tbuckley/cabot-search huggingface dataset:
Phase III study of first-line zolbetuximab + CAPOX versus placebo + CAPOX in Claudin 18.2<sup>+</sup>/HER2<sup>−</sup>advanced or metastatic gastric or gastroesophageal junction adenocarcinoma: GLOW.
Authors: Manish A. Shah, Jaffer A. Ajani, Salah-Eddin Al-Batran, Yung-Jue Bang, Daniel Catenacci, Peter C. Enzinger, David H. Ilson, Sunnie Kim, Florian Lordick, Kohei Shitara, Eric Van Cutsem, Ahsan Arozullah, Jung Wook Park, Rui-hua Xu
Journal: Journal of Clinical Oncology (2020)

TPS4648 Background: Gastric cancer is the fourth leading cause of cancer death worldwide. Capecitabine + oxaliplatin (CAPOX) is a standard first-line treatment for advanced gastric cancer. Claudin (CLDN)18.2 has emerged as a promising targetable biomarker. In healthy tissue, CLDN18.2, a tight junction protein, is confined to gastric mucosa (ie, cells in the pit and base regions of gastric glands). Upon malignant transformation, structural loss in gastric or gastroesophageal junction (G/GEJ) adenocarcinoma cells may allow antibodies more access to previously unavailable CLDN18.2. Zolbetuximab is a chimeric IgG1 monoclonal antibody that specifically binds to CLDN18.2 and mediates cell death through antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity. Results of a phase 2 study (NCT01630083) showed prolonged survival of patients with CLDN18.2-positive (CLDN18.2 + ) advanced G/GEJ adenocarcinoma treated with zolbetuximab + epirubicin, oxaliplatin, and capecitabine (EOX) vs EOX alone. Methods: This phase 3, double-blind, placebo-controlled study (NCT03653507) will enroll ~500 adult patients from global sites. Patients are required to have CLDN18.2 + /HER2 − locally advanced unresectable or metastatic G or GEJ adenocarcinoma that is radiographically evaluable per RECIST v1.1. Patients are not permitted to have received prior treatment with chemotherapy for advanced or metastatic G or GEJ adenocarcinoma. Patients will be randomly assigned 1:1 to receive either zolbetuximab plus CAPOX or placebo plus CAPOX. Randomization will be stratified by region (Asia vs non-Asia), number of metastatic sites (0 to 2 vs ≥3), and prior gastrectomy (yes vs no). Zolbetuximab will be administered at a loading dose of 800 mg/m 2 IV on Cycle 1 Day 1 followed by 600 mg/m 2 IV every 3 weeks. Central testing of tumor tissue will determine CLDN18.2 and HER2 status (if unknown); patients will be considered CLDN18.2 + if ≥75% of tumor cells demonstrate moderate-to-strong membranous immunohistochemical staining. The primary objective is to compare progression-free survival between treatment arms. Secondary endpoints are overall survival; objective response rate; duration of response; and the safety/tolerability, pharmacokinetics, and immunogenicity of zolbetuximab. As of January 31, 2020, 127 sites were active and open to enrollment. Clinical trial information: NCT03653507 .
FDA pooled analysis of time to treatment discontinuation (TTD) in frontline advanced renal cell carcinoma trials.
Authors: Elaine Chang, Yutao Gong, Chana Weinstock, Laura L Fernandes, Jessica Hawley, Thomas Gwise, Meredith M. Regan, Toni K. Choueiri, Brian I. Rini, David F. McDermott, Michael B. Atkins, Daniel L. Suzman, Amna Ibrahim, Shenghui Tang, Marc Robert Theoret, Paul Gustav Kluetz, Richard Pazdur, Julia A. Beaver
Journal: Journal of Clinical Oncology (2020)

5081 Background: Time to treatment discontinuation (TTD) has been proposed as a potential pragmatic real-world data (RWD) endpoint, and was closely correlated with progression-free survival (PFS) in pooled analyses of non-small cell lung cancer (NSCLC) and breast cancer trials across therapeutic classes (Blumenthal, Ann Onc 2019; Gao, SABCS Abstract P5-14-02). Methods: We analyzed data from all randomized patients (pts) in the phase 3 trials submitted to FDA 2016-18 evaluating a combination therapy (Rx) of an immuno-oncology agent and another systemic Rx (IO-X) versus sunitinib (SUN) for treatment-naïve advanced renal cell carcinoma (RCC). Protocols specified treatment until progression, but treatment beyond progression was allowed. TTD was defined as the time from the start of Rx to time of treatment discontinuation of both drugs in combination Rx or SUN. We measured TTD in treatment-defined subgroups (IO-X and SUN) and across all pts, and pt-level correlation (Pearson’s r) between TTD and PFS and between TTD and overall survival (OS). We also determined rates of disparity between TTD and PFS greater than 3 months. Results: Of 3758 pts (IO-X, n=1878; SUN, n=1880), 3190 pts (85%) had a TTD event, and 1899 pts (51%) had a PFS event. Median TTD was longer among pts receiving IO-X than SUN (12.3 versus 8.0 months). Regardless of drug class, more pts had early (TTD shorter than PFS by ≥ 3 months) TTD events than late TTD (13.4% versus 6.4%, overall). We found higher correlation between TTD and PFS in pts receiving SUN ( r = 0.89) than pts receiving IO-X ( r = 0.72). Overall, TTD was more closely associated with PFS ( r = 0.80) than with OS (0.61). Conclusions: Observed correlations of TTD to PFS were stronger compared to the correlation of TTD to OS. This may be expected because OS is farther removed in time from TTD than is PFS. In contrast to TTD in NSCLC, more than twice as many pts in RCC trials had early TTD than late TTD, regardless of Rx group, which may indicate earlier discontinuation with combination Rx due to additive toxicity. Limitations include the censoring of PFS and OS and the post-hoc nature of this analysis. [Table: see text]
A population survey of knowledge, attitude and behavior for risk factor and prevention of stroke in two urban districts of Beijing
Authors: Rong-rong Hua, Sheng-ping Wu, Xiao-juan Ru, Wen-zhi Wang, Bin Jiang, Hui Zhang, Qiu-ju Bao, Hong-mei Liu, Xiao-li Du
Journal: BMJ (2010)

Total 1350 subjects were selected by cluster random sampling from Chongwen District and Shijingshan District in Beijing with a populations of 100 000.Chongwen District represented a typical urban district and Shijingshan represtnted a newly extended urban district.Qualified investigators conducted face-to-face survey using  uniform questionnaire and measurement, dealing with  knowledge, attitude and behavior for risk factors of stroke in two districts.The results showed:in Chongwen District,  awareness rates of the diagnostic  of hypertension, antihypertensive drugs can lower  risk of cardiocerebral vascular disease, and criteria for obesity were 71.3%, 87.3% and 22.9% respectively,which were significantly higher than those in Shijingshan District.The awareness rate of bad temper may increase  risk of cardiocerebral vascular disease was lower in  Chongwen District.There were no significant differences in attitude between two districts.In Chongwen District  level of three risk factors (smoking and obesity) was significantly lower than Shijingshan, but action of self-examination was also significantly lower.Generally, there was higher level in health knowledge and lower level of risk factors in Chongwen District.The hypertension-related knowledge and behavior was not entirely consistent.It is necessary to transform knowledge into behavioral changes or intervention of risk factors in population with high awareness like Chongwen District.

Key words: 
Cerebrovascular accident;  Health knowledge, attitudes, practice
Developing post-treatment PET/CT volumetric prognostic index for non-small cell lung cancer.
Authors: Liu Liu, Jingmian Zhang, Mark K. Ferguson, Daniel E. Appelbaum, Yonglin Pu
Journal: Journal of Clinical Oncology (2020)

e21085 Background: The aim of this study is to model and validate a post-treatment PET/CT volumetric prognostic (ptPVP) index for risk assessment after definitive therapy for NSCLC. Methods: This IRB-approved retrospective cohort study included 1028 NSCLC patients diagnosed between 2004 and 2017. Variables included: pre-treatment whole-body metabolic tumor volume (MTVwb) measured on baseline FDG PET/CT, patient age, clinical TNM stage, ECOG performance status (PS), gender, tumor histology, treatment type, and survival outcomes. Patients were assigned to a modeling cohort (531 patients) for modeling ptPVP index and a clinical index with a multivariate Cox regression model. The ptPVP index was validated with a separate validation cohort (497 patients) by comparing the prognostic value of ptPVP index against its individual independent variables and the clinical index. Results: The ptPVP index generated from the modeling cohort was comprised of 5 variables including treatment type (surgery, no surgery, and no therapy), age, clinical TNM stage (stage I or II, III, and IV), PS ( 0, 1, and ≥ 2) and MTVwb. The clinical index was comprised of above 4 clinical variables without MTVwb. Univariate Cox models showed significant association of the ptPVP index with OS with Hazard ratio (HR) of 2.72 (95% CI = 2.39-3.09, p &lt; 0.001). The C-statistic of ptPVP index (0.71) was significantly greater than that of clinical index (0.68) (p = 0.001). In the validation cohort, univariate Cox models showed significant association of the ptPVP index with OS (HR = 3.09, 95% CI = 2.64-3.61, p &lt; 0.001). The ptPVP index showed greater prognostic power (C-statistic = 0.72) than that of the clinical index (C-statistic = 0.70, p = 0.001), treatment type (C-statistic = 0.66, p &lt; 0.001), MTVwb (C-statistic = 0.67, p &lt; 0.001), age (C-statistic = 0.58, p &lt; 0.001), clinical 9-group TNM staging (C-statistic = 0.66, p &lt; 0.001), and PS (C-statistic = 0.57, p &lt; 0.001). Multivariate Cox regression analysis demonstrated a significant association of ptPVP index with OS (HR = 3.06, 95% CI of 2.60-3.61, p &lt; 0.001) after adjusting gender and NSCLC histology. A better separation of Kaplan-Meier curves of patients grouped by ptPVP index than those grouped by clinical index, MTVwb, or clinical TNM stage was evident. Conclusions: The ptPVP index developed for NSCLC patients demonstrated moderately prognostic power and better prognostic ability than its individual independent variables and clinical index without MTVwb. It provides a practical quantitative risk assessment for the patient follow-up and management after initial treatment.
Prostate cancer screening patterns among LGBT populations.
Authors: Sung Jun Ma, Oluwadamilola Temilade Oladeru, Joseph Miccio, Katy Wang, Kristopher Attwood, Anurag K Singh, Daphne A. Haas-Kogan, Paula M Neira
Journal: Journal of Clinical Oncology (2020)

e19077 Background: More than 10 million Americans identify themselves as lesbian, gay, bisexual, and transgender (LGBT), and the majority of male-to-female (MTF) transgender individuals still have prostates even after surgical transitions. Guidelines on prostate specific antigen (PSA) screening for LGBT populations are limited, and informed and shared decision making are encouraged by various organizations. However, patterns of care for PSA screening in LGBT populations remains unclear. To address this knowledge gap, we conducted a cross sectional study to evaluate self-reported PSA screening and decision making among LGBT populations. Methods: The Behavioral Risk Factor Surveillance System database was queried for LGBT adults from 2014-2016 and 2018. Those with prior prostate cancer were excluded. Multivariable logistic regression was performed to evaluate the association of LGBT status with PSA screening, informed and shared decision making, after adjusting for demographic characteristics and survey weights. Results: A total of 164,370 participants were eligible for PSA screening (n = 156,548 for cisgender [CG]+straight, n = 156 for MTF+straight, n = 33 for MTF+gay, n = 52 for MTF+bisexual, n = 51 for MTF+other sexual orientation [SO], n = 3354 for CG+gay, n = 1641 for CG+bisexual, n = 2535 for CG+other SO), representing a weighted estimate of 1.2 million LGBT populations. When compared to CG+straight, CG+gay/bisexual cohorts were more likely to undergo PSA screening within the past 2 years (CG+gay: OR 1.08, p &lt; 0.001; CG+bisexual: OR 1.06, p &lt; 0.001), have ever received PSA screening (CG+gay: OR 1.30, p &lt; 0.001; CG+bisexual: OR 1.12, p &lt; 0.001), and be recommended for PSA screening by their physicians (CG+gay and bisexual: OR 1.16, p &lt; 0.001). All other cohorts were less likely to do so (all OR &lt; 1, p &lt; 0.05). MTF+gay and CG+gay participants were more likely to make informed decision (MTF+gay: OR 3.13, p &lt; 0.001; CG+gay: OR 1.09, p &lt; 0.001), while all other cohorts were less likely to do so (all OR &lt; 1, p &lt; 0.05). CG+gay participants were also more likely to share decision (OR 2.51, p &lt; 0.001), while there were no associations for all other cohorts (all p &gt; 0.05). Conclusions: Select gay populations were more likely to undertake PSA screening recommended by their physicians and participate in informed and shared decision making. However, other LGBT populations were less likely to make informed decisions, and transgender participants were less likely to undergo PSA screening. Further research efforts are needed to improve informed and shared decision making for PSA screening in such underserved population.
Phase II study of intraperitoneal submicron particle paclitaxel (SPP) plus IV carboplatin and paclitaxel in patients with epithelial ovarian cancer undergoing cytoreductive surgery.
Authors: Sally Anne Mullany, David S. Miller, Katina Robison, Kimberly Levinson, Yi-Chun Lee, Seiko Diane Yamada, Joan L. Walker, Maurie Markman, Alyson Marin, Peter Mast, Gere Dizerega
Journal: Journal of Clinical Oncology (2020)

e18046 Background: Although advances in chemotherapy, cytoreductive surgery, and maintenance therapy (SOC) improved PFS for high grade epithelial ovarian cancer, &gt; 20% of patients relapse during the first 6 months and 60% relapse after 6 months. Submicron particles (~800 nm) of paclitaxel (SPP) contain 1-2 billion molecules of pure drug that release tumoricidal levels of paclitaxel over many weeks. In a previous trial, percutaneous instillations of SPP in nonsurgical patients with intraperitoneal cancer were associated with reduced systemic and local toxicity as compared to standard chemotherapy regimens. (Williamson et al Cancer Chemo Pharm (2015) 75:1075). Methods: This study compared two dose-levels of IP SPP instilled in 200 ml of saline post-cytoreductive surgery. Eligible patients with primary (n = 6) or recurrent (n = 4) epithelial ovarian cancer who underwent complete cytoreductive surgery were enrolled to receive a single instillation of IP SPP followed by standard IV carboplatin and paclitaxel. Endpoints were PFS and evaluation of treatment-emergent adverse events. Clinical response was determined by CT scans and serum CA-125 measurements. Results: Of the 24 subjects screened, 10 were enrolled and received treatment: seven patients received 100 mg/m 2 and three received 200 mg/m 2 . For analysis purposes, 7 out of 10 subjects were evaluable (1 withdrew, 1 died unrelated to study drug during IV treatment and 1 was unevaluable). Upon completion of planned chemotherapy post-SPP instillation, the PFS at 6 months was 66% (4/6) and at 12-months 66% (4/6) using RECIST 1.1. One subject had a complete response at the end of IV treatment, but died (unrelated to study treatment) before PFS evaluation. There was one case of incision dehiscence and one case of vaginal cuff leakage after surgery. Conclusions: This pilot study supports further evaluation of IP SPP to treat peritoneal carcinomas. Clinical trial information: NCT03029585.
Acute gout attack during upper gastrointestinal bleeding: a report of 186 cases
Authors: Jianqiu Zhao, Xiangdong Lu, Shujun Wen
Journal: BMJ (2014)

The clinical data of 186 patients with acute gout attack during upper gastrointestinal bleeding were analyzed retrospectively.The ratio of male to female was 1.7∶1, smokers and alcohol drinkers accounted for 66.1% (123/186) and 62.4% (116/186) of patients were had underlying diseases.All patients had different degree of joint painful and fever, the blood uric acid levels were higher.Gastroscopic examinations were performed in 166 patients, of whom 88 cases received endoscopic intervention.The symptoms of gout were improved after treatment with dexamethasone and celecoxib; and the medication did not induce or increase gastrointestinal bleeding.


Key words: 
Gastrointestinal bleeding; Gout
新生儿缺氧缺血性脑病的病因及发病机制
Authors: 毛健
Journal: BMJ (2009)

缺氧缺血性脑病(hypoxic-ischemic encephalopathy,HIE)是新生儿常见的临床疾病,是围产期窒息所致的新生儿脑缺氧缺血性损伤,病理改变为脑水肿、选择性神经元坏死、颅内出血和脑室周围白质软化等,临床上可出现一系列中枢神经系统异常表现.严重者可导致新生儿死亡,幸存者多留有神经系统后遗症如智力低下、脑瘫、痉挛、癫痫和共济失调等.现就其病因和发病机制做一简介。
A phase II trial of preoperative FOLFIRINOX followed by gemcitabine-based chemoradiotherapy in patients with borderline resectable pancreatic ductal adenocarcinoma (BR PDAC).
Authors: Michael Wysota, Amanda Jirgal, Ana Acuna-Villaorduna, Shankar Viswanathan, Andreas Kaubisch, Eswar Gadde, Rafi Kabarriti, Sanjay Goel, Jennifer W. Chuy
Journal: Journal of Clinical Oncology (2020)

4638 Background: Preoperative (preop) therapy is widely accepted as the standard of care for patients (pt) with BR PDAC with limited evidence for a specific regimen. This study aimed to assess the efficacy of FOLFIRINOX (FOL) chemotherapy followed by gemcitabine-based chemo-radiotherapy (RT) as preop therapy in pt with BR-PDAC. Methods: This single arm Simon two stage phase II trial in pt with BR PDAC was conducted in two phases. The first phase included 4 cycles of FOL, and the second included weekly gemcitabine (1000 mg/m2) for 6 cycles with concomitant intensity-modulated RT (50.4 Gy in 28 fractions)(Gem/RT).The primary aim was to compare R0 resection rate (H 0 : ≤40% vs H a ≥60%) using one-sample one-sided Z test. Secondary outcomes, including overall survival (OS) and progression-free survival (PFS) were assessed using Kaplan-Meier method. Results: Of 22 enrolled pt, 18 (81.8%) completed preoperative treatment. Median age at diagnosis was 63.4 years and 12 (54.5%) were female. There were 10 (45.5%) Hispanics, 4 (18.2%) non-Hispanic black, and 8 (36.4%) non-Hispanic white. Tumor location was predominantly head/neck (21, 95.5%), 15 (68.1%) had T2/3, and 9 (40.9%) had N2 (clinical) disease. Fourteen (64.6%) pt, had venous involvement, 5 (22.7%) had arterial, and 3 (13.6%), both. In the first phase, 20 (90.9%) completed 4 cycles of FOL, 6 (27.3%) required dose-reduction and dose was delayed in 12 (54.5%). Stable disease (SD) was achieved in 10 (52.6%), partial response (PR) in 8 (42.1%) and disease progression (PD) in 1 (5.3%) pt. Of 21 pt that entered the second phase, 18 (85.7%) completed 6 cycles of Gem/RT, 5 (26.3%) required dose-reduction and dose was delayed in 6 (31.6%). SD was achieved in 10 (55.6%), PR in 3 (16.7%) and PD in 5 (27.8%). All pt experienced at least one grade 1 adverse event (AE) and 12 (54.5%) at least one grade 3/4 AE, of which neutropenia was the most common-11 (50%). Of the 15 (68.1%) pt who underwent surgical resection, 12 (80%) achieved R0 margins and 5 (33.3%) required vascular reconstruction. The R0 rate among pt that received &gt;1 cycle of FOLFIRINOX was 54.5%. Adjuvant chemotherapy was offered to 6/15 pt (40%). The PFS and OS will be reported. Conclusions: An R0 resection rate of 54.5% with this limited sample size is significant at the 10% level. Neoadjuvant FOLFIRINOX followed by concomitant Gem/RT was well-tolerated. The study will be amended to include adjuvant FOL in line with the PRODIGE intergroup adjuvant study results. Clinical trial information: NCT01897454 .
果酸联合红蓝光治疗寻常性痤疮临床效果观察
Authors: 王翠玲, 徐刚林, 金娟娟
Journal: BMJ (2012)

采用果酸联合LED红蓝光痤疮治疗仪对70例Ⅱ～Ⅲ级寻常性痤疮患者进行连续5个疗程的治疗,具有较好疗效,有效率达97.1％,明显优于对照组的57.1％,且不良反应小、安全性好,适用于那些不能耐受内服和长期外用药物的患者。
Racial disparities in obesity and comorbidities among women with early breast cancer.
Authors: Kirsten A. Nyrop, Allison Mary Deal, Hyman B. Muss, Emily Damone, Michael Lorentsen, Tucker Brenizer, Shlomit S. Shachar
Journal: Journal of Clinical Oncology (2020)

e19061 Background: Both comorbidities and obesity (body mass index/BMI 30 or higher) are observed in women at the time of early breast cancer (EBC) diagnosis. This study investigates age and obesity and their association with disparities in comorbidities between black and white women at EBC diagnosis. Methods: This is a retrospective chart review of women with EBC (Stage I-III) treated at a single institution. Relative risk (RR) with 95% Confidence Interval (CI) for individual comorbidities are calculated for black compared to white patients, adjusted for age and BMI. Results: In a sample of 548 women, 26% are black and 74% are white. 18% of black patients vs 28% of white patients were age 65 or older (p = .01). 62% of black vs 33% of white patients had obesity (p &lt; .0001). 63% of black vs 47% of white patients had 2 or more total comorbidities at diagnosis (p = .003). 33% of black vs 10% of white patients had 2 or more obesity-related comorbidities (p &lt; .0001). 60% of black vs 32% of white patients had hypertension (p &lt; .0001); 23% of black vs 6% of white patients had diabetes (p &lt; .0001); and 28% of black vs 18% of white patients had high cholesterol (p = .02). In multivariable (MV) analysis adjusted for age and BMI, black women had 45% higher risk for hypertension [RR 1.45 (1.19-1.75), p = .0002)] and 44% higher risk for diabetes [RR 1.44 (1.02-5.86), p &lt; .0001)] at EBC diagnosis. However, after adjustment, differences by race were no longer seen for &gt; = 2 total comorbidities, &gt; = 2 obesity-related comorbidities, heart disease, or thyroid disease. Conclusions: This study documents significant disparities between black and white women with EBC with regard to high rates of obesity, overall comorbidities and obesity-related comorbidities. Future research should assess the potential impact of weight management (avoiding weight gain) interventions in the first 2 years post diagnosis on improving OS and BCSS among patients with obesity and in reducing OS and BCSS disparities between black and white women.
Analysis of clinical features and current therapy for aspiration pneumonia in the elderly
Authors: 程真顺, 杨炯, 林宇辉, 叶燕青, 杨亦斌
Journal: BMJ (2010)

Totally, 125 elderly inpatients with aspiration pneumonia (AP) were enrolled from departments of respiratory medicine and neurology at Zhongnan Hospital, Wuhan during June 2005 to October 2009 for analysis. Results showed that listlessness was manifested in 70 cases (56%), primary neurological illness in 80 cases (64%), 57 of them (46%) complicated with respiratory failure and 26 died with case-fatality of 21%. Main pathogen for them was Gram-negative bacillus, accounting for 57% of the total. Two kinds or more of antibiotics had ever been administered in 98 cases (78%), with an average length of antibiotics use for 28 days, ranging from one day to 128 days. Nasal feeding was instituted for those with choking over their feeding and coughing, and their inspired feeding was aspirated from the trachea or bronchi and lavished with bronchoscopy, with 38 cases by tracheal intubation, 26 by tracheotomy and 42 with artificial ventilation. Their average duration of hospital stay spanned 28 days with an average cost of 25 000 RMB yuan per capita, significantly higher than that for those with common pneumonia. In conclusion, clinical features of these elderly patients with AP were not so typical, most of them manifest severe, with lots of medical cost and bad prognosis.

Key words: 
Pneumonia,aspiration ;  Aged ;