tbuckley/cabot-search huggingface dataset:
Outcomes of patients (pts) treated with prior blinatumomab (Blin) in ZUMA-3: A study of KTE-C19, an anti-CD19 chimeric antigen receptor (CAR) t cell therapy, in adult pts with relapsed/refractory acute lymphoblastic leukemia (R/R ALL).
Authors: Bijal D. Shah, Olalekan O. Oluwole, Maria R. Baer, Michael Russell Bishop, Houston Eccleston Holmes, Gary J. Schiller, William Bruce Donnellan, Kristen Marie Carr-O'Dwyer, Armen Mardiros, John M. Rossi, Tong Shen, Allen Xue, Rajul K. Jain, Remus Vezan, William G. Wierda
Journal: Journal of Clinical Oncology (2018)

7006 Background: KTE-C19 showed promising efficacy (71% complete response [CR] or CR with incomplete hematologic recovery [CRi]) and manageable safety for pts with R/R ALL in Phase 1 of ZUMA-3 (Shah ASH 2017; NCT02614066). Blin, a CD19/CD3 bispecific T cell engager, is FDA-approved for R/R ALL. The impact of prior blin on KTE-C19 efficacy is unknown. Here, we report responses to KTE-C19 in pts who received prior blin. Methods: Eligible pts were aged ≥ 18 y with R/R ALL (Ph+ allowed), ≥ 5% bone marrow blasts (documented CD19+), and ECOG 0-1. Pts received 2, 1, or 0.5 × 106 CAR T cells/kg after low-dose conditioning chemotherapy. Pts who received the 2 × 106 dose could not have prior blin. Outcomes assessed included efficacy, safety, product characteristics, and levels of CAR T cells and cytokines in blood. Results: As of July 31, 2017, 29 pts were evaluable for safety, 24 for efficacy. Six, 14, and 9 safety-evaluable pts received 2, 1, and 0.5 × 106 CAR T cells/kg, respectively. Pts with (n = 11) vs without (n = 18) prior blin had worse performance status (ECOG 0: 27% vs 44%) and were more likely to be R/R to ≥ 2nd-line therapy (55% vs 28%). With ≥ 8 wk of follow-up, 63% vs 75% of pts with vs without prior blin had CR or CRi, respectively. Overall, 88% (21/24) had minimal residual disease-negative remission (7/8 with vs 14/16 without prior blin). Of pts with vs without prior blin, 27% vs 28% had Grade ≥ 3 cytokine release syndrome and 36% vs 61% had Grade ≥ 3 neurologic events. KTE-C19 was manufactured successfully in both groups, with similar product characteristics (eg, CD4/CD8 ratio, % transduction). Pts with vs without prior blin had similar proportions of naïve (43% vs 36%) and effector memory (19% vs 20%) T cells. Postinfusion CAR T expansion was observed regardless of prior blin; peak CAR T cell levels occurred between Days 7 and 14 for both groups. Conclusions: While potentially confounded by multiple factors, these data demonstrate that prior blin did not preclude manufacturing of efficacious products. KTE-C19 continues to show promising efficacy and manageable safety in pts with R/R CD19+ ALL independent of prior blin. Clinical trial information: NCT02614066.
TCT-60 Stent Treatment of Branch Pulmonary Artery Stenosis in Children With Congenital Heart Disease After Cardiac Surgery
Authors: Saule Kadirova, Yu Pya, Serik Alimbaev, Frank Ing, Dmitrii Gorbunov, Almira Bajgalkanova, Marat Aripov, Abdurashid Musaev, Kudrat Rakhimov, Gulmira Momanova
Journal: Journal of the American College of Cardiology (2018)
Telehealth in radiation oncology: Service evaluation and patient satisfaction.
Authors: Sabe S. Sabesan, Elizabeth Hamilton, Ellie Van Veldhuizen, Amy Brown, Sean Brennan
Journal: Journal of Clinical Oncology (2018)

e18882 Background: Telehealth (TH) in radiation oncology at Townsville Cancer Centre was implemented in July 2011. The service has grown to include regular TH radiation oncology new and review clinics between satellite regions. Methods: A service evaluation was conducted, with TH consultations from July 2011 to December 2015 included. A random sample of patient charts was audited. Data including demographics, diagnosis, treatment, and TH appointment details were summarised through descriptive statistics. A satisfaction survey was completed by 106 patients, and analysed through descriptive statistics. Results: A total of 1,530 TH consultations were provided to 833 patients, including 305 new and 1,225 follow-up reviews. Median distance from the hospital was 327.3 kilometres (21.6 to 1130.1). A majority were male (71.1%) and median age was 65 (range 23 to 94). Prostate (32%), breast (12%) and head and neck (10%) were the most common cancer diagnoses. A majority of patients were undergoing radiation therapy for curative intent (73.3%). Survey responses were overall positive, with patients identifying that the travel and time savings were the most advantageous. When asked as to preference for future consultations, 54.7% indicated TH only, and 34.8% indicated a mix of TH and in-person consultations. Only 3.8% and 5.7% of respondents reported a level of dissatisfaction with vision or audio quality of the TH consults, respectively. Conclusions: Telehealth provides a valuable and effective way of engaging patients from rural and regional areas in the health service. Patient feedback overall was positive, indicating a high level of acceptability and satisfaction, particularly in regard to saving travel expenses and time.
A practical clinical score to predict early death after a comprehensive geriatric assessment (CGA) in elderly cancer patients: A prospective cohort study with 608 patients.
Authors: Jurema Telles O Lima, Anke Bergmann, Maria Julia Gonçalves Mello, Zilda Cavalcanti, Mirella Rebello Bezerra, Letícia telles Sales, Luiz Claudio Santos Thuler
Journal: Journal of Clinical Oncology (2017)

e21537 Background: Components of the comprehensive geriatric assessment (CGA) correlate with risk of early mortality in elderly cancer patients (ECP). However, its complexity and the time required for its administration. The aim of this study was to determine the impact of each CGA domain on overall survival(OS) and to first step for the development of a prognostic scoring system to stratify ECP. Methods: a prospective cohort study. Participants with a recent diagnosis of cancer were from eight hospitals and one cancer center in Brazil and were recruited during their first medical appointment at the outpatient oncologic clinic. A basal CGA was done before the care decision (ADL, Charlson Comorbidity Index- CCI, Karnofsky Performance status – KPS, GDS15, IPAQ, MMSE, MNA, MNA-SF, PS, PPS, Polipharmacy, QLQc30, TUG). During the follow up of six months, information about the treatments performed and early death was collected. OS was estimated using the Kaplan–Meier method, and survival curves were compared using the Log rank test for categorical variables. A multivariate Cox proportional hazards model was used to select early death risk factors. A clinical score considering the number of risk variables was created. Results: From 2015-2016, 608 ECP, mean age 71.9 (SD ±7.4; range 60-96), 50.7% male, were enrolled. 100 (16.4%) ECP died in less than six months of follow-up. In our multivariate model, controlled by age, site of cancer and cancer stage, the remaining significant risk factors were malnutrition/nonutrition determined by MNA (HR 3.3, 95%CI 1.81-5.99, p &lt; 0.001), KPS &lt; 50% (HR 2.44, CI 1.56-3.81, p &lt; 0.001) and CCI &gt; 2 (HR 1.6, CI 1.09-2.52, p = 0.018). The risk for early death according to the number of risk variables: three (HR 12.99, CI 5.69-29.60, p &lt; 0.001), two (HR 5.65, CI 2.61-12.24, p &lt; 0.001) or one (HR 2.7, CI 1.28-5.87, p = 0.009). Conclusions: a practical clinical score using three instruments of the CGA (MNA, KPS and CCI) can predict independent the risk for an early death in ECP. The development of a practical system for risk scoring, incorporating few clinical prognostic factors, helps to stratify patients into risk groups and to plan a personalized care.
Residential Proximity to Major Roadways at Birth, DNA Methylation at Birth and Midchildhood, and Childhood Cognitive Test Scores: Project Viva(Massachusetts, USA)
Authors: Cheng Peng, Martijn den Dekker, Andres Cardenas, Sheryl L. Rifas-Shiman, Heike Gibson, Golareh Agha, Maria H. Harris, Brent A. Coull, Joel Schwartz, Augusto A. Litonjua, Dawn L. DeMeo, Marie-France Hivert, Matthew W. Gilman, Sharon K. Sagiv, Yvonne de Kluizenaar, Janine F. Felix, Vincent W. Jaddoe, Emily Oken, Liesbeth Duijts, Diane R. Gold, Andrea A. Baccarelli
Journal: Environmental Health Perspectives (2018)

Background: Epigenetic variability is hypothesized as a regulatory pathway through which prenatal exposures may influence child development and health. Objective: We sought to examine the associations of residential proximity to roadways at birth and epigenome-wide DNA methylation. We also assessed associations of differential methylation with child cognitive outcomes. Methods: We estimated residential proximity to roadways at birth using a geographic information system (GIS) and cord blood methylation using Illumina's HumanMethylation450-array in 482 mother–child pairs in Project Viva. We identified individual CpGs associated with residential-proximity-to-roadways at birth using robust linear regression [false discovery rate (FDR)<0.05]. We also estimated association between proximity-to-roadways at birth and methylation of the same sites in blood samples collected at age 7–11 y (N=415). We ran the same analyses in the Generation R Study for replication (N=641). In Project Viva, we investigated associations of differential methylation at birth with midchildhood cognition using linear regression. Results: Living closer to major roadways at birth was associated with higher cord blood (and—more weakly—midchildhood blood) methylation of four sites in LAMB2. For each halving of residential-proximity-to-major-roadways, we observed a 0.82% increase in DNA methylation at cg05654765 [95% confidence interval (CI): (0.54%, 1.10%)], 0.88% at cg14099457 [95% CI: (0.56%, 1.19%)], 0.19% at cg03732535 [95% CI: (0.11%, 0.28)], and 1.08% at cg02954987 [95% CI: (0.65%, 1.51%)]. Higher cord blood methylation of these sites was associated with lower midchildhood nonverbal cognitive scores. Our results did not replicate in the Generation R Study. Conclusions: Our discovery results must be interpreted with caution, given that they were not replicated in a separate cohort. However, living close to major roadways at birth was associated with cord blood methylation of sites in LAMB2—a gene known to be linked to axonal development—in our U.S. cohort. Higher methylation of these sites associated with lower nonverbal cognitive scores at age 7–11 y in the same children. https://doi.org/10.1289/EHP2034
First report of ZNF518B gene expression as a prognostic factor in colorectal cancer development: Role in tissue invasiveness
Authors: F.G. Valiente, A.L. Riffo-Campos, A. Cervantes, G. López-Rodas, L. Franco, J. Castillo
Journal: Annals of Oncology (2018)

Background: Colorectal cancer (CRC) represents a relevant public health problem. Despite new therapeutic advances, prognosis of patients diagnosed with advanced disease is still poor. The identification of new markers involved in the mechanisms of invasiveness represents a priority in order to better understand cancer development and generate new therapeutic targets. We describe here the possible role of ZNF518B, a gene not yet well characterised, on tissue invasion. Human ZNF518B gene, which encodes a putative, zinc finger-containing transcription factor, yields two major alternative splicing isoforms. Methods: Expression of ZNF518B was determined by RT-qPCR in several CRC cell lines and in a commercial cDNA array from CRC patients. To explore the mechanisms that relate the expression of the gene with tumourogenesis, the effects of silencing ZNF518B on the phenotype of human CRC cell lines has been studied. Among these experiments, we have performed apoptosis assays by flow cytometry, proliferation by MTT assays, invasion and migration assays using transwells and adhesion to type I collagen plates assays. Results: The analysis of a cDNA array from CRC patients showed that the expression of the whole gene and of its two major isoforms is significantly increased in tumour tissues when compared to normal mucosa. By the analysis in CRC cell lines, we have demonstrated that the gene is not involved in cell proliferation, but plays a significant role in cell migration and invasiveness. These data, together with the changes in the epithelial-to-mesenchymal transition markers, strongly suggest that ZNF518B plays a role in tumour cell dissemination. Conclusions: ZNF518B might therefore be a candidate for invasiveness prognosis. Legal entity responsible for the study: INCLIVA-Universidad de Valencia. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.
TCT-91 Ultrathin Bioresorbable Polymer Sirolimus-Eluting Stents versus Thin Durable Polymer Everolimus-Eluting Stents in Patients Undergoing Coronary Revascularization (BIOFLOW V): Acute Coronary Syndrome Subgroup Analysis.
Authors: Ariel Roguin, David Kandzari, Erez Marcusohn, Jacques J. Koolen, Gheorghe Doros, Joseph Massaro, Hector Garcia-Garcia, Johan Bennett, Elie Gharib, Donald Cutlip, Ron Waksman
Journal: Journal of the American College of Cardiology (2018)
Impact of sex on toxicity and outcome in the BILCAP study.
Authors: Richard Fox, Anna Dorothea Wagner, Clive Stubbs, John Neil Primrose, John A. Bridgewater
Journal: Journal of Clinical Oncology (2018)

e16151 Background: The BILCAP study established capecitabine (cape) as adjuvant therapy for patients with curatively resected biliary tract cancer. An unexpected finding was the apparent lack of benefit of cape in women. We examine demographics, toxicity and outcome between sexes. Methods: Data were available for 210 patients who received Cape. Toxicities were categorized according to the National Cancer Institute’s Common Toxicity Criteria for Adverse Events, version 3. Adverse event data were summarised as worst grade at the patient level, and relative differences between male and females were quantified through odds ratios (ORs) estimated by logistic regression. Hazard ratios (HRs) were estimated by Cox survival modelling, with heterogeneity tested through interaction terms. Results: As expected, intrahepatic cholangiocarcinoma (22% vs 16%) and gall bladder cancer (27% vs 8%) were more common in women however other characteristics were well balanced. All grade fatigue (OR 2.17 (95%CI 1.12, 4.2), p = 0.022), nausea (OR 2.36 (95%CI 1.38, 4.03) p = 0.002), and vomiting (OR 2.59 (95%CI 1.33, 5.03), p = 0.005) were significantly increased in females. There was no significant difference in all grade haematological toxicities. Overall survival (OS) differed between the sexes with HR 0.76 (95%CI 0.59, 0.98; p = 0.0.035), Subgroup analyses revealed no heterogeneity, however, the trend suggested that that Cape benefited men, HR 0.70 (95%CI 0.50, 0.99), but less so for women, with HR 0.93 (95%CI 0.64, 1.35). Conclusions: Females appear to report more grade fatigue, nausea and vomiting than males but there is no apparent difference in haematological toxicity. There is no clear difference between the sexes in missed, delayed or reduced doses. It is unclear whether this imbalance in toxicities impacts on the overall survival difference between men and women. Clinical trial information: 72785446.
Abstract P268: Survival Advantage of Participating in Cohort Studies Varies Over Time
Authors: Zihe Zheng, Kunihiro Matsushita, Judith Hoffman-Bolton, Casey M Rebholz, Elizabeth Selvin, Lisa M Wruck, Josef Coresh
Journal: Circulation (2016)

Background: Volunteers in cohort studies are reported to have lower mortality (survival advantage) over non-participants. However, it is unclear if the early survival advantage in study participants compared to non-participants remains over time. Hypothesis: Cohort participation will be associated with survival advantage that diminishes over time. Methods: We had mortality follow-up among people who were covered by the Washington County private census (90,286, about 92% of all 94,881 Washington County residents). This census data was used to compare volunteers in 3 cohort studies (ARIC, CLUE1 &amp; 2) to non-participants at baseline and with respect to subsequent mortality adjust for demographics. Individual death data between 1975 and 2015 was obtained from Maryland Vital Statistics and National Death Index and analyzed using Kaplan-Meier graph. Cox regression models were used to estimate the hazard ratios for mortality comparing participants to non-participants in 5-year time periods since enrollment in each cohort. Results: The Washington County Private Census included 2,933 participants and 18,196 non-participants in ARIC study (recruited 1986-1989; born 1922-1943); 19,912 participants and 52,973 non-participants in CLUE1 (recruited 1974, born in 1877-1963); and 14,408 participants and 44,356 non-participants in CLUE2 (recruited 1989; born in 1893-1961). Participants in each study were more likely to be female, older, married, more educated and never smokers relative to non-participants. Cohort participation was associated with lower mortality as compared to non-participation during the first five years in all studies; this survival advantage diminished over time and after very long follow-up (&gt;20 years) participants actually had higher mortality than non-participants (Figure). Conclusion: In conclusion, the survival advantage associated with cohort participation was strongest in the first 5 years after study enrollment and diminished overtime and even reversed with very long follow-up.
REVERBa couples the circadian clock to hepatic glucocorticoid action
Authors: Giorgio Caratti, Mudassar Iqbal, Louise Hunter, Donghwan Kim, Ping Wang, Ryan M. Vonslow, Nicola Begley, Abigail J. Tetley, Joanna L. Woodburn, Marie Pariollaud, Robert Maidstone, Ian J. Donaldson, Zhenguang Zhang, Louise M. Ince, Gareth Kitchen, Matthew Baxter, Toryn M. Poolman, Dion A. Daniels, David R. Stirling, Chad Brocker, Frank Gonzalez, Andrew S.I. Loudon, David A. Bechtold, Magnus Rattray, Laura C. Matthews, David W. Ray
Journal: Journal of Clinical Investigation (2018)

The glucocorticoid receptor (GR) is a major drug target in inflammatory disease. However, chronic glucocorticoid (GC) treatment leads to disordered energy metabolism, including increased weight gain, adiposity, and hepatosteatosis - all programs modulated by the circadian clock. We demonstrated that while antiinflammatory GC actions were maintained irrespective of dosing time, the liver was significantly more GC sensitive during the day. Temporal segregation of GC action was underpinned by a physical interaction of GR with the circadian transcription factor REVERBa and co-binding with liver-specific hepatocyte nuclear transcription factors (HNFs) on chromatin. REVERBa promoted efficient GR recruitment to chromatin during the day, acting in part by maintaining histone acetylation, with REVERBa-dependent GC responses providing segregation of carbohydrate and lipid metabolism. Importantly, deletion of Reverba inverted circadian liver GC sensitivity and protected mice from hepatosteatosis induced by chronic GC administration. Our results reveal a mechanism by which the circadian clock acts through REVERBa in liver on elements bound by HNF4A/HNF6 to direct GR action on energy metabolism.
Hyperglycemia and survival in solid tumors: A systematic review and meta-analysis.
Authors: Reeta Barua, Arnoud J. Templeton, Bostjan Seruga, Alberto Ocana, Eitan Amir, Josee-Lyne Ethier
Journal: Journal of Clinical Oncology (2017)

e18158 Background: Diabetes is associated with adverse cancer outcomes. However, the effect of hyperglycemia independent of diabetes is unclear. Here we report on a meta-analysis exploring the effect of hyperglycemia on outcomes of solid tumors, and the influence of clinical factors on this association. Methods: A systematic search of electronic databases identified publications exploring the effect of hyperglycemia on overall (OS), disease-free (DFS) or progression-free survival (PFS). Definitions of hyperglycemia (fasting blood glucose, random blood glucose or HbA1c) and cut-offs varied between studies. Data from studies reporting a hazard ratio (HR) and 95% confidence interval (CI) or a p -value were pooled in a meta-analysis using generic inverse-variance and random effects modeling. Subgroup analyses were conducted based on method of hyperglycemia measurement (HbA1c, other) and tumor stage (early, advanced, mixed). Meta-regression was performed to evaluate the influence of clinical characteristics including baseline diabetes status on the HR for OS. All statistical tests were two-sided. Results: Eight studies comprising a total of 4342 patients were included. All studies reported HRs for OS. Two studies reported DFS outcomes, and two reported PFS. Hyperglycemia was associated with worse OS (HR 2.07, 95% CI = 1.70 - 2.52; P &lt; 0.001) and DFS (HR 1.61, 95% CI = 1.04 - 2.49; P &lt; 0.001), but did not decrease PFS (HR 1.08, 95% CI = 0.72 - 1.62; P = 0.71). The association with worse OS maintained in subgroups based on method of hyperglycemia measurement (subgroup difference P = 0.65) and tumor stage ( P= 0.47). Meta-regression analyses did not identify any factors significantly altering the magnitude of association between hyperglycemia and OS (see Table). Conclusions: Hyperglycemia is associated with adverse OS and DFS in patients with cancer, and the therapeutic role of optimal glycemic control warrants further investigation. [Table: see text]
Neoadjuvant denosumab for the treatment of resectable giant cell tumor of bone: First results of Russian multicenter study.
Authors: Alexander A. Fedenko, Anastasia Tararykova
Journal: Journal of Clinical Oncology (2018)

11521 Background: Giant cell tumor of bone (GCT) is a relatively rare, benign but locally aggressive osteolytic skeletal neoplasm of young adults. This study is non-interventional observational GCT treatment study in the Russian Federation (RF). Designed to detect epidemiology data as well as the clinical efficiency of surgical and/or denosumab (Db) treatment of GCT in the RF. Methods: Between August 2016 and October 2017, 112 adult patients (pts) with GCT were enrolled. Ten Russian Cancer Center are included in this study. The primary endpoint was Time-To-Progression (TTP). Adult and skeletally mature adolescent pts with resectable and unresectable GCT (N = 54) received subcutaneous Db 120 mg every 4 weeks with a loading dose of 120 mg SC on study days 8 and 15. Options for surgical treatment (N = 25) include intralesional curettage (InC) (alone or followed by filling of the defect with bone cement), marginal excision (MEx), a wide local excision, or en bloc resection with or without reconstructive surgery. Results: 112 pts were enrolled, 71 were evaluable for efficacy evaluation. Median follow-up was 12.5 months. Enrolled subjects were 51.8% women, median age 35 years old. The most commonly affected sites are the epiphyses of the long bones (63%), 44% of all cases affect the distal femur or proximal tibia. Less commonly involved vertebra (3.5%), pelvis (8%), the skull (0.8%) and the small bones of the hands (2.6%). Of 112 pts enrolled, 54 received Db, and 16 with resectable GCT were evaluable for efficacy and underwent surgery - InC and MEx. 6 (37.5%) of 16 pts had disease progression; TTP was 6 months after surgery (11 injection of Db in average). 25 of 71 pts received only surgical treatment, in 4 (16%) of 25 pts InC and MEx were performed, 2 (50%) of 4 pts had disease progression, TTP was 7 months after the surgery. Conclusions: In this study, only 37.5% of pts with resectable GCT, who received neoadjuvant Db, had disease progression vs 50% of pts, received only surgical treatment. This study confirms that neoadjuvant Db is a possible treatment option for the resectable GCT to avoid mutilating surgery and decrease the risk of recurrences. Further investigation is awaited.