tbuckley/cabot-search huggingface dataset:
Real-world outcomes and patient (pt) characteristics for the second-line (2L) treatment of gastric, esophageal, or gastroesophageal junction (GEJ) adenocarcinoma (EGAC).
Authors: Afsaneh Barzi, Lisa M. Hess, Yajun Zhu, Astra M. Liepa, Yun Fang, Craig Heath Kuder, Julie Beyrer, Joseph Chao
Journal: Journal of Clinical Oncology (2018)

e16011 Background: Multiple phase 3 randomized clinical trials (RCTs) have shown improved overall survival (OS) associated with continued treatment (tx) after disease progression among pts with EGAC. We evaluated the benefit associated with 2L therapy after 1L tx for advanced/metastatic EGAC in an unselected real-world pt population and identified factors associated with receipt of 2L therapy. Methods: This retrospective analysis used the Flatiron electronic medical records database that includes 5221 pts with advanced or metastatic gastric/esophageal cancer from 2011-2017. Eligible pts were ³18 y and had initiated first-line (1L) therapy on or after 1/1/2013. Pts with squamous carcinomas were excluded. Only those alive ³45 d following 1L therapy completion were considered candidates for 2L therapy to reduce survival bias. OS was defined as duration between 1L initiation and death, analyzed using Kaplan Meier method and log-rank test. Pt characteristics were compared using t-test or Chi-square. Results: 2664 pts met eligibility criteria (947 gastric, 794 GEJ, and 923 esophageal). The mean age was 66.4 years, 73.8% were white, and 75.6% were male. Of all patients, 58.8% received only one line of therapy. The mean duration of 1L tx was 3.3 mo (SD = 3.8). Of 1566 pts who did not continue to 2L tx, 258 (16.5%) were still receiving 1L tx at data analysis cutoff and 327 (20.9%) had died during 1L tx. There were 1270 pts who were considered candidates for 2L; of those, 816 (64.3%) were treated with 2L therapy and 454 (35.7%) were not. Median OS was 15.9 (95% CI 15.0-16.6) mo for those treated with 2L therapy and 9.9 (95% CI 8.8-10.4) mo for those who were not. Longer duration of 1L therapy (≥4 vs < 4 mo) and younger age were associated with receipt of 2L tx (both p < 0.0001). Conclusions: In this real-world database study of an unselected population, ~36% of pts with EGAC in this study did not receive 2L therapy after initial tx despite evidence for OS benefit from RCTs. Younger pts with longer 1L treatment were more likely to receive 2L therapy. Further research is needed to better identify the patient most likely to benefit from and to find ways to overcome barriers to 2L therapy.
Abstract 16849: Alirocumab Dosing in a Real World Setting: Data From an Open-label Treatment Extension to the ODYSSEY Program for Patients With Heterozygous Familial Hypercholesterolemia
Authors: G. Kees Hovingh, John R Guyton, Gisle Langslet, Robert Dufour, Marie T Baccara-Dinet, Chantal Din-Bell, Garen Manvelian, Michel A Farnier
Journal: Circulation (2016)

Introduction: ODYSSEY OLE (NCT01954394) is an open-label extension (OLE) study of four Phase 3 clinical trials (FH I, FH II, LONG TERM [LTS] and HIGH FH) evaluating long-term efficacy and safety of alirocumab (ALI) in patients with heterozygous familial hypercholesterolemia (HeFH) over up to 3.5 years of treatment. Objective: ALI can be administered as 75 or 150 mg Q2W, but how this dosing strategy is applied in daily practice is largely unknown. We assessed dosing strategies used during OLE. Methods: Patients were on maximally tolerated statin +/- other lipid-lowering therapy. Patients started on ALI 75 mg Q2W (patients enrolled from HIGH FH started OLE with 150 mg Q2W and were not analyzed here). Physicians could adjust the ALI dose based on clinical judgment and LDL-C level; if further LDL-C reduction was required the ALI dose could be increased to 150 mg Q2W. Results: 909 patients (mean age 54.6 years, 56.1% male) with HeFH were analyzed. At OLE entry, HeFH patients from LTS (n=318) had a higher mean ...
Mucus-penetrating budesonide nanosuspension enema for local treatment of inflammatory bowel disease
Authors: Abhijit A. Date, Gilad Halpert, Taarika Babu, Jairo Ortiz, Pranjali Kanvinde, Peter Dimitrion, Janani Narayan, Hannah Zierden, Kalpana Betageri, Olivia Musmanno, Helen Wiegand, Xinglu Huang, Sanjeev Gumber, Justin Hanes, Laura M. Ensign
Journal: Biomaterials (2018)
Phase II trial of umbilical cord blood-derived natural killer cells for multiple myeloma.
Authors: Nina Shah, Li Li, Jessica Mccarty, Indreshpal Kaur, Eric Yvon, Robert Z. Orlowski, Laurence Cooper, Simrit Parmar, Kai Cao, Chitra Hosing, Sairah Ahmed, Yago Nieto, Krina K. Patel, Qaiser Bashir, Stephanie Kent, Catherine Bollard, Richard E. Champlin, Katayoun Rezvani, Elizabeth J. Shpall
Journal: Journal of Clinical Oncology (2016)

TPS3100 Background: Multiple myeloma (MM) is an incurable disease characterized by immune dysregulation and exhaustion, whereby proliferation of malignant plasma cells is not checked by the native immune system. Allogeneic natural killer (NK) cells are active in various hematologic malignancies and may have a role against MM. We have recently completed a phase I, first-in-human trial of NK cells derived from umbilical cord blood (CB-NK cells) in conjunction with high dose chemotherapy and autologous stem cell transplant (SCT). In this high-risk patient group, there was no GVHD or infusion reaction and 10/12 patients achieved VGPR or better. We are now conducting a phase II trial of this novel adoptive cell therapy at the MTD of 1 e8 CB-NK cells/kg. Methods: This is a single-arm, phase II trial of CB-NK cells for MM patients undergoing SCT. A total of 33 patients will be enrolled. Patients with symptomatic MM who are candidates for autologous SCT are eligible. CB units with at least 4/6 match at HLA-A, B and DR are chosen. When possible, CB units with potential NK alloreactivity (as determined by KIR typing) are prioritized. On day (-19) CB units are thawed and mononuclear cells (MNCs) are cultured in a gas permeable bioreactor with irradiated (100 Gy) K562-based aAPCs expressing membrane bound IL-21 “Clone 9.mbIL21” (2:1 feeder cell:MNC ratio) and IL-2 (100 IU/mL) . On day 7, cells are CD3-depleted and remaining cells are re-stimulated with aAPC feeder cells and cultured for an additional 7 days. Patients receive lenalidomide (10 mg orally daily) from days (-8) to day (-2). Melphalan 200 mg/ m2 is given IV on day (-7). CB-NK cells are infused on day (-5) with autologous SCT on day (0). Peripheral blood is drawn for correlative analyses (in vivo CB- NK persistence and phenotype) at day (-4), day (0) and weekly thereafter. Responses at day 90 are determined by international Myeloma Working Group criteria. The primary endpoint is rate of complete response (CR) at 90 days after SCT. Secondary endpoints include in vivo persistence of CB-NK cells, in vivo CB-NK phenotype, PFS and OS. Modified Bayesian analysis is being utilized for ongoing toxicity and efficacy monitoring. Study was initiated in December 2014. Clinical trial information: NCT01729091.
Association of acute phase proteins with a serum proteomic test in previously treated patients with NSCLC.
Authors: Jeffrey Allen Borgia, Philip Bonomi, Jennifer Garrus, Fatima Saleem, Gabriela C Lobato, Cristina L. Fhied, Sanjib Basu, Joanna Roder, Sandra Close, Marta Batus, Mary J. Fidler
Journal: Journal of Clinical Oncology (2016)

e20649 Background: In a randomized phase III trial VeriStrat (VST), a multivariate serum proteomic test based on MALDI-TOF mass spectrometry, was shown to predict inferior outcomes in VST “POOR” classified patients (pts) receiving erlotinib compared with docetaxel or pemetrexed as a second line regimen for NSCLC. The objective of this study was to identify additional proteins associated with the VST signature and/or outcome. Methods: Pts with advanced NSCLC that received cytotoxic chemotherapy (ctx) (n = 53) or erlotinib (E) (n = 67) after failing at least one ctx regimen were included. Pretreatment sera were used to establish a VST label (“GOOD” or “POOR”) and determine circulating levels of 102 proteins using quantitative, multiplexed immunoassays (Luminex). This analysis focused on acute phase reactants. The Cox proportional-hazards regression and log rank tests were used to evaluate associations of biomarkers with overall survival (OS), whereas the Mann-Whitney U test was used to evaluate VST label associations with biomarker levels. Results: Median OS for the entire cohort was 7.3 months (mo.), and broke down into 6.0 mo. and 7.7 mo. for the E and ctx subgroups. A total of 45 (67%) adenocarcinoma pts received E, of which 17 (38%) pts had unknown EGFR mutation status, with only 3 having a never- smoking history. VST labels effectively stratified the cohort (p = 0.0004, median OS = 8.2 mo. GOOD vs 2.5 mo. POOR) and predicted survival within the E subset (p < 0.0001 vs. p = 0.3317 for ctx). Before adjusting for multiple testing, elevations of the acute phase reactants, C reactive protein and ferritin, and of IL-6 were associated with VST POOR labels (p < 0.0001, p = 0.0014 and p < 0.0001) respectively) and reduced OS (p < 0.0001, p = 0.0009 and p = 0.0163 respectively). In multivariate analysis, VST classification remained a significant predictor of OS for the entire cohort after adjustment for each of the acute phase reactants. Conclusions: Several acute phase reactants and IL-6, the chief regulator of the acute phase response, were associated with a VST POOR label and clinical outcomes suggesting an important role of this process in aggressive tumor behavior. Validation of these observations in a larger patient cohort is needed.
Genomic characterization of high-grade serous ovarian Cancer by using targeted RNA and DNAseq gene panels.
Authors: Salvador Blanch, Antonio Fernandez-Serra, Ignacio Romero, Zaida Garcia-Casado, Carmen Illueca, Pedro Mallol, Jose Antonio Lopez-Guerrero, Andres Poveda
Journal: Journal of Clinical Oncology (2016)

e17060 Background: Homologous recombination deficiency (HRD) is a major prognostic and predictive factor in High Grade Serous Ovarian Carcinoma (HGSOC). Konstantinopoulos et al. (JCO 2010) defined a 60-gene expression signature to identify a BRCAness phenotype that correlated with prognosis. The aim of this study is to validate the predictive and prognostic impact of this profile by RNAseq in a series of HGSOC. Methods: We selected FFPE samples from 45 HGSOC patients who underwent maximal surgical effort and received platinum-based therapy from 1992-2012. Median follow-up was 59 months. They were divided into three groups: Group 1, comprising 31 women with no family history of cancer and unknown BRCA status; Group 2, 9 women with germline BRCA1/2 (gBRCA) mutations; and Group 3, 5 women with matched samples of primary and recurrent tumors. We performed an RNAseq protocol with a Truseq custom targeted RNA (Illumina) expression including the mentioned signature and 5 further genes (BRCA1, BRCA2, PTEN, AKT and PIK3CA). In order to better genetically characterize Group 2 we used the BRCA Tumor MASTR Plus (Multiplicom) to characterize somatic mutations of BRCA. Additionally, a 32-gene panel (GeneRead DNAseq Targeted Panels V2) related with HGSOC was determined in 12 cases (Qiagen). Results: RNAseq profiling did not reproduce the defined predictive signature. Unsupervised hierarchical clustering of our expression analysis defined two groups of patients with no differences regarding relapse (log-rank p:0.91), platinum free interval (log-rank p:0.90) or overall survival (log-rank p:0.51). No association with the BRCAmutational status was found. All gBRCA mutations in Group 2 at somatic level were confirmed. Mutational analysis in 12 cases (9 of Group 2 and 3 out of 31 of Group 1) revealed 46 mutations including 14 deleterious (BRCA1, BRCA2, CUBN, ERBB2, TP53) and 11 with uncertain significance (BRCA2, CSMD3, EGFR, ERBB2, KIT, PDGFRA, PIK3CA, TP53). Conclusions: Targeted RNA and DNAseq panels provide information regarding the genomic landscape of HGSOC. These tools will require further validation before their clinical implementation.
Systemic therapies for recurrent/metastatic nasopharyngeal carcinoma (RM NPC).
Authors: Amy Prawira, Sjoukje Oosting, Tom Wei-Wu Chen, Ronak Saluja, Keemo Delos Santos, Lisa Wang, Lillian L. Siu, Kelvin K. Chan, Aaron Richard Hansen
Journal: Journal of Clinical Oncology (2016)

6031 Background: No randomized trials exist to guide clinical trial designs in RM NPC. As all published studies are single-arm trials, reliable historical progression-free survival (PFS) and overall survival (OS) data are not available. We aim to analyze existent literature to estimate the relative efficacy of available systemic regimens in RM NPC, as well as provide estimates of historical PFS and OS. Methods: We conducted a systematic search of MEDLINE, EMBASE and the Cochrane Library to March 2015. Clinical trials (in English only) investigating systemic therapies in adult patients (pts) with RM NPC were included. All relevant studies were assessed for quality using Downs and Blacks (DB) checklist (scored out of 27). Aggregate data analysis and student t-test were performed for all identified studies (model A). For studies that published analyzable Kaplan-Meier (KM) curves, survival data were extracted and marginal proportional hazards models were constructed (model B). Results: A total of 56 studies were identified and included in model A, 26 of which had analyzable KM curves and were included in model B. The 26 studies had significantly higher mean DB scores than the remaining 30 (17.3 [95% CI 15.5-19.0] vs 13.7 [95% CI 12.2-15.1], p = 0.002). For 2nd line+ pts, the estimated median OS [mOS] by model A is 11.5 mo (95% CI 10.1-12.9), while model B estimated this at 12.5 mo (95% CI 11.9-13.4). Table 1 presents the relative efficacy for first-line [FL] treatment regimens: combination [C] vs single-agent [S], and platinum [P] vs non-platinum [NP] based therapies. Conclusions: Our analysis supports the use of platinum-based combination chemotherapy in the first-line setting. We present the first aggregate estimates of OS for patients in 2nd line+ setting, which could inform the design of future clinical trials for RM NPC. Model A/mo (95% CI) P-value Model B/HR (95% CI) P-value FL C mPFS 8.4 (6.9-9.8) 0.007 0.48 (0.41-0.56) < 0.0001 FL S 3.5 (1.1-5.9) FL P mPFS 8.3 (7.0-9.6) 0.007 0.48 (0.41-0.56) < 0.0001 FL NP 3.5 (1.1-5.9) FL C mOS 17.8 (14.2-21.4) 0.020 1.16 (0.98-1.38) 0.084 FL S 8.2 (0.0-16.7) FL P mOS 17.4 (13.9-20.8) 0.023 1.16 (0.98-1.38) 0.080 FL NP 8.2 (0.0-16.7)
Performance characteristics and stage distribution of invasive epithelial ovarian/tubal/peritoneal cancers in UKCTOCS.
Authors: Usha Menon, Andy Ryan, Matthew Burnell, Aleksandra Gentry-Maharaj, Jatinderpal K Kalsi, Steven J Skates, Mahesh K B Parmar, Ian J Jacobs
Journal: Journal of Clinical Oncology (2016)

5507 Background: We report on the overall performance of the screening strategies and stage distribution of invasive epithelial ovarian/tubal/peritoneal (iEO/T/PP) cancers Methods: Postmenopausal women aged 50-74 were randomised (1:1:2 ratio) to annual multimodal (MMS) using the Risk of Ovarian Cancer Algorithm (ROCA) or ultrasound (USS) screening, or no screening (control, C). Women with abnormal screens had repeat tests and those with persistent abnormality underwent clinical evaluation and, where appropriate, surgery. Results: Of 202,638 women randomised, 50,624 MMS, 50,623 USS and 101,299 C were eligible for analysis. At median follow-up 11.1 years, 299 MMS, 259 USS and 574 C women developed iEO/T/PP cancers. In the C group, 26% (149/574; 95% CI 22.4, 29.7) were stage I/II/IIIA (low volume disease, LVD). In the subgroup of screen detected cancers, in both MMS (44.2%; 80/181; 95% CI 36.8, 51.8; p<0.0001) and USS (42.9%; 45/105; 95% CI 33.2, 52.9; p=0.00042) group, there was significantly more LVD compared to C. However, across all iEO/T/PP cancers, while proportions of women with LVD remained significantly higher in the MMS (40.1%; 120/299; 95% CI 34.5, 45.9; p<0.0001) versus C comparison, there was no evidence of a difference between the USS (23.9%; 62/259; 95% CI 18.9, 29.6; p= 0.57) and C. Conclusions: While LVD was significantly more frequent in women with screen detected iEO/T/PP cancers in both screen arms compared to C, when all iEO/T/PP cancers were analysed, the difference only persisted in the MMS arm. The latter is a reflection of the high sensitivity of multimodal screening. The findings are in keeping with the emerging mortality reduction observed in the MMS arm in UKCTOCS. Clinical trial information: ISRCTN22488978.Performance characteristics for iEO/T/PP cancers diagnosed <1 year of screen. MMS USS No. of women randomised 50640 50639 No. of women eligible for screening 50624 50623 No. of women screen years 345570 327775 No. of surgeries 736 1825 Total cancers <1 year of screen 210 166 Screen positives 181 105 Screen negatives 29 61 Sensitivity (%, 95% CI) 86.2 (80.8, 90.6) 63.3 (55.4, 70.6) Specificity (%, 95% CI) 99.8 (99.8, 99.9) 99.5 (99.4, 99.5) PPV (%, 95% CI) 24.6 (21.5, 27.9) 5.8 (4.7, 6.9) Surgery per screen positive 4.1 17.4
TCT-824 Statewide Variability in Radiation Doses Exceeding 5 Gy During Percutaneous Coronary Intervention: Data from the Blue Cross Blue Shield of Michigan Cardiovascular Collaborative (BMC2) Registry
Authors: Ryan Madder, Milan Seth, Theodore Schreiber, Amir Kaki, None Joseph Chattahi, Dan West, Thomas Hill, Ibrahim Shah, Thomas Earl, Mohan Madala, Hitinder Gurm, Simon Dixon
Journal: Journal of the American College of Cardiology (2018)
TCT-826 Effect of Allura Xpef FD10 ECO X-Ray Image Processing on Radiation Reduction During Cardiac Catheterization: A Single Center 717 Case Experience
Authors: J.R. Exequiel Pineda, Sharanyah Srinivasan, Alane Dy, Kwan Lee, Stefan Koester, Rishi Bhargava, Karl Kern
Journal: Journal of the American College of Cardiology (2018)
Tumoral cavitation in colorectal cancer patients with lung metastasis treated with bevacizumab and chemotherapy.
Authors: Hongfeng Gou, Yu Peng, Meng Qiu, Qiu Li, Dan Cao, Yu Yang, Feng Bi
Journal: Journal of Clinical Oncology (2018)

e15565 Background: Lung is the most common extra-abdominal metastatic site of colorectal carcinoma (CRC). Tumor cavitation induced by antiangiogenesis agents including bevacizumab in non-small cell lung cancer is common. Tumor cavitation in CRC patients with lung metastasis treated with bevecizumab has not been reported. This study was aimed to evaluate the efficacy and safety of bevacizumab for advanced unresectable colorectal cancer with lung metastasis and to investigate the frequency of tumor cavitation, and correlation of tumor cavitation with clinical outcome in patients receiving bevacizumab agents. Methods: Patients of advanced colorectal cancer with lung metastasis treated with bevacizumab in first or second line at West China Hospital, Sichuan University Cancer Center from April 2008 to November 2016 were recruited. We collected the data of the clinic pathalogical characteristics, overall survival (OS), progression free survival (PFS), objective response rate (ORR) and disease control rate (DCR). Results: Between April 2008 to November 2016, 60 patients metastatic colorectal cancer (mCRC) with lung metastasis were treated with bevacizumab plus chemotherapy. Of the 60 patients, 39 cases underwent first-line chemotherapy combination of bevacizumab and 21 cases underwent second-line chemotherapy combination of bevacizumab. The response rate (RR) was 43.6% (17/39), stable disease (SD) 51.3% (20/39) and the DCR was 94.9% (37/39) of the first-line treatment. The median OS and PFS of the first-line treatment were 32.4 and 15.5 months, respectively. Out of 60 patients, 12 patients (20%) developed cavitation after the initiation of bevacizumab therapy. The median overall survival of the patients with cavitation was longer than the patients without caivtion (42.1 vs 30.8 months) in the first-line treatment (p = 0.042) Conclusions: The combination of bevacizumab and chemotherapy had a promising efficacy in metastatic colorectal cancer (mCRC) with lung metastasis patients. Moreover, we found that overall survival was affected by the development of a new cavity during antiangiogenesis agent treatment.
Prevalence and predictors of active surveillance management for black males diagnosed with low risk prostate cancer.
Authors: Nicolette Taku, Vivek Narayan, Scarlett Bellamy, Neha Vapiwala
Journal: Journal of Clinical Oncology (2017)

e18019 Background: Consensus guidelines recommend that active surveillance (AS) be considered in the management of men with low risk prostate cancer (LRPC). The evidence supporting this recommendation is largely derived from studies in which men of African descent were underrepresented; thus, the appropriate implementation of AS in this population remains controversial. The objective of our study was to evaluate the prevalence and clinical predictors of an AS approach in black men (BM) diagnosed with LRPC following the 2010 inclusion of AS in LRPC management consensus guidelines. Methods: BM (N = 15,242) and non-Hispanic white men (WM) (N = 86,655) diagnosed with LRPC (as defined by PSA ≤ 10 ng/ml, Gleason score ≤ 6, clinical stage T1 – T2a) between 2010 and 2013 were identified from the National Cancer Database. Logistic regression models were used to assess the likelihood of pursuing an AS strategy over time, as well as to examine associations between sociodemographic characteristics (SDCs) and the receipt of AS. Results: Overall, 9% of BM with LRPC were managed with AS. On univariate analysis, the likelihood of BM undergoing AS increased from 2010 and was statistically significant ( p &lt; 0.001) for all subsequent years (2011: OR = 1.54, 95% CI 1.30-1.82; 2012: OR = 2.19, 95% CI 1.82-2.60; 2013: OR = 2.55, 95% CI 2.15-3.02). Uninsured BM were twice as likely as those with private insurance to pursue AS (OR 1.97, 95% CI 1.51-2.58, p &lt; 0.001). BM seen at academic cancer programs were also more likely to be managed with AS, when compared to those seen at community cancer centers (OR 1.47, 95% CI 1.37-1.60, p &lt; 0.001). BM were less likely than WM to receive AS (OR = 0.82, 95% CI 0.77 to 0.87, p &lt; 0.001). On multivariate analysis adjusted for SDCs, there was no significant difference in AS utilization between the two ethnic groups. Conclusions: The utilization of AS for BM with LRPC appears to be increasing, may be influenced by SDCs, and may not differ from the AS utilization for WM with LRPC. Given the observed elevated rates of post-prostatectomy adverse pathologic features among BM, further evaluation of the determinants of AS utilization and scrutinous consideration of the appropriateness of AS in this population is warranted.
Roles of microRNAs in T cell immunity: Implications for strategy development against infectious diseases
Authors: Bikash R. Giri, Ram I. Mahato, Guofeng Cheng
Journal: Medicinal Research Reviews (2018)

Abstract T cell immunity plays a vital role in pathogen infections. MicroRNA (miRNAs) are small, single‐stranded noncoding RNAs that regulate T cell immunity by targeting key transcriptional factors, signaling proteins, and cytokines associated with T cell activation, differentiation, and function. The dysregulation of miRNA expression in T cells may lead to specific immune responses and can provide new therapeutic opportunities against various infectious diseases. Here, we summarize recent studies that focus on the roles of miRNAs in T cell immunity and highlight miRNA functions in prevalent infectious diseases. Additionally, we also provide insights into the functions of extracellular vesicle miRNAs and attempt to delineate the mechanism of miRNA sorting into extracellular vesicles and their immunomodulatory functions. Moreover, methodologies and strategies for miRNA delivery against infectious diseases are summarized. Finally, potential strategies for miRNA‐based therapies are proposed.