tbuckley/cabot-search huggingface dataset:
Evaluation of minimal residual disease in relapsed/refractory multiple myeloma patients treated with venetoclax or placebo in combination with bortezomib and dexamethasone: BELLINI study analyses.
Authors: Philippe Moreau, Simon J. Harrison, Michele Cavo, Javier de La Rubia, Rakesh Popat, Vania Hungria, Hans Salwender, Kenshi Suzuki, Inho Kim, Andrew Spencer, Michael O'Dwyer, Wan-Jen Hong, Muhammad Jalaluddin, Xiaoqing Yang, James Michael Pauff, Paulo Cesar Maciag, Jeremy A. Ross, Shaji Kumar
Journal: Journal of Clinical Oncology (2020)

8547 Background: Venetoclax (Ven) is a selective, potent BCL-2 inhibitor that has synergistic activity with bortezomib (B) and dexamethasone (d). In the Phase 3 BELLINI trial, addition of Ven to Bd significantly improved median progression-free survival (PFS) and response rates, including minimal residual disease (MRD) negativity, but resulted in increased mortality vs placebo (Pbo). Here, we determine whether MRD negativity was associated with longer PFS and OS in relapsed/refractory multiple myeloma (RRMM) patients treated with Ven+Bd in the BELLINI dataset. Methods: In BELLINI (NCT02755597), RRMM patients (pts) sensitive or naïve to proteasome inhibitors with 1-3 prior lines of therapy were randomized 2:1 to Ven (800 mg) or Pbo plus B (1.3 mg/m 2 ) and d (20 mg). Next-gen sequencing MRD assessments were done on bone marrow aspirates at the time of suspected CR/sCR, and 6- and 12-months post confirmation of CR/sCR. Patients with a missing or indeterminate assessment were considered MRD positive. Evaluation of MRD in biomarker-defined subgroups (cytogenetics and BCL2 expression) was also performed and will be presented. Results: In total, 291 pts were randomized; 194 to Ven, 97 to Pbo. As of 13 Sep 2019, the median follow-up was 29 months. Ven + Bd demonstrated significantly higher MRD negativity rates ( &lt; 10 −5 ), including a higher proportion of pts achieving sustained MRD negativity (Table). In the Ven arm, the median (m)PFS was not reached for MRD negative pts vs 16.2 months for MRD positive pts (HR = 0.23, 95% CI: 0.10-0.54, p &lt; 0.001). While the mOS was not reached in the Ven arm, OS was significantly longer for MRD negative vs MRD positive pts (HR = 0.25, 95% CI: 0.08-0.80, p = 0.0194). Conclusions: The addition of Ven to Bd resulted in deep and durable responses, including higher rates of MRD negativity. MRD negativity in the context of Ven was associated with prolonged survival in patients with RRMM, consistent with the broader MRD body of evidence with other therapies in MM. Clinical trial information: NCT02755597 . [Table: see text]
Outcomes of patients (pts) with metastatic urothelial carcinoma (mUC) following discontinuation of enfortumab-vedotin (EV): Emergence of a new unmet need.
Authors: Catherine Curran, Gregory Russell Pond, Vera Kazakova, Petros Grivas, Leonidas Nikolaos Diamantopoulos, Ajjai Shivaram Alva, Christopher Su, Rohit K. Jain, Ankita Tandon, Jingsong Zhang, Andrea Necchi, Laura Marandino, Jaime R. Merchan, Trisha M. Plastini, Guru Sonpavde
Journal: Journal of Clinical Oncology (2020)

5048 Background: Enfortumab vedotin (EV) is an antibody drug conjugate recently approved to treat mUC following prior platinum and PD1/L1 inhibitors. The outcomes and patterns of therapy of pts following discontinuation of EV has yet to be studied. We investigated outcomes of pts who completed EV treatment for mUC at multiple institutions in order to identify benchmarks for evaluation of new agents following EV. Methods: Clinical data were obtained from mUC patients who had completed EV treatment from collaborating academic institutions. Descriptive stats were performed to describe the overall dataset and compare patient characteristics and outcomes of those who went on to receive further treatment post-EV and those who did not. Results: Data were available for 63 patients from 6 collaborating institutions: DFCI, University of Michigan, University of Washington, Moffitt Cancer Center, INT Milan and University of Miami. 17 (27%) were female and 46(73%) were male. The median age was 68 (range 43-83. The primary site of malignancy included bladder, upper tract, and other in 43 (68%), 19 (30%), and 1pt (.02%), respectively. The histologies included pure UC and mixed predominant UC in 49 (78%), and 14 pts (22%), respectively. 32 pts (51%) received further therapy after EV and 31pts (49%) did not. Longer duration of prior EV therapy was associated with receipt of post-EV therapy (p=0.0437). Treatments received post-EV were: trial therapy (n=14), PD1/L1 inhibitor (n=7), pemetrexed (n=4), taxane (n=3), carboplatin (n=2) and unknown in 2 pts. Objective response was observed in 3 of 32 pts (9.4%) who received therapy post-EV. The median duration of time from end of EV to death was 24 weeks. The median overall survival (OS) of those who received post-EV therapy and did not receive post-EV therapy was 37.5 weeks and 12 weeks, respectively. Conclusions: Outcomes of mUC following discontinuation of EV are dismal with only 51% receiving subsequent therapy. This study identifies an unmet need setting and establishes benchmarks for the interpretation of activity of new agents evaluated following EV.
昏迷患者2358例分析
Authors: 杜军, 林少宾, 刘燕妮, 刘卫民, 王二丁
Journal: BMJ (2004)

我们对我院1987～2000年以昏迷就诊的2 358例患者资料进行回顾性分析,报告如下. 1.临床资料:资料来自抢救记录,2 358例患者按不同年龄组、不同疾病种类进行系统统计,诊断均按抢救记录中的最后诊断名称.2 358中男性1 555例,女性 803例,男女比例1.52∶ 1.昏迷患者年龄≤10岁86例,11～20岁203例,21～30岁259例,31～40岁313例,41～50岁255例,51～60岁402例,61～70岁501例,71～80岁216例,81～90岁74例,≥ 91岁9例,其中以51～70岁发病较多.昏迷原因:外科疾病949例,其中脑挫裂伤569例、多发伤139例、硬膜下血肿59例、硬膜外血肿55例、坠落伤38例、其他病因86例;内科疾病1 409例,其中脑出血785例、药物中毒114例、各种休克83例、脑梗死71例、猝死56例、急性心肌梗死46例、其他病因254例.
The role of general practice department in tertiary comprehensive hospitals
Authors: Jiatang Zheng, Aimei Dong, Chunhua Chi
Journal: BMJ (2017)

医学模式的转变促进了全科医学的发生与发展。随着国家医疗改革的持续深化，在三级综合医院中设置全科医学科已势在必行，但其角色定位仍处于探索阶段。文章拟探讨三级综合医院设置全科医学科的意义，并提出以教学为主要形式培养全科医学人才应成为三级综合医院全科医学科建设与发展的价值导向及主要目标。
Meta-analysis and single-center experience on the comprehensive genomic characterization and landscape of <i>BRCA1</i> and <i>BRCA2</i> in Turkey.
Authors: Atil Bisgin, Ibrahim Boga, Ozge Sonmezler, Cem Mujde, Abdullah Hanta, Sevcan Tug Bozdogan
Journal: Journal of Clinical Oncology (2020)

e13611 Background: The detection of BRCA1 and BRCA2 mutations both somatic and germ-line became essential for the clinical management strategies of different cancers. Aiming at the identification of common and recurrent mutations that answer the questions about the association between a variant and phenotype, we collected the data of 1126 probands with pathogenic, likely pathogenic variants and variants of uncertain significance (VUS) distributed across 22 Turkish cities. Methods: Peripheral blood samples from 1126 individuals were collected and sequenced via the GeneReader (Qiagen, Hilden, Germany) and MiSeq (Illumina, San Diego, USA) NGS systems for BRCA1/ BRCA2 genes. QCI-Analyze and QCI-Interpret bioinformatics tools were used for bioinformatics analyses. Results: Total of 68 and 108 distinct variants were identified in BRCA1 and BRCA2 genes, respectively. Twenty novel variants were identified in both genes, while BRCA2 had higher heterogeneity. However, there had been no any recurrent mutations identified in any certain geographic region. Among all distinct mutations identified 11.9% were novel, corresponding to 12.8% of all carriers and 28.4% were VUS, corresponding to 32.1% of all carriers. Conclusions: This study presented with three important outcomes. First, a significant molecular heterogeneity in BRCAs among Turkish carriers were confirmed with 15.63% positivity rate. Most notably as the second, this is the first study showing the profiles of recurrent and common mutations that might be unique to Turkish landscape. In conclusion, it is critical to identify all the genetic variants, to aid in diagnosis, prevention, prognosis and treatment. Third and the last, the identification of novel mutations in BRCAs is a vital information that should be shared with mutation databases, in order to use for further clinical interpretation of Turkish population. Key words: Landscape of BRCA1/2, genetic testing, BRCA profiling, population data.
High neutrophil to lymphocyte ratio as a predictor for hyperprogressive disease in patients with metastatic non-small cell lung cancer treated with pembrolizumab as a second line.
Authors: Milla Petrova, Mariyana Eneva, Jeliazko Iliev Arabadjiev, Nikolay Vladimirov Conev, Eleonora Dimitrova, Krassimir Dimitrov Koynov, Teodora Karanikolova, Spartak Valev, Radostina Gencheva, Georgi Zhbantov, Anika Ivanova, Iva Sarbianova, Polya Penkova, Konstanta Timcheva, Ivan Donev
Journal: Journal of Clinical Oncology (2020)

e21546 Background: In this study we evaluated the incidence of early non-responders (which are potential hyper-progressors (HP)) and its relation to Neutrophil-Lymphocyte Ratio (NLR), Platelet-Lymphocyte Ratio (PLR) as well as their dynamics in patients with Non-small Cell Lung Cancer (NSCLC) treated with pembrolizumab (P) as a second line. Methods: Patients with metastatic NSCLC (n=119) whose tumors expressed PD-L1≥1% were retrospectively analyzed between Apr 2017 and Oct 2019. All patients received platinum-containing chemotherapy (CT) as a first line treatment. Hematological parameters of interest were absolute neutrophil (ANC), absolute lymphocyte (ALC) and platelet (APC) counts, enabling calculation of NLR (ANC/ALC) and PLR (APC/ALC). NLR1 and PLR1 were calculated before CT, NLR2 and PLR 2 – before the first P infusion. ΔNLR (NLR2-NLR1) and ΔPLR (PLR2-PLR1) were calculated. The tumor response was assessed according to the RECIST (version 1.1) at every 3 months. Early progressors (EP) were defined as non-responders at the first computed tomography scan evaluation of the CT. As HP on P were considered patients with time to progression ≤ 3 months, clinical deterioration and appearance of ≥2 new lesions in organ already involved or spread to a new organ. Results: Twelve (10.1%) patients in the CT group were EP. Fourteen (11.8%) patients in the immunotherapy group were assessed as HP. Four patients (3.4%) did not respond either to CT or to P and had clinical aggravation. HP had significantly higher NLR2 (9.1±1.9 vs 4.8±3.2, p&lt;0.001), PLR2 (400±173.8 vs 214.7±117.3, p&lt;0.001), ΔNLR (2.3±1.9 vs 0.3±2.0, p=0.001), ΔPLR (107.9±167.3 vs 0.6±94.9, p=0.012) than the rest of the patients. ROC analysis revealed that at the optimal cutoff values of all markers, NLR2 achieved the greatest AUC=0.855 (95% CI, 0.77-0.93) and could distinguish between patients with or without hyperprogressive disease (HPD) with sensitivity of 85.7% and specificity of 72.4%. HP had significantly shorter mean OS - 12.5 months (95%, CI 10.9-14.1) than the rest – 32.2 months (95%, CI 28.4-36.1). Patients who did not respond either to CT or to P had significantly shorter mean OS – 9.2 months (95%, CI 6.6-11.8) than the rest – 29.8 months (95%, CI 26.4-33.4). NLR was found to be an independent predictive factor for HPD, HR=1.22 (95% CI,1.11-1.35; p&lt;0.001). Conclusions: Our data suggest that the incidence of intrinsic aggressive disease phenotype, irrespective of treatment, is low. NLR is a novel predictive marker for HPD.
Post-hoc power of clinical trials supporting anticancer drug approval by FDA.
Authors: Michelle Nadler, Alexandra Desnoyers, Ramy Saleh, Eitan Amir
Journal: Journal of Clinical Oncology (2020)

2018 Background: Regulatory approval of drugs is based typically on randomized control trials (RCTs) observing statistically significant superiority of an experimental agent over a prior standard. Statistical significance can result from large effect size and/or over-sampling (as a result of large sample size or long follow-up). Here we explore the source(s) of statistically significant results in trials supporting anti-cancer drug approval by the FDA. Methods: We searched Drugs@FDA to identify anti-cancer drug approvals for solid tumors (excluding lymphoma) from 2015-2019. We retrieved corresponding manuscripts and associated appendices and extracted data on study characteristics, statistical plan, primary outcomes and accrual and follow-up times. Post-hoc power was calculated based on observed results and was compared to expected effect size and power in the statistical plan. We explored associations with higher than expected power resulting from over-sampling using binary logistic regression. Results: We identified 75 unique drug-approvals reporting 94 endpoints. The most common tumour types were lung, breast, melanoma, and renal cell carcinoma. The most common endpoints were progression free survival and overall survival (OS). In 74 endpoints (79%), observed power was greater than expected power. The magnitude of higher than expected power ranged from 0.1 to &gt; 20%. Of these, 59 (80%) had an effect size greater than predicted in the statistical plan. In 44/74 over-powered endpoints (60%), post-trial power was 100%. When post-hoc power was calculated based on expected effect size rather than observed effect size, 50 endpoints (85%) remained over-powered. Higher than expected power resulting from over-sampling was associated with OS compared to other endpoints (OR 3.03), with targeted agents compared to immunotherapy (OR 1.63) and inversely associated with year of approval (OR 0.57). Conclusions: Most cancer drug approvals result from statistically significant studies which are over-powered due to greater than anticipated effect size. Approximately 1 in 5 studies are over-powered likely due to over-sampling. In this setting, benefit observed in RCTs may not translate to the real-world setting.
Clinical implications of assumptions in cost-effectiveness analyses of systemic therapies for metastatic colorectal cancer.
Authors: Koen Degeling, Martin Vu, Hendrik Koffijberg, Hui-Li Wong, Miriam Koopman, Peter Gibbs, Maarten J. IJzerman
Journal: Journal of Clinical Oncology (2020)

e16021 Background: Considerable variation is observed in model-based cost-effectiveness analyses of systemic therapies for metastatic colorectal cancer (mCRC). This review provides a comprehensive and detailed discussion of structural and methodological assumptions in such analyses, and how those might impact health and economic outcomes. Methods: Five databases (EMBASE, MEDLINE, Cochrane Library, Health Technology Assessment, and National Health Service Health Economic Evaluation Database) were searched for model-based health economic evaluations of systemic mCRC treatment. Study selection, appraisal using the Consolidated Health Economic Evaluation Reporting Standards checklist, and data extraction was performed by two reviewers independently. Data extraction included general study characteristics, economic methods and assumptions, model structures and modelling technique, evidence used, extrapolation methods, validation efforts, and analyses performed. Economic outcomes were indexed to 2019 US$. Results: The search yielded 1,418 publications of which 54 were included, representing 51 unique studies. Most studies focused on first-line treatment (n = 29, 57%), followed by third-line treatment (n = 13, 25%). Although most studies mentioned consideration of further treatments (n = 29, 57%), this was typically only done by means of a lumpsum treatment cost (n = 21). Studies used varied modelling techniques and model structures, and different control strategies were adopted by studies aiming to estimate the cost-effectiveness of the same treatment. Only 15 studies (29%) reported some sort of model validation. Health economic outcomes for specific strategies differed substantially between studies. For example, survival following first-line treatment with fluorouracil, leucovorin, and oxaliplatin ranged from 1.21 to 7.33 years, with treatment costs ranging from US$8,125 to US$126,606. Conclusions: Model-based cost-effectiveness analyses of systemic mCRC treatments have adopted varied modelling methods and structures, which has resulted in substantial different health economic outcome estimates between studies, for example in terms of overall survival and average treatment cost per patient. Models generally focus on first-line treatment without considering the use of downstream treatments, suggesting these studies likely present biased results. This may impact the uptake of new systemic therapies.
Application of TeamSTEPPS in training community diabetes management team
Authors: Xiuying Mao, Shanzhu Zhu, Hua Yang, Zhijie Yu, Yuezhong Tang, Jing Lu, Hefeng Hua, Donghao Xu, Jiang Yue, Huan Cheng
Journal: BMJ (2019)

One hundred and fifty diabetic patients, who received management by community family doctors and hospital consortium (1+1+1) team for at least 1 year, were enrolled from January 2017 to May 2017. After that they continued to receive the management for 1 more year by the team which were trained with TeamSTEPPS (team strategies and tools to enhance performance and patient safety). The management effect before and after TeamSTEPPS training was compared. After the TeamSTEPPS training, the team management ability was improved, so that the compliance of diabetic patients with medical advice, regular examination of blood glucose, regular follow-up assessment, health education, regular exercise and diet control were all better than before, and the differences were statistically significant (all P<0.01). Fasting blood glucose, postprandial 2 h-blood glucose, glycosylated hemoglobin and LDL-C levels were all lower than before, and the achieved rate of the above indicators were also increased (P<0.05). It is suggested that application of TeamSTEPPS in team training can effectively enhance the management ability for chronic disease of family doctors and improve compliance and clinical indicators of patients with diabetes under management.


Key words: 
Diabetes, type 2; Community health services; Disease management; Treatment outeome
Utility of Computed Tomography for the Diagnosis of Invasive Aspergillosis in Hematological Malignancy
Authors: Jie Jin, Wu Depei, Yang Liu, Si Si Pan, Jean Li Yan, Jalal A. Aram, Yin-jun Lou, Haitao Meng, Xiaochen Chen, Xian'an Zhang, Ilan S. Schwartz, Thomas F. Patterson
Journal: Blood (2017)
Communication of genetic testing results and cascade testing among Mexican carriers of cancer-associated variants and their families.
Authors: Yanin Chavarri Guerra, Andrés Rodríguez-Faure, Laura Margarita Bolano Guerra, Jose Luis Rodriguez Olivares, Jazmin Arteaga, Danielle Castillo, Rosa Mejia, Josef Herzog, Kathleen Reilly Blazer, Jeffrey N. Weitzel
Journal: Journal of Clinical Oncology (2020)

e13541 Background: Most hereditary cancer syndromes exhibit autosomal dominant inheritance. Therefore, communicating results to family members and performing cascade testing is crucial in order to identify individuals at risk and offer them appropriate risk-reducing strategies. The process of communicating medical information within families is highly variable and might be affected by several factors (including culture, education, understanding of results, and family conflicts) which remain understudied among individuals living in developing countries. We sought to investigate communication of results and cascade testing reach within the families of Mexican individuals carrying cancer-associated pathogenic variants (PVs). Methods: Individuals seen at a single center in Mexico City carrying a cancer-associated PV and enrolled in the Clinical Cancer Genomics Community Research Network (CCGCRN) were included. Carriers received genetic counseling at the time of results disclosure, a family letter was provided to facilitate the communication of results, and cascade testing was offered. After &gt;3 months from results disclosure, participants were surveyed regarding genetic testing results communication patterns, performance of cascade testing, and surveillance behaviors. Data was analyzed using descriptive statistics. Results: Among 354 probands, 53 (15%) were identified as carriers of a cancer-associated PV. Mean age was 48.3 (range 21-82) years. Cascade testing (≥1 family member) was initiated in 74% of families (n = 39), with a median of 3 (range 0-16) family members tested per proband. 53 carriers responded the survey (29 probands and 24 relatives). 98% (n = 43) had shared results with their family, and 53% (24/45) had shared them with their treating physicians. Most respondents were receiving active surveillance (n = 36, 80%); with 43% (n = 15) reporting having at least one barrier for complying with surveillance (financial: n = 8; distance to the hospital: n = 3). Around half of the carriers perceived their cancer risk to be of ≥50%. Conclusions: Our results show that both the communication of genetic testing results and the proportion of cascade testing within Mexican families are high. Family involvement in health care decision-making is common in Mexico, as in other Latin American countries, which might lead to improved family communication. However, strategies to improve communication with providers are needed in order to tackle barriers and improve surveillance of individuals carrying cancer associated PVs.
Molecular profiling and clinical characteristic of malignant melanoma in younger patients.
Authors: Jomjit Chantharasamee, Karlton Wong, Bartosz Chmielowski
Journal: Journal of Clinical Oncology (2020)

e22087 Background: Combination of clinical and molecular data has not yet been well established in adolescent and younger adult patients with melanoma Methods: We performed a retrospective analysis of the molecular profiles and clinical outcome of patients diagnosed at the age younger than 40 treated at UCLA during 2010 to 2019. Patient’s molecular profile, characteristics, and treatment outcome were described using descriptive statistic. Kaplan-Meier curve was used for disease-free survival (DFS) and overall survival (OS). Results: 150 patients with a median age of 29 year (12-39) were analyzed. 101 (67.3%) patients had cutaneous melanoma, 49 (32.7%) had localized uveal melanoma. Of those 101, 23.8% had pre-existing benign or congenital nevus. 70/101 (69.3%) was stage I-II, 26/101 (25.7%) stage III and 5/101 (4.9%) stage IV. Of those 37 patients with molecularly characterized tissue, 23 (62%) had BRAF mutation including 17 V600E, 4 V600 unknown codon, 2 G469A, 2 NRAS and 1 NF-1 mutation. 11/37 were BRAF negative. 79.6% of patients who were not tested were stage I. For patients with stage III, 16/26 (61%) received adjuvant immunotherapy, none of adjuvant targeted therapy. At 35.1 months follow-up time, 27/96 (28%) localized cutaneous melanoma experienced relapse. 1-year DFS was 73% in adjuvant vs. 90% in no adjuvant immunotherapy group. Among 49 uveal melanoma patients, the median age was 27 years old. 23/49 (49%) had a T1 tumor, 18/49 (36.7%) T2, 6/49(12.2%) T3, 1/49(2%) T4. At 45 months follow-up time, three (6.1%) patients developed metastasis. 5-year DFS and OS was 90% and 100%, respectively. 45 patients had tissue for gene expression profiling and/or FISH testing. 15/45 (33%) had class IA, 13/45 (28%) had class IB, and 8/45 (17.7%) had class 2. 24 samples were analyzed by FISH: 14 with disomy 3, 5 with complex disomy 3 with gain of chromosome 6 or 8, and 5 with monosomy 3. Conclusions: Similarly to general population, most of younger patients with melanoma are diagnosed with stage I disease. Among patients with stage III melanoma treated with adjuvant immunotherapy 1-year DFS was comparable to the general population. Patients with stage III who did not receive adjuvant therapy had an excellent DFS which confirms that the decision on selecting patients for treatment was appropriate. The prognosis of younger patients with uveal melanoma was much better than predicted by molecular testing, and much better than expected regardless of gene expression profile or cytogenetic testing.