tbuckley/cabot-search huggingface dataset:
ELLA01-1: A study to determine the utility of TP53 mutations as a prognostic biomarker in adenoid cystic carcinoma.
Authors: Robert Metcalf, Khaireah Mubarak, Becky Bola, Samuel Rack, David Morgan, Tracy Hussell, Andrew Wallace, Guy Betts, Kevin Joseph Harrington
Journal: Journal of Clinical Oncology (2020)

6585 Background: TP53 mutations are reported in 5% of patients with adenoid cystic carcinoma (ACC). Whilst TP53 mutations are associated with adverse clinical outcomes across multiple tumour types, their prognostic significance in ACC is unknown. We sought to determine the utility of TP53 mutations as a prognostic biomarker in a prospective cohort of ACC patients. Methods: From April 2017 to September 2019, 146 patients with ACC were prospectively recruited to an ethically approved study. DNA was extracted from archival FFPE samples and underwent targeted next generation sequencing (Qiagen GeneRead DNAseq Targeted Panel V2 n = 134; Foundation Medicine; n = 12). Clinical, pathological and outcome data were collected on all patients and Kaplan-Meier survival analysis was performed to test for survival differences between TP53 mutated and wild-type ACC. Results: 146 ACC patients (mean age 48 years, range 16-79) underwent DNA extraction and next generation sequencing for TP53 mutations. The primary site was major salivary gland in 47% and minor salivary gland in 48% (other 5%). Analysis was successful in 122/146 patients (84%). Recurrent or metastatic disease was present in 94% (115/122) at study entry. TP53 alterations were identified in 9% (11/122), most frequently within the DNA binding domain (9/11). Non-pulmonary visceral metastases were seen more frequently in TP53 wild-type than in TP53 mutated ACC (44% vs. 10%; p = 0.042), and other clinical parameters were balanced between groups. During follow-up from diagnosis (median follow up 6.6 years), death occurred in 45% of patients with TP53 mutation and in 23% with TP53 wild-type ACC (p = ns). In TP53 mutated ACC, median overall survival was significantly shorter (5.3 vs. 16.3 years), and 10-year survival rate significantly lower (42% vs. 82%) than TP53 wild-type ACC (log-rank p = 0.013). Conclusions: In this cohort of patients with ACC, TP53 mutations were seen with a higher frequency than previously reported. This may be explained by the high frequency of recurrent or metastatic disease at study entry. TP53 mutation was associated with a statistically significant reduction in overall survival in patients with recurrent and metastatic ACC. These findings suggest that stratifying by TP53 status may be of clinical value to inform follow-up strategy in addition to established clinical, pathological and genomic biomarkers.
Assessing risk-based LDCT screening strategies versus the current USPSTF lung cancer screening recommendations at an institutional setting.
Authors: Carol Velez Martinez, Aswani Thurlapati, Samina Hirani, Constance Larea Cole, Jade Abad, Kavitha Beedupalli, Richard P. Mansour
Journal: Journal of Clinical Oncology (2020)

e13572 Background: Lung cancer is the leading cause of cancer related deaths in men and women with 1.76 million deaths worldwide in 2018 [1]. Given its high prevalence and mortality, trials were developed to improve screening strategies. National-Lung-Screening-Trial showed a 20% relative-risk-reduction in mortality in people screened with annual low-dose-CT-scan [2] leading to the implementation of current USPSTF guidelines. We used USPSTF screening criteria to estimate the proportion of non-small cell lung cancer (NSCLC) patients that would have been screening-eligible at our institution.Upon chart review 33% of overall lung cancer patients at our institution did not meet the screening guidelines. We decided to investigate the need to modify the current screening guidelines of our institution based on individual risk assessment. Methods: We conducted a retrospective observational cohort study of the new diagnoses at Louisiana-State-University-Shreveport from 2011-2015. Patients were categorized into high-risk (groups 1 and 2), moderate risk, and low risk according to 2018 NCCN Lung Cancer Screening Guidelines Version 1.2020 [3]. To differentiate between high-risk group 2 and moderate risk, the Tammemagi lung cancer risk calculator was employed, considering 1.3% threshold of lung cancer risk over 6-year time frame [4]. According to NCCN, high-risk group 1 and 2 are eligible for annual low-dose-CT-scan. Results: 33% of overall lung cancer patients at our institution did not meet the screening guidelines criteria, among the 33% ineligible for screening, only 12.5% fell under the high-risk category based on the Tammemagi calculator. Conclusions: Despite using individual risk assessment based on Tammemagi calculator, 87.5% of lung cancer patients ineligible to current USPSTF guidelines are still missing the eligibility for screening at our institution. We believe more efficient risk prediction models have to be developed to improve selection of individuals for lung cancer screening.
Quality-adjusted life year in 304 treated nasopharyngeal carcinoma palients
Authors: Yan-ning Li, Gao-ming Huang
Journal: BMJ (2008)

To evaluate quality-adjusted life year(QALY) and relevant impact factors in 304 patients with nasopharyngeal carcinoma(NPC),post-radiotherapeutic subjects were surveyed by means of questionnaire and simplified Washington University-quality of life(UW-QOL).QALYs were calculated and impact factors were identified.Duration of follow-up and age were negatively correlated with QALY.Patients at lower N stage had increased QALY.Decreased QALY was found in recurrent patients.Due to coconsideration to the lost quality of life and survival,QALY could serve as an effective method to evaluate the burden of disease in NPC patients.
中山古镇人群体重指数及腰臀比的变化分析
Authors: 潘英, 徐恩, 谢海峰, 吴桂昌, 王剑威, 梁睿, 陆雪芬
Journal: BMJ (2006)

比较分析2000年与1996年广东省中山古镇人群体重指数、腰臀比的变化.发现1996年男性、女性的体重指数分别为22.3±7.1和21.7±3.3,腰臀比分别为0.85±0.07和0.83±0.09.2000年的男性、女性体重指数分别为23.3±3.5和23.6±15.53,腰臀比分别为0.88±0.08和0.89±1.65. 2000年较1996年体重指数、腰臀比有明显上升。
Venetoclax (Ven) added to intensive chemo with cladribine, idarubicin, and AraC (CLIA) achieves high rates of durable complete remission with low rates of measurable residual disease (MRD) in pts with newly diagnosed acute myeloid leukemia (AML).
Authors: Tapan M. Kadia, Guillermo Garcia-Manero, Musa Yilmaz, Courtney Denton Dinardo, Marina Konopleva, Guillermo Montalban-Bravo, Gautam Borthakur, Elias Jabbour, Nitin Jain, Michael Andreeff, Nicholas James Short, Ghayas C. Issa, Maro Ohanian, Prithviraj Bose, Naval Guastad Daver, Sa A Wang, Rebecca Tidwell, Zeev Estrov, Farhad Ravandi, Hagop M. Kantarjian
Journal: Journal of Clinical Oncology (2020)

7539 Background: Ven is a BCL2 inhibitor that is approved in combination with lower intensity therapy for pts with newly diagnosed AML who are ineligible for intensive chemo. We previously reported the safety and efficacy of cladribine and araC with idarubicin in young and fit pts with AML. Here, we studied the combination of ven with the intensive CLIA regimen in newly diagnosed AML. Methods: Pts &lt; 65 yrs with newly diagnosed FLT3-wildtype AML were enrolled. Induction was cladribine 5 mg/m 2 IV on D 1-5, followed by ara-C 1.5 g/m 2 IV on D 1-5, idarubicin 10 mg/m 2 IV D 1-3, and ven at an effective dose of 400mg PO on D2-8. There was no ramp up for ven and dose modifications for CYP3A4 inhibitors were made. Consolidation consisted of up to 5 more cycles of CLIA+Ven. All pts underwent baseline next generation sequencing and MRD testing by multiparameter flow cytometry at the time of response. Results: 18 pts are enrolled, with a median age of 50 yrs (range, 18-64). Baseline pt characteristics are in Table. 16 pts were evaluable for response and 2 are too early. 14 of 16 pts (88%) achieved a remission, including 10 (63%) complete remission (CR) and 4 (25%) CR with incomplete count recovery (CRi). The median time to response was 1 cycle and the median number of cycles given was 2 (1-5). 10 of the 14 responders (71%) had undetectable MRD at the time of remission. Both nonresponding pts had a complex karyotype and 1 had a TP53 mutation. With a median follow up of 4.5 months (0.2 – 11.2), none of the responding pts have relapsed. 8 of the 14 responders (57%) have received allogeneic stem cell transplant. The median survival has not been reached; the 6-month OS and RFS are 90% and 100%, respectively. Treatment was well tolerated, with 0% 4-week mortality. The median days to ANC ≥ 1 and Platelets ≥ 100 were 30 (19-49) and 26 (18-39), respectively. Tumor lysis syndrome was not seen. The most common adverse events were neutropenic fever, pneumonia, nausea, and liver transaminitis. Conclusions: The addition of ven to CLIA was safe and effective in newly diagnosed pts with AML. The combination was not associated with early mortality or prolonged myelosuppression, but did result in high rates of durable MRD negative remissions. Clinical trial information: NCT02115295 . [Table: see text]
北京市高血压患者血压控制情况及影响因素分析
Authors: 杨晓辉, 李海宴, 姚崇华
Journal: BMJ (2004)

2000～2001年中国心血管健康多中心合作研究调查资料显示,35～74岁的中国成年人的高血压治疗率为28.2%,控制率仅为8.1%[1].因此,深入了解影响目前北京市药物治疗的高血压患者的血压控制的因素,可以为更有效地控制高血压提供参考。
Daily Temperature and Bacillary Dysentery: Estimated Effects, Attributable Risks, and Future Disease Burden in 316 Chinese Cities
Authors: Zhidong Liu, Michael Xiaoliang Tong, Jianjun Xiang, Keith Dear, Changke Wang, Wei Ma, Liang Lu, Qiyong Liu, Baofa Jiang, Peng Bi
Journal: Environmental Health Perspectives (2020)

Background: Bacillary dysentery (BD) remains a significant public health issue, especially in developing countries. Evidence assessing the risk of BD from temperature is limited, particularly from national studies including multiple locations with different climatic characteristics. Objectives: We estimated the effect of temperature on BD across China, assessed heterogeneity and attributable risks across cities and regions, and projected the future risk of BD under climate change. Methods: Daily BD surveillance and meteorological data over 2014–2016 were collected from the Chinese Center for Disease Control and Prevention and the China Meteorology Administration, respectively. A two-stage statistical model was used to estimate city-specific temperature–BD relationships that were pooled to derive regional and national estimates. The risk of BD attributable to temperature was estimated, and the future burden of BD attributable to temperature was projected under different climate change scenarios. Results: A positive linear relationship for the pooled effect was estimated at the national level. Subgroup analyses indicate that the estimated effect of temperature on BD was similar by age (≤5y or >5y) and gender. At baseline, estimated attributable risks for BD due to average daily mean temperatures above the 50th percentile were highest for the Inner Mongolia (16%), Northeast China (14%), and Northern China (13%). Most of the individual cities in the same regions and most of the cities in the Northwest, Southern, and Southwest regions, had high attributable risks (≥5%). The Northern, Northeast, Inner Mongolia, Northwest, and Southern China regions were identified as high risk for future BD, with estimated increases by the 2090s compared with baseline of 20% (95% confidence interval: 11%, 27%), 15% (6%, 20%), 15% (−1%, 22%), 12% (1%, 19%), and 11% (5%, 15%), respectively, under Representative Concentration Pathway 8.5. Conclusions: The positive association between temperature and BD in different climatic regions of China, and the projection for increased risk due to climate change, support efforts to mitigate future risks. https://doi.org/10.1289/EHP5779
Efficacy of pelvic floor muscle stimulation physiotherapy for female patients with overactive bladder
Authors: Huafeng Zhang, Jia Zhao
Journal: BMJ (2015)

A total of 210 female patients with overactive bladder(OAB) were divided into M receptor blockage(M, n=71), pelvic floor muscle stimulation physiotherapy(S, n=70) and combination(C, n=69) groups. After one course of treatment, the OAB symptom scores were compared to pre-treatment values(P<0.05). After a second course, the overall response rate was 69% in group S. Pelvic floor muscle stimulation physiotherapy provided excellent sustained outcomes.


Key words: 
Urinary bladder, overactive; Electric stimulation therapy
不同多普勒踝肱比冠心病患者心血管结构和功能比较
Authors: 蔡丽萍, 方平, 宋维, 谭跃萍, 沈若宇, 林继军, 袁志忠, 周长林
Journal: BMJ (2004)

采用多普勒法测定73例冠心病患者的多普勒踝肱比,并比较踝肱比＜1(A组)与踝肱比＞1(B组)患者心脏及血管结构与功能的指标及冠状动脉造影结果,显示A组的颈动脉、股动脉中内膜厚度、左室舒张末期内径和左室重量均明显大于B组,左室射血分数明显小于B组,3支病变发生率明显高于B组,差异有显著性。
Effects of compliance with long-term antihypertensive treatment on carotid arterial intimal-medial thickness in the elderly with hypertension
Authors: 翟丽华, 吴瑛, 梁旭, 董少红, 杨纯玉
Journal: BMJ (2005)

目的 观察依从性差异对应用氨氯地平+培哚普利降压长期疗效的影响.方法对79名血压≥160/100 mm Hg(1 mm Hg=0.133 kPa)的老年高血压患者给予氨氯地平+培哚普利治疗,随访(3.3±0.5)年,分别在治疗前及治疗后第1、2、3年检测其血压、颈动脉内中膜厚度(IMT)和颈动脉斑块的Crouse积分.随访结束时,根据实际服药情况将患者分为依从治疗组(A组,41例)和非依从治疗组(B组,38例),比较两组治疗后血压和颈动脉参数的差异.另设同期体检的血压正常的老年人为对照组(C组,33例).结果 A、B组的6个位点平均颈动脉IMT(MIMT)、双侧颈总动脉平均IMT(MCCA-IMT)、双侧颈内动脉平均IMT(MICA-IMT)和颈动脉斑块的Crouse积分均较C组显著增高(均P<0.01).A组治疗后收缩压、舒张压达标率较B组显著增高(分别为80.5%～87.8%比18.4%～23.7%,85.4%～95.1%比52.6%～60.5%,均P＜0.01),MIMT、MCCA-IMT、MICA-IMT及颈动脉斑块的Crouse积分均较B组显著下降(均P<0.01).B组3年后总的心、脑血管事件发生率较A组显著增高(31.58%比12.20%,P<0.05).结论长期联合应用氨氯地平+培哚普利能有效降低血压、逆转大动脉结构异常、延缓动脉粥样硬化进展,这些益处的获得有赖于患者良好的依从性。
Predictors of increased episode expenditure and exceeding target price under the oncology care model.
Authors: Seojin Park, Dexter Waters, Ryan Thomas, Andrew Jehyun Song, Karen Walsh, Valerie Pracilio Csik, Amy Leader, Vittorio Maio
Journal: Journal of Clinical Oncology (2020)

e19403 Background: The Oncology Care Model (OCM) incentivizes participants to keep episode expenditure below target price; however, little is known about the adequacy of adjustments in target price calculation. This study investigates predictors of increased expenditures and explores how these predictors are associated with exceeding target price for hematologic and solid malignancies. Methods: Non-decedent OCM episodes, categorized as hematologic malignancies (HMs) or solid malignancies (SMs), from 7/1/2016 - 7/1/2018 attributed to our institute were analyzed. Multiple linear regression was used to identify factors associated with increased episode expenditure. Multiple logistic regression was used to evaluate whether such factors increased likelihood of expenditure exceeding target price. Results: Of 1,975 episodes, 499 (25.3%) were HMs and 1,476 (74.7%) were SMs. 54.3% of HMs and 35.2% of SMs had episode expenditure exceeding target price. In HMs, novel therapy use (NT), inpatient admission (INPT), Part B drug use (PB), Part D use (PD), and radiation therapy (XRT) were associated with increased episode expenditure. Of those, INPT and PD increased the likelihood of expenditure exceeding target price. XRT decreased the likelihood of expenditure exceeding target price (Table). In SMs, NT, INPT, emergency department visit, home health aides, durable medical equipment use, PB, PD, XRT, and surgery were associated with increased episode expenditure. Of those, NT, INPT, PB and PD increased the likelihood of expenditure exceeding target price. XRT and receipt of surgery decreased the likelihood of expenditure exceeding target price (Table). Conclusions: INPT and PD significantly increased episode expenditures in both HMs and SMs, leading to expenditures exceeding target prices determined by the OCM benchmark risk-adjustments in both cancer types. NT and PB were significant predictors of increased expenditure and the likelihood of exceeding target price in SMs, but not in HMs. Our findings suggest that there may be opportunities to improve the current model by refining the adjustment for these factors to better reflect real world expenditures. [Table: see text]
Sarcopenia as a negative predictive marker for treatment with pembrolizumab as a second line in patients with metastatic non-small cell lung cancer.
Authors: Milla Petrova, Gerogi Valchev, Nikolay Vladimirov Conev, Eleonora Dimitrova, Bozhil Robev, Marsella Boneva, Boian Pavlov, Velko Minchev, Teodora Karanikolova, Spartak Valev, Radostina Gencheva, Georgi Zhbantov, Anika Ivanova, Constanta Timcheva, Ivan Donev
Journal: Journal of Clinical Oncology (2020)

e21541 Background: In this multicentric retrospective study we evaluated the incidence of clinical benefit rate (CBR) and its relation to Neutrophil-Lymphocyte Ratio (NLR) and psoas major muscle area (PMMA), 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 = 84) whose tumors expressed PD-L1≥1% were retrospectively analyzed between Apr 2017 and Dec 2019. All patients received platinum-containing chemotherapy (CT) as a first line treatment. Absolute neutrophil, and absolute lymphocyte count enabled calculation of NLR; NLR1 - before CT, NLR2 – before P infusion. ΔNLR was calculated. Area of PMMA was calculated at L3 position on computed tomography. CBR was defined as the proportion of patients with a partial response or stable disease for at least six months since no patients with complete response were recorded. PMMA was calculated before CT and before the P infusion; (% change rate of PMMA = ([1-PMMA before P / PMMA before CT]*100). Patients with the change rate of PMMA≥10% were considered with sarcopenia - 30 (35.7%). Results: CBR was 72.6%. There were not significant correlations between NLR, PMMA and their dynamics. Patients without clinical benefit (CB) had significantly higher values of ΔNLR (1.38±2.2) and ΔPMMA (11.2±10.7) than patients with CB - ΔNLR (0.12±1.88; p = 0.023) and ΔPPMA (8.9±13.5; p = 0.001). ROC analysis revealed that at the optimal cutoff values of all markers, ΔPMMA achieved the greatest AUC = 0.738 (95% CI, 0.77-0.93) and could distinguish between patients with or without CB with sensitivity of 77.3% and specificity of 83.6%. Sarcopenic patients had significantly shorter mean progression-free survival (PFS) – 6.5 months (95%, CI 5.1-8.1) than the rest – 20.8 months (95%, CI 16.7-24.1). Moreover in the multivariable analysis, ΔNLR (HR 1.19, 95% CI 1.05-1.38, p = 0.01) and ΔPPMA ≥10 % (HR 5.4, 95% CI 2.82-10.19, p &lt; 0.001) were found to be independent predictive factors for shorter PFS. Conclusions: Our data suggests that ΔPMMA and ΔNLR are potential predictive markers, which may identify patients appropriate for immunotherapy as a second line treatment.
Comprehensive analysis of advanced-stage solid tumors from TCGA reveal widespread variation of genomics evidence levels across cancer types.
Authors: Dilhan Weeraratne, Elisa Napolitano Ferreira, Miguel Mitne Neto, Hu Huang, David Brotman, Ana Maria Fraga, Rodrigo Fernandes Ramalho, Matheus Burger, Aloisio Souza Felipe-Silva, Jane Snowdon
Journal: Journal of Clinical Oncology (2020)

e13547 Background: Improved scalability and affordability of next generation sequencing (NGS) has pivoted cancer care toward genomics-driven treatment decisions. Particularly in advanced-stage or refractory cancer, clinical insights gleaned from NGS have become an integral option as these patients have typically exhausted all lines of available therapy. As precision oncology evolves, NGS is expected to have a differential impact based on the cancer type. In this study, a comprehensive NGS panel was used to determine the strength of clinical evidence in various advanced stage tumor samples from The Cancer Genome Atlas (TCGA). Methods: A hybrid capture panel, Oncofoco, was developed to evaluate SNVs, INDELs, CNVs and TMB in 366 genes. The panel’s utility was validated by interrogating a broader cohort of 2847 TCGA samples (advanced tumors with T3 or T4; or N &gt; = 1; or M &gt; = 1). Watsonä for Genomics, an artificial intelligence offering, was used for variant interpretation and annotation of the 366 genes. A clinical evidence classification system that evaluated the strength of biomarker/drug response associations was used for annotation with level 1/R1 strongest and level 4 weakest from clinical literature, FDA drug labels and guidelines (PMID:28890946). Results: The highest level of evidence for the top nine frequently occurring advanced stage cancers in TCGA is shown in Table. Conclusions: Thyroid cancer and cutaneous melanoma have emerged as the cancer types with the most level 1 evidence (FDA approved drugs) owing to BRAF V600E mutations. Kidney and prostate cancers show no cases with level 1 evidence and also had the largest fraction of unactionable tumors. Over half of colorectal cancer cases had level R1 resistance evidence attributed to KRAS and NRAS mutations. The clinical utility of NGS in late-stage refractory cancer varies widely by tumor type. The presence of level 3 and level 4 evidence in all cancer types bodes well for the development of new targeted drugs. [Table: see text]
DNA methylation signatures predicting liver metastasis of colorectal cancer: A proof-of-concept pilot study.
Authors: Jianming Ying, Weihua Li, Kaihua Liu, Cong Xiao, Shuyu Wu, Hua Bao, Xue Wu, Xiaonan Wang, Yang Shao
Journal: Journal of Clinical Oncology (2020)

e16080 Background: Liver metastasis (LIM) is the leading cause of death in colorectal cancer (CRC) patients. Early detection of LIM may improve outcome in CRC patients. The aim of this study was to evaluate the feasibility of predicting LIM of CRC using methylation profiles. Methods: We performed Roche targeted (~5.5 million methylation sites) bisulfite sequencing of matched primary, metastatic and their adjacent normal tissue samples from 5 CRC patients with LIM, 5 patients with lung metastasis (LUM) and 8 patients without metastasis in the training cohort (n = 48 samples). Differential methylation regions (DMR) of LUM were identified and a predictive model was developed. The model was further validated in primary tumor sample from nine patients (6 with LIM). Results: By comparing primary tumor vs adjacent normal tissues and metastatic tumor vs adjacent normal tissues in CRC patients with LIM, we identified 28954 common DMRs which indicating the methylation characteristic of CRC with LIM. Similarly, 16187 DMRs were identified in patients with LUM. 9179 DMRs are shared in both LIM and LUM comparisons which should be the common characteristic of CRC tumor tissue regardless of the location of metastasis. 7008 DMRs are LUM specific and 19775 DMRs are LIM specific. In order to predict LIM in primary, early changes in LIM specific DMRs should be identified. Hence, we further selected 4134 DMRs by chossing significantly differentically methylated regions between LIM primary tissues and LUM primary tissues. To increase the ability of distinguishing LIM from other normal tissues and non-matastasis CRC tumors, 1215 DMRs were finally selected which also showed increasing or decreasing trend of methylation level through the progression of CRC. The final 1215 biomarkers were used to construct a random forest model using methlylation profile of 5 CRC patients with LIM as positive training data and 5 CRC patients with LUM as well as 8 patients without metastasis as negative training data. Through the feature recursive elimination method, one methylation site (chr8.72468901-72469000) was identified with ROC of 0.9 in the training dataset. The predictive model was validated in an independent dataset which is composed of 6 patients with LIM and 3 patients without metastasis, and achieved an AUC of 0.87. Conclusions: Our findings demonstrate the utility of methylation biomarkers for the molecular characterization of metastatic precursors, with implications for prediction and early detection of liver metastasis in CRC.