tbuckley/cabot-search huggingface dataset:
Ki-67 versus MammaPrint/BluePrint for assessing luminal type breast cancer.
Authors: Chen Tian, Lili Fu, Jiyu Wei, Pengfei Yin, Henghui Zhang
Journal: Journal of Clinical Oncology (2020)

e13673 Background: Ki-67 is widely used for risk stratification in patients with ER+/HER2- breast cancer. The multigene assay, MammaPrint/BluePrint (MP/BP) test, is validated as a good predictor of recurrence in patients with Luminal type breast cancer and a good tool of molecular subtyping classification. Previous study showed that MP/BP test was able to re-stratify 54% of patients with a Luminal-B pathological subtyping (PS) to a low-risk Luminal A-type group. But there is no study directly show the comparison between Ki67 and MP/BP test result. Here in this study, we compare Ki-67 with MP/BP test result in Chinese patients with luminal type breast cancer. Methods: Formalin-fixed, paraffin-embedded (FFPE) tumour samples or fresh tumour samples from 1008 eligible breast cancer patients were collected from 122 hospitals in China. Tumor RNAs were isolated from samples and analyzed using RNA sequencing technology. Ki-67 protein expression were assessed in FFPE tissue blocks by IHC. The pathology subtyping of patient was categorized based on the 2013 St. Gallen. Comparison of MP/BP result with Ki-67 IHC was performed. Concordance between subtyping by the MP/BP and PS was also evaluated. Results: Of 1008 patients with ER+/HER2- breast cancer, 640 were MP Low-Risk and 368 were MP High-Risk. MammaPrint index was significantly associated with Ki-67 expression (p &lt; 0.001). Among the patients with Ki-67 value lower than 15%, 81.11% were MP Low-Risk, while 65.12% of patients with Ki-67 value between 15%-20% and 46.67% of patients with Ki-67 value between 21%-30% were MP Low Risk. Of the patients with Ki-67 value higher than 30%, 77.24% were MP High-Risk. Among the 453 patients with PS Luminal-A tumours, 77 (17%) were categorized as Luminal-B by MP/BP test. While among the 555 patients with PS Luminal-B tumours, 265 (48%) were categorized as Luminal-A by MP/BP test. Conclusions: Our results show that for the patients with low Ki-67 value ( &lt; 15%) or high Ki-67 value ( &gt; 30%), the risk prediction by MP test are mostly agree with Ki-67 IHC, while for the patients with intermediate Ki-67 value (15-30%), MammaPrint test may provide more information. And compare with the traditional pathological factors, MP/BP test can help to identify a large group of patient with low risk of recurrence.
Final analysis of relapse-free survival in a multicenter, double-blind, placebo-controlled trial of seviprotimut-L polyvalent melanoma vaccine after resection of high-risk melanoma.
Authors: Craig L. Slingluff, Brent A. Blumenstein, Karl D. Lewis, Robert Hans Ingemar Andtbacka, John Robert Hyngstrom, Mohammed M. Milhem, Svetomir Markovic, Omid Hamid, Leonel Fernando Hernandez-Aya, Tawnya Lynn Bowles, Prejesh Philips, Sekwon Jang, Jose Lutzky, Anna Bar, Peter D. Beitsch
Journal: Journal of Clinical Oncology (2020)

10017 Background: Seviprotimut-L is a vaccine prepared from antigens of 3 human melanoma cell lines, administered with alum. Prior formulations induced T cell and antibody responses and improved survival in a small phase II clinical trial. Part B1 of MAVIS (Melanoma Antigen Vaccine Immunotherapy Study, a three part, Phase III clinical program), was a multicenter, double-blind, placebo-controlled trial to assess efficacy of seviprotimut-L, with the primary endpoint of relapse-free survival (RFS). The goal of Part B1 was to guide design of the pivotal Part B2. Methods: Patients with AJCC v7 stage IIB-III cutaneous melanoma, after surgical resection, age 18-75, ECOG PS 0-1, were randomized 2:1 to seviprotimut-L 40 mcg or placebo, injected subcutaneously every 2 weeks x 5, then monthly x 4, then every 3 months x 9. Patients were stratified by stage (IIB/C, IIIA, IIIB/C). Target enrollment was 325. The study was powered for assessment of RFS, with target hazard ratio (HR) of 0.625, one-sided alpha of 0.10, and power 80%. Final data are presented. Results: 347 patients were randomized. Arms were well-balanced. Treatment-related adverse events (AEs) led to discontinuation in 0.4% and 0%, respectively, for vaccine and placebo arms. There were no treatment-related SAEs. By intent-to-treat (ITT) analysis, RFS was not significantly longer for seviprotimut-L in the full study population but trended toward benefit (HR 0.88). Subgroup analysis based on planned stratification revealed the hazard ratio (HR) for the Stage IIB/IIC subset (randomization stratum, n=111) to be 0.65 (95% CI [0.37, 1.17]), favoring seviprotimut-L. Age can decrease immune competence: RFS was longer with vaccine for patients age &lt;60 overall (N = 191, HR = 0.64 [0.38, 1.08]) and among Stage IIB/C patients (N = 52, HR = 0.32 [0.12, 0.86]). The effect modification interaction p value for age for stage IIB/IIC patients was 0.056. In a multivariable RFS model, for IIB/IIC patients &lt;60 with ulceration (n=38), HR = 0.209 [0.07,0.61]. For overall survival, for patients &lt; 60, HR = 0.41 [0.33,1.14] (n=191, 19 deaths) and for those ≥60, HR = 0.92 [0.39,2.12] (n = 156, 24 deaths). Conclusions: Seviprotimut-L is very well-tolerated. Subgroup efficacy analyses identified populations who may benefit from Seviprotimut-L: those with Stage IIB/IIC melanoma and those under age 60. These data support design of the definitive part B2 of the MAVIS phase III trial to test seviprotimut-L for stage IIB/C patients, with stratification by age and ulceration. Clinical trial information: NCT01546571.
Neoadjuvant TCH (docetaxel/darboplatin/trastuzumab) versus EC-TH (epirubicin/cyclophosphamide followed by docetaxel/ trastuzumab ) in patients with HER2-positive breast cancer (neoCARH): A randomised, open-label, multicenter, phase II trial.
Authors: Hong-Fei Gao, Zhiyong Wu, Ying Lin, Xiangyang Song, Yin Cao, Zhenzhen Liu, Qian-Jun Chen, Liulu Zhang, Ci-Qiu Yang, Mei Yang, Teng Zhu, Jieqing Li, Fei Ji, Min-Yi Cheng, Kun Wang
Journal: Journal of Clinical Oncology (2020)

585 Background: The optimal neoadjuvant treatment for HER2-positive breast cancer is unknown. We wanted to compare the efficacy and safety of the anthracycline regimen EC-TH versus nonanthracycline regimen TCH in neoadjuvant setting for HER2-positive breast cancer. Methods: Patients with stage II or III HER2-positive breast cancer were randomly assigned to either four cycles of epirubicin/cyclophosphamide followed by four cycles of docetaxel and trastuzumab (EC-TH) every 3 weeks during all chemotherapy cycles, or six cycles of docetaxel and carboplatin plus trastuzumab (TCH) every 3 weeks. The primary endpoint was pathological complete response (defined as the absence of invasive tumour cells in breast and axilla, ypT0/is ypN0). This trial is registered with ClinicalTrials.gov, number NCT03140553. Results: From September 2016 to November 2019, 140 patients were randomly assigned, and 131 were evaluable for the primary end-point. The pathological complete response was recorded in 25 (38.5%, 95% confidence interval [CI] 26.6–50.2) of 65 patients in the EC-TH group and in 37 (56.1%, 44.1–68.0) of 66 in the TCH group (p=0.044). In the EC-TH group, 15 (23.1%) of 65 patients underwent breast-conserving surgery. In the TCH group, 21 (31.8%) of 66 patients underwent breast-conserving surgery. There was no difference in the proportions of patients undergoing breast-conserving surgery between the two treatment groups (p=0·262). The most common adverse events were neutropenia (in 23 [35.4%] of 65 patients in the EC-TH group vs 27 [40.9%] of 66 in the TCH group), anemia(in 33 [50.8%] of 65 patients in the EC-TH group vs 34 [51.5%] of 66 in the TCH group) and thrombocytopenia (in 5 [7.7%] of 65 patient in the EC-TH group vs 17 [25.8%] of 66 in the TCH group). Conclusion: This is the first multicenter prospective randomised phase II trial compare EC-TH with TCH for neoadjuvant therapy in HER2-positive breast cancer. There was a similar incidence of AEs but a higher pCR rate in TCH arm compared with the EC-TH arm. TCH regimen might be a preferred approach in patients with HER2-positive breast cancer. Long-term follow-up is required to confirm these results. Clinical trial information: NCT03140553 .
Co-mutation features in treatment-naïve EGFR-mutant lung adenocarcinoma.
Authors: Jun Zhao, Zaiwen Fan, Donghong Chen, Minglei Zhuo, Zhen Liang, Lin Li, Yun Gao, Xiaorong Wang, Zhuo Yu, Cunliang Cai, Dapeng Dong, Jingquan Zhao, Wenguang Gu, Min Zhang, Rongrong Chen, Xuefeng Xia
Journal: Journal of Clinical Oncology (2020)

e21616 Background: In Chinese patients with lung adenocarcinoma, the positive rate of EGFR mutation was 40% - 50%, EGFR-TKIs therapy for lung cancer was also aimed at this part of patients. However, different EGFR mutation types have different therapeutic effects, this study focuses on different EGFR mutation types to divide the population of lung adenocarcinoma. Methods: We retrospectively reviewed gene test results of two hundred and sixty-two treatment-naïve adenocarcinoma patients. Tumor tissues (199, 76%), plasma (46, 17.5%) and other samples (17, 6.5%) were subject to next-generation sequencing using a 59-gene panel, which enables simultaneously assess SNV, Indel, rearrangements and CNV variations. Results: There were 174 females. These patients were divided into four groups, which 139 were EGFR L858R, 99 were EGFR exon 19 deletion, 7 were EGFR 20 ins and 17 were uncommon EGFR mutations, the co-mutation proportions with EGFR were 84.9% (118/139), 76.8% (76/99), 71.4% (5/7) and 94.1% (16/17) respectively. The mean numbers of co-mutation genes in L858R and exon 19 deletion were 4.173 and 3.258 (p&lt;0.05). TP53 mutation was detected in 14.3% (1/7) 20ins group, which had a significant difference to L858R (59.7%, 83/139) and uncommon mutation groups (70.6%, 12/17) (p&lt;0.05). Meanwhile, EGFR amplification proportion in L858R (18%, 25/139) and exon 19 deletion (6.1%, 6/99) were significantly different (p&lt;0.05). The actionable mutations associated with target therapy involved in multiple pathways, for example, the HRR pathway and cell cycle pathway, related genes had no significant difference among the four groups. In these lung adenocarcinoma patients, we also found 6 EGFR T790M (2.3%, 6/262). Three cases accompanied with exon 19 deletion, and another three were L858R, no distribution in 20ins and uncommon groups. Conclusions: The phenomenon of concurrent gene mutation in treatment-naïve EGFR-mutant lung adenocarcinoma is common. EGFR mutant subgroups have different co-mutation features, like gene number and mutated genes. It may be the factor leading to different therapeutic effects of EGFR-TKIs, and indicate the importance of multiplex molecular test and further researches of target therapies.
"Balint group"performed as core skill course of doctor-patient communication in general practice residents standardized training program
Authors: Liying Chen, Zeling Zhu, Jia Zhang, Feifei Huang, Lin Su, Qiaohua Qiao, Lizheng Fang
Journal: BMJ (2017)

Communication between doctors and patients is an important way to establish good doctor-patient relationship. It is crucial to master doctor-patient communication skills and arts for general practitioners who will extensively serve the people in community for life-long time after completion of residency training. To improve the communication skills and to enhance the clinical competency of general practitioners, we applied the Balint special group activities as core of doctor-patient communication course in residency training program. Through 3 years of practice, we found that the application of Balint group enriched the teaching contents and form of general practice residency training; improved doctor-patient communication skills, and enhanced the competency and professionalism of general practice trainees.


Key words: 
Inservice training; Psychoanalytic therapy; General practitioner
Causal inferencing of -omics data from The Cancer Genome Atlas: Lung adenocarcinoma tumors for mechanistic disease characterization and feature engineering.
Authors: Nimisha Schneider, Sergey Korkhov, Alexis Foroozan, Scott Marshall, Renee Deehan
Journal: Journal of Clinical Oncology (2020)

e21016 Background: Advances in high throughput measurement technologies (-omics data) have made it possible to generate high complexity, high volume data for oncology research. Researchers are often confronted many more measurements than samples (p &gt; &gt; &gt; n), which poses challenges for both modeling the complexity of disease at the molecular mechanism level, and overfitting when generating predictive models with complex data. Here, we applied a prior knowledge-driven approach to characterize and classify heavy versus light smokers with lung cancer from The Cancer Genome Atlas, an open source repository that catalogs, harmonizes and hosts -omics data collected from samples generously donated from cancer patients. Methods: We applied a reverse inferencing approach to systematically interrogate RNAseq measurements from tumor and control biopsies against a knowledgebase of directed gene networks curated from published experiments. If patterns observed in the data are significantly similar to those in a network, an inference about the directional activity of that network can be made; e.g., the increased transcriptional activity of NFKB. Our library was nucleated through an open sourced knowledge graph and enhanced with updated and relevant knowledge using the open sourced Biological Expression Language framework. Directed networks were either qualitatively scored and used to build disease models, or semi-quantitatively scored and used as classification features. Results: In LUAD tumors, we detected a pattern of gene signatures which indicated a tumor stem cell-like phenotype characterized by predicted decreases in the activity of pro-differentiation factors and an increased response to hypoxia. Analysis of patients with heavy ( &gt; 40) versus light ( &lt; 10) pack-year burden suggested an augmented dedifferentiation profile in heavy smokers. In this example, improved classification was observed through features compression through directed network scoring compared to using individual RNA measurements selected by filtration methods. Conclusions: In-silico analysis of lung cancer patient biopsies generated hypotheses implicating stem cell signaling in tumors, and a further stratification of this signal based on patient pack year burden. Mechanistic modeling may be a useful application to the overfitting problem often encountered with -omics data in translational studies. Data from other TCGA indications can be used to evaluate the consistency of this type of approach
Phase II clinical trial of nab-paclitaxel plus gemcitabine in elderly patients with previously untreated locally advanced or metastatic pancreatic adenocarcinoma: BIBABRAX study.
Authors: Jaime Feliu Batlle, Monica Jorge Fernandez, Teresa Macarulla, Bartomeu Massuti, Ana Albero, Federico Gonzalez, Guillermo Alfonso Quintero Aldana, J. Ignacio Delgado Mingorance, Ana Fernandez Montes, Carmen Garcia Piernavieja, Manuel Valladares-Ayerbes, Carlos García Girón, Rebeca Mondejar, Pilar Vicente, Esther Casado, Irene Gonzalez Cebrian, Guillermo Lopez-Vivanco
Journal: Journal of Clinical Oncology (2020)

4615 Background: FOLFIRINOX and nab-paclitaxel plus gemcitabine (nab-P+G) are the standard of care in the first-line treatment of mPC patients (pt) with good performance status. However, no standards of care exist for elderly ( &gt; 70 years) pt as they are usually excluded in clinical trials. This study aimed to evaluate whether the clinical benefit of nab-P+G could be extended to elderly pt with mPC. Methods: This was an open-label, single-arm, multicenter, phase II trial, to assess the efficacy and safety of Nab-P+G in elderly pt (≥ 70 years) with ECOG PS 0–1 and untreated unresectable locally advanced or metastatic PC. Pt received four-week cycles of intravenous (i.v.) nab-paclitaxel 125 mg/m2, followed by i.v. gemcitabine 1,000 mg/m2, on days 1, 8 and 15, until disease progression. Efficacy was evaluated according RECIST v 1.1 criteria and safety according NCI-CTCAE v 4.0 criteria. Results: Eighty pt were enrolled in the study. Median age was 74.6 years (range 70-87.9), 57.5% were men, 71% had ECOG PS 1 and 86% metastatic disease. 16.3% of patients had a history of prior tumor surgical resection, 12.5% received chemotherapy and 3.8% radiotherapy. Primary tumor was located in head (32.5%), tail (25.0%) and body (22.5%). Nab-P and G was reduced in 49% and 41% of pt respectively. 15 pt definitely interrupt study treatment due to toxicity: neurotoxicity (7), asthenia (5), neutropenia (1), leukocytosis (1) and hepatotoxicity (1). Time until definite deterioration (reduction ≥10 points as compared to baseline in EORTC-QLQ C30) was 1.6 months and deterioration-free rate at 3 months was 54.3%. Overall response rate was 13.8%, clinical benefit rate 67.5%, median PFS 7.2 months and median OS 9.2 months. The most common treatment-related adverse events were asthenia (60.0%), diarrhea (40.0%), neutropenia (33.8%), hair loss (28.8%), thrombocytopenia (26.3%), and nausea (23.8%). Only asthenia and neutropenia presented a relatively high incidence of grade 3 and 4 toxicities (21.3%). At least 1 SAE was reported in 55% of pt. Conclusions: BIBABRAX study confirms the clinical benefit of nab-P+G in an elderly population with mPC, in terms of survival, clinical response and tolerance, therefore it could be considered a treatment option for elderly patients. However, it was unable to demonstrate the preplanned benefit on the quality of life. Further research is needed on treatment strategies that could reduce deterioration of the quality of life in these pt. Clinical trial information: NCT02391662 .
Prior Therapeutic Experiences, Not Expectation Ratings, Predict Placebo Effects: An Experimental Study in Chronic Pain and Healthy Participants
Authors: Luana Colloca, Titilola Akintola, Nathaniel R. Haycock, Maxie Blasini, Sharon Thomas, Jane Phillips, Nicole Corsi, Lieven A. Schenk, Yang Wang
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Introduction:&lt;/i&gt;&lt;/b&gt; Many clinical trials fail because of placebo responses. Prior therapeutic experiences and patients’ expectations may affect the capacity to respond to placebos in chronic disorders. &lt;b&gt;&lt;i&gt;Objective:&lt;/i&gt;&lt;/b&gt; The scope of this study in 763 chronic orofacial pain and healthy study participants was to compare the magnitude and prevalence of placebo effects and determine the putative role of prior therapeutic experiences vs. expectations. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We tested placebo propensity in a laboratory setting by using 2 distinct levels of individually tailored painful stimulations (high pain and low pain) to reinforce expectations and provide a hypoalgesic experience (conditioning phase). Afterwards, both levels of pain were surreptitiously set at a moderate pain level to test for placebo effects (testing phase). Pain and expectation ratings were assessed as primary outcomes using visual analog scales. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; In both chronic pain and healthy participants, placebo effects were similar in magnitude, with the larger prevalence of responders in the healthy participants. Although chronic pain participants reported higher pain relief expectations, expectations did not account for the occurrence of placebo effects. Rather, prior experience via conditioning strength mediated placebo effects in both pain and healthy participants. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; These findings indicate that participants with chronic pain conditions display robust placebo effects that are not mediated by expectations but are instead directly linked to prior therapeutic experiences. This confirms the importance of assessing the therapeutic history while raising questions about the utility of expectation ratings. Future research is needed to enhance prediction of responses to placebos, which will ultimately improve clinical trial designs.
Comparison of different regimens in treatment of depressive disorder in diabetic patients with nephropathy
Authors: Yu Wang, Jing-qiu Cui, Xiao-jun Ren, Ping Feng
Journal: BMJ (2010)

Two hundred and four patients with diabetic nephropathy and depressive disorder were randomly assigned to the control group (40 cases), St.John's Wort extract (SWE) group(40 cases) ,SWE +psychotherapy group ( 40 cases), SWE + physicotherapy group ( 40 cases ) and SWE + psychotherapy +physicotherapy group (44 cases), all patients were treated for 12 weeks.The therapeutic effects were evaluated with Hamilton Rating Scale for Depression-17 (HAMD-17).The percentage reduction in HAMD scores in SWE + psychotherapy + physicotherapy group was the highest ( 86% ), and those for SWE, SWE +psychotherapy, SWE + physicotherapy and control groups were 47%, 55%, 60% and 13%, respectively (x2 =47.331, P =0.000).After 12 weeks of treatment, glycosylated hemoglobin(HbA1c) and urinary albumin excretion rate (UAER) were reduced in all 4 treatment groups compared with the control group.The levels of HbA1 c and UAER in SWE + psychotherapy + physicotherapy group were significantly lower than those in others ( F = 15.754,74.025, all P = 0.000).St.John' s Wort extract with psychotherapy and physicotherapy can efficiently improve the depressive disorder in type 2 diabetic patients with nephropathy, as well as control blood glucose and reduce UAER of patients.

Key words: 
Diabetic nephropathies;  Depression
Global supply-chain effects of COVID-19 control measures
Authors: Dabo Guan, Daoping Wang, Stephane Hallegatte, Steven J. Davis, Jingwen Huo, Shuping Li, Yangchun Bai, Tianyang Lei, Qianyu Xue, D’Maris Coffman, Danyang Cheng, Peipei Chen, Xi Liang, Bing Xu, Xiaosheng Lu, Shouyang Wang, Klaus Hubacek, Peng Gong
Journal: Nature Human Behaviour (2020)
以苔藓样丘疹、斑块为表现的慢性光化性皮炎一例
Authors: 陈旭, 陈浩, 冯素英, 顾恒, 靳培英
Journal: BMJ (2011)

患者男,67岁,因面颈部、双上肢红斑、丘疹、斑块伴瘙痒3年于2009年9月在本院就诊.3年前开始在面部、耳部、颈后及双侧上肢出现红斑、丘疹,伴瘙痒感,无明显渗液.皮疹持续存在,日晒后加重.之后面部皮疹逐渐融合,形成斑块.曾于外院就诊,诊断考虑慢性光化性皮炎(chronic actinic:dermatitis,CAD),光敏试验检测中波紫外线敏感,给予口服抗组胺药物及激素(剂量不详),结合外用药物治疗,病情无明显缓解.既往体健,否认高血压、糖尿病等慢性病史.否认肿瘤病史.体检:一般情况良好,系统检查无明显异常发现,全身浅表淋巴结未触及肿大。