tbuckley/cabot-search huggingface dataset:
Safety and efficacy of bevacizumab biosimilar in glioma.
Authors: Gunjesh Kumar Singh, Hollis D'souza, Sujay Srinivas, Dilip Harindran Vallathol, Mounika Boppana, Annu Rajpurohit, Abhishek Mahajan, Amit Janu, Abhishek Chatterjee, Rahul Krishnatry, Tejpal Gupta, Rakesh Jalali, Vijay Maruti Patil
Journal: Journal of Clinical Oncology (2020)

e14541 Background: Anti-VEGF antibody Bevacizumab (Avastin: Roche Pharma AG) is the recommended drug for recurrent glioma. Multiple low-cost bio-similars of this drug are now available however their clinical efficacy has never been compared against the original molecule. The aim of the current analysis is to compare the overall survival (OS) between recurrent glioma patients with bio-similar and innovator molecule. Methods: Adult recurrent glioma patients treated with bevacizumab from 1st July 2015 to 30th July 2019 were identified from the Neuro-Medical Oncology database. These patients were either offered Avastin or Bevacizumab biosimilar (BevaciRel: Reliance Life sciences or Bryta: Zydus Oncosciences) depending upon the financial affordability. The primary endpoint of the study was OS. It was defined as the time in months from the start of bevacizumab to death. Progression-free survival (PFS) was defined as the time in months from the start of bevacizumab to progression or death. The time to event variables was estimated using Kaplan Meier method. The median with its 95% confidence interval (CI) was calculated using Brookmeyer and Crowley method. The estimates were compared between the original and bio-similar bevacizumab cohort using the log-rank test. The hazard ratio was calculated using COX regression analysis. Results: There were 82 patients, out of which 57 received innovator and 25 received bio-similar bevacizumab. At median follow up of 26 months, 76 patients had an event for progression. The median PFS was 3.66 (95% CI 2.08 to 5.25) and 3.3 months (95% CI 2.38 to 4.21) in innovator and bio-similar arm respectively (Log-rank test P-value = 0.072). The hazard ratio for progression was 0.61 (95% CI 0.35 to 1.05; P-value = 0.075). At the time of data cutoff, there were 69 deaths. The median OS was 5.53 (95% CI, 5.07 to 5.99) vs 7.33 months (95% CI, 5.63 to 9.03) in innovator and bio-similar arm respectively (Log-rank test P-value = 0.51). The hazard ratio for death was 1.21 (95% CI, 0.67 to 2.17; p-value = 0.51). Conclusions: In the brain tumor patients, both innovator and bio-similar bevacizumab seem to have similar clinical efficacy.
Defining patient-elicited concepts unique to adolescents and young adults with cancer.
Authors: Viswatej Avutu, Kathleen Lynch, Marie Barnett, Jacqueline Vera, Julia Lynne Glade Bender, William D. Tap, Thomas Michael Atkinson
Journal: Journal of Clinical Oncology (2020)

12118 Background: Adolescents and young adults (AYAs) require a multidisciplinary approach to cancer care due to complex biopsychosocial variables and varied developmental maturity. Currently, age and diagnosis determine referral to pediatric or adult oncology with differing care paradigms and service utilization. These issues, in conjunction with differences in tumor biology and lower accrual to clinical trials, have contributed to marginal improvements in outcomes for AYAs. Compounding this dilemma is a lack of validated patient-reported outcome measures (PROs) for AYAs. Tracking standardized PROs longitudinally is a crucial step in understanding psychosocial variables, identifying tailored needs, improving outcomes and standardizing care. However, developing a PRO tool for AYAs first requires identifying AYA-unique domains. Methods: Three, 90-minute focus groups were conducted with AYAs treated at Memorial Sloan Kettering in the context of 1) pediatric oncology, 2) medical oncology, and 3) either service. Topics explored included: experiences of cancer care as an AYA; physical, social and emotional concerns; and information needs, including appropriateness, timing, and depth of information. Thematic content analysis of transcripts was performed by four interdisciplinary coders in weekly iterative consensus rounds. Phase one consisted of identification of key domains to guide line-by-line coding with NVivo software. Phase two consisted of independent review and categorization of codes, followed by three successive consensus meetings to identify distinct themes. Results: A mean of 6 patients (range 5-7) participated in each of the 3 groups; the total sample (n = 17) included 9 males and 8 females, ages 19-35 years (median 26). Four AYA-unique themes were identified: 1. AYAs have an uncertain sense of the future and desire more engagement in conversations pertaining to survivorship, long-term effects and transition to outpatient life. 2. Cancer as an AYA is a socially-isolating experience, prompting a strong desire to connect with peers during and post-treatment. 3. AYAs want control over who can be present during discussions with their care team as the presence of loved ones can impede or facilitate communication. 4. AYAs may be living far away from loved ones during treatment and lack supports needed to help them navigate treatment and daily life. Conclusions: Concept elicitation via focus groups identified novel themes related to survivorship, isolation, communication and social support, which can inform development of AYA-specific PROs.
慢性足痛的影像学诊断
Authors: 钱占华, 白荣杰
Journal: BMJ (2011)

随着现代生活快节奏的加剧和社会老龄化的进展,越来越多的人受到慢性足痛的困扰,慢性足痛已成为临床上最常见的症状之一,严重影响患者的日常生活.导致慢性足痛的病因较多,即使详细地了解病史和对患者进行全面的体格检查,也很难明确慢性足痛的根本病因[1].因此,影像学检查在慢性足痛的病因诊断中具有十分重要的价值.本文对慢性足痛的病因、临床及影像诊断的价值进行综述,以提高对慢性足痛的认识。
Efficacy of salmon calcitonin combined with zoledronic acid in treatment of senile primary osteoporosis
Authors: Xiaoming Shen, Chenglong Huang, Gang Chen, Suiliang Gong
Journal: BMJ (2016)

One hundred and twenty patients with senile primary osteoporosis were enrolled in the study from January 2012 to April 2013, including 41 males and 79 females. Patients were randomly assigned to two groups: 60 patients in study group were treated with salmon calcitonin combined with zoledronic acid (salmon calcitonin 50 IU i. m, q. d for 7 d, then 100 IU q. i.d for 7 d, followed by zoledronic acid 5 mg i. v gtt/y); 60 cases in control group were treated with alendronate (70 mg p. o/wk). Both groups received the same doses of calcium. Visual analogue scale (VAS) scores were assessed before, and 1, 6 and 12 months after treatment, 12-Item Short-Form Health Survey (SF-12) and bone mineral density (BMD) were assessed before and 12 months after treatment. There were no significant differences in all baseline parameters between two groups (P>0.05). After 1 month of treatment, the VAS scores of study group was lower than that of the control group (2.1±3.0 vs. 4.2±3.1, P 0.05). Compared to those before treatment, physical component summary and mental component summary of SF-12 scores after 1 year of treatment were improved significantly in both groups (P<0.05). Also, BMD was significantly improved after 1 year of treatment in both groups (P<0.05). The incidence of side effect in study group was lower than that in control group (16% vs. 20%, P<0.05). The results indicate that salmon calcitonin combined with zoledronic acid is an effective, safe, reliable and well tolerated therapy for senile primary osteoporosis. The long-term outcomes remain to be determined.


Key words: 
Osteoporosis; Drug therapy
Total cost of lung cancer care associated with broad panel versus narrow panel sequencing.
Authors: Rogelio Alberto Brito, Bob Cullum, Kevin Hastings, Elisea Avalos-Reyes, Rebecca Karos, Kjel Andrew Johnson
Journal: Journal of Clinical Oncology (2020)

7077 Background: Many lung cancer patients are diagnosed late with advanced or metastatic disease. Targeted therapies can improve quality of life and increase the chances of progression-free survival versus conventional treatments. An understanding that there may be more than one driver mutation associated with a specific lung tumor is crucial for the timing and delivery of the most effective line of therapy. Broad panel sequencing (BPS) minimizes tissue use and enables personalized treatment that decreases the use of ineffective agents and unwarranted side effects, in addition to opening pathways to early clinical trials. However, many payors do not reimburse for BPS. The objective of this study was to determine if BPS leads to lower total cost of care versus narrow panel sequencing (NPS). Methods: We identified new lung cancer patients who completed BPS (Current Procedural Terminology (CPT) code 81455, 51+ genomic test) or NPS (CPT code 81445, 5-50 genomic test) using medical claims from January 1, 2018, to March 31, 2019. We defined total cost of care as allowed costs paid for medical and pharmacy claims across a six-month time period from the first gene sequencing panel. We also compared the allowed costs of BPS and NPS. A Student’s t-test was used to compare differences and results are presented as mean +/- standard deviation. Results: From January 2018 to March 2019, we identified 45 patients who underwent BPS sequencing and 399 patients who underwent NPS. The average BPS cost was $1,977 +/- $2,713 versus the average NPS lab cost $719 +/- $1,087, p &lt; 0.0001. The average 6-month per member per month (PMPM) total cost was $11,535 +/- $9,168 among those who underwent BPS compared to $20,039 +/-19,642 in those who underwent NPS. This difference of $8,504 was statistically significant, p = 0.0022. Conclusions: BPS has been shown to optimize treatments in patients with lung cancer. These initial results of claims suggest that while lung cancer patients undergoing BPS have higher total sequencing costs than those undergoing NPS, BPS significantly reduces overall total cost of lung cancer care. Identifying the broader genomic landscape of a patient’s tumor earlier will empower oncology providers and lung cancer patients with information to make timely, precise treatment decisions that are ultimately more cost effective.
Impact of corticosteroids use on efficacy of immune checkpoint inhibitors in cancer patients: A meta-analysis.
Authors: Jiarui Li, Kaili Yang, Lin Zhao, Chunmei Bai, Zhao Sun
Journal: Journal of Clinical Oncology (2020)

e15234 Background: Corticosteroids are commonly used for management of cancer-related symptoms or immune-related adverse events (irAEs) in cancer patients treated with immune checkpoint inhibitors (ICIs). However, given the inhibitory effects of corticosteroids on a broad range of immune responses, it is presumed that the use of these agents may affect the clinical outcomes of ICIs. This meta-analysis aims to explore the impact of corticosteroids use on the efficacy of ICIs in cancer patients. Methods: We conducted a search covering electronic databases (MEDLINE, EMBASE, and CENTRAL), conference abstracts (ASCO and ESMO) and reference lists to identify relevant studies. Studies that reported clinical outcomes of patients with corticosteroids administration before and/or after the initiation of ICIs treatment were eligible for evaluation. The primary outcomes included progression-free survival (PFS) and overall survival (OS). The random-effects model was utilized to synthesize the effect sizes of individual studies. Results: The initial literature search identified 1,900 records. After study selection, a total of 15 studies with 14,123 patients were included in the quantitative analysis. Corticosteroids use significantly reduced PFS (HR = 1.84; 95% CI: 1.30–2.61; P = 0.001) and OS (HR = 1.41; 95% CI: 1.18–1.68; P &lt; 0.001) in cancer patients treated with ICIs. In subgroup analysis, corticosteroids use for cancer-related symptoms was associated with a shorter PFS (HR = 1.98; 95% CI: 1.40–2.78; P &lt; 0.001) and OS (HR = 1.88; 95% CI: 1.25–2.83; P = 0.003), but their use for irAEs did not show a detrimental impact on OS (HR = 1.05; 95% CI: 0.77–1.44; P = 0.740). Conclusions: This meta-analysis indicated that corticosteroids use might hinder the efficacy of ICIs in cancer patients. The indications of corticosteroids use should be strictly controlled during the course of immunotherapy.
How the NIH Genetic Testing Registry and Medical Genetics Summaries can help oncologists adopt pharmacogenetics guidelines.
Authors: Adriana Jose Malheiro, Laura Charlotte Dean, Marilu A Hoeppner, Vitaliy Lyoshin, Baoshan Gu, Chao Chen, Chunlei Liu, Zenith Maddipatla, Wenyao Shi, Wonhee Jang, Douglas Hoffman, George Zhou, Shanmuga Chitipiralla, Joe Mitchell, Donna R. Maglott, Brandi L. Kattman
Journal: Journal of Clinical Oncology (2020)

e14141 Background: Oncology is one of the few medical specialties where pharmacogenetic dosing is becoming a routine part of patient management. In the US, oncology drugs account for one-third of all drugs with pharmacogenetic data in their labeling. The NIH Genetic Testing Registry (GTR, www.ncbi.nlm.nih.gov/gtr ) is a freely available database of orderable genetic tests voluntarily provided by laboratories, and supports easy identification of both diagnostic and therapy-based tests. Medical Genetics Summaries (MGS, www.ncbi.nlm.nih.gov/books/NBK61999 ) presents actionable pharmacogenetic information by collating guidelines from authoritative professional (e.g. FDA, CPIC) and medical (e.g. ASCO) societies. MGS is regularly updated and can be found by searching PubMed. To increase oncologist adoption of pharmacogenetic recommendations, we analyzed the relationship between genetic tests in GTR and practice guidelines in MGS. Methods: The GTR database was queried to extract content, and we consulted the FDA Table of Pharmacogenomic Biomarkers in Drug Labeling. Results: Of the 90 oncology drugs that have pharmacogenetic information in their labeling, 29 drugs have at least one test for drug response in GTR. The oncology drugs most tested are mercaptopurine and irinotecan with 13 tests each, followed by thioguanine (12) and tamoxifen (9). For the remaining 61 drugs, only one drug (Pertuzumab) has a guideline, which is summarized in MGS. In total, MGS offers 10 summaries focused on oncology drugs. The 90 drug labels mention 49 distinct biomarkers (e.g. genes and variants). All 49 biomarkers can be interrogated using tests via the GTR. In total, GTR has approximately 3,500 tests for cancer diagnostics, 500 tests for cancer management, and 37 pharmacogenetic tests for cancer drugs. Conclusions: Searching for a genetic test in GTR by biomarker (100% coverage) is more efficient than by drug name (32% coverage) because of how laboratories describe their tests. Clinicians need to quickly find the best pharmacogenetic test and how tests are represented in the community affect the ability to search and find them. This presentation will show busy clinicians how to optimally use GTR and MGS. This work was supported by the Intramural Research Program of the National Library of Medicine, National Institutes of Health.
Risk assessment and prevention strategies for falls in the elderly
Authors: Wei Li
Journal: BMJ (2016)

跌倒的发生严重威胁到老年人的健康甚至生命，应充分认识到老年人跌倒的危害性。通过阐述老年人跌倒风险的评估和筛查手段，帮助临床医生从庞大的老年人群体中快速识别出高风险人群，进而针对具体的危险因素采用多重预防策略，以达到预防跌倒发生的目的。
Prevalence of <i>prkdc</i> mutations and association with response to immune checkpoint inhibitors in solid tumors.
Authors: Yi Li, Chuan-ben Chen, Yu Chen, Yan-Fang Guan, Yingying Huang, Jing Lin, Gang Chen, Xuefeng Xia, Lianpeng Chang, Xin Yi
Journal: Journal of Clinical Oncology (2020)

e15250 Background: Predictive biomarkers of response to immune checkpoint inhibitors (ICIs) help to identify cancer patients who will benefit from immunotherapy. PRKDC is an important gene relates to DNA double-strand break (DSB) repair and central T-cell tolerance. We aim to investigate the association between PRKDC mutations and tumor mutation burden (TMB), tumor microenvironments (TME), and response to ICIs. Methods: The whole exome sequencing data of 4022 solid tumor samples from the Cancer Genome Atlas (TCGA) and the panel-based sequencing data of 4652 solid tumor samples from GenePlus-Beijing, China were used to analyze TMB. The mRNA expression data of 3541 solid tumor samples from TCGA was used to explore the effect of PRKDC mutation on TME. Four ICIs-treated cohorts were analyzed for verifying the correlation between PRKDC mutation and the response to ICIs. Results: In TCGA datasets and GenePlus datasets, we both found that the TMB in PRKDC mutation samples were significantly higher than PRKDC wild-type samples(P &lt; 0.05, P&lt;0.0001 respectively). When compare to other pivotal DNA damage response (DDR) genes, it showed an identical effect of the degree in TMB by PRKDC mutation with MMR ( PMS2/ MLH1/ MSH2/ MSH6) genes, POLE/D1 and BRCA1/2 mutation (P &gt; 0.05). Further, in TCGA datasets, it showed that PRKDC mutation samples were associated with significant expression increase of CD8+ T cells, NK cells, immune-checkpoint, chemokines etc compared to PRKDC wild-type samples (P &lt; 0.05). In ICIs-treated cohorts, we also found the PRKDC mutation was associated with superior survival(median PFS, not reached (NR) vs. 6.8 months HR, 0.2893 95% CI, 0.1255-0.6672 P = 0.0650, Hellmann cohort; median OS, 1184 days vs. 250 days HR, 0.5126 95% CI, 0.2715-0.9679 P = 0.1020, Allen cohort), and the superiority was significantly in multivariate Cox regression analyses (HR, 0.361 95% CI,0.155-0.841; P = 0.018, Allen cohort; HR, 0.240 95% CI,0.058-0.998; P = 0.050, Hellmann cohort). Conclusions: PRKDC mutations are associated with an increased TMB, an inflamed TME and a better response to ICIs, it may be a potential predictive biomarker for ICIs-immunotherapy.
Exploring impact of mutations in non-<i>BRCA</i> DNA damage response (DDR) and non-DDR genes on efficacy in phase III EMBRACA study of talazoparib (TALA) in patients (pts) with germline <i>BRCA1/2</i> mutated (g<i>BRCA</i>m) HER2-negative (HER2-) advanced breast cancer (ABC).
Authors: Jennifer Keating Litton, Douglas Laird, Hope S. Rugo, Johannes Ettl, Sara A. Hurvitz, Miguel Martin, Henri Roche, Young-Hyuck Im, Annabel Goodwin, Joanne Lorraine Blum, Wolfgang Eiermann, Ying Chen, Silvana Lanzalone, Jijumon Chelliserry, Akos Czibere, Lee A. Albacker, Garrett M. Frampton, Lida A. Mina
Journal: Journal of Clinical Oncology (2020)

1018 Background: Loss-of-function mutations in genes encoding components of the homologous recombination DNA damage response (DDR) machinery, notably BRCA1/2, are associated with tumor sensitivity to poly(ADP-ribose) polymerase inhibitors (PARPi). In EMBRACA, the PARPi TALA showed an improvement in progression-free survival (PFS) (HR [95% CI] 0.54 [0.41-0.71], P &lt; 0.001) vs physician's choice of chemotherapy (PCT) in g BRCAm HER2− ABC. Methods: Baseline tumor tissue from 308 pts (71%; intent-to-treat) was sequenced using the FoundationOne CDx panel. Mutations summarized below were known/likely pathogenic single-nucleotide variants, insertions, deletions, or rearrangements. Best tumor response (BOR) was using RECIST 1.1 by Investigator (confirmation of CR or PR not required). Results: 296/308 (96%) of evaluable pts exhibited ≥1 tumor BRCA mutation, with 7 of the remaining 12 exhibiting BRCA copy number alterations deemed pathogenic. Mutations in other genes implicated in DDR and/or potential sensitization to PARPi were rare, with mutations detected in BARD1, CDK12, FANCG, STAG2 (each 0.3%), ATR, BRD4, FANCC, PALB2, RAD51B (0.6%), ATM, BRIP1 (1.0%), NBN (1.3%), CHEK2, FANCA (1.6%), and ARID1A (2.3%). No association was observed between total number of DDR mutations, including BRCA1/2, and best tumor response (BOR) [odds ratio of 1 vs ≥2 DDR mutations (95% CI): TALA, 0.76 (0.31-1.87), P = 0.55; PCT, 0.98 (0.27-3.51), P = 0.97]. TP53 and PIK3CA were the most commonly mutated non- BRCA genes in BRCAm tumors (52.0 and 10.8%, respectively). TP53 mutations were more prevalent in BRCA1m vs BRCA2m tumors (85.2 vs 24.8%). PIK3CA mutations were more prevalent in BRCA2m vs BRCA1m tumors (15.9 vs 5.2%). With TALA, PFS was significantly shorter in pts with TP53 mutations than without [HR (95% CI) 1.693 (1.186-2.418), P = 0.0033]. A similar, non-significant, trend was evident with PCT [HR (95% CI) 1.439 (0.859-2.411), P = 0.1614]. PIK3CA mutational status had no impact on PFS in either arm. Conclusions: Selection based on g BRCA mutational status is appropriate to identify HER2─ ABC pts with potential for clinical benefit from TALA, with the total number of tumor mutations in BRCA1/2 and other DDR genes not impacting response (within the g BRCAm subset). TP53 mutations were associated with shorter PFS, likely reflecting the worse outcomes observed in g BRCA1m patients. Additional correlative analyses are ongoing. Clinical trial information: NCT01945775 .
Association between prediabetes and risk of cardiovascular disease and all cause mortality: systematic review and meta-analysis
Authors: 黄裕立, 蔡晓燕, 麦炜颐, 李美君, 胡允兆
Journal: BMJ (2017)

目的
评估不同定义下的糖尿病前期状态与心血管疾病及全因死亡的相关性。


设计
基于前瞻性队列研究的荟萃分析。


数据来源
来自PubMed、Embase和谷歌学术的相关研究。


纳入标准
来自普通人群的前瞻性队列研究，且该研究需报告在校正多种其他危险因素后，糖尿病前期人群发生复合心血管事件、冠心病、卒中或全因死亡的相对风险（RR）和95%可信区间（CI）。


评估方法
两位研究者分别根据预定的纳入标准进行筛查和选择合适研究数据。糖尿病前期的定义包括：（1）美国糖尿病协会（ADA）定义的空腹血糖受损（IFG-ADA，空腹血糖5.6~6.9 mmol/L）；（2）世界卫生组织（WHO）定义的空腹血糖受损（IFG-WHO，空腹血糖6.1~6.9 mmol/L）；（3）糖耐量异常（IGT，口服葡萄糖耐量试验2小时血糖7.8~11.0 mmol/L）；（4）ADA定义的糖化血红蛋白(HbA1c)轻度升高：39~47 mmol/mol（5.7%~6.4%）；或（5）英国国家健康与临床优选研究所（NICE）定义的HbA1c轻度升高：42~47 mmol/mol （6.0%~6.4%）。分别从纳入分析的研究中提取以上不同定义下糖尿病前期状态相关的全因死亡和心血管风险进行分析。


结果
最终纳入53项前瞻性队列研究，共1 611 339个体的数据进行分析。中位随访时间为9.5年。与正常血糖人群相比，糖尿病前期(包括IFG-ADA、IFG-WHO、IGT)增加复合心血管疾病（RR值分别为IFG-ADA 1.13、IFG-WHO 1.26、和IGT 1.30）、冠心病（RR值分别为1.10、1.18和1.10）、卒中（RR值分别为1.06、1.17和1.06）或者全因死亡风险(RR分别为1.13、1.13和1.32)。HbA1c轻度升高（39~47 mmol/mol或42~47 mmol/mol）与复合心血管疾病风险(RR值分别为1.21和1.25)和冠心病风险(RR值分别为1.15和1.28)增加有关，但不增加卒中和全因死亡风险。


结论
IGT、IFG或HbA1c轻度升高等糖尿病前期状态均与心血管疾病风险增加相关。当患者空腹血糖浓度在5.6 mmol/L或HbA1c在39 mmol/mol以上时，健康风险可能已经开始升高。