tbuckley/cabot-search huggingface dataset:
Neutrophil-to-lymphocyte ratio (NLR) to predict the short-term and long-term outcomes of gastric cancer patients.
Authors: Ryoichi Miyamoto, Satoshi Inagawa, Naoki Sano, Sosuke Tadano, Masayoshi Yamamoto
Journal: Journal of Clinical Oncology (2017)

e15560 Background: Preoperative NLR was well known as highly repeatable, cost-effective and widely available long-term postoperative prognostic marker of gastric cancer patients. However, the utility of preoperative NLR to predict short-term outcomes in gastric cancer patients remains unclear. In this study, we addressed whether the preoperative NLR is a predictive value of short-term outcome in gastric cancer patients. Methods: We retrospectively evaluated 154 consecutive gastric cancer patients. Mean NLR was calculated, and 3.5 was set as cut-off value. The patient characteristics and perioperative outcomes were respectively compared. In addition, median survival times (MSTs) were also compared. In terms of stage II/III (UICC 7th) gastric cancer patients, median disease-free survival times (MDFSTs) were compared between the two groups. Results: The patients were then divided into two groups: low-NLR group (n = 110) and high-NLR group (n = 44). Among low-NLR group and high-NLR group, significant differences were respectively observed in preoperative symptoms [56 (51%) vs. 31 (70%); p = 0.027] and perioperative outcomes including postoperative complications [3 (2.7%) vs. 5 (11.3%); p = 0.015], intraoperative blood loss (158 ± 168 g vs. 232 ± 433 g; p = 0.022), and intraoperative blood transfusion [0 vs. 3 (6.8%); p = 0.042]. MSTs and MDFSTs were significantly differed (812 vs. 594 days; p = 0.04, 848 vs. 475 days; p = 0.03, respectively). Conclusions: The present study indicated that preoperative NLR influenced not only long-term outcomes but also perioperative outcomes in gastric cancer patients. Preoperative NLR is also a useful predictive value of short-term outcomes in gastric cancer patients.
Safety, tolerability and outcomes of immunotherapy in minority underserved population.
Authors: Ahmed T Ahmed, Hashim Mann, Aakash Putta, Rohit Agrawal, Barbara Yim, Shweta Gupta
Journal: Journal of Clinical Oncology (2018)

e15004 Background: Immune Checkpoint Inhibitors (ICIs) have shown remarkable efficacy, durable responses and prolonged overall survival compared to chemotherapy in many solid tumors. However, most studies with ICIs have included a majority white patient population. In this study, we studied treatment outcomes and adverse events in patients treated with ICIs in an underserved population of predominantly African American (AA) and Hispanics. Methods: We screened all patients from January 2015 to December 2017 who received ICI for any solid tumor. We studied treatment outcomes including PFS, OS, adverse effects (AE) and compared it to landmark trials. We excluded patients with incomplete data and those who did not receive ICIs. Results: A total of 162 patients were screened and 125 were included for analysis. There were 47 (38%) Non-Small Cell Lung Cancer (NSCLC), 25 (20%) Head & Neck (H&N), 21 (17%) melanomas, 13 (10%) Renal Cell (RCC), 6 (5%) urothelial, 7 (6%) Small-Cell Lung and 1 each of colon, breast, neuroendocrine, Merkel-cell, mesothelioma and esophageal cancer. Males comprised 65.6% of all patients. There were 52 (42%) AA, 40 (32%) Hispanics and 26 (21%) Whites. Forty-six (95.8%) patients with NSCLC received Nivolumab with mPFS 3.4 months and 6.9 months OS. Sixteen (67%) patients with H&N cancer received pembrolizumab with mPFS 4.5 months and mOS of 6.1 months. All RCC patients received nivolumab with mPFS 2.98 months and OS of 7.1 months. Overall, Hispanics showed a trend towards worse PFS (4 mo) compared to AA (5.4 mo) and Whites (5.9 mo), but OS was not different between the groups. PFS and OS were similar for men versus women. Any AEs was seen in 39% with grade 3 or 4 in 8%, and grade 5 in 2%. Ten (8%) patients dropped treatment due to AEs. Most frequently encountered toxicity was hypothyroidism and most frequent grade 4 toxicity was pneumonitis. Two patients died, one with fulminant hepatitis and TLS after nivolumab and another with TLS after nivolumab and ipilimumab. Conclusions: ICIs were well tolerated in the inner-city minority population. There was a trend towards worse PFS in Hispanics, which needs to be studied further in this subgroup. Although rare, grade 5 toxicity of TLS was seen and clinicians need to keep a high index of suspicion.
Measuring mercaptopurine (6MP) adherence using red cell 6MP metabolite levels in children with acute lymphoblastic leukemia (ALL): A COG AALL03N1 study.
Authors: Anna Lynn Hoppmann, Torrey Hill, Yanjun Chen, Wendy Landier, Lindsey Hageman, William E. Evans, Anne L. Angiolillo, Bruce C. Bostrom, Jacqueline N. Casillas, Glen Lew, Kelly W. Maloney, Leo Mascarenhas, A. Kim Ritchey, Amanda M. Termuhlen, William L. Carroll, Florence Lennie Wong, Mary V. Relling, Smita Bhatia
Journal: Journal of Clinical Oncology (2017)

10514 Background: Non-adherence to 6MP (monitored with medication event monitoring system [MEMs]) is associated with an increased risk of relapse in children with ALL.(JAMA Oncol, 2015) Self-report over-estimates true medication intake, particularly in non-adherent patients.(Blood, 2017) However, monitoring adherence using MEMs is logistically difficult. We investigated whether red cell 6MP metabolite levels (thioguanine nucleotide [TGN] and methylated mercaptopurine [MMP]) taken together, could identify non-adherent patients. Methods: The analysis included children with ALL in maintenance. To minimize variability in TGN and MMP levels due to pharmacogenetics, we excluded TPMT heterozygotes and homozygote mutants. We also excluded Asians to remove variability due to NUDT15. TGN and MMP levels were drawn at 6 consecutive monthly time points for each patient and averaged. TGN and MMP levels (pmol/8 x 10 8 red cells) were standardized, adjusted for 6MP dose intensity, and then analyzed using cluster analysis (Spath, H. [1980]). Results: The 373 patients eligible for analysis yielded 5 clusters. Cluster #1 (n = 119; mean MMP: 15,656; mean TGN: 158); Cluster #2 (n = 211; MMP: 6,042; TGN: 135); and 3 very small outlying clusters (total N = 43). Adjusting for age, sex, race/ethnicity, cytogenetics and NCI risk, we found that patients in Cluster #2 were 2.6 times as likely to be non-adherent (MEMs-based adherence &lt; 95%) compared to Cluster #1 (95% CI 1.5-4.4; P= 0.0007). Mean MEMs-based adherence was significantly higher for patients in Cluster #1 (94.3%) when compared to those in Cluster #2 (87.8%, p = 0.0002). Using Fine-Gray proportional subdistribution hazards models for competing risks and adjusting for clinical and sociodemographic factors, we found that patients in Cluster #2 were at a 2.3-fold higher risk of relapse compared with those in Cluster #1 (95%CI, 1.0-6.4, p = 0.058). Conclusions: These findings illustrate the potential for using a combination of red cell TGN and MMP levels in identifying non-adherent patients. We propose to use these and clinical and demographic factors associated with non-adherence in creating an adherence calculator.
The impact of induction chemoimmunotherapy (iCIT) on the immune status of patients (pts.) with non-small cell lung cancer (NSCLC).
Authors: Elena Yurievna Zlatnik, Oleg Ivanovich Kit, Igor N. Turkin, Yury N. Lazutin, Anna Pavlovna Kharitonova, Inna Arnoldovna Novikova, Gennadiy Z. Sergostyants, Liubov Yu Vladimirova, Galina I. Zakora, Olesya N. Selyutina, Elena Bondarenko, Sergey P. Pyltsin, Anna V. Chubaryan, Tamara G. Ayrapetova, Pavel A. Anistratov, Igor A. Leyman, Rukiyat Isaeva
Journal: Journal of Clinical Oncology (2016)

e20058 Background: In recent years, new methods of induction CIT with recombinant cytokines have developed. Refnot drug in iCIT demonstrated improvement of the overall response rate to the treatment of NSCLC (J. Clin. Oncol; 2015; 33 suppl.: abstr. e 18523). The purpose of the study was to analyze iCIT influence on the immune status during the treatment. Methods: 65 pts. with stage IIВ-IIIВ NSCLC, randomized in two groups, received 2 courses of induction CT with cisplatin 75 mg/m2 i. v. on day 1 and gemcitabine 1000 mg/m2 i.v. on days 1 and 8. The main group (n = 33) received Refnot (tumor necrosis factor-thymosine alpha-1 recombinant) as well: 50000 IU/m2 on days 3, 5 and 7; the control group (n = 32) received CT only. The direct results of treatment were evaluated according to the REGIST criteria 3 weeks after the completion of the course. Immune status was assessed before the treatment and 21 days after the 1st and 2nd courses of induction chemotherapy: populations and subpopulations of lymphocytes were determined using BD FACS Canto II Flow Cytometer and a panel of antibodies to T-, B- and NK-cells (CD3, CD4, CD8, CD19, CD16/56). Results: 90% of patients in the main group and 87% in the control completed induction therapy. The overall response rate was 73.3% in main and 46.4% in the control group (p = .063): CR-3 (10%) vs. 1 (3.6%), PR- 19 (63.3 %) vs. 12 (42.8%), SD-7 (23.3%) vs. 13 (43.3%), PD-1 (3.3%) vs. 2 (7.1%). Squamous cell carcinoma - 13 (44.2%) vs.14 (53.8%), adenocarcinoma - 16 (55.2%) vs. 12 (46.2%). The control group showed the decrease in NK-cell level from 18.96±2.47 to 9.84±1.65% after 2 courses of induction chemotherapy with an increased level of CD3+CD4+ lymphocytes. The content of NK-cells in patients of the main group did not change; the 1st course resulted in an increase in CD3+CD4+ level, the 2nd course – in an increase in CD3+CD8+ lymphocytes which content statistically significantly exceeded the indices in the control group (35.9±3.65 and 24.06±2.19, respectively; P < .05). Conclusions: Chemoimmunotherapy with Refnot results in positive changes in the immune status with satisfactory direct results of induction treatment.
Effect of Aspirin on Disability-free Survival in the Healthy Elderly
Authors: John J. McNeil, Robyn L. Woods, Mark R. Nelson, Christopher M. Reid, Brenda Kirpach, Rory Wolfe, Elsdon Storey, Raj C. Shah, Jessica E. Lockery, Andrew M. Tonkin, Anne B. Newman, Jeff D. Williamson, Karen L. Margolis, Michael E. Ernst, Walter P. Abhayaratna, Nigel Stocks, Sharyn M. Fitzgerald, Suzanne G. Orchard, Ruth E. Trevaks, Lawrence J. Beilin, Geoffrey A. Donnan, Peter Gibbs, Colin I. Johnston, Joanne Ryan, Barbara Radziszewska, Richard Grimm, Anne M. Murray
Journal: New England Journal of Medicine (2018)

Information on the use of aspirin to increase healthy independent life span in older persons is limited. Whether 5 years of daily low-dose aspirin therapy would extend disability-free life in healthy seniors is unclear.From 2010 through 2014, we enrolled community-dwelling persons in Australia and the United States who were 70 years of age or older (or ≥65 years of age among blacks and Hispanics in the United States) and did not have cardiovascular disease, dementia, or physical disability. Participants were randomly assigned to receive 100 mg per day of enteric-coated aspirin or placebo orally. The primary end point was a composite of death, dementia, or persistent physical disability. Secondary end points reported in this article included the individual components of the primary end point and major hemorrhage.A total of 19,114 persons with a median age of 74 years were enrolled, of whom 9525 were randomly assigned to receive aspirin and 9589 to receive placebo. A total of 56.4% of the participants were women, 8.7% were nonwhite, and 11.0% reported previous regular aspirin use. The trial was terminated at a median of 4.7 years of follow-up after a determination was made that there would be no benefit with continued aspirin use with regard to the primary end point. The rate of the composite of death, dementia, or persistent physical disability was 21.5 events per 1000 person-years in the aspirin group and 21.2 per 1000 person-years in the placebo group (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11; P=0.79). The rate of adherence to the assigned intervention was 62.1% in the aspirin group and 64.1% in the placebo group in the final year of trial participation. Differences between the aspirin group and the placebo group were not substantial with regard to the secondary individual end points of death from any cause (12.7 events per 1000 person-years in the aspirin group and 11.1 events per 1000 person-years in the placebo group), dementia, or persistent physical disability. The rate of major hemorrhage was higher in the aspirin group than in the placebo group (3.8% vs. 2.8%; hazard ratio, 1.38; 95% CI, 1.18 to 1.62; P<0.001).Aspirin use in healthy elderly persons did not prolong disability-free survival over a period of 5 years but led to a higher rate of major hemorrhage than placebo. (Funded by the National Institute on Aging and others; ASPREE ClinicalTrials.gov number, NCT01038583 .).
Combining circulating tumor cells and circulating cancer associated macrophage-like cells for accurately predicting responsiveness of new line therapies in late stage cancers.
Authors: Daniel Adams, Raymond C. Bergan, R. Katherine Alpaugh, Stuart S Martin, Martin J. Edelman, Rena G. Lapidus, Saranya Chumsri, Massimo Cristofanilli, Cha-Mei Tang, Steven H. Lin
Journal: Journal of Clinical Oncology (2018)

12032 Background: The discovery of cancer associated macrophage like cells (CAMLs) as independent prognostic indicators of survival has highlighted the need for more in depth analysis of blood based diagnostics. As CTCs & CAMLs are isolated in parallel from a single blood sample and both are prognostic for therapy response, we hypothesized that monitoring CTCs & CAMLs before and after initiation of therapy might increase their prognostic value in a large array of cancer subtypes. Methods: A prospective 2 year blind multi-institutional study was undertaken to evaluate CTCs & CAMLs before, and after, induction of a new line therapy. Patients with breast (n = 12), esophageal (n = 20), NSCLC (n = 23), prostate (n = 12), and SCLC (n = 7) in Stage III (n = 45) or Stage IV (n = 30) disease were recruited. A baseline (BL) blood sample was taken prior to induction of a new therapy and a 2nd sample (T1) taken after initiation of systemic therapy (~30 days). Blood was filtered by CellSieve filtration. The quantities and subtypes of CTCs & CAMLs were analyzed based on OS hazard ratios (HRs) by censored univariate & multivariate analysis. Results: CTCs were identified in 16% of patients at BL, with a single CTC being prognostic for OS (HR = 4.8 95%CI1.5-14.9, p = 0.018). Further, CTCs were found in 19% of samples at T1 and also prognostic for OS (HR = 4.3 95%CI1.7-10.7, p = 0.005). However, CTCs were rare in lung (7%), esophageal (5%) and prostate cancers (17%), but common in breast (58%). In contrast, CAMLs were found in 97% of BL, with ≥50µm CAMLs being a prognostic for OS (HR = 2.8, 95% CI 1.3-5.9, p = 0.011). At T1, the OS prognostic value of ≥50µm CAMLs increased (HR = 3.1 95% CI 1.5-6.6, p = 0.005). Further, after induction of systemic therapy, the presence of both, > 5 CTCs or a ≥50µm CAML was 92% accurate at predicting survival of patients within 24 months, with OS HR = 3.4 95%CI1.6-7.2, p = 0.002. Conclusions: Our data suggests that simultaneous measurement of both CTCs and CAMLs may increase the prognostic value of blood based diagnostics and may be predictive of benefit of subsequent therapies.
FRI0126 Patients’ concerns about and perception of biosimilars in rheumatology : a french survey
Authors: L. Frantzen, J.-D. Cohen, S. Tropé, M. Beck, R. Diebold, M. Sittler, A. Munos, L. Arnaud, J.-E. Gottenberg, J. Sibilia, N. Afif, C. Sordet
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patient adhesion to biosimilars DMARDs have become a big medico-economic issue. Indeed, savings will depend on penetration rate of biosimilars on the biologics market. Like generics, biosimilars are unknown by the general population and patients reluctance appears to be an obstacle to the diffusion of these therapeutics. <h3>Objectives</h3> To assess patients‘knowledge, information and concerns about biosimilars and to identify levers and obstacles to adhesion to biosimilars prescription. <h3>Methods</h3> National cross-sectional study assessing information, knowledge and concerns about biosimilars of french patients treated for a rheumatism (whether they were treated by a bDMARDs or not). The data were collected from march to july 2017 by an online assessment. <h3>Results</h3> 629 patients answered the assessment. 43% knew the definition of biosimilars. 65% felt unsufficiently informed about biosimilars. The principal sources of information were the rheumatologist and the patient associations. 44% of patients treated with a biosimilar were not informed before they received a biosimilar. Patients concerns focused on molecular structure (46%), efficacy (60%) and tolerance (57%) comparatively to originator bDMARDs. Receiving information about biosimilars and understanding the definition of biosimilarity were two characteristics associated with better adhesion to biosimilars. The rheumatologist was considered the most influent source of information about biosimilar. Patients trust him concerning the decision to switch from the originator biologic to its biosimilar. Patient were reluctant to substitution by the pharmacist (2%). <h3>Conclusions</h3> Biosimilars are largely unknown by french patients at present. Information seems to be instrumental in patient adhesion to biosimilars and in the preservation of the therapeutic relationship. <h3>References</h3> [1] Jacobs I, Singh E, Sewell L, Al-Sabbagh A, Shane LG. Patient attitudes and understanding about biosimilars: an international cross-sectional survey. Patient Prefer Adherence. MAI2016;937. [2] Beck M, Michel B, Rybarczyk-Vigouret M-C, Levêque D, Sordet C, Sibilia J, et al. Rheumatologists’ Perceptions of Biosimilar Medicines Prescription: Findings from a French Web-Based Survey. BioDrugs Clin Immunother Biopharm Gene Ther. Déc2016;30(6):585–92. <h3>Disclosure of Interest</h3> None declared
EGR1-Mediated Transcription of lncRNA-HNF1A-AS1 Promotes Cell-Cycle Progression in Gastric Cancer
Authors: Hai-Ting Liu, Sen Liu, Lei Liu, Ran-Ran Ma, Peng Gao
Journal: Cancer Research (2018)

Abstract Long noncoding RNAs (lncRNA) are dysregulated in various human cancers and control tumor development and progression. However, the upstream mechanisms underlying their dysregulation remain unclear. Here, we demonstrate that the expression of hepatocyte nuclear factor 1 homeobox A antisense RNA 1 (HNF1A-AS1) is significantly upregulated in gastric cancer tissues. Overexpression of HNF1A-AS1 enhanced cell proliferation and promoted cell-cycle progression, whereas knockdown of HNF1A-AS1 elicited the opposite effects. Early growth response protein 1 (EGR1) directly bound the HNF1A-AS1 promoter region and activated its transcription. Overexpression of EGR1 enhanced cell proliferation and promoted cell-cycle promotion, similar to the function of HNF1A-AS1. HNF1A-AS1 functioned as competing endogenous RNA (ceRNA) by binding to miR-661, upregulating the expression of cell division cycle 34 (CDC34), which is a direct target of miR-661. EGR1 and HNF1A-AS1 enhanced the expression of cyclin-dependent kinase 2 (CDK2), CDK4, and cyclin E1 but inhibited the expression of p21 by promoting CDC34-mediated ubiquitination and degradation of p21. Taken together, these findings suggest that EGR1-activated HNF1A-AS1 regulates various pro- and antigrowth factors to promote the development of gastric cancer, implicating it as a possible target for therapeutic intervention in this disease. Significance: This study provides novel insights into mechanisms by which the noncoding RNA HNF1A-AS1 contributes to gastric cancer progression through modulation of the cell cycle. Cancer Res; 78(20); 5877–90. ©2018 AACR.
Benefit of second-line chemotherapy for advanced biliary tract cancer.
Authors: Florian Moik, Jakob M. Riedl, Thomas Winder, Angelika Bezan, Christopher Rossmann, Joanna Szkandera, Anne-Katrin Kasparek, Renate Schaberl-Moser, Martin Pichler, Herbert Stoger, Michael Stotz, Armin Gerger, Florian Posch
Journal: Journal of Clinical Oncology (2017)

e15621 Background: Second-line chemotherapy (2LCTX) is increasingly applied in patients (pts) with advanced biliary tract cancer (aBTC), although no randomized trial has so far demonstrated the benefit of this intervention over best supportive care (BSC) alone. In the absence of randomized data, we thus conducted a comparative effectiveness analysis of survival outcomes in aBTC pts treated with BSC±2LCTX. Methods: In this single-center cohort study, we retrospectively included 80 pts with metastatic, recurrent, or inoperable aBTC who completed 1 st -line CTX at our department between 2003 and 2016. Thirty-eight of these pts (48%) received 2LCTX+BSC (Fluoropyrimidine (FP) mono: n = 26 (68%), FP-based combination CTX: n = 9 (24%), Others: n = 3 (8%)). Primary endpoint was 18-month overall survival (OS). An inverse-probability-of-treatment-weighted analysis (IPTW) was implemented to rigorously account for imbalances in prognostic variables between the two study groups. Results: During a median follow-up of 14.8 months, we observed 49 deaths. Six-month, 12-month, and 18-month OS estimates were 77%, 53% and 23% in the BSC+2LCTX group, and 29%, 21%, and 14% in patients in the BSC group, for a univariable hazard ratio (HR) for OS of 0.36 (95%CI: 0.20-0.64, p = 0.001). However, pts receiving 2LCTX+BSC had a significantly higher prevalence of favorable prognostic variables, such as a higher Karnofsky Index (p = 0.0001), lower serum bilirubin (p = 0.03), higher hemoglobin (p = 0.002), and higher serum albumin (p = 0.0007). After careful adjustment for these imbalances using IPTW, 2LCTX+BSC was not associated with an OS benefit over BSC alone (Adjusted HR = 0.62, 95%CI: 0.30-1.29, p = 0.201). In IPTW analysis, 6-, 12-, and 18-month OS were 51%, 33% and 14% in the BSC+2LCTX group, and 35%, 29%, and 19% in patients in the BSC group. The beneficial association of 2LCTX with OS was highly time-dependent, with IPTW HRs of 0.07 (p = 0.002), 0.42 (p = 0.05), and 0.53 (p = 0.11) after 3, 6, and 12 months, respectively. Conclusions: Within the limitations of a non-randomized study, our data support the concept that 2LCTX is associated with a short-term OS benefit in pts with aBTC.