tbuckley/cabot-search huggingface dataset:
Targeting G1-S phase cell-cycle alterations with CDK4/6 inhibitor-based genomically matched personalized therapy approach.
Authors: Jacob J. Adashek, Shumei Kato, Ryosuke Okamura, Noor Khalid, Suzanna Lee, Van Thomas Nguyen, Jason K. Sicklick, Razelle Kurzrock
Journal: Journal of Clinical Oncology (2020)

3623 Background: Although CDK4/6 inhibitors are established as a standard treatment option for hormone receptor-positive, HER2-negative metastatic breast cancer patients, its benefit in other solid tumors is unclear. Moreover, no clear biomarker exists that predicts the response to CDK4/6 inhibitors. Herein, we investigated the factors associated with clinical outcomes from CDK4/6 inhibitor-based therapy, used alone or in combination with other therapies targeting genomic co-alterations, among diverse cancer patients with potentially sensitizing alterations in G1-S phase cell-cycle alterations (defined as CDK4/6 amplifications, CCND1/2/3 amplifications or CDKN2A/ B alterations). Methods: We interrogated molecular profiles of 2,457 patients with diverse solid tumors for G1-S phase cell-cycle alterations and co-altered genes using clinical-grade next generation sequencing (182-465 genes). Results: G1-S phase cell-cycle alterations occurred in 20.6% (507/2,457) of patients with 99% of those with cell cycle alterations (N = 501/507) harboring at least one characterized co-alteration (median, 4; range, 0-24). Significant improvement in median PFS was observed when CDK4/6 inhibitor-based therapies matched a larger proportion of tumor alterations, often by being given together with other drugs that were matched to genomic co-alterations, hence achieving a high Matching Score (high Matching Score [≥50%] vs. low Matching Score [ &lt; 50%]: all cohorts including breast cancer [N = 58]: PFS: 6.2 vs. 3.2 months, P = 0.001; non-breast cancer cohort [N = 40]: PFS 6.2 vs. 2.0 months, P &lt; 0.001 [multivariate]). (Matching Score roughly equivalent to number of alterations targeted divided by total number of characterized alterations). In contrast, targeting CDK4/6 alone in patients harboring cell-cycle pathway alterations along with other co-alterations, without targeting the genomic co-alterations, did not improve PFS even in patients who received matched CDK4/6 inhibitors as part of a combination regimen. Representative cases that were successfully treated with a matched combination strategy will also be presented. Conclusions: Most patients with G1-S phase cell-cycle alterations harbored co-genomic alterations. Our current study suggests that targeting co-alterations along with cell cycle molecular alterations may be necessary to achieve better clinical outcome. Further clinical investigation with larger numbers of patients are required.
Unraveling metabolism heterogeneity in colorectal cancer and its implications in pan-cancer cohort.
Authors: Qijing Wu, Qiong Huang, Mengting Sun, Bishan Liang, Xingbin Hu, Dongqiang Zeng, Chunlin Wang, Xiaoxiang Rong, Zhenzhen Wu, Shaowei Li, Ling Wang, Zhiqi Yao, Yajing Liu, Fei Sun, Wangjun Liao, Min Shi
Journal: Journal of Clinical Oncology (2020)

e16016 Background: Colorectal cancer (CRC) molecular subtype has been emphasized and links to biological and clinical behavior. However, comprehensive metabolism of CRC has not been characterized. Subtype-specific metabolic differences and immunometabolism phenotypes remain unclear. Therefore, this study performed metabolism clustering and explore its relation with immune phenotypes as well as prognosis predictive value. Methods: Transcriptome of TCGA CRC cohort was utilized to generate 113 KEGG metabolism pathway scores via GSVA algorithm. Consensus clustering were used to identify metabolism subtypes. Bioinformatic algorithms were applied in classification and survival analysis. Results: Energy metabolism-oriented subtype, featured by nitrogen metabolism and immune-inflamed, correlated with good prognosis (log rank P &lt; 0.001). Pyrimidine synthesis activated most in nucleotide metabolism-oriented subtype, which was immune-deserted. Stroma metabolism-oriented subtype, characterized by glycosaminoglycan (GAG) biosynthesis and immune-suppressive phenotype, was an independent risk factor for overall survival (multivariate Cox: HR = 2.30 95% CI 1.23-4.28, P = 0.009). Clinical cohort from Nanfang Hospital composed of RNA-Seq data from 26 pre- and post-treatment samples in mCRC patients receiving mFOLFOX+Bevacizumab were classified. 22 were identified and 8 of them were pre-treatment, 4 of which were nucleotide subtype being 100% PR. The rest were stroma subtype with SD or PD, indicating drug resistance in stroma subtype. Interestingly, GAG chondroitin sulfate featured in stroma subtype outperformed other metabolisms in predicting negative prognosis (HR = 1.42 95% CI 1.18-1.71, P &lt; 0.001). We then tested GAG metabolism in TCGA pan-cancer cohort. Chondroitin sulfate and heparan sulfate metabolism subtype correlated inversely with bladder (HR = 1.23 95% CI 1.06-1.43, P = 0.007) and breast cancer (HR = 1.27 95% CI 1.10-1.47, P = 0.001) patients’ survival, respectively. Keratan sulfate subtype predicted worse survival in glioblastoma, pancreatic and liver cancer (HR = 1.31 95% CI 1.09-1.57, P = 0.003; HR = 1.31 95% CI 1.06-1.61, P = 0.01; HR = 1.23 95% CI 1.04-1.46, P = 0.02). These indicated a pan-cancer relevant role of GAG disorder. Conclusions: CRC metabolism subtypes unraveled metabolism heterogeneity with prognosis value. CRC stroma subtype and other stroma-involved cancers share active GAG metabolism, which may lighten common targeting strategies in multiple stroma-accompanied cancers.
Uterine cancer histology and stage at presentation in black and white women: A cohort study of 488,000 patients.
Authors: Mary Kathryn Abel, Cheng-I Liao, Kathleen M. Darcy, Chunqiao Tian, Amandeep Kaur Mann, Yassmina McDonald, Kenneth Williams, George Larry Maxwell, Daniel Stuart Kapp, John K. Chan
Journal: Journal of Clinical Oncology (2020)

6089 Background: Although mortality among black women diagnosed with uterine cancer is higher than in white women, the reason for this difference is not completely understood. We proposed to investigate the differences in the incidence and presentation of uterine cancer histology among black women compared to white women. Methods: Data were obtained from the United States Cancer Statistics (USCS) and the National Cancer Database (NCDB) between 2004 and 2016. Chi-squared tests were used for statistical analyses. Results: Of 488,811 patients with uterine cancer, 411,904 (84.3%) were white and 51,093 (10.5%) were black. Based on USCS data, the incidence of endometrioid carcinoma in white women was 19.63 (per 100,000 per year) compared to 12.53 in black women. However, the incidence of high-risk histologies was higher in black women, particularly for serous tumors (3.32 vs. 1.29), clear cell tumors (0.59 vs. 0.31), carcinosarcoma (2.88 vs. 1.05), and leiomyosarcoma (1.02 vs. 0.48). Using the NCDB database, we evaluated the proportion of these histologies based on race. Compared to white women, black women have a higher proportion of serous (14.2% vs. 5.6%), clear cell (2.4% vs. 1.3%), carcinosarcoma (12.3% vs. 4.5%), and leiomyosarcoma (4.3% vs. 1.7%). black women were less likely to have endometrioid (52.7% vs. 75.9%) and mucinous (0.4% vs. 0.8%) tumors. In addition, black women were more likely to have stage III or IV disease at presentation when all histological subtypes were combined (22.8% vs. 17.7%). However, of those with endometrioid and grade 1 tumors, black women did not have more advanced stage at presentation compared to white women (3.8% vs. 4.7%). Conclusions: Compared to white women, black women are more likely to be diagnosed with serous, clear cell, carcinosarcoma, and leiomyosarcomas at a more advanced stage upon presentation, but they are less likely to have endometrioid tumors. More research is needed to understand why this disparity exists.
Impact on 30-day survival of time taken by a critical care transport team to reach the bedside of critically ill children
Authors: Sarah E. Seaton, Padmanabhan Ramnarayan, Christina Pagel, Patrick Davies, Elizabeth S. Draper, Victoria Barber, Robert Darnell, Patrick Davies, Elizabeth S. Draper, Laura Drikite, Matthew Entwistle, Ruth Evans, Emma Hudson, Enoch Kung, Will Marriage, Stephen Morris, Paul Mouncey, Christina Pagel, Anna Pearce, Eithne Polke, Fatemah Rajah, Padmanabhan Ramnarayan, Sarah E. Seaton, Jo Wray
Journal: Intensive Care Medicine (2020)
Clinical trial feasibility assessment and start-up tool (CTFAST).
Authors: Amanda Tice, Richard Dima, Wasif M. Saif, Melissa Panzo, Sarah R. Vaiselbuh
Journal: Journal of Clinical Oncology (2020)

e14089 Background: Selecting the right clinical trials for patients remains a challenging job. The better the match between a clinical trial and the target patient population before conducting a study, the more likely the study will successfully reach the target goal of recruitment. We developed a feasibility assessment scoring system based on our vast clinical research experience, managing multiple sites across a large health system, applicable to oncology as well. Methods: Our feasibility team (FT) is responsible for identifying clinical trials and determining if they are an appropriate match for our institution and unique patient population. Once a potential trial is identified, FT performs a feasibility assessment of the research protocol to determine the resources required to conduct the trial. We developed a Clinical Trial Feasibility Assessment &amp; Start-up Tool (CTFAST) to help sites streamline their feasibility assessments and track their trial through the start-up phase. With CTFAST a feasibility score is generated based on the cumulative value assigned to several items such as: sponsor, study type, pharmacokinetic studies, trial phase, etc. A feasibility scale is assigned as follows: &gt; 25 – Accepted; 15-25 – On Hold; &lt; 15- Rejected. Accepted studies are assigned a color coded priority track (fast, intermediate, routine), that allows team members to prioritize their studies accordingly. Once a study is accepted, the study is processed for enrollment. Results: CTFAST has increased productivity and clinical trial revenues by 40%. CTFAST allows for early identification of bottlenecks in workflow, thereby improving outcomes. By appropriately matching of clinical trials to our site, enrollments increased by 50% with an expanded clinical trial portfolio across 9 different departments. Study start-up times have been reduced to a minimum of 21 days and the use of time &amp; effort has been optimized. Conclusions: CTFAST is replicable across all clinical trial sites and provides an expansive and critical feasibility analysis that is not attainable by traditional querying of investigators and questionnaires. It is an excellent work flow improvement tool as it critically analyzes all aspects of a study, prior to enrollment. When conducting an effective feasibility analysis the clinical trial site can optimize clinical trial outcomes.
Getting rurality right: Investigating cancer across the rural-urban interface.
Authors: Amy K. Taylor, Andrea Schiefelbein, Jienian Zhang, John Krebsbach, Melissa C. Skala, John Eason, Noelle K. LoConte
Journal: Journal of Clinical Oncology (2020)

e19063 Background: Trends in oncology examine the influence of rural characteristics on cancer patient (pt) treatment and outcomes. Current definitions of rurality are broad and varied, with multiple standardized definitions. Few analyses exist to compare definitions and quality in assessing oncologic outcomes. We aim to determine which index is most suitable to define rurality in cancer research. Methods: 1,567 pancreatic cancer pts from the University of Wisconsin Cancer Registry, representing 84 Midwestern counties and 452 zip codes, were assigned rurality codes based on three indices spanning 1983-2013: Rural-Urban Continuum Code (RUCC), Rural-Urban Commuting Areas (RUCA), and Index of Relative Rurality (IRR). RUCC and IRR were assigned to pts at the county level and RUCA at the zip level. Pt rurality was compared across the three indices and over time via the median and interquartile range and inspected visually with violin plots. We compared indices with Spearman’s Rank Order Correlation (SROC). Results: RUCC 2003, RUCA 2004 (zip), and IRR 2000 were concordant in terms of metropolitan, micropolitan, and rural designations for 66.9% (1,049) of pancreatic cancer registry pts. The rural designation for almost one-third (489, 31.2%) of pts was discordant by one or two levels across the three indices (i.e. classified as metropolitan in one index and micropolitan or rural in another). SROC was 0.73 between RUCC 2003 and RUCA 2004 (zip) indices, 0.82 between IRR 2000 and RUCA 2004 (zip), and 0.85 between RUCC 2003 and IRR 2000. Across the 84 counties of registry pts’ residence, the median and interquartile range of RUCC decreased from 6 (3-7) in 1983 to 4 (2.25-6) in 2013 and of IRR decreased from 0.49 (0.44-0.53) in 2000 to 0.49 (0.43-0.53) in 2010. Across the 452 zip codes, RUCA decreased from 4 (1-10) in 1998 to 3 (1-8) in 2004. Pts’ median RUCC decreased from 3 (2-6) in 1983 to 3 (2-4) in 2013, median RUCA (zip) decreased from 2 (1-7) in 1990 to 1 (1-6) in 2000, and IRR remained constant at 0.42 (0.38-0.49) in 2000 and 2010. Conclusions: RUCC is preferable for state-level cancer studies incorporating rurality as it best distributes pts across the rural-urban interface compared to RUCA (skews urban) and IRR (skews central). County boundaries (RUCC) are consistent over time versus zip (RUCA) and census tract (RUCA). Our findings suggest that while the extremes of rural and urban are well-defined, rurality as a continuum is inconsistently measured. Researchers should continue to incorporate other measures of vulnerability to achieve health equity.
Investigation on the needs of oral hygiene knowledge for outpatients in community
Authors: Ming-yue Fan, Hui-qin Zhang, Lei Zheng
Journal: BMJ (2009)

Investigation of the needs of oral hygiene knowledge for outpatients in community was carried out by randomly sampling of 100 outpatients aged from 35 to 44 years old and 100 outpatients in age of 65 -74 years in community to do a comprehensive questionaire originally designed. The study items included dental equipment asepsis, the use of oral individual instrument box, prevention of oral cross-infection, the choice of toothpaste and toothbrush, the methods of toothbrushing, the use of toothpick and tooth floss, prevention from caries and periodontal diseases, the scaling, and the oral health care for the elderly. The investigation showed that there are needs so great and so urgent for dentists to work hard on.

Key words: 
Community health services;  Health education; dental
A phase Ib/II study of eribulin with cyclophosphamide (EC) in patients (pts) with advanced breast cancer (ABC).
Authors: Ozge Gumusay, Jonathan R. Renslo, Chiara A. Wabl, Amy Jo Chien, Michelle E. Melisko, Melanie Catherine Majure, Siti D. Rahmaputri, Mark Moasser, John Park, Hope S. Rugo
Journal: Journal of Clinical Oncology (2020)

e13079 Background: Eribulin is an effective microtubule inhibitor for the treatment of ABC. Based on encouraging efficacy with docetaxel/cyclophosphamide, we hypothesized that eribulin combined with cyclophosphamide (EC) would be effective with tolerable toxicity. The aim of the study was to determine the maximum tolerated dose (MTD) of EC, followed by a dose expansion study to estimate the clinical benefit rate (CBR) of EC in pts with ABC. Methods: Study eligibility included pts with histologically confirmed ABC with any number of prior lines of therapy. Pts were treated using a dose escalation strategy with cohort expansion once MTD was determined. Dose level 0 (DL0): E 1.1 mg/m 2 on days 1 and 8, C 600 mg/m 2 on day 1 of a 21-day cycle. DL1: E 1.4 mg/m 2 on days 1 and 8, C 600 mg/m 2 on day 1 of a 21-day cycle. Phase II expanded enrollment at DL1. The primary objective of the phase II study was CBR [(complete response (CR), partial response (PR), and stable disease (SD)]. Secondary objectives were response rate (RR), duration of response (DOR), time to progression (TTP), and safety. Using a 2-stage design, responses in 3 of the first 22 pts allowed continued enrollment to a planned 40. Results: No dose limiting toxicities (DLT) were identified in phase Ib (n = 6). 3 pts were treated at DL0 and 3 at DL1, the MTD. 44 pts with ABC were enrolled at the MTD and are included in the analysis. 31 pts had HR+/HER2- disease, 12 pts had triple negative disease (TNBC), 1 pt had HR+/HER2+ disease. Median age was 56 yrs, prior treatment (rx) for ABC included a median of 1 line of hormone rx (range 0-6) and 2 lines of prior chemorx (range 0-7). CBR was 79.5% (35/44; 7 PR, 28 SD) and median PFS 16.4 wks (95%CI:13.8-21.1 wks). Longer PFS was observed in those with HR+ disease vs TNBC (18.1 vs 10.8 wks; P = 0.067). Adverse events (AE) of any grade included fatigue (68.2%, n = 30), neutropenia (ntp) (59.1%, n = 26), nausea (56.8%, n = 25), constipation (50%, n = 22), peripheral neuropathy (47.7%, n = 21), dyspnea (40.9%, n = 18), headache (36.4%, n = 16), and anorexia (36.4%, n = 16). The most common grade 3/4 AE ntp (47.7%, n = 21); 3 pts had febrile ntp. Dose reductions due to ntp were required to 500 mg/m 2 C (n = 17) and to 1.1 mg/m 2 in eribulin (n = 12). Conclusions: EC in heavily pretreated ABC resulted in an encouraging CBR of 79.5% and PFS of 16.4 wks, comparing favorably to single agent E (PFS 14.8 wks). Dose reduction and delays were due primarily to ntp. EC is an effective combination therapy with manageable toxicity in ABC. Clinical trial information: NCT01554371 .
Clinical information analysis of neurological emergency: a report of 1979 cases
Authors: Rui Luo, Yuhui Chen, Yin Wang
Journal: BMJ (2014)

For this cross-sectional study, the clinical data of 1979 patients at our emergency department from October 2012 to June 2013 were collected and analyzed.The relevant data included gender, age, visit time, complaints, signs and diagnosis.The ratio of female: male was 1 to 0.71.The age groups of 50-59 and 70-79 years were the most.The peak of visit time was 8-10 am accounting for 21.26%.The common complaints included dizziness, headache and paralysis.The most frequent emergency diseases were acute cerebral vascular accident, dizziness or vertigo due to various diseases, headache and peripheral neuropathy.Ischemis stroke was the top one disease in elders.


Conclusion
The middle-aged and elderly are the main populations at our emergency department.And cerebrovascular disease is a common disease.


Key words: 
Emergency; Neuroscience
A survey of cannabis use for symptom palliation in breast cancer patients by age and stage.
Authors: Marisa C. Weiss, Meghan Buckley, Julianne Hibbs, Adam Leitenberger, Melissa Jenkins, Terri W. McHugh, Nancye Green, Sharon Larson
Journal: Journal of Clinical Oncology (2020)

12108 Background: Most US states have legalized medical cannabis for the treatment of serious conditions, including cancer. It is not well known which symptoms breast cancer patients seek to control with cannabis. Methods: Members of the Breastcancer.org and Healthline communities were invited to participate in this survey between 12/16/2019 and 1/19/2020. Eligibility criteria included age ≥18 years, resident of the US and a breast cancer diagnosis within the past 5 years. Eligible respondent data were analyzed for the symptomatic profile of cannabis users. Symptoms were compared between two groups using a Chi-square test of independence. The survey was led by Socanna, conducted by Outcomes Insights, and supported by a grant from Ananda Health/Ecofibre. Results: Among the 832 respondents who completed screening, 725 met the eligibility criteria, and 612 (84%) completed the survey. The median age of respondents was 57 years, and 85% had non-metastatic disease An estimated 42% of respondents have used medical cannabis to treat symptoms or side effects of breast cancer. Medical cannabis users reported using cannabis to treat insomnia (70%), joint and muscle aches, discomfort, stiffness, or pain (59%), anxiety (57%), and stress (51%). The medical cannabis users less than 50-year-old were more likely to use cannabis to treat these symptoms than their over 50-year-old counterparts, however, the differences were not statistically significant. Medical cannabis users under age 50 used cannabis significantly more than over 50 to treat nausea/vomiting (58% vs 40%; p = 0.010) and inflammation (34% vs 20%; p = 0.021). Medical cannabis users with metastatic disease were more likely to use medical cannabis to treat chronic pain 60% vs 41%; p = 0.017) than non-metastatic users. Post-surgery patients were most likely to use cannabis for nerve pain; and those who were beyond treatment, for stress. Patients suffered an average of 5 symptoms. Conclusions: A significant proportion of breast cancer patients reported using cannabis to treat a combination of symptoms from their cancer and its treatment. Although younger patients are somewhat more likely to use this form of palliative management, older patients are suffering from the same symptoms and their use is nearly as high. More research is needed on the personalization of safe and effective symptomatic management with medical cannabis, for people of all ages, stages, and forms of treatment.