ying Fan, Fei Ma, Binghe Xu
Journal: Journal of Clinical Oncology (2021)

541 Background: Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is markedly heterogeneous and lacks specific targets. The aim of this study is to explore potential predictors and therapeutic targets based on clinical and genetic characteristics. Methods: 138 patients with triple-negative breast cancer after surgical treatment were 1:1 randomly assigned to the paclitaxel combined with carboplatin (TCb) group or the epirubicin combined with cyclophosphamide sequential paclitaxel (EC-T) adjuvant chemotherapy group. PD-L1 was retrospectively analyzed by surgically resected specimens, and 733 cancer-related genes were detected by NGS. Pathway enrichment analysis was performed using DAVID for functional enrichment genetic alterations. Cox regression models and Kaplan-Meier were used to evaluate disease-free survival (DFS). Results: In this study, there was no significant difference in DFS between the TCb and EC-T groups. 31 (22.5%) of 138 TNBC patients were positive for PD-L1 expression, including 15 (10.9%) patients positive for PD-L1 in tumor cells (TCs) and 29 (21.0%) patients positive for PD-L1 in tumor-infiltrating immune cells (TICs). Patients with positive PD-L1 expression, either in TCs or TICs, achieved better DFS [HR=0.13 (95% CI: 0.02-0.93), p=0.016], the difference was also shown in the EC-T group [HR=0 (95% CI: 0- inf), p=0.037], but not in the TCb group [HR=0 (95% CI: 0.04-2.1), p=0.189]. In addition, we identified 7 patients with mutations in DNA topoisomerase IIIα(TOP3A), a homologous recombination (HR)-related gene, and patients with mutations in this gene had worse DFS than those without mutations [HR=4]. However, there was no statistically significant association between BRCA mutation and response to either therapeutic regimens. Conclusions: In this TNBC patient population, immunohistochemistry (IHC) and NGS analyses identified potential prognostic markers. PD-L1 positive and TOP3A mutation were significantly associated with early triple-negative breast cancer prognosis.
Corticosteroid use and its impact on the efficacy of immunotherapy in multiple tumor types.
Authors: Blessie Elizabeth Nelson, Benjamin Greiner, Angelina Hong, Shelby Tipton, Marissa Lee, Andre Dixon, Rohit Venkatesan
Journal: Journal of Clinical Oncology (2021)

e14583 Background: Studies have suggested that concurrent corticosteroid use may decrease the efficacy of immunotherapy for cancer treatment, however, the data remains limited. The purpose of this study is to expand upon the previous literature to analyze the outcomes of patients with the following cancer sites: renal cell, lung, melanoma, urothelial, head and neck, hepatocellular, or breast cancer who received immunotherapy and steroids concurrently. Our primary objective was to analyze the overall survival (OS) and objective response rate (ORR) of patients receiving immunotherapy with corticosteroids compared to immunotherapy alone. Methods: A retrospective cohort study was conducted of patients receiving immunotherapy plus corticosteroids compared to immunotherapy alone using University of Texas Medical Branch patients. Patients receiving nivolumab, pembrolizumab, atezolizumab, ipilimumab, durvalumab, or avelumab between January 1, 2012-August 2020 with one of the following cancers were included in the analysis: Renal cell carcinoma, lung carcinoma, melanoma, urothelial carcinoma, head and neck carcinoma, hepatocellular carcinoma, and breast cancer carcinoma. The resulting sample was then separated into two arms. The experimental sample received any of the following steroids either as part of their therapeutic regimen or for symptom management and within 30 days of immunotherapy initiation or at any time during the immunotherapy regimen: dexamethasone, prednisone, methylprednisolone, or hydrocortisone. The control did not receive steroids within 30 days of initiation or during the course of their immunotherapy regimen. Weibull regression models were then constructed to compute hazard ratios for OS at 6 months, 12 months, and 3 years. ORR - complete and partial response, stable disease, and disease progression - between the two arms was assessed using a chi-squared test. Results: Two hundred and sixty patients met inclusion criteria. Of this, 164 received corticosteroids. Our sample was primarily male (70.38%), white (66.54%), and had 0-1 comorbidities (83.08%), lung cancer (45%), and metastases (81.92%). There was no significant difference between the two arms regarding sex, age, number of comorbidities, ECOG score, cancer type, or race. There was no statistically significant difference in OS between the experimental and control arm at 6 months (HR: 1.01; 95%CI 0.63-1.62), 12 months (1.02; 95% CI 0.69-1.51), or 3 years (1.06; 95% CI 0.79-1.42). There was no significant difference in ORR at 6 months between the two arms (2 = 6.3, p=0.178). Conclusions: There was no statistically significant difference in OS or PFS between the two study arms. This study suggests that corticosteroid use does not affect immunotherapy efficacy as previous literature suggests. Larger studies are needed to assess the impact of corticosteroids on immunotherapy efficacy in patients with cancer.
A cross-sectional study on the effectiveness of antiemetic regimens for chemotherapy-induced nausea and vomiting: A single center retrospect study of 1,000 patients.
Authors: Luo Cong, Mingge Shang, Lei Chen, Xu Qi, Li Jingjing, Qing Wei, Jieer Ying
Journal: Journal of Clinical Oncology (2021)

e24055 Background: Chemotherapy-induced nausea and vomiting (CINV) is a common symptom in patients who undergoing chemotherapy, it is very important to control CINV to maintain dose intensity and patients' quality of life. To analyse the current situation of CINV for the tumor patients who undergoing chemotherapy, we used a cross-sectional survey to assess CINV status in those patients, and whether the drugs used by doctors in each department met the guidelines, and compared the efficacy of different antiemetic regimens on acute and delayed CINV overall post-chemotherapy periods. Methods: 1,000 patients were randomly selected from 5,468 patients with chemotherapy discharged from different departments of Zhejiang cancer hospital in China between April 1 and April 30, 2019, and there were 87 responses totally. Medical records were collected on patient’s department (internal medicine, surgery, radiotherapy, interventional) , chemotherapy regimens, anti-vomiting program, etc. Patients' feedbacks were recorded by CTCAE4.03 standard using MASCC antiemetic tool (Mat). Participants reported the frequency, severity, and impact on daily life of CINV from the day of chemotherapy administration up to 5 days thereafter and nausea and vomiting, as well as pharmacologic and chemotherapy used. Results: A total of 66 antineoplastic drugs were investigated, of which 52 were given intravenously and 14 orally.There were 9, 7, 50 drugs with high, moderate and low emetic risk respectively.The most prescribed prophylactic regimens for the management of CINV were aprepitant, 5-HT3R, H1-RA and dexamethasone and metoclopramide. The overall incidence of CINV were 44.34%, 24.57% and 39.66% patients reported nausea or vomiting in the acute and delayed phases. 19.89% patients had both acute and delayed CINV. The consistency rate of antiemetic with guideline was 63.19% in internal medicine department, 61.41% in surgery department and 52.91% in radiotherapy department, which showed a significant gap between the actual use of drugs and the recommended guidelines(P = 0.001). In 875 patients, 518 patients received guideline recommended antiemetic regimen, the CINV rates of complete response (CR), defined as no vomiting with no rescue medication, were 61.58%. While the CR rates in other 357 patients were 47.06%(P &lt; 0.001). Nausea was more frequent across the overall observation period(43.77% VS 18.86%). However, vomiting was more sever and had a greater impact on life than nausea. Conclusions: Overall, adherence to the guideline recommendations in different departments were poor with varying degrees. Future studies should set hard outcomes, such as the absence of any symptoms, as a primary end point.The standardized management of CINV in patients needs to be further strengthened and doctors need to use drugs more regularly to reduce the occurrence of CINV in patients.