bluuebunny/crossref_metadata_2025_split huggingface dataset:
Survival study of RTA 744 (currently a single agent phase I study) alone and in combination with temozolomide in orthotopic model of glioma
Authors: Conrad C. A. , Meyer C. , Madden T. , Priebe W. , Lang F. F. 
Published: March 2020

1577 Background: Treatment for high-grade gliomas represents an area of significant unmet medical need, largely because few agents cross the blood-brain barrier (BBB). RTA 744744 (WP744, 4’-O-benzyldoxorubicin hydrochloride) is a potent topoisomerase II poison and novel anthracycline screened for its ability to circumvent P-gp and MRP1allowing it to cross the BBB. To assess the drug’s potential in gliomas, RTA 744 was tested alone or in combination with temozolomide in an intracranial xenograft model of glioblastoma multiforme (GBM). It was hypothesized that a DNA repair inhibitor such as RTA 744 would enhance the effects of temozolomide. In vitro cell based assays confirmed this hypothesis and led to in vivo testing of this novel combination. Methods: U87MG cells were implanted into the right basal ganglia of nu/nu mice via an implantable screw system. In all studies, groups of 5 or 6 mice received PBS, temozolomide, RTA 744, or the combination of RTA 744 and temozolomide administered IP. PBS and temozolomide were given on a QDx5 schedule, and several schedules were tested for RTA 744. The primary endpoint in these studies was survival. Results: In the single agent study, by day 33, all 5 of the control animals had died compared with just one of the RTA 744-treated animals. Median survival for control animals was 28 days versus 37 for RTA 744-treated animals (T/C=132%). In the combination study, median survival was 30 days for controls, 40 days for temozolomide alone (T/C=133%), and 48 days for animals receiving the optimal combination of RTA 744 and temozolomide (T/C=160%). One animal in the combination group survived to day 78, whereas no control or Temodar treated animals survived past days 32 and 45, respectively. Conclusions: RTA 744 demonstrated potent single agent activity in a rigorous preclinical model of GBM. The combination of RTA 744 and temozolomide produced survival results significantly better than those from any chemotherapeutics tested in this model. This data supports the current Phase 1 trial of RTA 744 in patients with brain tumors as well as future trials testing the combination of RTA 744 and temozolomide. [Table: see text]
Comparison of red blood cell transfusion rates of epoetin alfa and darbepoetin alfa in an inpatient oncology setting
Authors: Vekeman F. , McKenzie R. S. , Watson S. , Mody S. , Lefebvre P. , Piech C. T. , Duh M. S. 
Published: March 2020

16002 Background: Epoetin alfa (EPO) and darbepoetin alfa (DARB) are used to treat cancer-related anemia and to reduce the requirements for blood transfusions. To date, limited information on the relative effectiveness of these agents in the inpatient setting is available. This analysis evaluated red blood cell (RBC) transfusion rates in cancer patients receiving EPO or DARB during hospitalization. Methods: An analysis of electronic inpatient hospital records from the Premier Perspective Comparative Hospital Database was conducted to compare RBC transfusion rates in cancer patients receiving EPO or DARB therapy. Study subjects were identified through hospitalizations recorded between 07/2002 and 03/2005 from over 500 hospitals nationwide. Patients were required to be ≥18 years old, have a primary admitting diagnosis of cancer and be treated with EPO or DARB during hospitalization. Patients who had received renal dialysis were excluded. To minimize effects of outliers, 5% of patients with extreme doses in each group were excluded from the dosing analysis. In addition to descriptive statistics on transfusion requirements, a multivariate logistic model was employed to isolate the effect of an individual erythropoietic agent on the risk of RBC transfusion after controlling for patient demographics, comorbidities, admission characteristics, use of IV or oral iron and hospitalization severity markers. Results: Among the 24,814 EPO and 2,990 DARB study patients, mean age and gender distribution at admission were similar (age: EPO 65.3 years, DARB 64.5 years; %women: EPO 53%, DARB 55%). Mean cumulative dose per inpatient stay was EPO 61,656 ± 50,274 Units and DARB 259 ± 340 mcg. RBC transfusions occurred in 37.9% of EPO patients compared to 39.8% of DARB patients (p=0.0404). Transfused EPO patients received a mean of 2.24 units versus 2.20 units for DARB patients (p=0.2111). After adjusting for covariates, the multivariate model confirmed that DARB treatment was associated with a higher risk of transfusion compared to EPO (odds ratio: 1.2, 95% CI: 1.1–1.3, p=0.0007). Conclusions: This analysis of inpatients with cancer indicates DARB treatment is associated with a higher risk of receiving RBC transfusion compared to treatment with EPO. [Table: see text]
Human resource (HR) costs of chemotherapy infusion reactions (IR) in community oncology
Authors: Ogle J. , Fortner B. V. , Moore K. , Zhu L. , Schwartzberg L. S. 
Published: March 2020

16013 Background: Chemotherapy IR are the dose limiting factor for many agents and have clinical consequences ranging from patient symptom burden to death. No work has been done to describe the provider burden of chemotherapy IR. The purpose of this analysis was to describe the clinical interventions associated with mild and severe IR and estimate the associated HR costs. Methods: Staff from a single, free standing, community oncology practice were surveyed regarding involvement in the management of mild and severe chemotherapy IR using a modified time and motion survey to identify tasks required to manage CIR and the HR time required. Mild and severe chemotherapy IR HR events were created. Salary averages for each type of staff were used to estimate HR costs. Results: 39 staff participated in the survey and were 85% (n = 33) female, average age 44, with M = 7.6 years experience. 21 distinct tasks (e.g. initial assessment, patient monitoring, infusion stopped, notify physician) were identified representing the management of the mild and severe chemotherapy IR. 11 types of staff indicated routine participation in ≥ 1 IR related task. Total HR time was 188 and 194 minutes for mild and severe IR respectively, resulting in HR cost of $124 and $187. Conclusions: The above methodology will be used in an expanded analysis of 20 outpatient practices. Recent changes in cancer treatment reimbursement have resulted increased interest in practice efficiency and provider cost. Definitions for quality care should consider minimization of unnecessary direct and indirect costs and maximization of practice efficiency. Models such as the one described are needed to understand provider costs. Clinical processes and chemotherapy agents that reduce rates and severity of CIR should reduce HR burden related to CIR. [Table: see text] [Table: see text]
Electronic medical record (EMR) in the oncology setting tested: A first hand experience
Authors: Hesita E. L. 
Published: March 2020

16043 Background: Current data indicate that America’s medical system has been slow to embrace technology in relation to the use of the electronic medical record (EMR). The disruption caused by hurricane Katrina in the lives of cancer patients living in the city of New Orleans may prove to be an eye-opening experience that will persuade healthcare providers to change the traditional way of storing medical records. This study focuses on the experience of displaced New Orleans cancer patients. Methods: An anonymous validated questionnaire was completed by a random group of returning patients six weeks after the hurricane. This random group of patients evacuated to various states across the country. The focal questions asked were: the degree of difficulty in obtaining records, whether the alternate oncologist had to order further test(s), and whether the patients agree to having their medical records in an electronic format. Results: Of the total of 75 respondents, 93% are served by an institution in the New Orleans area that utilizes EMR while 7% are served by various institutions within the New Orleans area that do not have EMR. Overall, 81% stated ease in obtaining their records (within 1–4 days) while 19% stated difficulty (7 days or greater). Only 3% of the patients with EMR indicated difficulty while 100% of the non-EMR patients stated difficulty. For patients with EMR, 83% of the alternate oncologists did not order further tests, while 100% of the alternate oncologists ordered further testing for patients without EMR. In terms of patients’ sentiments regarding EMR, 76% agree to have EMR while 24% disagree. Conclusions: EMR in the oncology setting may prove to be an essential component in the delivery of quality patient care in terms of safety, cost effectiveness, and preservation of privacy. The majority of the patients surveyed agree to a form of electronic record-keeping based on their first-hand experience. No significant financial relationships to disclose.
Reproducibility of diagnosis in patients with myelodysplastic syndrome
Authors: Burger J. A. , Borthakur G. , Pierce S. , Kantarjian H. , Estey E. 
Published: March 2020

16506 Background: The myelodysplastic syndromes (MDS) have been considered notoriously difficult with regard to reliability of diagnosis and proper classification. The diagnosis and subclassification of MDS is based on hematopathology studies on the peripheral blood and marrow, along with cytogenetic and clinical information. Determination of single or multiple lineage dysplasia, percentage of myeloblasts, grading of cellularity, fibrosis, and iron content are essential for establishing the diagnosis of MDS. Methods: We reviewed the diagnosis of 112 patients who were referred to MD Anderson Cancer Center (MDACC) with an outside diagnosis of MDS. Results: Between July and December 2005, 112 patients were referred to MDACC with a diagnosis of MDS (bone marrow blast percentage <30%). Upon review of bone marrow studies performed at MDACC, diagnosis of MDS was confirmed in 83 patients. Acute myelogenous leukemia (AML) was diagnosed in 11 patients, and 3 patients were diagnosed to have myeloproliferative disorder (MPD) or chronic myelomonocytic leukemia (CMML). Alternate diagnosis offered in 18 patients included other cause of anemia (6), normal marrow (3), large granular lymphocyte leukemia (2), uncertain (2), immune thrombocytopenia (1), and multiple myeloma (1). Excluding 14 patients with AML or MPD/CMML (since they may represent natural progression of disease), diagnosis other than MDS was established in 15% (18/98) of patients. Conclusions: Upon review, diagnosis other than MDS is made in a significant percentage of patients referred with a diagnosis of MDS. As such, repeat blood and marrow workup and evaluation by more than one hematopathologist increases the accuracy of diagnosis in MDS and should be mandatory for clinical trials in MDS. No significant financial relationships to disclose.
A prospective randomized phase II trial of splenic irradiation (SI) versus supportive therapy (ST) for patients (Pts) with hypersplenism (HS) secondary (2ry) to splenic periportal fibrosis (SPPF)
Authors: Eid S. , Elbeih E. , Hamid A. , Helal S. 
Published: March 2020

16511 Background: HS 2ry to SPPF is a common problem in Egypt as a result of prevalence of bilharziasis. ST is the only option for the majority of pts who have poor performance status (PS) and cannot tolerate/refuse surgery. Methods: Aim of study was to evaluate the effect of SI versus ST on patients with HS 2ry to SPPF. Assessment of treatment was based on changes in Red Cell indices (RCI), Platelet indices (PI), splenic volume (SVol), and splenic vein diameter (SVD). In this study we had 19 evaluable Pts, 10 had SI and 9 had ST. Those who received SI had a twice weekly course of 1.5 Gy for a total of 3 weeks. RCI & PI were measured each visit, SVol & SVD (measured by duplex-Doppler US were measured initially, 3 & 6 months (mos) after treatment). Results: SVol & SVD increased significantly after 3 and 6 mos of ST, compared to insignificant decrease after 3 and 6 mos of SI. Platelet count (PC) significantly increased in all follow-ups (FU) after SI till 1.5 years compared to insignificant decreases in ST group after 3 and 6 mos. FU of mean platelet volume (MPV) and platelet distribution width (PDW) increased in ST group and decreased significantly in SI. Red blood cell (RBC) count and hemoglobin (Hb) levels increased significantly after SI till 6 and 9 mos respectively compared to insignificant decrease in RBC count and significant decrease in Hb level after 6 mos of ST. Changes in white blood cell counts were insignificant. After SI, changes in SVol showed significant positive correlations with changes in SVD and significant negative correlations with changes in PC. Changes in MPV showed significant positive correlation with changes in SVD. Side-effects (SE) seen with SI were moderate and transient. Conclusions: SI is a promising new modality of treatment with acceptable SE for pts with HS. Dose and schedule of SI should be modified according to pts PS. Changes in SVD are highly correlated with the degree of platelet and red cell turnover. Its predictive value for HS should be studied further. No significant financial relationships to disclose.
Clinical characterization of first cycle reactions in patients with chronic lymphocytic leukemia treated with oblimersen
Authors: Kolibaba K. S. , Chanan-Khan A. A. , Bociek G. , Boyd T. , Moore J. , O’brien S. 
Published: March 2020

16514 Background: Serious adverse reactions during the first treatment cycle characterize many drugs used for chronic lymphocytic leukemia (CLL), including rituximab, alemtuzumab, flavopiridol, lenalidomide, and oblimersen. Termed cytokine release reactions (CRRs), these events have occurred more commonly in pts with bulky disease and elevated leukocyte counts, and some have been fatal. Rapid increases in serum levels of tumor necrosis factor-α, interleukin-6, interleukin-2, interferon-γ, and other cytokines may result in symptoms including fever, chills, nausea, vomiting, hypotension, and dyspnea. Ex vivo treatment of CLL cells with oblimersen induce release of vasoactive interleukin-8. First cycle reactions, including tumor lysis syndrome (TLS), proved dose-limiting in a phase 1–2 trial of oblimersen in pts with relapsed or refractory CLL. To characterize these reactions, we evaluated data from this single-agent study and from a phase 3 randomized clinical trial of oblimersen with fludarabine and cyclophosphamide (Flu/Cy). Methods: Data on investigator assessment of CRR and TLS were obtained from both studies, which included 155 pts; 40 were treated with oblimersen alone (3–7mg/kg/d by CIV for 5–7 days) and 115 with oblimersen (3 mg/kg/d × 7 days) in combination with Flu/Cy. Results: Of 145 pts treated with oblimersen 3mg/kg/d, either alone or with Flu/Cy, 2 pts (1.3%) experienced CRR and TLS, respectively. Two CRRs occurred in 10 pts treated with 4–7mg/kg/d. Reactions typically began 24–48 hours after starting treatment. CCR was usually associated with spiking fever, nausea, dehydration, rigors, and back pain. Rarely pts developed hypotension, acidosis, or reversible renal insufficiency, usually with a reduction in WBC. Symptoms lasted 1 day to several weeks (1 pt). In most cases, reactions were reversible with intensive supportive care, including IV fluids, pressors, and antibiotics; 1 death from TLS and 1 from CCR occurred during cycle 1. There was no definitive correlation with baseline measures of disease burden. Conclusion: First cycle oblimersen reactions are uncommon but represent a risk. Early symptoms (fever, nausea, and dehydration) require aggressive treatment, which may prevent progression of the reaction. [Table: see text]
Gemtuzumab ozogamicin for treatment of relapsing/refractory acute myelogenous leukemia (AML)
Authors: Case D. C. , Boyd M. A. , Hedlund J. A. , Ervin T. J. 
Published: March 2020

16531 Background: Gemtuzumab ozogamicin is a calicheamicin-conjugated anti-CD 33 monoclonal antibody studied and utilized in relapsed and refractory acute myelogenous leukemia. Methods: At our center we treated a series of refractory patients (<60 years old) and relapsed patients (>60 years old) with gemtuzumab ozogamicin over a 3 year period. We treated 20 patients: 14 males and 6 females with an age range of 21 to 77 years (median 64 years). Seven patients were refractory to multiple regimens (<60 years old) and 13 were relapsing from initial therapy (>60 years old). Cytogenetic analysis revealed 60% were intermediate-risk and 40% were poor-risk. The goal of therapy was complete remission (≤ 5% leukemia blast cells in the marrow. ≥ 9 g/dl hemoglobin, ≥1500/ul absolute neutrophil count, and platelet count ≥100,000/ul). Patients received gemtuzumab ozogamicin 9 mg/m2 I.V. days 1 and 5. All patients received at least one dose. Patients achieving complete remission were eligible to receive monthly doses of gemtuzumab ozogamicin after complete remission was obtained. Results: Of the 7 refractory patients (<60 years old), there were no complete remissions. Of 13 relapsing patients (>60 years old) there were 2 complete remissions. One patient was 64 and the other 67 years old. Both remissions lasted 2 months. All patients were treated in the hospital. Chills/fever with treatment occurred in 40% of patients. Fever/neutropenia was universal. Thirty percent had elevation of liver function tests. Conclusions: Gemtuzumab ozogamicin as a single agent is capable of producing complete remission in a small number of relapsing patients >60 years old. Remissions are short. No significant financial relationships to disclose.
Fixed-dose single administration of pegfilgrastim vs daily filgrastim in patients with breast cancer and lymphoma undergoing autologous peripheral blood stem cell transplantation
Authors: Boy D. , Gonella R. , Barbero V. , Nencioni A. , Patrone F. , Ballestrero A. 
Published: March 2020

16534 Background: Pegylated filgrastim is a new formulation of a granulocyte colony-stimulating factor that has a long circulating half-life, permitting a single dose of filgrastim per cycle of chemotherapy. Methods: To evaluate whether a single subcutaneous injection of pegfilgrastim (6 mg) is as safe and effective as daily filgrastim (5 mcg/kg/day), 40 consecutive autologous stem cell transplantations performed for breast cancer and lymphomas have been analysed. Median age was 47 yrs (20–61) and 48 yrs (30–63) in pegfilgrastim and filgrastim group, respectively. All patients had normal bone marrow biopsy. The first cohort of patients received 5 mcg/kg/day of filgrastim starting from day 5 post transplantation and the second cohort of patients received a single subcutaneous injection of 6 mg pegfilgrastim on day 5 after transplantation. Results: Median duration of grade 4 neutropenia in the pegfilgrastim and filgrastim groups was 7 (4–9) and 6 (5–9) days, respectively (P 0.29). Neutropenic fever incidence was significantly higher in filgrastim group, 9/20 vs 16/20 (P 0.048), the median duration was not significantly different, 1 (1–6) vs 3 (1–7) days. The grade 3–4 mucositis was higher in filgrastim patient group, 4/20 vs 13/20 in pegfilgrastim and filgrastim, respectively (P 0.009). The adverse events observed during post-transplant aplasia were attributable to complications arising from myelo-suppressive chemotherapy or the primary disease. The only occurring adverse event considered to be cytokine related was mild to moderate bone pain. The overall incidence of bone pain requiring non-narcotic analgesia was not statistically different, 20% (4/20) in pegfilgrastim patients and 40% (8/20) in filgrastim patients. The patients in filgrastim group received a mean of 9.8 daily injections. Conclusions: A single injection of pegfilgrastim administered at day 5 post transplant shows comparable safety and efficacy profiles to daily injections of filgrastim and may be cost-effective. No significant financial relationships to disclose.
Complete 18FDG positron emission tomography (PET) response after induction chemotherapy (IC) is correlated with long survival in patients (pts) with locally advanced non-small cell lung cancer (LA NSCLC)
Authors: Schallier D. , Everaert H. , Neyns B. , Baelde N. , Meysman M. , Fontaine C. , De Grève J. 
Published: March 2020

17004 Background: PET and computerized axial tomography scan (CT) are complimentary tools in the diagnosis and treatment of pts with LA NSCLC. Recent data have shown that response to IC as determined with PET has a better prognostic relevance for long term outcome than CT (Hoekstra et al JCO 2005;23:33:8362–70). Methods: PET and chest CT were performed before and after 3 cycles of IC in pts with LA NSCLC (D. Schallier et al, Suppl JCO 2005;23:165:7285, 6915). Response was defined according to WHO and EORTC criteria for CT and PET respectively (complete response: CR; partial response: PR; stable disease: SD; progressive disease: PD). PET images corrected for attenuation were acquired in 3D on a Siemens Accel camera starting 60 minutes after administration of 307–606 MBq 18FDG. The maximal standardized uptake value (SUVmax) within the tumor was measured and a SUVmax value ≥2.5 was used as a cut off. PET responses were classified either as complete (resolution of the enhanced uptake within the tumor) or non-complete. For each subgroup, classified according to CT and PET response, time to progression (TTP) and survival (S) was calculated and analysed statistically according to Kaplan-Meier and log rank test. Results: 21 pts were eligible for the PET and CT confrontation. Characteristics: 14 male, 7 female; median age 70 y (39–78); median KS: 90 (80–100); stage III A: 9; stage III B: 12; T1,2,3,4: 4/3/7/7; N0,1,2,3: 4/1/11/5. Response: CT: 12 PR; 9 SD; PET: 6 CR, 9 PR, 5SD, 1PD. Nine/12 PR on CT were also CR (5) and PR (4) on PET. Median TTP was correlated significantly with PR and CR (versus SD and non-CR) on CT and PET respectively (288 versus 606 days, p = 0.045 for CT and 299 versus median not reached p = 0.024 for PET); with a median follow up of 19+ month, median S was not significantly correlated with PR on CT but was highly significantly correlated with CR on PET (439 days versus median not reached p = 0.005). Conclusions: Assessment of response to IC using CT or PET largely overlaps. PET appears to be a more ‘sensitive‘ tool to measure response. CR on PET provides a better accuracy for determination of long term outcome than CT. The present results corroborate previously published results. No significant financial relationships to disclose.