tbuckley/cabot-search huggingface dataset:
Molecular determinants of outcome for metastatic castration-sensitive prostate cancer (mCSPC) with addition of apalutamide (APA) or placebo (PBO) to androgen deprivation therapy (ADT) in TITAN.
Authors: Felix Y Feng, Shibu Thomas, Clemente Aguilar-Bonavides, Michael Gormley, Neeraj Agarwal, Gerhardt Attard, Alexander William Wyatt, Elai Davicioni, Deborah S. Ricci, Angela Lopez-Gitlitz, Julie S. Larsen, Simon Chowdhury, Kim N. Chi
Journal: Journal of Clinical Oncology (2020)

5535 Background: In TITAN, addition of APA to ADT improved radiographic progression-free survival (rPFS) and overall survival (OS) versus PBO plus ADT in patients (pts) with mCSPC. In this post hoc analysis, we performed transcriptome-wide profiling of tumor samples and assessed association of molecular subtypes with rPFS. Methods: The DECIPHER platform (Decipher Biosciences, Inc.) was used to assess gene expression in archival primary prostate tumors from TITAN. Samples were classified into high versus low to average risk of metastases (DECIPHER genomic classifier [GC] &gt; 0.6 and ≤ 0.6, respectively), basal and luminal A/B (PAM50 classifier), and androgen receptor activity (AR-A) signature high and low. Associations between subtypes with rPFS were assessed with Cox proportional hazards model. Results: The biomarker population included 222 pts (APA, 110; PBO, 112). Benefit in rPFS from APA in the biomarker population (HR [95% CI]; p value; 0.49 [0.31-0.78]; 0.002) resembled that in the overall study population (0.49 [0.40-0.61]; &lt; 0.0001). The majority of TITAN pts had GC high scores (n = 166, 75%). GC high risk subtype in the PBO group had poorer prognosis for rPFS than GC low to average risk subtype (median rPFS 18.2 mos for GC high vs not reached [NR] for GC low to average, 0.28 [0.11-0.69]; 0.006), but there was no difference in prognosis between high and low to average GC risk subtypes in the APA group (GC high NR vs GC low to average NR; 0.81 [0.35-1.89]; 0.625). Pts were further stratified based on basal/luminal and AR-A signatures. Basal (n = 112, 50%) and AR-A low (n = 96, 43%) subtypes, known to be nonresponsive to ADT, both showed significant benefit from APA vs PBO (0.30 [0.16-0.57]; &lt; 0.001 and 0.25 [0.12-0.52]; &lt; 0.001, respectively). The majority of AR-A low subtype (74%, 71/96) overlapped with basal subtype. Further conclusions for risk of rPFS in GC low, luminal, and AR-A high subtypes and OS across all subtypes will be assessed as more events occur. Conclusions: In TITAN, addition of APA to ADT improved rPFS for all subtypes of pts with mCSPC. APA overcame the poor prognosis of GC high risk subtype and prolonged rPFS in ADT-resistant AR-A low and basal molecular subtypes, suggesting APA is beneficial especially for the highest risk molecular subtypes. Clinical trial information: NCT02489318 .
Impact of cancer related stress on illness beliefs and glycemic control in breast cancer survivors with comorbid diabetes.
Authors: Jenny J. Lin, Janey James, Mita Goel, Yael T Harris
Journal: Journal of Clinical Oncology (2020)

e24053 Background: Cancer and diabetes mellitus (DM) are leading causes of death in the US and survivors with comorbid DM have a significantly higher mortality. Furthermore, posttraumatic stress disorder (PTSD) can be triggered by life-threatening illnesses such as cancer; however, little is known about the impact of cancer-related PTSD (Ca-PTSD) on illness beliefs and glycemic control. We undertook this study to assess factors associated with DM management in breast cancer survivors with DM. Methods: We recruited women with Stage 0-IIIA breast cancer diagnosed in the past 10 years, who had completed chemotherapy and/or hormonal therapy and had pre-existing DM on ≥1 oral DM medication. The Impact of Event Scale-Revised (IES-R) was used to assess distress caused by cancer. A total IES-R score of ≥33 identified those with probable Ca-PTSD. Cancer and DM related beliefs were assessed using the Illness Perception Questionnaire. Objective adherence to DM medication was assessed using electronic caps that record bottle openings. Wilcoxon rank-sum tests were used to examine the relationship between Ca-PTSD and illness beliefs. Pearson correlation tests were used to assess the relationship between cancer related stress, DM medication adherence, and glycemic control. Results: Of 111 women recruited to date, mean age was 65.4 years and 37% were black, 31% white, 14% Hispanic, 6% Asian, and 8% other. Of these, 15% had probable Ca-PTSD. Survivors with Ca-PTSD were more likely to believe the consequences of cancer and DM were more severe (median score 23.5 vs. 19.0 [p &lt; 0.001] and 24.0 vs. 16.0 [p &lt; 0.001], respectively), that cancer and DM were more cyclical or recurrent (15.0 vs. 9.0 [p = 0.002] and 13.0 vs. 8.5 [p = 0.002], respectively), and there was greater emotional impact due to cancer and DM (24.0 vs. 16.5 [p &lt; 0.001] and 23.0 vs. 14.0 [p &lt; 0.001], respectively). Additionally, those with Ca-PTSD were less likely to understand their cancer (14.0 vs. 20.0, p = 0.004). Furthermore, as cancer-related stress scores increased, glycemic control worsened (r = 0.23, p = 0.03) and DM medication adherence decreased (r = -0.23, p = 0.04). Conclusions: Breast cancer survivors with comorbid DM who have Ca-PTSD are more likely to have negative beliefs about both cancer and DM. Cancer-related stress is also associated with poorer glycemic control and DM medication adherence. Providers should be aware of the impact of cancer related stress on beliefs about comorbid illnesses and increase interventions that support cancer survivors to better manage their comorbidities.
Comparison of response using mRECIST versus RECIST 1.1 Criteria in advanced hepatocellular carcinoma: A retrospective analysis of multicenter clinical trials.
Authors: Jayant Narang, Surabhi Bajpai, Rudresh Jarecha, Manish Sharma, Oliver Bohnsack
Journal: Journal of Clinical Oncology (2020)

4595 Background: mRECIST 2010 criteria for Hepatocellular Carcinoma (HCC) response assessment were focused on a concept of measuring viable tumor tissue showing enhancement in arterial phase of contrast enhanced CT/MRI, whereas RECIST 1.1 focuses mainly on the morphological measurements quantifying the tumor size irrespective of viability of the tumor and associated response to therapy. RECIST 1.1 does not address measures of antitumor activity other than tumor shrinkage, underestimating responses in HCC. Methods: We retrospectively analyzed multiple, phase III, multi-center clinical trials using both mRECIST and RECIST 1.1 criteria, read separately. The intent was to compare the overall responses at post-baseline assessments read independently by the two criteria. A total of 1682 subjects with 6159 post-baseline imaging timepoints were included in the analysis. The Overall response rate (ORR) as measured by sum of complete response (CR) and partial response(PR) and the Complete response rate (CRR) were evaluated. In addition, we also assessed the number of not evaluable (NE) time points by each criteria separately. We tested the following hypotheses 1. mRECIST may have better ORR and CRR compared to RECIST 1.1. 2. RECIST 1.1 may have more timepoints with Stable disease (SD) compared to mRECIST. 3. mRECIST may have more Not evaluable (NE) timepoints due to stringent imaging specifications. Results: The results are tabulated in the table below: Conclusions: The results above suggest that mRECIST shows more than double the CRR than RECIST 1.1, and the ORR is 62% higher using mRECIST than RECIST 1.1. Stable disease as expected was more commonly observed in RECIST 1.1 analysis. A NE response was 60% more common in mRECIST criteria evaluation. Our analysis confirms that reduction in viable tumor/enhancing area using contrast-enhanced radiologic imaging is the more optimal method to assess treatment response in HCC, and using RECIST 1.1 tumor measurement of a longest diameter as the sole measure of response, may not be adequate in response assessment for HCC. Our analysis validates and supports more widespread adoption of mRECIST in HCC tumor response assessment. Our results also indicate the need for uniform image acquisition and rigorous image quality control for a valid response in mRECIST criteria. [Table: see text]
Characterization of NRG1 gene fusion events in solid tumors.
Authors: Sushma Jonna, Rebecca Feldman, Sai-Hong Ignatius Ou, Misako Nagasaka, Jeffrey Swensen, Wolfgang Michael Korn, Hossein Borghaei, Ari M. Vanderwalde, Gilberto Lopes, Jorge J. Nieva, Alexander I. Spira, Edward S. Kim, Stephen V. Liu
Journal: Journal of Clinical Oncology (2020)

3113 Background: NRG1 fusions are actionable genomic alterations detected across tumor types. The NRG1 gene encode for neuregulin, which serves as a ligand for ERBB3 and ERBB4 receptors and activates downstream signaling through the MAPK and PI3K pathways. Here, we update the detection of NRG1 gene fusions across tumor types and further describe fusion characteristics. Methods: Samples submitted for clinical molecular profiling that included RNA-sequencing (Archer Dx or Caris MI transcriptome) were retrospectively analyzed for NRG1 fusion events. All NRG1 fusions with ≥ 3 junction reads were identified for manual review and for characterization of fusion class, intact functional domains, domain prediction, breakpoints, frame retention and co-occurring alterations by NGS. Results: A total of 82 NRG1 fusion events (0.2% of 44,570) were identified. Among the fusions identified, the distribution across tumor types was as follows: non-small cell lung cancer (NSCLC, 54%), breast cancer (11%), ovarian cancer (7%), pancreatic cancer (7%), cholangiocarcinoma (6%), colorectal cancer (5%), and other (10%). Forty-two unique fusion partners were identified, the most common being CD74 (23%), ATP1B1 (9%), SLC3A2 (7%), RBPMS (6%) and SDC4 (4%). Almost half (47%) of all fusion events are expected to include the transmembrane domain contributed by the NRG1 fusion partner. Lung and pancreatobilliary cancers had the highest rates of transmembrane domain retention from their fusion partners (63.6% and 54.5%, respectively). In all other tumor groups, most fusion partners lacked transmembrane domains. In 15% of cases, the chimeric transcripts are predicted to lead to increased expression of NRG1. The most commonly reported breakpoints in NRG1 occur in exon 6 and exon 2. While fusions with the NRG1 breakpoint at exon 2 retain the immunoglobulin (Ig) domain and all downstream portions (including EGF-like domain), those at exon 6 do not contain the Ig portion and result in shorter chimeric proteins. The breakpoints in all CD74:NRG1 fusions, the most common fusions in NSCLC, occur at exon 5 or 6 and cause truncation of domains upstream of the EGF-like domain. In ATP1B1:NRG1 fusions, the most common fusions in pancreatobilliary cancers, the breakpoints are at exon 1 or 2 and retain the Ig domain. Conclusions: NRG1 fusion products are diverse across tumor types, but the significance of these variations is not clear. The biological and clinical implications of retaining certain domains of NRG1 (such as the Ig domain) and of fusion partners warrants further investigation.
The DISCO App: A pilot test of an electronic patient intervention to reduce the financial burden of cancer through improved cost communication.
Authors: Lauren M. Hamel, David W. Dougherty, Theresa A. Hastert, Erlene Kuizon Seymour, Seongho Kim, Hadeel Assad, Jasminder Phalore, Susan Eggly
Journal: Journal of Clinical Oncology (2020)

1 Background: Financial toxicity, the burden of treatment cost, affects 30-50% of people with cancer in the US. Although experts recommend patients and oncologists discuss treatment cost to identify patients who need assistance, cost discussions occur in fewer than half of cancer treatment discussions. We pilot-tested the feasibility and efficacy of the Discussions of Cost (DISCO) App, a patient communication intervention designed to improve cost discussions and other financial toxicity-related outcomes during and following oncology treatment consultations. The DISCO App provides an individualized list of cost-related questions patients can ask their oncologist, specific to a patient’s economic situation. Methods: While waiting to see their oncologist, newly diagnosed patients with breast or lung cancer (n=32) used the DISCO App on an iPad. Clinic visits were videorecorded and patients completed pre- and post-intervention measures of self-efficacy for managing treatment costs, self-efficacy for interacting with oncologists, cost-related distress, and perceptions of the DISCO App. A trained coder observed the recordings to determine the presence of a cost discussion, the cost-related topic, and any emergent factors. Results: Findings showed increases in patients’ self-efficacy for managing treatment costs (p=.02) and interacting with oncologists (p=.001). Cost-related distress decreased but not significantly (p=.20). Patients reported the DISCO App was understandable (M=4.5 out of 5), useful as they talked with their oncologist (M=4.0), and 84% of patients reported needing less than 15 minutes to use the DISCO App. Most (94%) interactions were videorecorded (in two cases technical difficulties prevented videos from being collected); all (100%) of the videorecorded interactions included a cost discussion. The most frequently discussed topics were: insurance, time off from work, and financial navigation. Frequently, the oncologist asked the patient for his/her question list and discussed/answered the questions. Conclusions: Findings suggest the DISCO App is feasible to implement in the clinic and effective in improving patient-oncologist cost discussions and financial toxicity-related outcomes. Patient acceptance of the DISCO App and oncologist engagement suggested the intervention prompted cost discussions. Next steps include conducting a longitudinal randomized controlled trial to determine the effectiveness of the DISCO App on financial toxicity, and other outcomes. Clinical trial information: NCT03676920 .
Effect of cardiac troponin T on prognosis in the elderly patients with chronic heart failure
Authors: 衣欣, 胡奉环, 张力新, 安磊
Journal: BMJ (2007)

目的 探讨心肌肌钙蛋白T(cTnT)对老年慢性心力衰竭预后的影响.方法 对60例不同心功能级别老年慢性心力衰竭患者测定血清cTnT、肌酸激酶(CK)、肌酸激酶同工酶(CK-MB),并根据cTnT是否阳性分组,比较其住院期间的心脏事件(恶性心律失常、心力衰竭反复或加重、死亡)的发生情况.结果 心功能Ⅱ级者CK(89.1±13.6)mmol/L,CK-MB(7.9±1.4)mmol/L,cTnT阳性0例;心功能Ⅲ级者CK(88.2±13.4)mmol/L,CK-MB(7.5±1.8)mmol/L,cTnT阳性4例;心功能Ⅳ级者CK-MB(8.0±1.6)mmol/L,CK(93.3±14.2)mmol/L,cTnT阳性14例.cTnT阳性组恶性心律失常发生6例(33.3%),心力衰竭反复或加重8例(44.4%),死亡3例(16.7%);cTnT阴性组恶性心律失常发生1例(2.4%),心力衰竭反复或加重2例(4.8%),死亡1例(2.4%).cTnT阳性组心脏事件发生率高于cTnT阴性组(P＜0.05).结论 cTnT与老年慢性心力衰竭的预后有密切的关系,对判断估测老年慢性心力衰竭患者预后有较好的预测价值。
专科医生看全科：谈谈我对全科医生制度建立的一些建议
Authors: 胡大一
Journal: BMJ (2011)

获悉国务院常务会议决定建立全科医生制度，我十分兴奋，这是新中国建立以来医疗卫生发展和医疗卫生改革上具有历史意义和里程碑意义的一件大事。我们一直希望能够在新的医疗改革中重构和推出新的医疗卫生服务资源的合理分布。我国目前医疗资源过度集中在大城市、大医院，“看病贵，看病难”问题十分突出，同时也加剧了医患矛盾，这样的分布是不合理的。我始终觉得建立为公众健康和患者服务的分级医疗网络，培养建立全科医生制度是合理分配医疗资源的关键性措施。
Analysis of clinical features in patients with influenza A/H1N1
Authors: 张奕, 刘白薇, 王小莉, 杨鹏, 黎新宇, 庞星火, 邓瑛, 钱海坤, 王全意
Journal: BMJ (2011)

A total of 3499 cases of influenza A (H1N1) were included in this study for analysis.Epidemiological and clinical data of these cases were input into EpiData software and analyzed by SPSS software. Throat swabs were collected from the cases and detected for nucleic acid of influenza A ( H1N1 )virus using real-time polymerase chain reaction (RT-PCR) with fluorescence quantitative method, and time of viral excretion and clinical features of the cases were analyzed. Results showed that 0. 37% of the cases were in-apparent and asymptomatic and the most common symptom of the cases was fever (86. 77% ).Throat swabs converted to negative on the sixth day of onset in average, and no factors related to the time of conversion was found with logistic regression analysis.

Key words: 
Influenza A virus,H1N1 subtype ;  Signs and symptoms ;
A phase Ib study of oral Chk1 inhibitor LY2880070 as monotherapy in patients with advanced or metastatic cancer.
Authors: Wilson H. Miller, Quincy S. Chu, Nathaniel Bouganim, Derek J. Jonker, Gerald Batist, Najwa J Buhlaiga, Stephanie Lheureux, Jennifer L. Spratlin, Thierry Alcindor, Patricia S Smith, Joel Owen, Sara L. Zaknoen, John R. Stille, Caroline Fortier, Darcy Vincett, Amit M. Oza
Journal: Journal of Clinical Oncology (2020)

3579 Background: LY2880070 (LY) is an orally-administered, selective adenosine triphosphate-competitive inhibitor of checkpoint kinase 1 (Chk1). LY blocks the checkpoint response, and Chk1 inhibition results in mitotic catastrophe to produce apoptosis. Methods: This 2-part, open-label multi-center study explores the safety, pharmacokinetics (PK) and anti-tumor activity of LY in patients with advanced or metastatic cancers. The primary objective of this study was to determine the maximum tolerated dose (MTD) for multiple escalating oral doses of LY. Secondary objectives were to: 1) Characterize the dose-limiting toxicities (DLTs) and overall safety profile for LY; 2) Evaluate the PK of LY; and 3) Evaluate the anti-tumor activity of LY. Patients received LY orally in 21-day cycles in two treatment arms: 1) A multiple ascending dose (MAD) arm in patients with normal/intermediate CYP2D6 metabolism; or 2) An arm with LY administered as monotherapy to CYP2D6 poor metabolizers. Results: The MTD in normal/intermediate CYP2D6 metabolizers was 200 mg BID daily. A dose of 400 mg QD was not tolerated even with the use of anti-emetics. However, BID administration (same total daily dose) made LY tolerable. Dose-limiting toxicities were predominantly vomiting, nausea, and fatigue, and appeared to be correlated with C max . The mean half-life was 5.35 (+/- 2.3) hours. BID dosing provided maintenance of the AUC (3271.4 h∙ng/mL 200 mg BID vs 3377.9 h∙ng/mL 400 mg QD) while lowering C max (350.0 ng/mL 200 mg BID vs 691.9 ng/mL 400 mg QD) and increasing C min , compared to QD dosing of the same total daily dose. Importantly, BID administration of 200 mg LY resulted in a median C min at steady-state that remains above the IC 80 for 12 h/day and above the IC 50 for 24 h/day. Five patients had a best response of SD for a duration of ≥ 6 cycles. Conclusions: LY was tolerated in a daily BID schedule. The toxicity profile can be modulated by changing the dosing frequency from QD to BID while administering the same daily dose. LY may be a potential combination therapy with DNA damaging agents. Study #: NCT02632448 . This study is sponsored by Esperas Pharma Inc., 1255 boul. Robert-Bourassa #1610, Montreal, Qc, H3B 3X3. Clinical trial information: NCT02632448 .
Bedside closestool improve constipation and anxiety symptoms for patients with acute intracerebral hemorrhage
Authors: Jianhua Huang, Ping Su
Journal: BMJ (2014)

Objective
To investigate the effect of defecation modes on constipation and anxiety in patients with acute intracerebral hemorrhage.


Methods
Sixty three conscious patients with acute hintracerebral hemorrhage were recruited in this study. Twenty five patients chose bedside closestool for defecation according their own intention and 38 chose in bed defecation. The incidence of constipation was documented and the severity of anxiety was evaluated with Zung self-rating anxiety scale (SAS) at day 7, 14, 21 and 28 after admission in two groups.


Results
Patients using bedside closestool for defecation had significantly lower rate of constipation between day 14-28 after admission (χ2=63.0, P<0.01) and lower SAS scores at day14, 21 and 28 after admission (t=6.7, 7.7 and 9.8, all P<0.01) than those with in bed defecation.


Conclusions
The bedside mode of defecation may improve constipation and anxiety in patients with acute intracerebral hemorrhage.


Key words: 
Cerebral hemorrhage; Constipation; Anxiety; Defecation modes
NIVACOR: Phase II study of nivolumab in combination with FOLFOXIRI/bevacizumab in first-line chemotherapy for advanced colorectal cancer RASm/BRAFm patients.
Authors: Angela Damato, Francesco Iachetta, Nicola Normanno, Francesca Bergamo, Evaristo Maiello, Alberto Zaniboni, Lorenzo Antonuzzo, Guglielmo Nasti, Giuseppe Tonini, Roberto Bordonaro, Francesca Di Fabio, Alessandra Romagnani, Annalisa Berselli, Carmine Pinto
Journal: Journal of Clinical Oncology (2020)

TPS4118 Background: FOLFOXIRI (fluorouracil, leucovorin, oxaliplatin, and irinotecan) plus bevacizumab has been shown to be one of the therapeutic regimens in first line with the highest activity profile in patients (pts) with metastatic colorectal cancer (mCRC) unselected for biomolecular alterations. Tumors co-opt the PD-1/PD-L1 signaling pathway as one key mechanism to evade immune destruction. Anti-PD-1 monoclonal antibodies are FDA approved only for DNA mismatch repair deficient/microsatellite instability-high (MMRd/MSI-H), which are only about 5% among all mCRC. Nowadays, there are no data demonstrating anti-PD1 activity in stable and proficient (MMRp/MSS) disease. Another critical therapeutic target is the Vascular Endothelial Growth Factor A (VEGF-A), which acts on endothelial cells to stimulate angiogenesis; his inhibition with bevacizumab increase immune cell infiltration, giving a strong rationale for combining VEGF targeted agents with immune checkpoint inhibitors. Based on evidence, we explore the combination of triplet chemotherapy (FOLFOXIRI) with bevacizumab and nivolumab in pts with mCRC all- RAS/BRAF mutant regardless of microsatellite status. Methods: This is a prospective, open-label, multicentric phase II trial where pts with mCRC RAS/BRAF mutant in first line will receive nivolumab in combination with FOLFOXIRI/Bevacizumab every 2 weeks for 8 cycles followed by maintenance with bevacizumab plus nivolumab every 2 weeks. Bevacizumab will be administered intravenously at dose of 5 mg/kg every 2 weeks and nivolumab intravenously as a flat dose of 240 mg every 2 weeks. The primary endpoint is the overall response rate (ORR) and our hypothesis is that the treatment is able to improve the ORR from 66% to 80%. Secondary endpoints include overall survival, safety, time to progression, duration of response. Collateral translational studies evaluate the tumor mutational burden, and genetic alterations by circulating free DNA (cfDNA) obtained from plasma samples. The trial is open to enrollment, 4 of planned 70 pts have been enrolled. Clinical trial information: EudraCT Number: 2018-002893-38. Clinical trial information: NCT04072198 .