bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACT for prevention and prophylaxis of cancer-associated thrombosis (CAT).
Authors: Tsoukalas Nikolaos , Christopoulou Athina , Papandreou Christos N , Kapodistrias Nikolaos , Koumarianou Anna , Peroukidis Stavros , Kalofonos Haralabos , Samelis Georgios , Andreadis Charalampos , Ardavanis Alexandros , Samantas Epaminontas , Bokas Alexandros , Ligdas Athanasios , Athanasiadis Ilias , Barbounis Vasileios , Kentepozidis Nikolaos K. , Mavroudis Dimitrios , Athanasiadis Athanasios , Papakotoulas Pavlos , Boukovinas Ioannis 
Published: May 2020

e14135 Background: CAT is the 2nd leading cause of death in oncology patients and there is need for thrombosis management across the natural history of cancer because of its dynamic nature. Anticoagulant therapy is the cornerstone of prevention and treatment, since thrombosis interferes with cancer treatment, increases health care resource utilization, imposes emotional and economic burden. Methods: A prospective observational study conducted by HeSMO across Greece, aiming to record the clinical practice of CAT prophylaxis in patients with solid tumors. Ambulatory, high risk for thrombosis, active cancer patients who received thromboprophylaxis are enrolled after signing informed consent. Results: Preliminary results are collected from 17 oncology departments. From the 272 enrolled patients, 176 (64.7%) have completed second visit (3-4 cycles of anticancer treatment). Primary cancers included: lung 31.3%, pancreas 26.1%, colorectal 13.6%, gynecological cancers 10.2%, stomach 7.8%, bladder 6.3%, and others.75.6% of the patients had metastatic disease. 1/3 of the patients were smokers or ex-smokers, and 33% underwent surgery. Most of patients (65.9%) were at 1st line treatment and 17.6% at 2nd line. The vast majority (90.3%) were treated with High-Risk for Thrombosis Chemotherapy Agents (HRTCAs) such as cisplatin etc. Regarding Khorana score, 65.1% had ≥2. In particular, 86.7% of patients with Khorana score ≤1 received HRTCAs while 95.4% of patients with score = 2.All patients received thromboprophylaxis, specifically: 93.0% tinzaparin, 5.2% fondaparinux and 1.8% other (enoxaparin, bemiparin) with average duration 5.3±3.1 months. 67.1% of the patients received higher than standard prophylactic doses. 3 patients (1.7%) experienced thrombotic events (2 DVT and 1 PE). These 3 patients had metastases and were treated with HRTCAs. Five grade 1 bleeding events were reported (2.8%). Conclusions: Thromboprophylaxis of CAT is both safe and effective. Oncologists are alerted about CAT negative influences in cancer patients’ prognosis. Apart from Khorana score, factors such as metastases, use of HRTCAs along with drug-drug interactions, increase the LMWHs usage often in higher than prophylactic doses in CAT management. Clinical trial information: NCT03909399.
To scan or not to scan: An evaluation of preoperative MRI use in primary breast cancer assessments.
Authors: McKenzie Tesia , Matinho Davina , Scott Olivia , Khan Arbaz , Lachica Mila , Topilow Arthur A. , Johnson Miller Denise , Secic Michelle 
Published: May 2020

e14146 Background: Breast cancer (BC) is the most common invasive cancer in adult females.The role of preoperative MRI in assessing the extent of primary breast cancer remains controversial. This study’s objective is to determine if MRIs performed after the diagnosis of invasive/non-invasive-breast cancer will identify additional breast cancers. We hypothesize that preoperative MRIs will result in the discovery of additional significant lesions, leading to changes in surgical treatment. Methods: A retrospective study of 389 BC patient charts were reviewed, dated from January 2000- July 2019. Files were collected from an office in the Breast Cancer Surgery Department. Information on each patient’s imaging studies, treatment, demographics, surgery, and pathology were collected and stored in anonline cloud system. Summary statistics, including proportions, percentages, and difference of proportion hypothesis tests were utilized to interpret the data. All statistical tests were conducted at a 95% confidence interval. Results: We reviewed the charts of 335 patients that met eligibility criteria. In 221 newly diagnosed cancers, a preoperative MRI was taken before treatment. 127 cancers (57.5%)showed additional finding.In BC patients with additional preoperative MRI findings, we observed 61.4%true positive and 38.6%false positive results. These values are comparable to prior studies.We determined that the treatment plan was altered in 17.6%of all patients who received an MRI and in 30.7%of patients with a true positive MRI finding, which is also consistent with previous literature.A majority of the treatment changes were from Lumpectomy to Mastectomy. Conclusions: Literature on MRI use in BC diagnosis exists; our study differs by focusing on newly diagnosed breast cancers.We discovered 35.3% of preoperative MRIs identified a true additional finding in known breast cancer. In addition, our true positive rate (61.4%) and false positive rate (22.2%) of MRI findings is comparable to those of previous studies. Plans were changed in 30.7% of additional findings supporting the idea that preoperative MRI studies are useful when organizing surgical treatment. Further studies to demonstrate the impact on local recurrence rates and overall survival, may clarify the true role of pre-operative MRI in these cases.
Safe handling system construction for hazardous drugs (HDs) through the HD exposure surveillance by National Hospital Organization Network in Japan.
Authors: Aogi Kenjiro , Watanabe Kenichi , Watanabe Takanori , Matsui Akira , Sato Yasuyuki , Yasojima Hiroyuki , Yamashita Yoshinori , Ootsuka Shinya , Tokunaga Eriko , Anami Setsuko ,   NHO Network Study Group for Constructing the Safe Handling System of Hazardous Drugs in Japan
Published: May 2020

e14147 Background: In Japan, much labor has been devoted to handle occupational exposure to hazardous drugs (HDs) after the publication of a guideline for preventing HD exposure on cancer treatments in 2015. However, the safe HD handling systems have not yet constructed in Japanese hospitals. To find out the current HD exposure and construct the safe HD handling system, a multi-institutional surveillance of HD exposure in the National Hospital Organization (NHO) cancer hospitals was commenced from Feb 2016 to Mar 2018. Methods: Thirty-two NHO institutes joined in this survey. HD surveys were performed 3 times in each institute, evaluating cyclophosphamide and fluorouracil exposures using wipe and sampling sheet methods at 18 places in outpatient chemotherapy and pharmacology units. To share information and discuss about HD exposure handling procedures, the study group meeting was held several times. Furthermore, HD handling system in each hospital was evaluated using handling system scoring established by Yoshida in Osaka Institute of Public Health. As an additional study, factors affecting commitment wills of staffs were also evaluated during the safe HD handling system construction using a multiple regression model. Results: As HD control systems constructed, HD exposure in each hospital was improved gradually with construction of the handling system. Staffs’ commitment to their institutes was shown as the result of safety awareness improvement induced by the HD safe handling system construction (standardization coefficient β: 0.346). Conclusions: HD exposures were improved in NHO cancer hospitals through the HD exposure evaluation with constructions of the safe HD handling system.
The incidence of treatment related acute kidney injury in cancer patients: A retrospective analysis.
Authors: Baralo Bohdan , Hossain Samia , Hanif Muhammad , Khokhar Suhail , Mulla Sana , Keshava Vinay E. , Krupadev Archen , Gudipally Sindusha , Modi Simple , Thirumaran Rajesh 
Published: May 2020

e14150 Background: Development of the Acute kidney injury (AKI) in the patients receiving chemotherapy and immunotherapy is a factor associated with higher admission to the hospital, prolonged hospitalization, increased morbidity and mortality, dose reduction, moving to less effective regimens, inability to enroll in clinical trials. Methods: A retrospective cohort of the 95 patients, who received chemo immunotherapy in the infusion center of Mercy Fitzgerald Hospital in 2018-2020 were analysed. The pool of the patients had multiple oncological pathologies and were on different chemo immunotherapeutic regimens. All creatinine levels before starting chemotherapy, before and after each cycle were assessed. We used a Kidney Disease: Improving Global Outcomes criteria to define AKI (at least 1.5 increase in creatinine within 7 days of cycle or 0.3 creatinine increase in 48 hours) and grades of AKI. We considered AKI related to chemotherapy, if it developed in specified timeframe after chemotherapy defined above. The cases when patient did not meet criteria for AKI, but had a patterns suggestive of it (no repeat test within 7 days, but repeat test within 3 weeks, with increase in creatinine > 37.5%) were defined as potentially missed AKI. Results: 12 patients developed chemoimmunotherapy related AKI (12.63%). 1 patient had 3 episodes of the AKI related to chemotherapy. 4 patients received platinum-based chemotherapy. On average every patient received 12cycles of chemotherapy. After the first two cycles of chemotherapy AKI developed in 7 Patients (58.33%). 10patients had AKI after 7 cycles (83.33%). It worth mentioning that only 42% of the chemotherapeutic cycles had follow-up creatinine within 7 days. 7 patients (7.37%) had fallen under a potentially missed AKI criteria. 2 more patients were diagnosed with AKI that was not related to the chemotherapy. Conclusions: In our study there was a significant incidence of AKI in the patients receiving chemoimmunotherapy. Current guidelines do not advocate close monitoring(weekly) of renal function in patients receiving chemoimmunotherapy unless the patient receives an chemotherapeutic agent known to cause nephrotoxicity. Repeat creatinine within 7 days after chemotherapy may be necessary to allow early detection of AKI, that can potentially to improved outcomes. Large prospective studies may be necessary to confirm our findings that very close monitoring of renal function can improve detection of the AKI and outcomes due to possibility of early intervention.
Upfront or delayed radiation with next generation tyrosine kinase inhibitor therapy in driver mutation positive NACLC brain metastasis.
Authors: Yang Mike , Palmer Joshua David , Mo Xiaokui , Carbone David Paul , Welliver Meng XU 
Published: May 2020

e14503 Background: NSCLC with driver mutations may be managed with SRS, WBRT, and TKIs. Prior studies have demonstrated a worse survival with a delay in brain radiotherapy. We sought to determine if there is a difference in CNS PFS, OS, and cumulative incidence of intracranial brain failure (CI IBF) with next generation TKIs. Methods: A total of 69 patients with driver mutation NSCLC patients with brain metastasis were included. CNS PFS was measured from brain metastasis diagnosis. CI ICF was measured as any new or progressive disease on MRI Brain imaging. Results: The 1 year OS was 65.7% vs 60% (p = 0.9) for the RT and TKI arms. The CNS PFS was 82% vs 72% and CI ICF 13.5% vs 22% in the RT vs TKI arms, respectively. Conclusions: There was no difference in overall survival in our cohort when giving TKI therapy upfront or delayed with radiation. There was a clinically meaningful improvement in CNS PFS at 1 year but was not significant. There findings warrant further study.
Assessment of patient-reported outcomes in patients treated with radiation therapy to brain malignant tumors.
Authors: Yang Li , Xu Zhiyuan , Zhang Hang , Kong Feng-Ming Spring 
Published: May 2020

e14521 Background: Patient reported outcome is limited in patients with radiation therapy (RT) to brain tumors. The purpose of this study is to exam Patient Reported Outcome Measures (PROM) at baseline and end for RT in patients receiving RT to brain malignant tumors. Methods: This is a prospective study of quality of life. Patients ≥ 18-year old requiring RT to brain primary or metastatic malignant tumors were eligible. The PROM was assessed by self-administrated questionnaire PROMIS-29 Profile v2.1 and was completed prior to and at end of RT. Raw scores directly got from the PROMIS questionnaire were translated to T-scores according to the recommendation by the PROMIS INSTRUMENTS. A T-score of 50 is the average for general population and a higher PROMIS T-score represents more of the concept being measured. Results: Between July 2019 and December 2019, a total of 23 patients enrolled and completed PROMIS questionnaire and 19 completed questionnaire at end of RT. The median age was 55 (range 21-67), fifteen were men. The median doses of local brain RT and WBRT were 60Gy (range 40.05-60Gy) and 25Gy (range 20-36Gy), respectively. For the seven domain teams, physical function, anxiety, depression, fatigue, sleep disturbance, ability to participate in social roles and activities and pain interference, the number of patients with each T-score greater than 50 was 8 (34.8%), 13 (56.5%), 8 (34.8%), 6 (26.1%), 6 (26.1%), 13 (56.5%) and 9 (39.1%) at baseline and 7 (36.8%), 9 (47.4%), 7 (36.8%), 6 (31.6%), 6 (31.6%), 9 (47.4%) and 5 (26.3%) at end of RT, respectively. Physical function and sleep disturbance at end of RT was correlated with the corresponding value at baseline (Fisher’s exact test P = 0.045 and 0.017, respectively). None of the 7 domain teams’ T-scores changed significantly at end of RT. Pain intensity evaluated by NRS decreased significantly (mean 0.89 vs 1.53, P = 0.048). There is no difference in the mean T-score for all the 7 domain teams and NRS pain intensity between the local or whole brain RT patients at baseline and end of RT. Conclusions: This preliminary study demonstrated that brain RT did not alter PROM significantly in patients with primary or metastatic malignant brain tumors but decreased pain intensity in those patients.
Venous thromboembolic events in glioblastoma patients: Common complication but not a major reason for death.
Authors: Gramatzki Dorothee , Eisele Amanda , Seystahl Katharina , Le Rhun Emilie , Rushing Elisabeth Jane , Roth Patrick , Stahel Rolf A. , Weller Michael 
Published: May 2020

e14530 Background: Venous thromboembolic events (VTE) are a major complication in cancer patients. Anticoagulant use is the appropriate treatment for acute VTE in cancer patients, although associated with increased risk for bleeding, especially in brain tumor patients. In glioblastoma patients it remains unclear whether occurrence of VTE is associated with survival and to what extent thromboprophylaxis is necessary and efficient. Methods: Frequency, risk factors, and treatment of VTE as well as its complications were assessed in an epidemiological glioblastoma cohort in the Canton of Zurich, Switzerland, in the years 2005 to 2014. Association of clinical data with survival were retrospectively analyzed using the log rank test. Results: Four-hundred-nineteen patients diagnosed with isocitrate dehydrogenase wildtype glioblastoma were identified in the 10-year time-frame. Median overall survival (OS) was 12.4 months (95% CI 11.4-13.4) with a median follow up of 64.5 months (95% CI 46.6-82.4).VTE were seen in 65 patients (15.7%; 5 patients with missing information on VTE).Median time from diagnosis of glioblastoma to occurrence of VTE was 2.0 months (95% CI 0.8-3.1). A history of VTE was found in 6 patients (9.2%). Thirty-nine patients were on steroids (62.5%; 1 patient with missing data) at time of diagnosis of VTE, and 35 patients (56%; 3 patients with missing data) had a Karnofsky Performance Score of less than 70%. At the time patients were diagnosed with VTE the majority of patients (93.8%) were treated with therapeutic anticoagulation. Complications resulting in stop of anticoagulation occurred in 11 patients (18.0%; 4 patients had no anticoagulation) mainly because of intracranial bleedings (9 patients). OS was not different (p = 0.355) between patients who were diagnosed with VTE and those who were not. Tumor progression (283 patients, 77.3%) was the major reason for death (366 patients with confirmed death) in this patient cohort, only 3 patients (0.8%) died because of confirmed VTE and another 5 patients (1.4%) had an unexpected sudden death. Conclusions: Although VTE was identified in 65 patients (16%) diagnosed with glioblastoma, VTE was no major reason for death. On a population-based level these data do not support the implementation of primary thromboprophylaxis in this cohort of patients.
Differential expression of KDM1A and SMAD7 genes in gliomas depending on the tumor grade.
Authors: Pushkin Anton A. , Alliluev Ilya A. , Rostorguev Eduard E. , Kavitskiy Sergey E. , Kuznetsova Natalya S. , Timoshkina Natalya N. , Kit Oleg I. 
Published: May 2020

e14549 Background: Gliomas are the most common type of primary brain tumors characterized by pronounced proliferation and aggressive infiltration. The purpose of the study was to analyze the expression of genes participating in the EGFR, TGF-B, HH/GLI, NOTCH and HIF1-alpha signaling pathways, transcription factors HBP1, MSI1/2 and demethylating agents in samples of various glioma types. Methods: The study included paired samples (tumor and physiologically unchanged neural tissue) obtained from 75 patients with histologically verified glial tumors of various grades (G2 - 21, G3 - 11, G4 - 43 patients). Relative expression of 15 genetic loci (EGFR, SMAD4, SMAD7, SMO, NOTCH1, NOTCH2, HBP1, HIF1A, EGLN1, EGLIN3, KDM1B, KDM1A, MSI1, MSI2, TET1) was measured by RT-qPCR. The PSMC, TBP and RPLO genes were used as the reference sequences. The 2−ΔΔ Сt method was used to analyze the qPCR data. Statisical processing of the results was performed with the Statistica 10 program (StatSoft Inc., USA). Results: G2 gliomas showed a significant change in the relative expression of the KDM1A gene (p = 0.00572); G3 - a significant change in the relative expression of the HIF1A gene (p = 0.012726); G4 - significant changes in the relative expression of the EGFR (p = 0.021324), SMAD4 (p = 0.016534), SMAD7 (p = 0.000003), HBP1 (p = 0.003264), HIF1A (p = 0.007612), EGLN1 (p = 0.001623), EGLN3 (p = 0.004231) genes. Registered changes in the expression of the KDM1A and SMAD7 genes in the studied sample significantly differentiated the G2 and G4 glial tumors (p = 0.013 and p = 0.049, respectively). G2 tumors were characterized with increased expression of the KDM1A gene and decreased by more than 1.1 times in 95% of patients. 88% of patients with G4 tumors demonstrated no changes or a decrease in the KDM1A gene expression and decreased SMAD7 expression by more than 1.5 times. Conclusions: The established significant change in the expression of the KDM1A and SMAD7 genes depending on the tumor grade can be used for the differential diagnosis of gliomas.
Phase I trial characterizing the pharmacokinetic profile and NK and CD8+ t cell expansion with n-803, a chimeric IL-15 superagonist, in healthy volunteers.
Authors: Wrangle John M. , Rubinstein Mark P , Mart Caroline , Azar Joseph H. , Williams Cameron , Swiderska-Syn Marzena , Macpherson Linda , Beall Jonathan , Hill Elizabeth Goodwin , Lee John H. , Rock Amy , Soon-Shiong Patrick 
Published: May 2020

e15008 Background: The oncotherapeutic promise of IL-15, a potent immune stimulant, is limited by short serum half-life. The fusion protein N-803 is an IL-15 superagonist complex that has > 20-fold longer half-life in vivo vs IL-15. This study characterized the pharmacokinetic (PK) profile, biological activity, and safety of N-803 after subcutaneous administration to healthy human volunteers. Methods: Volunteers were randomized 1:1 to receive 1 mg/mL or 2 mg/mL N-803. Each subject received 2 doses of N-803: 10 µg/kg followed 24 days later by 20 µg/kg. After each dose, PK and safety measures were assayed for 9 successive days. Primary endpoint was the PK profile of N-803; secondary was safety; and exploratory endpoints were cytokine levels, immune cell characterization, and immunogenicity. Results: N-803 resulted in no grade ≥3 or serious adverse events (AEs). Mild injection site reactions, chills, and pyrexia were the most common AEs. Serum N-803 concentrations peaked 10.3-15.4 hours after administration and declined with a half-life of 20.0-20.7 hours. Peak N-803 serum concentrations were dose-dependent, with a 1.5-fold increase in Cmax after administration of 20 µg/kg vs 10 µg/kg. In the peripheral blood, N-803 induced a transient decline, followed by a significant increase (3-fold) in NK cell number that persisted for ≥24 days. N-803 also caused a significant proliferation of NK (22-fold increase in Ki-67+ cells), CD8+ (27-fold) and CD4+ T (11-fold) cells; however, increased cell number occurred only in NK cells. N-803 administration also increased serum levels of interferon gamma, IL-10, and IL-6. One of 14 evaluable subjects had measureable anti-N-803 antibodies at the end-of-study visit. Conclusions: N-803 results in prolonged elevation of drug serum concentrations, contrasting with rapid clearance of recombinant human IL-15 (ie, half-life of ~20 vs < 1 hour). N-803 administration was well-tolerated in healthy volunteers, without evidence of adverse systemic inflammatory responses, and resulted in proliferation of NK cells and CD8+ T cells, as well as sustained increases in NK cell number. Findings in this study are consistent with published results from N-803 administration in treating liquid tumors and lung cancer. Our results demonstrate N-803 administration potentiates the proliferation and activity of lymphocytes with antitumor and antivirus properties, and suggest this investigational product holds promise in treatment of cancer as well as infectious disease such as HIV. Clinical trial information: NCT03381586 .