bluuebunny/crossref_metadata_2025_split huggingface dataset:
Teleoncology: Prospects and challenges for cost effective cancer care.
Authors: Majeed Ammara , Lakhani Midhat , Ashraf Afia , Grewal Udhayvir Singh , Thirunagari Prem , Wahab Ahsan , Hassan Hamza , Faisal Muhammad Salman , Raziq Fazal I , Anwer Faiz 
Published: March 2020

e23182 Background: An estimated 20.3 million cancer survivors are expected to be around by 2026. Estimated national expenditure for cancer care in 2017 were $147.3 billion and expected to increase every year. Cancer treatment is complex and requires management decisions, counselling, psychological support to be made by multidisciplinary teams. For rural and remote patients, these teams may be composed of local clinicians, and experts from distant urban centers using telemedicine (TeleMed). Methods: We used 2 databases to study Teleoncology (TelOnc) since 2002. Results: Scope of TelOnc includes cancer Telegenetics, Telepathology, remote supervision, symptom management, survivorship care, palliative care, and increase access to cancer clinical trials. Mobile applications support symptom management, lifestyle modification, and medication adherence. TeleMed can support the oncologist with interactive tele-education. Future TelOnc models would include web-based tools, mobile technologies and remote chemotherapy supervision. TeleMed had a high patient satisfaction rate. In a survey 82.21% participants were satisfied with their TeleMed experience, only 2.14% was not satisfied. Challenges: Despite an area of growing need, few studies have prospectively evaluated its efficacy in cancer. Even fewer data is available in young adults (group with liking for technology) with cancer. Lack of uniform model for reimbursement and hurdles of interstate practice license for providers are unique challenges. Conclusions: TeleMed / TelOnc can improve access to medical care, reduce healthcare costs, (Table) and reduce geographic health disparities. [Table: see text]
Dealing with emotional states during cancer diagnosis and treatment by using cognitive strategies in oncology patients: Comparison to noncancer population.
Authors: Kieszkowska-Grudny Anna , Rucinska Monika , Osowiecka Karolina 
Published: March 2020

e23184 Background: Diagnosis of cancer is perceived by individuals as a life-threatening event. Patients (pts) experience a great distress, as well as a various emotions and apply diverse cognitive strategies to deal with them during cancer diagnosis and its treatment. State of mind can help in emotions management and could be supportive or destructive during treatment.Employing adaptive strategies may help them to cope better this specific traumatic event and help doctors to get higher compliance with their pts.Therefore, it is important first to recognize these strategies and then arrange personalized psychological support for them in cooperation with oncologist. Methods: 197 individuals were included into the study between 11.2017 and 12.2018: 115 cancer pts ( Me= 62years) and 82 healthy subjects ( Me= 45years). All subjects filled out: Cognitive-Emotional Regulation Questionnaire(with 4 non-adaptive strategies (NAS)–self-blame, blaming others, catastrophizing, rumination and 4 adaptive strategies (AS)–acceptance, refocus on planning, putting into perspective, attention to something positive), and demographic data. Statistical analyses were based on t-Students test and linear correlation (significance level: p < .05). Results: Significant differences were observed between cancer patients and healthy group in all types of cognitive strategies. Cancer pts tend to catastrophize more frequently ( p < .01) and employed planning strategies less often ( p < .001), but generally had more AS( p < .01), especially attention to sth positive and acceptance ( p < .001). In cancer group NAS, especially catastrophizing ( p < .05) and rumination ( p < .001) correlate negatively with education and place of living, which means that less educated pts and living in the countryside had more NAS. In contrast, cancer pts living in cities used more AS( p = .001), mainly attention to sth positive, refocus on planning ( p < .01) and putting into perspective ( p < .001). The older pts less often applied focus-on-planning strategy ( p < .01). Conclusions: Cancer pts rarely used planning strategies and tend to develop an extremely negative future vision, but generally had more AS to deal with traumatic event then healthy population. More attention should be given to pts with cancer who are older, live in in the countryside and are less educated.
Profiling cancer-related distress and problems: A latent class analysis approach.
Authors: Rossi Alessandro , Marconi Maria , Mannarini Stefania , Minelli India , Fusi Chiara , Anderboni Monica , Rossini Chiara , Di Lucca Giuseppe , Verusio Claudio 
Published: March 2020

e23191 Background: Psychological distresses, emotional troubles, social difficulties as well as both physical and practical issues are all among oppressive problems that oncological patients have to face almost every day. On one hand, these problems seem to have a strong impact on quality of life; and to the other hand, these issues seem to be related to specific cancer-related variables ( e.g.: type and localization of the tumor). Thus, the aim of the study was to use a Latent Class Analysis (LCA) approach to profile a latent structure accounting for the covariance between psychological distress and everyday problems due to cancer. A one-factor model with three classes was hypothesized, which comprised distress and cancer-related problems as indicators and age, type of medical treatment as well as type and localization of tumor as external variables that moderate the latent structure. Methods: Patients ( N = 264, 62.3% female, mean age = 65.3, SD = 12.4) were enrolled at the Oncology Day Hospital, “Presidio Ospedaliero” of Saronno, ASST Valle Olona, Italy. Using the standardized Distress Thermometer and Problem List (TD&PL; NCCN, 2015) patients were tested for: (A) distress; (B) practical problems (Cronbach’s α = .63); (C) social difficulties (Cronbach’s α = .65); (D) emotional issues (Cronbach’s α = .86) and (E) physical problems (Cronbach’s α = .77). Results: First of all, a CFA was performed to test the original factorial structure of the DT&PL. The original five factor solution was supported by adequate fit indices: RMSEA = .063; CFI = .924. Then, the LCA (10000 bootstrap resampling) shows the goodness-of-model fit [χ2 = 10.01; p = .11; LRχ2 = 9.30; p = .09] and the goodness-of-classification quality [Entropy = .80 ( > .7); Average-Latent-Class-Assignment-Probability: .975, .900, and .902 for Class1, Class2, and Class3, respectively]. The LCA identified a latent variable with three classes (VLMR = 193.38; p < .001; Class1 = .49%; Class2 = .23%, and Class3 = .28%). In addition, interactions with the latent variable were found for age ( β = .12; p = .039), type of medical treatment ( β = .29; p = .009), as well as type and localization of tumor ( β = .20; p = .025). Conclusions: These results provided a better understand of psychological distress and cancer-related issues: each class represents a specific “profile” – moderated by age, type of medical treatment, and type and localization of tumor. These results recommend paying more attention to the specific profile expressed by the patient suggesting new ways to improve their quality of life.
Comparative analysis of molecular aberration in different genders for identification of key pathways in hepatocellular carcinoma.
Authors: Yu Li , Tieshan Feng , Li Lifeng , Chen Shifu , Xiaoliang Liu 
Published: March 2020

e23192 Background: The incidence rate of hepatocellular carcinoma (HCC) varies significantly between genders, being higher in men than in women. While the molecular mechanisms remain unexplored, we systematically analyzed the gene expression and SNV signature to identify key molecular aberrations and pathways. Methods: Gene expression and simple nucleotide variation data of 407 HCC patients with HCC including 140 females and 267 males were collected. We identified genes with differential mutation frequency in two cohorts using Fisher’s exact test (p-value < 0.05), and Deseq2 to identify differential expression genes (FDR < 0.05 and fold change > 2). Enrichment analysis was applied using the Kyoto Encyclopedia of Genes and Genomes (KEGG) and the Reactome database (p adjust < 0.05). Results: In total, 103 genes with differential mutation frequency in two cohorts were identified. Of these genes, 57 genes were differentially expressed, and the number of up-regulated genes in males and females were 21 and 36, respectively. The genes that show significant up-regulation in males are KDM5D and ANKFN1 which have the log2(fold change) of 7.49 and 4.45. The genes that show significant up-regulation in females are SYT13 and SCD5 which have the log2(fold change) of 2.33 and 2.29. The result of enrichment analysis showed that the up-regulated genes in males and females were involved in different biological pathways. In males, the up-regulated genes mainly participated in the PPAR signaling pathway. In females, the up-regulated genes mainly participated in the Rho GTPase cycle, regulation of insulin secretion and integration of energy metabolism. Conclusions: In this study, 57 genes with differential mutation frequency and differential expression between males and females with HCC were identified based on TCGA dataset. Enrichment analysis result indicated that these genes are mainly involved in signaling pathways relevant to carcinogenesis and metabolism.
A phase II study of ADI-PEG 20 in combination with gemcitabine and docetaxel for the treatment of soft tissue sarcoma.
Authors: Van Tine Brian Andrew , Bui Nam , Prudner Bethany , Bomalaski John S. , Wu Bor-Wen , Chawla Sant P. , Ganjoo Kristen N. , Oppelt Peter John , Hirbe Angela C. 
Published: March 2020

TPS11079 Background: The combination of gemcitabine (G) and docetaxel (D) is a standard second line therapy for soft tissue sarcoma (STS) with a modest response rate. Recent studies have looked to add agents to enhance response. We have shown that argininosuccinate synthase 1 (ASS1) expression is silenced in 88% of all sarcomas (n = 708) (Bean et al., 2016, Cell Death and Disease), and that this loss is associated with a reliance on extracellular sources of the amino acid arginine. The arginine depleting enzyme PEGylated arginine deiminase (ADI-PEG 20) depletes extracellular arginine. Preclinical studies have demonstrated that arginine starvation and D administration induce c-Myc-driven hENT1 surface expression overcoming intrinsic cell surface G transporter related resistance. To test this hypothesis, we opened this multi-institutional randomized phase II trial examining the safety and efficacy of ADI-PEG 20 with G + D in STS (NCT03449901) in July of 2018. Methods: Eligible patients are adults with metastatic or unresectable histologically or cytologically confirmed FNCLCC grade 2 or 3 STS that would be standardly treated with G and/or D. Patients are treated with ADI-PEG 20 at a dose of 36 mg/m2 via intramuscular injection on Day -7 of Cycle 1 and then on Days 1, 8, and 15 of each subsequent cycle. G will be given intravenously at a dose of 750 mg/m2 over 90 minutes on Days 1 and 8 and D will be given intravenously at a dose of 75 mg/m2 over 60 minutes on Day 8 of each cycle. The median PFS of metastatic sarcoma patients receiving the standard G + D treatment was estimated to be 6.2 months in a randomized phase II study (Maki et. al., 2007, JCO). With the addition of ADI-PEG 20, we target to improve the median PFS to 9 months, a 45.2% (2.8 months or 12 weeks) improvement in patients treated on G + D + ADI-PEG 20 against the null hypothesis median PFS of 6.2 months to achieve 80% power to detect the improvement in PFS at a 5% alpha level. Tumor specimens (pre- and post-ADI-PEG 20 during week -1) and blood are collected for correlative studies including metabolomics, pharmacodynamics, immunogenicity and ASS1 biomarkers. Quality of life will be measured using FACT-G7. Clinical trial information: NCT03449901.
MIRROS: An ongoing randomized phase 3 trial of idasanutlin + ARA-C in patients with relapsed or refractory acute myeloid leukemia.
Authors: Montesinos Pau , Esteve Jordi , Konopleva Marina , Martinelli Giovanni , Ottmann Oliver , Rodriguez-Veiga Rebeca , Röllig Christoph , Wei Andrew , Vey Norbert , Chiu Idy , Monnet Annabelle , Ott Marion Gabriele , Fenaux Pierre 
Published: March 2020

TPS7063 Background: The prognosis for patients (pts) with relapsed or refractory (R/R) acute myeloid leukemia (AML) is poor, with 3-year overall survival rates ~10–30% after intensive chemotherapy-based approaches. Despite the advent of targeted therapies, considerable unmet medical need remains in this population. Idasanutlin (RG7388; RO5503781) is an orally available small molecule that binds to the murine double minute 2 (MDM2) protein and blocks MDM2 interaction with p53. This stabilizes and activates p53 and facilitates cell cycle arrest and apoptosis, preventing tumor growth. A phase 1b study of idasanutlin + ARA-C in pts with R/R AML, irrespective of TP53 mutation status (NCT01773408), has shown a composite complete remission (CR) rate (CR plus CR with incomplete platelet or hematologic recovery) of 29% (Martinelli et al. 2016). Methods: MIRROS (NCT02545283; WO29519) is an international, phase 3, double-blind, randomized study comparing idasanutlin (300 mg bid) + ARA-C (1 g/m2 qd) days 1–5 versus placebo + ARA-C in 440 pts with first or second R/R AML, with or without TP53 mutation. The primary endpoint is overall survival in pts with wild-type (WT) TP53. Secondary endpoints include CR, overall remission rates, event-free survival (EFS) and percentages of pts undergoing hematopoietic stem cell transplantation. MIRROS integrates phase 2 trial methodology into the phase 3 design by incorporating an interim analysis (IA) in 120 pts with WT TP53, using a high bar on the odds ratio for durable CR and EFS to assess for futility. Stop/go gating criteria for safety were also implemented. The IA was performed by an independent data monitoring committee and study continuation criteria were successfully met in mid-2017. This innovative strategy has allowed acceleration of the idasanutlin development program while maintaining a robust trial design. As of December 31 2018, 351 pts had been enrolled. The MIRROS study is ongoing and its results will inform the potential role of idasanutlin and MDM2 inhibition in the treatment of R/R AML. Clinical trial information: NCT02545283; WO29519.
A phase I study of milademetan in combination with quizartinib in patients (pts) with newly diagnosed (ND) or relapsed/refractory (R/R) FLT3-ITD acute myeloid leukemia (AML).
Authors: Daver Naval Guastad , Zhang Weiguo , Graydon Richard , Dawra Vikas , Xie Jingdong , Kumar Prasanna , Andreeff Michael 
Published: March 2020

TPS7067 Background: Fms -like tyrosine kinase 3 internal tandem duplication ( FLT3-ITD) mutations occur in ≈ 25% of pts with AML and are associated with poor prognosis. Quizartinib is a highly potent, selective, next-generation type II FLT3 inhibitor. In the phase 3 QuANTUM-R trial, quizartinib prolonged overall survival vs salvage chemotherapy in pts with R/R FLT3-ITD AML. MDM2 downregulates the p53 tumor suppressor and is upregulated in pts with AML. Targeting MDM2 may restore p53 activity in pts with wild-type p53 AML. Milademetan, a novel and specific MDM2 inhibitor, showed activity in an ongoing phase 1 trial in pts with AML or myelodysplastic syndromes (MDS). Preclinical studies have shown that quizartinib plus milademetan may act synergistically to target FLT3-ITD and restore p53 activity in FLT3-ITD/ TP53 wild-type AML [Andreeff et al. ASH 2018, abstract 2720]. Methods: This open-label phase 1 study (NCT03552029) has 2 parts: dose escalation (part 1) followed by dose expansion (part 2), with 2 planned cohorts. Key inclusion criteria include FLT3-ITD AML (primary or secondary to MDS) and adequate renal, hepatic, and clotting functions. Key exclusion criteria include acute promyelocytic leukemia, prior treatment with a MDM2 inhibitor, QTcF interval > 450 ms, significant cardiovascular disease, and unresolved toxicities from prior therapies. Dose escalation and expansion cohort 1 includes R/R pts. Expansion cohort 2 includes ND pts unfit for intensive chemotherapy. During dose escalation, quizartinib will be administered once daily in 28-day cycles, with 3 proposed levels (30, 40, and 60 mg). Milademetan will be administered on days 1-14 of each 28-day cycle, with 3 proposed levels (90, 120, and 160 mg). The quizartinib dose will be escalated first, followed by the milademetan dose with no simultaneous escalation, guided by modified continual reassessment with overdose control. Primary objectives are safety and tolerability, optimum dosing schedule, maximum tolerated dose, recommended dosing for the expansion cohort, and phase 2 dosing. Secondary objectives are pharmacokinetics and preliminary efficacy. This study is recruiting. Clinical trial information: NCT03552029.
ZUMA-8: A phase 1/2 multicenter study evaluating KTE-X19 in patients (pts) with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).
Authors: Flinn Ian , Marris Michael , Wierda William G. , Coutre Steven , Pagel John M. , Byrd John C. , Goyal Lovely , Goodman Krista , Zheng Yan , Milletti Francesca , Murugappan Swaminathan , Brown Jennifer R. 
Published: March 2020

TPS7566 Background: Despite treatment advances, CLL is largely incurable. First-line targeted therapy with ibrutinib mostly produces durable remissions, but high-risk disease or many prior therapies increases relapse risk (Ghia P, et al. Haematologica. 2014). Relapse after ibrutinib is associated with a poor outcome (Maddocks KJ, et al. JAMA Oncol. 2015). Allogeneic stem cell transplantation potentially offers long-term remissions but has a high risk of morbidity/mortality (Shustik C, et al. Ann Hematol. 2017). Autologous T cells expressing a CD19-specific chimeric antigen receptor (CAR) with a CD28 costimulatory domain may be efficacious against CLL (Kochenderfer JN, et al. Blood. 2012). KTE-X19 is an autologous anti-CD19 CAR T cell therapy under investigation for R/R hematologic malignancies and may offer longer durable remissions with manageable safety in pts with R/R CLL. ZUMA-8 is a Phase 1/2 multicenter study for pts with R/R CLL. Methods: Adult pts must have R/R CLL with ≥ 2 prior treatment regimens, disease progression on ibrutinib, ECOG 0-1, and adequate organ function. Phase 1 will enroll 12-18 pts to assess dose-limiting toxicities (DLTs) with a 6 + 3 dose escalation/de-escalation design; 30 more pts may be enrolled to further assess safety. Phase 2 will enroll ≈60 pts to evaluate efficacy and safety. Pts will undergo leukapheresis followed by optional bridging therapy. Cyclophosphamide (500 mg/m2) and fludarabine (30 mg/m2) conditioning chemotherapy will be given on Days -5, -4 and -3. KTE-X19 will be given on Day 0 at 0.5, 1 or 2 × 106 KTE-X19 cells/kg. The primary endpoint is incidence of DLTs for Phase 1 and independent review committee-assessed objective response rate (ORR) per iwCLL 2018 criteria for Phase 2. Secondary endpoints include complete remission (CR) rate, investigator-assessed ORR, minimal residual disease (MRD) negativity rate, MRD-negative CR rate, duration of response, progression-free survival, overall survival, safety, and patient-reported outcomes (Phase 2). Serum cytokine and blood KTE-X19 cell levels over time and level of anti-KTE-X19 antibodies are exploratory endpoints. Accrual is ongoing. Clinical trial information: NCT03624036.
ENGINE: Phase III randomized study of enzastaurin/R-CHOP versus placebo/R-CHOP in frontline high-risk diffuse large B-cell lymphoma patients with novel genomic biomarker DGM1.
Authors: Smith Stephen , Zhu Jun , O'Connor Owen A. , Luo Wen , Shazer Ronald L. , Zhang Lei , Han Isabel , Jivani Manoj A. , Liu Young , Nowakowski Grzegorz S. 
Published: March 2020

TPS7569 Background: Progress in genome technology allows analysis of previously completed trials to identify patients subgroups potentially benefiting from therapy. Enzastaurin is a potent inhibitor of protein kinase C beta (PKC- b) and suppresses the phosphoinositide 3-kinase (PI3K)/AKT pathway. The safety and efficacy of Enzastaurin has been tested in more than 60 clinical trials including 2 major studies in DLBCL: (1) PRELUDE (A phase III maintenance trial of Enzastaurin vs Placebo, N=758) ( Crump, 2016), and (2) S028 (A randomized phase II study of Enzastaurin/R-CHOP vs R-CHOP in frontline intermediate/high-risk DLBCL, N=101) ( Hainsworth, 2016). DNA samples extracted from blood of patients from PRELUDE were retrospectively genotyped using whole genome SNP arrays. From the genome wide screening a novel genetic biomarker, DGM1, was identified showing high correlation with response to Enzastaurin treatment ( Luo, ASH 2018). Importantly, these findings were replicated in the phase II S028 study. In the S028 study the hazard ratio (HR) for OS in high-risk (IPI ≥ 3) DGM1 positive (+) patients who received Enzastaurin/R-CHOP was 0.28 (0.1-0.81) when compared to subjects who received R-CHOP, a benefit favoring Enzastaurin (p=0.018). These data suggest that addition of Enzastaurin to R-CHOP may significantly improve outcome in frontline high-risk DGM1 (+) DLBCL. The ENGINE study was initiated to validate this finding in a prospective study. Methods: Adult patients must have untreated CD20+ DLBCL, IPI ≥ 3. Patients are randomized 1:1 to Enzastaurin/R-CHOP or Placebo/R-CHOP for 6 cycles during combination phase. Each subject’s treatment assignment will be unblinded after response assessment at the end of the combination phase. Subjects randomized to the investigational arm who have a complete or partial response will have the option to continue in the single agent phase to receive Enzastaurin for up to 2 additional years. The study intends to enroll approximately 235 patients with primary endpoint of OS in DGM1 (+) patients. The study is ongoing with 51 sites open in the US and China. As of 22 Jan 2019, 70 patients have been randomized. Clinical trial information: NCT03263026.