tbuckley/cabot-search huggingface dataset:
Trabectedin and radiotherapy in soft-tissue sarcoma (TRASTS) study: An international, prospective, phase II trial in localized myxoid liposarcoma—A collaborative Spanish (GEIS), Italian (ISG) and French (FSG) group study.
Authors: Alessandro Gronchi, Nadia Hindi, Jean-Yves Blay, Andres Redondo, Roberta Sanfilippo, Carlo Morosi, Josefina Cruz Jurado, Pablo Luna Fra, Javier Martinez-Trufero, Claudia Maria Valverde Morales, Jesus Romero, Javier Peinado, Claudia Sangalli, Marie Pierre Sunyach, Cleofe Romagosa, Dominique Ranchère-Vince, Antonio Gutierrez, Paolo De Tos, Javier Martin Broto
Journal: Journal of Clinical Oncology (2020)

11514 Background: Myxoid liposarcoma (ML) exhibits especial sensitivity to trabectedin (T). In prospective series, T showed responses in 44% of patients (pts) with ML. ML is also sensitive to radiation therapy (RT) and preclinical data suggested radiosensitizing properties of T. Preoperative short-course of T with concurrent low-dose RT was conducted in a multicenter, European, phase I/II trial. We present here the data from the phase II part in pts with centralized diagnosis of locally advanced, resectable ML. Methods: Pts received 3 cycles (C) of T in combination with RT (45 Gy) in 25 fractions (1.8Gy/fraction). The phase I part of the study had the classic 3+3 design. Dose Levels for T were: -1 (1.1 mg/m 2 ), 1 (1.3 mg/m 2 ) and 2 (1.5 mg/m 2 ) Results were already reported (EClincalMedicine 2019;9:35-43) and the dose selected for the phase 2 part was 1.5 mg/m2. RECIST responses were evaluated preoperatively at week 10. Surgical specimens were processed for histologic changes and residual tumor. Results: From July 2016 to September 2019, 47 pts (M/F 31/16) with median age 43y (18-77) and median tumor size 11 cm (3-25 cm), 20 low and 24 high grade (3 not available) were enrolled in the phase II part of the study. The major grade 3/4 toxicities were neutropenia (21.3%), ALT (14.9%), GGT (8.5%) and AST (8.5%) elevation. There were no deaths due to toxicity. 43/47 patients received the planned 3 pre-operative T cycles. All pts completed RT. 1 patient started RT before the first cycle of T and was excluded from the analysis. All pts were evaluable for response: 14 achieved PR (30%), 32 SD (70%). All pts underwent surgery (37 [86%] R0/ 5 [12%] R1/ 1 [2%] R2/ 3 not available). Median viable residual tumor was 10% (0-90) with 23/43 pts (53%) with ≤ 10% viable remaining tumor. Of them 6/43 (14%) had complete responses. At a median FU of 18 months (3-41) one pt developed local recurrence and 2 distant metastases. No deaths were observed. The corresponding 2-yr disease-free survival and overall survival were 97% (95% confidence interval 95-100) and 100%. Conclusions: T in combination with RT was feasible and well tolerated in the preoperative setting. The activity of the combination compares favorably with the administration of T/RT alone. This regimen could potentially become an alternative to anthracycline+ifosfamide concurrent to RT in high risk localized ML. Clinical trial information: NCT02275286 .
Variant allele frequency of circulating tumor DNA mutations detected in preoperative blood is indicator for lymph node metastasis in early stage lung cancer.
Authors: Rusi Zhang, Xinyi Liu, Wenzhuan Xie, Mengli Huang, Lanjun Zhang
Journal: Journal of Clinical Oncology (2020)

e21057 Background: The advances in deep sequencing technologies makes circulating tumor DNA (ctDNA) detection in preoperative plasma a more and more significant indicator in early stage cancers. In particular, it allows us to learn a lot about tumor progression before surgery. Plasma variant allele frequency (VAF) of preoperative ctDNA mutations had been verified to correlate with tumor sizes in early lung cancers. Identification of lymph node (LN) metastasis status before surgery in patients with lung cancer is valuable for prognosis and treatment strategy decisions. To evaluate whether ctDNA predict the LN metastasis status, we conducted this analysis. Methods: Preoperative plasma and the matched leukocyte before treatment were collected from 38 early stage lung cancer patients, in which 8 cases with lymph node metastasis. 150-gene panel sequencing were performed on the specimens and the sequencing data were used as primary cohort. Multivariable logistic regression analysis was used to develop a prediction model based on the DNA and other clinical characteristics. The performance of the model was assessed by its calibration, discrimination and clinical usefulness in the public TRACERx 100 early lung cancers cohort. Results: The proportion of high variant allele frequency (HAF proportion) of mutations was significantly associated with LN status (p &lt; 0.05, for both primary and validation cohorts). A prediction model was developed and predictors included the HAF proportion, smoking status and tumor size. The C-index of the model was 0.419 in primary cohort. In external validation cohort, the AUCs for LN positive was 0.678. Conclusions: Based on pan-gene panel deep sequencing, a big proportion of high variant allele frequency mutations in a single patient indicates advanced disease progression, which may reflect in LN involvement status. A logistic regression model was constructed using ctDNA and clinical characteristics. It showed considerable performance in the prediction of LN metastasis in early lung cancers.
北京大学全科医学学科建设研讨会纪要
Authors: 王维民, 续岩, 杨晓征
Journal: BMJ (2012)

在卫生部科技教育司、社区卫生与妇幼保健司和教育部高教司的支持下,由北京大学医学部主办的北京大学全科医学学科建设研讨会于2011年10月18日至19日在京召开.卫生部、教育部、北京市卫生局和中华医学会的相关领导嘉宾出席了会议,来自英国牛津、剑桥、伯明翰大学的4名特邀全科医学专家与全国各地70多家医学院和医院、社区卫生服务中心近300名代表就全科医学学科建设相关问题展开了研讨.同期,北京大学医学部举办了北京大学第三医院第二 门诊部、航天医院永定路社区卫生服务中心两个社区卫生教学基地的揭牌仪式。
脂肪肝的CT及MRI影像诊断
Authors: 唐业欢, 王叶, 叶慧义
Journal: BMJ (2012)

脂肪肝是肝脏常见的良性非肿瘤性病变.脂肪肝的明确诊断、动态检测和疗效评估是目前临床关注的热点.超声和CT平扫对弥漫性脂肪肝诊断的敏感性和特异性较高,对局灶性脂肪肝有时难与其他肝占位性病灶鉴别,而MRI扫描对诊断有极大的帮助。
介导过敏反应的自身抗体在自身免疫性疾病中的临床意义
Authors: 刘亚楠, 李莉
Journal: BMJ (2012)

自身免疫性荨麻疹的发病与机体产生针对IgE高亲和力受体α链(FceRIα)或IgE的自身抗体、补体等免疫分子有关,同时抗FceRJα自身抗体可能与内源性哮喘、伴有过敏症状的其他疾病密切相关.该抗体的检测将有助于相关疾病的深入研究与诊断治疗
A randomized phase II/III trial of conventional paclitaxel and carboplatin with/without bevacizumab versus dose-dense paclitaxel and carboplatin with/without bevacizumab, in stage IVB, recurrent, or persistent cervical carcinoma (JCOG1311): Results of the phase II part.
Authors: Mitsuya Ishikawa, Ryo Kitagawa, Taro Shibata, Hideki Tokunaga, Takashi Iwata, Shin Nishio, Toshio Takada, Masahiko Mori, Koji Horie, Wataru Kudaka, Masahiro Kagabu, Michihiro Tanikawa, Hiroaki Kobayashi, Nobuo Yaegashi
Journal: Journal of Clinical Oncology (2020)

6027 Background: A randomized controlled trial was conducted to assess the efficacy and safety of dose-dense, weekly paclitaxel plus carboplatin (ddTC) with or without bevacizumab (Bmab) compared to conventional, tri-weekly paclitaxel plus carboplatin (cTC) with or without Bmab, in metastatic or recurrent cervical carcinoma not amenable to curative treatments with local therapy. Methods: Patients were randomly assigned to either a cTC or a ddTC regimen. After Bmab was approved in Japan (in May 2016) the protocol was amended, and patients on both arms received Bmab if not contraindicated. The cTC was paclitaxel 175 mg/m 2 intravenously (IV) for 3 h on day 1 followed by carboplatin at an area under the curve of five IV for 1 h on day 1. The ddTC was paclitaxel 80 mg/m 2 IV for 1 h on day 1 followed by carboplatin at an area under the curve of five IV for 1 h on day 1 and paclitaxel 80 mg/m 2 IV for 1 h on day 8 and day 15. Both cTC and ddTC treatments were repeated every three weeks, for up to nine cycles. Bmab 15 mg/kg IV was repeated until progression or unacceptable toxicity. The primary endpoint of phase II was the response rate (RR) in patients with measurable lesion, who had received Bmab. If the RR of the ddTC + Bmab arm was greater than that of the cTC + Bmab arm for more than 5%, the study would proceed to phase III, which had overall survival (OS) as its primary endpoint. The planned sample size in the phase II part was 56 to select the ddTC arm with a probability of at least 75% if the difference of RR was 15% or more (45% vs. 60%). Results: Patient accrual started in October 2015. It was suspended in May 2019 because the number of Bmab-treated patients with measurable lesions reached 56. In total, 122 patients were enrolled and randomly assigned to either the cTC arm (cTC: 29 patients; cTC + Bmab: 32 patients) or the ddTC arm (ddTC: 30 patients; ddTC + Bmab: 31 patients). The primary analysis of the phase II part was conducted in November 2019. The RRs of each regimen were 67.9% [95% CI, 47.7-84.1] (19/28, cTC + Bmab), 60.7% [40.6-78.5] (17/28, ddTC + Bmab), 55.2% [35.7-73.6] (16/29, cTC), and 50.0% [29.9-70.1] (13/26, ddTC). Conclusions: The study did not meet the primary endpoint of phase II. Dose-dense, weekly paclitaxel plus carboplatin is not promising for metastatic or recurrent cervical carcinoma. Clinical trial information: jRCTs031180007.
Geographic and demographic disparities in breast cancer outcomes: A population-based study.
Authors: Rohit Gosain, Yara Abdou, Medhavi Gupta, Maithreyi Sarma, Adrienne Groman, Shipra Gandhi
Journal: Journal of Clinical Oncology (2020)

7028 Background: Breast cancer (BC) is one of the leading causes of cancer-related mortality worldwide, with over 2 million new cases diagnosed each year. Area of residence has been shown to affect survival, but its impact on BC is unknown. The purpose of this study is to address the potential disparities in BC outcomes between the urban area (UA) and rural area (RA). Methods: We obtained data based on BC patients’ (pts) area of residence; UA vs RA, using the Surveillance, Epidemiology, and End Results (SEER) database treated from 1975-2016. Different socio-demographic variables and tumor characteristics (cts) from both groups were analyzed. Disease specific survival (DSS) and overall survival (OS) were analyzed by Kaplan-Meier methods. Multivariable analyses were conducted using Cox regression models. Results: A total of 99,339 and 872,742 pts were analyzed from RA and UA respectively. Pt cts, including age, sex, marital status, insurance status were similar across both RA and UA. There were a higher number of Black and Hispanic pts in the UA compared to RA. A total of 264,191 pts had receptor subtype data available. A slightly higher percentage of triple negative BC (TNBC) pts was seen in the RA compared to UA (13.5% v 12.7%) whereas UA had a higher percentage of HER2+ BC (18% v 17.3%). There were 95.4% early/locally advanced (stage I-III) and 4.6% metastatic pts. UA pts had significantly improved DSS and OS regardless of stage, grade or other tumor cts compared to RA pts. When stratified by receptor subtype, UA had significantly improved DSS and OS in hormone positive (HR+) (OS HR of 0.86; DSS HR of 0.87; p &lt; 0.05) and HER2+ pts (OS HR of 0.87; DSS HR of 0.83; p &lt; 0.05). However, there were no significant differences seen between UA and RA pts with TNBC. Conclusions: To our knowledge, this is the first study to report BC outcomes based on geographic disparities. Interestingly, HR+ and HER2+ UA pts had better outcomes than RA pts, whereas TNBC pts had similar survival regardless of residence area. Perhaps this disparity is partly due to the longer duration of treatment needed with hormonal therapy in the adjuvant setting making compliance an important factor to take into account in RA pts, in addition to complicated decision making with upcoming data in HER2 + cancer in the early stage setting. Access to healthcare, differences in surgical and systemic approaches of pt care, management of treatment-related toxicities and environmental factors are all potential factors that may affect outcomes in BC pts. Based on the above data, further studies are needed to further evaluate and reduce such disparities.
A multicenter study comparing granulocyte-colony stimulating factors to antibiotics for primary prophylaxis of taxotere/cyclophosphamide-induced febrile neutropenia in patients with early-stage breast cancer.
Authors: Mark J. Clemons, Dean Fergusson, Anil A. Joy, Judith Meza-Junco, Julie A. Price Hiller, John Robert Mackey, Xiaofu Zhu, Mohammed FK Ibrahim, Bassam Mohammed Basulaiman, Arif Ali Awan, Marta Sienkiewicz, Lisa Vandermeer, Lacey D. Pitre, Nancy Alice Nixon, Brian Hutton, Gregory Russell Pond, John Frederick Hilton
Journal: Journal of Clinical Oncology (2020)

7001 Background: Docetaxel-cyclophosphamide (TC) adjuvant chemotherapy is commonly used in patients with early stage breast cancer (EBC). Due to the risk of febrile neutropenia (FN) with TC, primary prophylaxis with either ciprofloxacin (cipro) or granulocyte-colony stimulating factors (G-CSF) is recommended. Despite significant differences in costs (7-120 $US/course [cipro] vs. 2100-7000 $US/dose [G-CSF]) and toxicity profiles, optimal primary FN prophylaxis is unknown. We performed a pragmatic randomised trial comparing the superiority of G-CSF to cipro. Methods: EBC patients receiving TC chemo were randomized to receive cipro or G-CSF as primary FN prophylaxis. The primary outcome is a composite of either treatment-related hospitalisations or FN. Secondary outcomes included: chemo dose reductions, delays, discontinuations and incidence of C. difficile infections. Primary analysis was performed with the intention to treat (ITT) population. Results: 455 eligible patients were randomized to cipro (227) or G-CSF (228). 37/227 (16.3%) patients on cipro had a hospitalization, compared with 25/228 (11.0%) on G-CSF (Fisher’s exact test p-value=0.10). Relative risk (RR) of hospitalization for patients on G-CSF:0.68, 95%CI=0.42 to 1.09. Patients on cipro were statistically significantly more likely to be hospitalized for FN (30/227, 13.2%) vs 9/228 (4.0%) patients on G-CSF(p&lt;0.001). RR of developing FN and being hospitalized for patients on G-CSF: 0.44, 95%CI=0.26 to 0.76. There was no significant difference between groups for chemo dose reductions, delays, and C. difficile rates. Twenty patients on cipro (8.8%) and 9 on G-CSF (3.9%) discontinued chemo early (p=0.036). RR of discontinuing chemo: 0.43, 95%CI=0.19 to 0.96. Conclusion: G-CSF was superior to cipro at reducing FN. While a trend towards reduced hospitalizations was also observed with G-CSF, it did not attain statistical significance. However, as 18 patients would need to be treated with G-CSF to prevent one hospitalization compared to cipro, this would suggest a cost of over $100000 $US to prevent a hospitalization. A formal cost-effectiveness analysis will be performed. Clinical trial information: NCT02173262, NCT02816112 .
碱性成纤维细胞生长因子治疗复发性口腔溃疡的临床研究
Authors: 孙衍龙, 田蕊, 席茹
Journal: BMJ (2007)

探讨碱性成纤维细胞生长因子(bFGF)治疗复发性口腔溃疡的临床疗效.将162例复发性口腔溃疡患者随机分为两组:治疗组85例,用bFGF治疗;对照组77例,用0.2%洗必泰溶液治疗.结果示治疗组显效率与总有效率分别为47.1%和90.6%,对照组分别为15.6%和64.9%,两组比较差异有统计学意义.提示bFGF对轻型口腔溃疡和疱疹样口腔溃疡疗效显著。
Hypromellose – A traditional pharmaceutical excipient with modern applications in oral and oromucosal drug delivery
Authors: Eliška Mašková, Kateřina Kubová, Bahijja T. Raimi-Abraham, Driton Vllasaliu, Eva Vohlídalová, Jaroslav Turánek, Josef Mašek
Journal: Journal of Controlled Release (2020)
全科社区师资教学能力评价浅析
Authors: 杨华, 顾杰, 祝墡珠
Journal: BMJ (2012)

全科社区师资教学能力的评价对于推动全科医师规范化培训非常重要.我国对于评价全科师资教学能力的相关研究多为描述性的理论研究,而针对具体评价指标和评价方法的研究尚不多.可借鉴国外实践和研究中的一些评价指标和方法,结合我国国情,建立适合我国全科教育模式的师资教学能力评价指标体系。
Outcomes of statin use in veterans with prostate cancer: A retrospective single-center experience.
Authors: Brian Warnecke, Juan Garza, Paromita Datta, Annie Hung, Michael Mader, Tamna Wangjam
Journal: Journal of Clinical Oncology (2020)

e17612 Background: Prostate cancer is the most common cancer in men in the United States. Death in prostate cancer patients is often reported to be non-prostate cancer related, attributed to other medical conditions. As prostate cancer is associated with a prolonged survival, care of these patients includes optimizing other co-morbidities, such as cardiovascular disease. There are multiple reports and epidemiological studies of statins decreasing the risk, progression, and overall mortality of prostate cancer. Previously we had gathered data on 300 patients diagnosed with prostate cancer at the VA in San Antonio. The results indicated that using statins has a statistically significant positive effect at delaying death by prostate cancer, with a p-value of 0.018. We have updated our results with the addition of 105 patients. Methods: This is a retrospective observational study with chart review of 405 patients diagnosed with prostate cancer from 1995 to 2010, in a VA Hospital in San Antonio, Texas. Variables included age of diagnosis, statin use, type of statin (1st, 2nd, or 3rd generation), dose of statin (6 levels of dosage were identified), length of statin use, time followed in months (from time of diagnosis to either death or the end of the study period), death, and cause of death. The Cox proportional hazards regression model was used to estimate the hazard function, with age at diagnosis used as a covariate. Primary end point was death by prostate cancer (33 patients) and secondary end points- death by any cancer (71 patients), and death by all causes (205 patients). Results: The hazard ratio for use of statins at least 6 months was 0.56, with 95% confidence limits of 0.41 to 1.13, and a p-value of 0.118, indicating no statistically significant effect of statin usage and delay in death by prostate cancer. Secondary endpoint of death by all causes was significantly affected by statins, while death by any cancer showed no significant effect. The study was unable to conclude if the type of statin, dose of statin or the length of statin use had a significant effect in reaching the different end points. Conclusions: The addition of 105 more patients to this study has changed our previous statistically significant primary endpoint results.Concomitant statin use may not help prevent death from prostate cancer or death from any cancer, but may help prevent death from all causes. This updated primary endpoint data conflicts with multiple prior epidemiological studies and raises questions on the impact of statin usage on men with prostate cancer.
Utilization and trends in palliation-directed treatments for stage II-IV anal squamous cell carcinoma patients.
Authors: Srinidhi Radhakrishnan, Suleyman Yasin Goksu, Saikripa Radhakrishnan, Vicente Morales-Oyarvide, Nina Niu Sanford, Mohsin Soleja, Stephen Haff, Muhammad Shaalan Beg, Syed Mohammad Ali Kazmi
Journal: Journal of Clinical Oncology (2020)

4059 Background: Anal squamous cell carcinoma (ASCC) is associated with significant symptom burden including pain, bleeding, and obstructive symptoms. However, the proportion of patients requiring palliation-directed treatments in ASCC is unknown. Palliation-directed treatments can control and improve symptoms and affect quality of life. We aimed to study trends, factors, and outcomes associated with utilization of palliation-directed treatment in ASCC. Methods: Using the National Cancer Database (NCDB), adult patients with stage II-IV ASCC diagnosed 2004-2015 were identified and stratified by receipt of palliation-directed treatments. Using chi-square test and logistic regression, we evaluated the associations of demographic, clinical, and pathological factors with palliation-directed treatment utilization. Results: Out of 17,988 ASCC patients in this study, palliation-directed treatments were used by 504 patients (2.8%) with stages II-IV ASCC as first line treatment. Two percent received palliation-directed surgery, chemotherapy, and radiotherapy, 0.3% received pain management, and 0.4% utilized combination therapy approach. On univariable analysis, palliation-directed treatments were associated with older age, lower income level ( p=0.004), Medicare insurance, and higher comorbidity score ( all other p&lt;0.001). Palliation-directed treatments were also more frequent in academic/research facilities ( p=0.01), in East North Central USA ( p=.001), and in stage 4 versus stage 2/3 ASCC ( p&lt;.001). Palliation-directed treatments have increased in recent years (2004-06 vs. 2013-15; p=.005) and were more frequently used within 6 months of patient death ( p&lt;.001). On multivariable analysis stage 4 disease and life expectancy &lt; 6 months were the only variables that maintained significance. Conclusions: In our study, palliation-directed treatments were used by 2.8% of the patients as codified by NCDB. Its use was higher in stage 4 ASCC and within the last six months of life. Palliation-directed treatment utilization has incrementally increased in recent years. Additional research is warranted in determining the phase of care wherein palliation-directed treatments are utilized in ASCC.
Strengthen the standardized treatment of ventricular tachycardia
Authors: Feng Guangxun, Zhu Jun
Journal: BMJ (2019)

室性心动过速是临床常见的心律失常，临床表现呈多样性。在实际临床工作中，室性心动过速的分层诊疗、不同室性心动过速的处理原则、电复律的指征和操作、服用抗心律失常药物患者的长期随访、健康指导仍存在一定的误区、短板，《室性心动过速基层诊疗指南（2019年）》对室性心动过速患者的筛查、诊疗、分级管理、药物治疗及随访评估都给出了具体的建议和要求，将有助于规范室性心动过速的诊疗。
Prognostic biomarker candidates of neoadjuvant chemotherapy for luminal B-positive locally advanced breast cancer.
Authors: Zhaoyun Liu, Jinjin Wang, Chenxi Yuan, Zhiyong Yu, Wendy Wu, Lin Wu, Jinming Yu
Journal: Journal of Clinical Oncology (2020)

e12638 Background: In the last decade, the treatment approach for locally advanced breast cancer (BC) patients has partly shifted from adjuvant treatment to neoadjuvant treatment. Systemic neoadjuvant treatment can downstage the tumor for less extensive surgery and improve cosmetic outcomes. Differential subtypes of BC responded unevenly to neoadjuvant chemotherapy. Luminal B type with the relatively higher prevalence (40% in all 4 subtypes) had better therapeutic effect to neoadjuvant treatment than luminal A type, but worse than HER2-positive patients. Methods: We enrolled 87 BC patients for genotyping with multiple cancer-related genes. Among them, 17 patients were luminal A, 21 were HER2-negative luminal B, 23 were HER2-positive luminal B, 17 were HER2-positive and 9 were triple-negative. According to the RECIST, the patients were divided into 1-4 and 5 grades. Fisher test was used to analyze the difference of SNV and CNV between the two primary tumors, as well as TMB difference between post-neoadjuvant chemotherapy and past-neoadjuvant chemotherapy. Results: Base mutations in all patients showed discrepant preference between 1-4 grades and 5 grade groups, G-to-A in 1-4 grades, while A-to-G, A-to-T and G-to-T in 5 grade. In luminal B group (combine liminal B-negative and luminal B-positive groups), FLT4 gene mutation occurred more frequent in 5 grade than 1-4 grades (4/16 vs 0/28, P = 0.01). CNV analysis in NFKBIA and ZNF217 distinguished the two therapeutic efficiency groups in luminal B-positive group. The amplification of NFKBIA and ZNF217 was higher in 1-4 grades than 5 grade (8/14 vs 1/9, P = 0.036; 9/14 vs 1/9, P = 0.017). TMB difference between post and past neoadjuvant chemotherapy in luminal B-positive group was also significant in 5 grade (4.36 vs 1.99, P = 0.002). Conclusions: NFKBIA and ZNF217 amplification notably differentiated the 1-4 grades and 5 grade groups in luminal B-positive patients, suggesting the potential prognostic biomarkers of neoadjuvant chemotherapy in this locally advanced breast cancer subtype, which would be improved by further large-scale cohort study. The differences of TMB and FLT4 gene mutation were also found between the two therapeutic efficiency groups.