tbuckley/cabot-search huggingface dataset:
Evaluation of patient characteristics, perceptions and experience in cancer clinical trial in National Cancer Center in China: Identifying factors affecting subjects’ satisfaction and stress.
Authors: Shiyu Jiang, Peng Liu, Sheng Yang, Jianliang Yang, Yan Qin, Lin Gui, Shengyu Zhou, Jianping Xu, Yongkun Sun, Puyuan Xing, Hongnan Mo, Bo Lan, Bo Zhang, Dawei Wu, Hong Fang, Le Tang, Yan Sun, Yuankai Shi
Journal: Journal of Clinical Oncology (2018)

e18802 Background: Patient characteristics, perceptions and experience concerning cancer clinical trials (CCT) may affect study accrual and quality. Our study aimed to evaluate 1) subjects’ perceptions toward CCT 2) satisfaction and stress in CCT and 3) the influencing factors.(NCT03412344) Methods: CCT subjects, receiving treatment or in follow-up in National Cancer Center in China were eligible. A questionnaire was delivered after informed consent. Stress and satisfaction were evaluated via an ordinate scale and a 11-point scale (0 to 10) respectively. Results: Among the 199 participants, 83.92% declared willingness to join CCT again; 72.86% had enough time to make decision for trial participation; 87.44% had very positive impression of doctors; 73.87% claimed complete awareness of the participating trial; 3.52% doubted the significance and scientificity of CCT; 33.17% deemed CCT time-consuming; 73.87% scored satisfaction scale ≥9; 25.63% claimed moderate stress or higher. Median distance to the clinical center was 450.0 km. Patient self-reporting satisfaction was negatively associated with stress (Rho = -0.304, p < .0001). In the logistic regression analysis, enough time for trial participation decision (Odds ratio, OR = 0.363, p = 0.0003), better impression of doctors (OR = 0.412, p = 0.047) and less time consumption in the trial (OR = 0.434, p < 0.0001) were positive factors of satisfaction. Financial compensation also seemed to be a positive factor (OR = 0.825, p = 0.091). Individuals with more prior medical cost (OR = 1.225, p = 0.026), less time consumption (OR = 2.352, p < .0001) and more tests in CCT (OR = 0.636, p = 0.035) were less likely to experience stress. Moreover, phase 3 study subjects bear less stress than phase 2 (OR = 0.294, p = 0.032) but more stress than phase 1 (OR = 1.178, p = 0.009). Conclusions: Our study addressed the influencing factors of CCT subjects’ satisfaction and stress, indicating measures such as providing enough time for participation decision making and taking individual time consumption into consideration may optimize subjects’ experience and improve study accrual and quality.
Can minocycline ameliorate symptom burden in patients with pancreatic cancer? A phase II randomized trial.
Authors: Xin Shelley Wang, David R. Fogelman, Qiuling Shi, Tito R. Mendoza, Raza H Bokhari, Charles S. Cleeland
Journal: Journal of Clinical Oncology (2016)

e21636 Background: In patients with newly diagnosed pancreatic cancer, symptom burden can be driven by both rapid disease progression and aggressive cancer therapy. Abatement of symptoms is a highly significant agenda for patient care. Minocycline is a readily available, low-cost antibiotic with reported anti-inflammatory properties. We investigated whether minocycline, given its capacity to cross the blood–brain barrier, could serve as a mechanism-driven symptom intervention to reduce symptom burden and improve outcomes in patients with pancreatic cancer. Methods: Adult patients with newly diagnosed, advanced pancreatic cancer and scheduled for chemotherapy were enrolled in this randomized, placebo-controlled phase II clinical trial. Participants were equally randomized to receive either minocycline (100 mg twice daily) or matching placebo. Feasibility, toxicity, and patient-reported outcomes data were prospectively collected. The MD Anderson Symptom Inventory (0–10 scale) was used to measure symptom severity weekly. The 6-week (±2 days) area under the curve (AUC) for was used to compare minocycline’s efficacy between the intervention and control groups Results: We enrolled 45 patients from 01/2013–10/2015; of these, 10 patients dropped out during the study (4 by patient request, 6 due to rapid disease progression). The remaining 31 patients contributed 3 cycles (6 weeks) of study drug (18 minocycline and 13 placebo). The most severe symptoms for both treatment groups were fatigue, poor appetite, drowsiness, pain, and disturbed sleep. No grade 3+ study medication-related adverse events occurred. The treatment groups did not differ statistically in terms of symptom severity, controlled for disease progression. In addition, minocycline had no effect on delaying the development of severe symptoms during standard chemotherapy. Conclusions: This study produced negative findings on minocycline’s ability to treat disease-driven and treatment-related symptoms during standard chemotherapy. In this very ill patient population, a high drop-off rate due to disease suggests poor feasibility for trials in patients with advanced pancreatic cancer receiving chemotherapy. Clinical trial information: NCT01693523.
Abstract 82: Wnt11 Regulates Chamber Specific Neonatal Cardiomyocyte Proliferation During Perinatal Circulatory Transition
Authors: Marlin Touma, Xuedong Kang, Fuying Gao, Yan Zhao, Reshma Biniwale, Jau-Nian Chen, Giovanni Coppola, Brian Reemtsen, Yibin Wang
Journal: Circulation Research (2017)

Background: Fetal to neonatal transition of heart involves major changes in cardiomyocytes (CMC) including proliferative capacity. However, the chamber specific CMC proliferation programs of remain poorly understood. Elucidating the mechanisms involved is critical to develop chamber specific therapies for newborn infants with single ventricle physiology and other congenital heart defects (CHDs). Methods: Transcriptomes of mouse left ventricle (LV) and right ventricle (RV) were analyzed by RNA-seq at postnatal days 0 (P0), P3 and P7. R package and Ingenuity suite were used for weighted gene co-expression network analysis (WGCNA) and gene ontology studies. Mechanistic analysis was conducted using gain and loss of function approaches. Results: Mouse neonatal cardiac transcriptome was mostly affected by developmental stage. WGCNA revealed 5 LV and 8 RV modules that were significantly correlated with maturation stage and highly preserved between both ventricles at P0 and P7. In contrast, P3 specific gene modules exhibited the largest chamber specific variations in cell signaling, involving proliferation in LV and Wnt signaling molecules, including Wnt11, in RV. Importantly, Wnt11 expression significantly decreased in cyanotic CHDs phenotypes and correlated with O2 saturation levels in hypoxemic infants with Tetralogy of Fallot (TOF). Notably, Perinatal hypoxia treatment in mice suppressed Wnt11 expression, induced CMC proliferation, downregulated Rb1 expression and enhanced Rb1 phosphorylation more robustly in RV vs. LV. Remarkably, Wnt11 inactivation was sufficient to induce myocyte proliferation in perinatal mouse heart and reduced Rb1 expression and phosphorylation in primary neonatal CMC. Importantly, downregulated Wnt11 in hypoxemic TOF infantile heart was also associated with Rb1 suppression and inversely correlated with proliferation marker Plk1 in human. Conclusion: Using integrated systems genomic and functional biology analyses of perinatal cardiac transcriptome, we revealed a previously uncharacterized function for Wnt11 in chamber specific growth and cyanotic CHD. Reduction of Wnt11 expression by hypoxia plays a critical role in neonatal CMC proliferation via modulating Rb1 expression and activity.
Nasal High Flow Delivered within the Helmet: A New Noninvasive Respiratory Support
Authors: Tommaso Mauri, Elena Spinelli, Massimiliano Mariani, Amedeo Guzzardella, Chiara Del Prete, Eleonora Carlesso, Donatella Tortolani, Paola Tagliabue, Antonio Pesenti, Giacomo Grasselli
Journal: American Journal of Respiratory and Critical Care Medicine (2018)
Atmospheric Dust, Early Cases, and Localized Meningitis Epidemics in the African Meningitis Belt: An Analysis Using High Spatial Resolution Data
Authors: Maxime Woringer, Nadège Martiny, Souleymane Porgho, Brice W. Bicaba, Avner Bar-Hen, Judith E. Mueller
Journal: Environmental Health Perspectives (2018)

Background: Bacterial meningitis causes a high burden of disease in the African meningitis belt, with regular seasonal hyperendemicity and sporadic short, but intense, localized epidemics during the late dry season occurring at a small spatial scale [i.e., below the district level, in individual health centers (HCs)]. In addition, epidemic waves with larger geographic extent occur every 7–10 y. Although atmospheric dust load is thought to be an essential factor for hyperendemicity, its role for localized epidemics remains hypothetic. Objectives: Our goal was to evaluate the association of localized meningitis epidemics in HC catchment areas with the dust load and the occurrence of cases in the same population early in the dry season. Methods: We compiled weekly reported cases of suspected bacterial meningitis at the HC resolution for 14 districts of Burkina Faso for the period 2004–2014. Using logistic regression, we evaluated the association of epidemic HC-weeks with atmospheric dust [approximated by the aerosol optical thickness (AOT) satellite product] and with the observation of early meningitis cases during October–December. Results: Although AOT was strongly associated with epidemic HC-weeks in crude analyses across all HC-weeks during the meningitis season [odds ratio (OR) = 6.82; 95% CI: 4.90, 9.50], the association was no longer apparent when controlling for calendar week (OR = 0.92; 95% CI: 0.60, 1.50). The number of early meningitis cases reported during October–December was associated with epidemic HC-weeks in the same HC catchment area during January–May of the following year (OR for each additional early case =1.14; 95% CI: 1.06, 1.21). Conclusions: Spatial variations of atmospheric dust load do not seem to be a factor in the occurrence of localized meningitis epidemics, and the factor triggering them remains to be identified. The pathophysiological mechanism linking early cases to localized epidemics is not understood, but their occurrence and number of early cases could be an indicator for epidemic risk. https://doi.org/10.1289/EHP2752
Alectinib versus crizotinib in treatment-naive anaplastic lymphoma kinase-positive (ALK+) non-small-cell lung cancer: CNS efficacy results from the ALEX study
Authors: S. Gadgeel, S. Peters, T. Mok, A.T. Shaw, D.W. Kim, S.I. Ou, M. Pérol, A. Wrona, S. Novello, R. Rosell, A. Zeaiter, T. Liu, E. Nüesch, B. Balas, D.R. Camidge
Journal: Annals of Oncology (2018)

BackgroundThe phase III ALEX study in patients with treatment-naive advanced anaplastic lymphoma kinase mutation-positive (ALK+) non-small-cell lung cancer (NSCLC) met its primary end point of improved progression-free survival (PFS) with alectinib versus crizotinib. Here, we present detailed central nervous system (CNS) efficacy data from ALEX.Patients and methodsOverall, 303 patients aged ≥18 years underwent 1:1 randomization to receive twice-daily doses of alectinib 600 mg or crizotinib 250 mg. Brain imaging was conducted in all patients at baseline and every subsequent 8 weeks. End points (analyzed by subgroup: patients with/without baseline CNS metastases; patients with/without prior radiotherapy) included PFS, CNS objective response rate (ORR), and time to CNS progression.ResultsIn total, 122 patients had Independent Review Committee-assessed baseline CNS metastases (alectinib,n = 64; crizotinib,n = 58), 43 had measurable lesions (alectinib,n = 21; crizotinib,n = 22), and 46 had received prior radiotherapy (alectinib,n = 25; crizotinib,n = 21). Investigator-assessed PFS with alectinib was consistent between patients with baseline CNS metastases [hazard ratio (HR) 0.40, 95% confidence interval (CI): 0.25–0.64] and those without (HR 0.51, 95% CI: 0.33–0.80,P interaction = 0.36). Similar results were seen in patients regardless of prior radiotherapy. Time to CNS progression was significantly longer with alectinib versus crizotinib and comparable between patients with and without baseline CNS metastases (P < 0.0001). CNS ORR was 85.7% with alectinib versus 71.4% with crizotinib in patients who received prior radiotherapy and 78.6% versus 40.0%, respectively, in those who had not.ConclusionAlectinib demonstrated superior CNS activity and significantly delayed CNS progression versus crizotinib in patients with previously untreated, advancedALK+ NSCLC, irrespective of prior CNS disease or radiotherapy.Clinical trial registrationClinicalTrials.gov NCT02075840
Evaluation of photosensitivity in dabrafenib treated metastatic melanoma patients: Results from a phase IIa study.
Authors: Thomas K. Eigentler, Kamran Ghoreschi, Mark Berneburg, Claus Garbe
Journal: Journal of Clinical Oncology (2016)

e21077 Background: Dabrafenib (DAB) and vemurafenib (VEM) are highly efficacious in melanomas harbouring BRAF V600 mutations. Serious photo toxicity (PT) has been reported in ~30% of patients (pts.) treated with VEM but only in ~2% of pts. treated with DAB. PT depends on patient’s habits of exposure and sun protection. However, the exact frequency of photosensitivity has to be determined by systematic photo testing. Methods: Primary objective was to characterize the potential of DAB to sensitize skin to UV exposure. We assumed the incidence of PT with DAB is > 0% but lower than those with VEM. An exact binomial test (p = 0.05, 2-sided) had 84% power to detect a difference between the Null hypothesis p0 of 0.8 and the alternative proportion pA of 0.3. Sample size was 10. Photo testing with UVA1/UVB-irradiation was done per standardized protocols: UVA1 (20-100J/cm2) and UVB (according to patient’s minimum erythema dose, up to 200mJ/cm2) without DAB (d1) and 2h after taking DAB (d2). PT was evaluated using the maximal occurring grade (G0: no erythema [ery], G1: light ery., G2: markedly ery., G3: ery. and induration) over 5 days follow-up. Adult patients (ECOG 0-2) with advanced melanoma and BRAF V600 mutation were eligible. All pts. received DAB 150 mg BID po according to the approved preparation. Results: Ten pts. were included (05/2014 - 07/2015). In all pts. UVA1 and UVB grades were documented before DAB intake (UVA1 - 4 pts. with G1, 5 pts. with G2 and 1 pt. with G3; UVB - 4 pts. with G0, 2 pts. with G1, 3 pts. with G2 and 1 pt. with G3). After DAB intake UVA1 and UVB grades were documented repeatedly (max. extent: UVA1 - 3 pts. with G1, 5 pts. with G2 and 2 pts. with G3; UVB - 3 pts. with G0, 1 pt. with G1, 4 pts. with G2 and 2 pts. with G3). In 2/10 cases an increase in PT grades from G1 to G2 and from G2 to G3 occurred in the UVA1 irradiated areas. For UVB an increase in 4 cases was seen (G1 to G2, G2 to G3, G0 to G1 and G1 to G2). None of the patients felt major discomfort due to irradiation. Conclusions: In contrast to published data of PT under VEM the observed PT of DAB was negligible low for UVA1. In the UVB irradiated area 4/10 pts. got an increase in PT by one grade after DAB intake. However, this increase in PT did not induce any clinical discomfort in the majority of pts. Clinical trial information: NCT02052193.
Risk of hematological and gastrointestinal toxicities in patients with advanced neuroendocrine tumors treated with everolimus: A meta-analysis of phase 3 randomized controlled trials.
Authors: Anita Sultan, Kyaw Zin Thein, Sriman Swarup, Somedeb Ball, Lukman Aderoju Tijani, Sanjay Awasthi, Catherine Jones, Fred L. Hardwicke
Journal: Journal of Clinical Oncology (2018)

e16184 Background: Neuroendocrine tumors (NET) are uncommon and can develop from multiple primary sites. Inhibition of mTOR signaling pathway has shown antiproliferative effects on NET and hence, everolimus (E), an mTOR inhibitor, has been employed. Yet, there are notable safety concerns. We performed a systematic review and meta-analysis of randomized controlled trials (RCT) to determine the risk of hematological and gastrointestinal (GI) toxicities. Methods: MEDLINE, EMBASE databases and meeting abstracts from inception through January 2018 were queried. Phase 3 RCTs that mention hematological and GI toxicities as adverse effects were incorporated in the analysis. The primary meta- analytic approach was a fixed effects model using the Mantel-Haenszel (MH) method. It was used to calculate the estimated pooled risk ratio (RR) with 95% confidence interval (CI). Results: A total of 1133 patients with advanced NET were eligible. Studies compared E+ octreotide (O) vs O or E vs placebo. The RR of all-grade side effects were as follows: anemia, 4.45 (95% CI: 2.73-7.25, p < 0.001); thrombocytopenia, 37.25 (95% CI: 7.39-187.69, p < 0.001); nausea, 1.25 (95% CI: 0.96-1.62, p = 0.09); vomiting, 2.18 (95% CI: 1.37-3.46, p = 0.001); diarrhea, 2.21 (95% CI: 1.73-2.84, p < 0.001); stomatitis, 3.86 (95% CI: 3.15-4.73, p < 0.001); dysgeusia, 4.35 (95% CI: 2.70-7.02, p < 0.001); and hyperglycemia, 4.08 (95% CI: 2.39-6.95, p < 0.001). The RR of high-grade side effects were as follows: anemia, 8.14 (95% CI: 2.02-32.77, p = 0.003); thrombocytopenia, 18.77 (95% CI: 2.52-139.62, p = 0.004); nausea, 1.81 (95% CI: 0.44-7.37, p = 0.40); diarrhea, 3.65 (95% CI: 1.66-8.02, p = 0.001); stomatitis, 25.00 (95% CI: 5.00-125.02, p < 0.001); dysgeusia, 2.09 (95% CI: 0.22-19.41, p = 0.51); and hyperglycemia, 4.15 (95% CI: 1.76-9.75, p = 0.001). Conclusions: Our study showed that patients on everolimus experienced a significant increase in all grades of stomatitis with a relative risk of 25 for grade 3 and 4 stomatitis, compared to control arm. They also contributed to all grades of hyperglycemia, diarrhea and hematological toxicities as well as all-grade vomiting and dysgeusia.
TCT-119 Impact of Clinical Syndrome on Outcomes After PCI: Analysis From a Large Pooled Randomized Trial Dataset
Authors: Masaru Ishida, Akiko Maehara, Aaron Crowley, Pieter Smits, Clemens von Birgelen, Martin Leon, Patrick Serruys, Ori Ben-Yehuda, Gary Mintz, Gregg Stone
Journal: Journal of the American College of Cardiology (2018)
Retrospective review of metastatic uveal melanoma (mUM) at NYU Perlmutter Cancer Center (NYU-PCC).
Authors: Juraj Kavecansky, Paul Finger, Melissa Wilson, Kathleen M. Madden, Rajni Kannan, Anna C. Pavlick
Journal: Journal of Clinical Oncology (2017)

e21040 Background: Uveal melanoma (UM) is the most common primary intraocular malignancy in adults, despite its rare incidence of 5 per 1,000,000. UM metastasis (mets) occurs in approximately 50% of patients (pts). The published median survival from the time of mets is only 6 to 12 months (mos). To date there is no curative therapy for pts with mUM. Methods: This is a retrospective review of pts evaluated at NYU-PCC with UM between January 1, 2011 and December 31, 2016. Data collected include: ophthalmic treatment, time from ophthalmic diagnosis, systemic metastatic sites, genetic mutations (muts), systemic treatment and survival. Results: During this 5-year interval, 100 UM pts were referred to NYU-PCC. 58 pts were diagnosed with high-risk primary T3/T4 sized tumors and remained disease-free during this period. For the remaining 42 pts that developed mUM, primary ophthalmic treatments included: 12 enucleations, 27 brachytherapy and 3 received none since they had synchronous UM and mUM. Therapy for mUM included liver-directed therapy (LDT) such as TACE, 90 Y brachytherapy, or radiofrequency ablation; or systemic therapy. These mUM pts had a median survival of 17 mos. 20 mUM pts are male; 22 pts are female; Ages: 33-96; 24 deceased and 18 alive. Of the latter, 5 are NED and 13 are alive with disease on treatment. 24 deceased mUM pts treated initially with LDT lived on average 14 mos longer than those treated with any systemic therapy alone; pts with LDT had a median survival of 24 mos, compared to 10 mos for those treated only with systemic therapy (p = 0.0075). There was no correlation between time of ophthalmic diagnosis and time to onset of mets and survival (R 2 value 0.00243). Genetic analysis of met tumors was available on 9 pts. 3 of 5 pts with GNA11 muts are alive compared to 1 of 4 pts with GNAQ muts. Conclusions: Pts with mUM treated initially with LDT had significantly longer survival compared to pts treated with systemic therapy alone. Whether longer survival in these pts is an effect of LDT, earlier treatment of mets, or a more indolent disease remains to be determined. Our study demonstrates mUM pts survive an average of 17 mos, which is higher than historically reported. Significance of GNAQ or GNA11 requires further investigation.
Development and validation of a molecule based nomogram to predict relapse in stage I NSCLC.
Authors: Qixing Mao
Journal: Journal of Clinical Oncology (2018)

e20544 Background: Stage I NSCLC is a curable disease by surgery. However, up to 30% recurrence rate impedes the effect of curative surgery, which shortens the prognosis. Optimal postoperative adjuvant therapy is still ambiguous for stage I NSCLC. Here, we aimed to develop and validate a feasible tool to predict the recurrence of stage I NSCLC. Methods: In discovery phase, multiple eligible datasets and published signatures were used to select statistically significant genes thought to be predictive by Least Absolute Shrinkage and Selector Operation and Support Vector Machine-Recursive Feature Elimination. In the training phase, candidate genes were used to generate a recurrence related signature in TCGA cohort by penalized Cox regression. Recurrence related signature and other clinical variables were selected to develop a nomogram by back stepwise variable selection. In validation phase, the performance of nomogram was further tested via two independent GEO cohorts. Results: 11 eligible microarray data sets and 7 published signatures were included in discovery phase. 42 significant genes were highlighted as candidate predictors by two algorithms. A 13-gene based signature related to recurrence were generated by penalized cox regression and categorized training cohort into high-risk and low risk subgroups with significantly different recurrence free survival (HR = 8.873, 95% CI:4.228-18.480 P< 0.001). The performance of signature was tested in two external cohorts (HR = 3.556, 95%CI:1.587-7.996, P= 0.001; HR = 2.586, 95%CI:1.226-5.286, P= 0.007). Furthermore, a nomogram integrating recurrence related signature, age, and histology was developed to predict the recurrence-free survival in the training cohort, and it performed well in the two external validation cohorts (concordance index: 0.737, 95%CI:0.732-0.742, P< 0.001; 0.666, 95%CI: 0.650-0.682, P< 0.001; 0.651, 95%CI:0.637-0.665, P< 0.001 respectively). Conclusions: The proposed nomogram is a promising tool for estimating recurrence free survival in stage I NSCLC, which might have tremendous value in guiding adjuvant therapy. Prospective studies are needed to test the clinical utility of the nomogram in individualized management of stage I NSCLC.