bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of randomized trial results and altered regulatory policies on ESA use, transfusions, and thrombosis: A longitudinal analysis over a 3-year period of resource utilization data from a large comprehensive oncology program
Authors: Shapira I. , Raftopoulos H. , Gralla R. J. , Pelc K. , Gleason K. 
Published: August 2020

6611 Background: Recent randomized trials and meta-analyses demonstrated unexpected findings with ESA use with chemotherapy. Results revealed an overall increase in thrombosis rates with the use of ESAs as well as decrements in survival in some malignancies, particularly with breast and head and neck cancers (Bohlius, JNCI, 2006; Raftopoulos, Proc ASCO, 2008; Bennett, JAMA 2008). Benefits with ESA use have resulted in an average 1–1.5g/dl rise in hemoglobin. The impact on quality of life and fatigue remains controversial. Toxicity issues have led to restricted labeling by the FDA and reimbursement decisions by the Centers for Medicare and Medicaid Services (CMS). Despite these risks associated with the use of ESAs, concerns regarding increased use of transfusions remain prominent. A longitudinal study to assess the impact of these ESA policies was conducted to assess the demand on transfusion services and ESA use over time. Methods: Our center comprises a large comprehensive combined hematology and oncology program and has a non- restrictive transfusion policy, allowing physician discretion and the capacity to accommodate all out-patient transfusions. We analyzed ESA use over the 3 year period, 2006–2008. 2006 functioned as our baseline; 2007 was the year of initial FDA and CMS changes; 2008 allowed us to see if practice changes would persist. Results: We present in the table below, our data on ESA use and transfusion resource utilization. Conclusions: With over 60,000 patient visits during 3 years, longitudinal assessment reveals a continued, marked decrease in ESA use. Despite liberal transfusion policies, there has been little effect on transfusion rates. Increases in transfusions are commensurate with a rise in patient visit volume. We are now evaluating whether this marked decrease in ESA use translates into decreased thrombosis rates over this 3-year period at our cancer center. [Table: see text] No significant financial relationships to disclose.
Impact of direct physician-to-physician contact on accelerating oncology clinical trial accrual
Authors: Eckardt J. R. , Ku N. , DeMaggio A. , Reese M. , Levonyak M. , Jain V. 
Published: August 2020

6613 Background: The development of more effective oncology agents is critically dependent on the completion of clinical trials; currently, >4000 oncology trials listed in www.clinicaltrials.gov are accruing pts in the US. Unfortunately, only 3–5% of new cancer pts participate in clinical trials and most trials do not meet their projected accrual timelines. Barriers to pt accrual include physician awareness & attitudes, access to protocols, administrative burdens to conduct clinical trials, cost to physicians and pts, and pt concerns about participation in research trials. To overcome at least some of these barriers, we investigated a strategy to improve clinical trial accrual that optimizes trial placement and awareness through a direct physician to physician intervention. Methods: For each site, a customized enrollment plan is established after initial assessment of interest and accrual potential. Implementation of the enrollment plan includes clinical communications and medical support delivered through direct physician to physician interactions. From Feb 2008 to December 2008, we implemented this strategy to increase accrual to 5 oncology trials (2 placebo controlled randomized trials and 3 phase II trials in breast cancer, non-Hodgkin's lymphoma and soft tissue sarcoma). Results: The implementation of direct physician to physician intervention resulted in a measurable improvement of between 50 - 300% in the monthly accrual to each of these 5 trials. Despite being significantly behind projections, 2 of the trials have now completed accrual on schedule. In the ongoing phase III study, accrual has improved from an average of 3.8 pts/mo to 13.5 pts/mo. Conclusions: The use of our current model of optimizing trial placement and awareness through a direct physician to physician intervention has been successful in significantly accelerating clinical trial accrual in 5/5 trials initiated to date. [Table: see text] [Table: see text]
Is squamous cell histology an adverse prognosticator for survival of malignancies of the upper urinary tract?
Authors: Rizack T. , Mega A. , Berz D. 
Published: August 2020

6617 Background: Carcinomas of the renal pelvis and ureter are rare diseases, accounting for only about 1% of all urogenital malignancies. Previous reports suggest that squamous cell histology is associated with inferior survival. We present the largest population based analysis to date of survival in patients with upper urinary tract malignancies. Methods: We analyzed the Surveillance, Epidemiology and End Results database for cancer specific survival rates in patients with renal pelvis and ureteral malignancies who were diagnosed between 1973 and 2003 in the SEER catchment geographic areas. The primary exposure of interest was the underlying histology, squamous cell versus transitional cell differentiation. We performed descriptive statistics, non parametric survival analysis, and cox proportional hazard analysis. Results: We identified 13,213 eligible patients, 7,716 renal pelvis and 5,497 ureteral carcinomas. Among this cohort, 179 patients had squamous cell carcinoma (SCC), 12,395 had transitional cell carcinoma (TCC), including 121 papillary, and 619 had other histologies. Overall, patients with SCC histology fared worse. The median overall survival time was 10 months for SCC and 63 months for TCC. The cox analysis revealed a HR 0.42 (95% CI 0.36–0.47) for TCC when compared to SCC and corrected for decade of diagnosis, age, gender, prior treatment, and race. The difference between the two groups was entirely attributable to survival differences in patients with loco-regional disease. However, when stratified by lymph node involvement this difference disappeared for patients with locally involved lymph nodes (p = 0.84) and for patients with clear lymph nodes (p = 0.92). Conclusions: SCCs of the upper urinary tract present at a higher clinical stage and appear to represent more aggressive disease when compared to other histologies. However, when appropriately staged according to lymph node status, the survival of TCC and SCC of the upper urinary tract is identical when compared stage by stage. No significant financial relationships to disclose.
Psychosocial impact of cancer-related symptoms among patients with lung cancer
Authors: Walker M. , Peltz G. , Houts A. , Pohl G. , Schwartzberg L. , Stepanski E. , Marciniak M. 
Published: August 2020

6621 Background: Patients with lung cancer may experience adverse physical symptoms due to cancer, cancer treatment, or comorbid medical conditions. These cancer-related symptoms (CRS) may be associated with functional impairment (FI), and may affect psychosocial functioning. Methods: We conducted a retrospective analysis of self reported symptom burden with the 38-item Patient Care Monitor survey (PCM), collected as part of routine clinical care in 1,384 lung cancer patients identified by ICD-9 codes at 8 community oncology practices in the US. Structural equation models were built among 672 randomly selected patients to examine the relationships of CRS and of FI on psychosocial symptoms and to determine whether FI mediates the effect of CRS. Results: Patients were 47.7% female, with mean age of 66 years (23–91), 65% Caucasian, 16% African American, 19% other/unknown race. Stage of disease was 19% stage IV, 22% stage I-III, and 59% unspecified. Histological type was 36% adenocarcinoma, 18% squamous cell, 37% unspecified, and 9% other. The most common comorbidities were anemia, other malignancies, and respiratory disease. Depressive disorder was recorded for < 5% of patients. Surveys were collected between 2005 and 2008, ranging up to 5 years after the start of treatment (median 79 days after start of chemotherapy). Half (50.4%) of surveys were collected while the patient was in active treatment. Model findings supported a 1 factor measurement model of 19 CRS items, and a 1 factor measurement model of 8 FI items. Findings supported a 2 factor model of 11 psychosocial items, with resulting factors reflecting acute distress and despair. CRS were less severe longer after the start of chemotherapy, and not significantly worse during vs. off chemotherapy. More severe CRS significantly predicted more severe acute distress and despair, and more severe FI. In contrast to expectations and some previous research, FI was not significantly related to acute distress and despair, and did not mediate the effect of CRS on acutedistress and despair. Conclusions: Cancer related symptoms are associated with FI and with psychosocial outcomes in lung cancer patients. However, FI does not appear significantly related to psychosocial outcomes. [Table: see text]
Enrollment of lung cancer patients on clinical trials at an NCI comprehensive cancer center
Authors: Keedy V. L. , Horn L. , Hayes A. , Spencer B. , Garcia G. , Campbell N. , Sandler A. , Carbone D. , Johnson D. H. 
Published: August 2020

6633 Background: Enrollment of cancer patients (pt) in clinical trials is considered essential in order to improve cancer care. However, cancer clinical trials participation remains low. Understanding barriers to pt enrollment is necessary to overcome this problem. Previous reports have identified pt age, race, and ethnicity, disease stage, performance status (PS) and relationship with their health care provider as factors that can influence the enrollment of pts in clinical trials. Methods: We conducted a retrospective review of the charts of all lung cancer pts seen in the Thoracic Oncology Clinic at Vanderbilt Ingram Cancer Center between November 2005 and November 2008. A total of 1075 lung cancer pts were seen. Results: 577 charts (of a planned 1075) have been audited to date. Pt demographics: median age = 64 yrs; male = 54%; Caucasian = 92%, African American = 4%, and Asian = 1%; NSCLC = 80%, SCLC = 17%. Male pts were more likely than females to be eligible for a clinical trial (p = 0.056). A study protocol was available for 57% of pts; 52% of pts proved eligible; 36% were entered into a study (11% total population). Significantly more protocols were available for NSCLC pts compared to pts with SCLC (p ≤ 0.001); there was also a non-significant trend towards higher enrollment of eligible NSCLC pts. There was no difference in eligibility between ethnicity; the percentage of eligible pts enrolling on trials was similar between Caucasian & African American pts (46% and 43%); no Asian pts were enrolled. The most common reasons for not enrolling included a preference for treatment closer to home (29%), patient refusal (19%), PS (19%), and co-morbidities (17%). The distance pts traveled was inversely correlated with likelihood of study participation. Conclusions: A total of 11% of lung cancer pt evaluated in our Thoracic Oncology Clinic were enrolled in clinical trials. Our data suggest additional strategies are needed to attract minority groups, increase enrollment of women and pts with comorbidities and poor PS. Travel distances influence pt willingness to participate in clinical trials. Strategies are needed to overcome this factor. No significant financial relationships to disclose.
A randomized trial of anthracycline dose intensification during induction of younger patients with acute myeloid leukemia: Results of Eastern Cooperative Oncology Group study E1900
Authors: Fernandez H. F. , Sun Z. , Litzow M. R. , Luger S. M. , Paietta E. M. , Dewald G. , Ketterling R. P. , Rowe J. M. , Lazarus H. M. , Tallman M. S. 
Published: August 2020

7003 Background: In younger adults with newly diagnosed acute myeloid leukemia (AML), anthracycline dose intensification during induction may improve complete remission (CR) rates; however, an improvement in overall survival (OS) in a randomized trial has not been demonstrated. This unresolved issue led the ECOG to compare standard dose (SDD) to high-dose daunorubicin (HDD) in induction. Methods: Adult patients with previously untreated AML were randomized to receive either SDD (45 mg/m2/d) or HDD (90 mg/m2/d) each for 3days combined with standard-dose cytarabine (100 mg/m2/d) for 7 days by continuous intravenous infusion. Those achieving a CR were allocated to allogeneic hematopoietic stem cell transplantation (HSCT) or high-dose cytarabine (with or without a single dose of gemtuzumab ozogamicin) prior to autologous HSCT. Intravenous busulfan and cyclophosphamide was the preparative regimen for both allogeneic and autologous HSCT. The primary end point of this study was OS from the time of induction randomization. Results: 633 patients, age 18 to 60 (median 48) years, were entered in this study. There were no differences in patient demographics or disease characteristics between the two groups at presentation. In an intention-to-treat analysis, HDD resulted in a significantly higher CR rate (63.3% vs. 47.7%, p = 0.0003) than SDD. Induction deaths were similar between the two groups (5.4 vs. 5.0%, p = ns). 334 (52.8%) patients entered the consolidation phase. 57.4% of HDD and 48.1% of the SDD patients, received consolidation therapy on study, and 28.7% and 23.1% proceeded to HSCT respectively. Median OS was superior for the HDD (23.7 months) over the SDD (15.1 months) group (p = 0.005). In subgroup analysis, patients with favorable or intermediate-risk cytogenetics or age <55 years benefited from the HDD. Conclusions: We demonstrate for the first time in a prospective randomized trial that intensifying induction therapy through a higher daily anthracycline dose, in the setting of identical intensive consolidation therapy, results in a higher CR rate as well as prolonged OS. In younger AML patients a higher dose of anthracycline in induction should be considered the new standard of care. No significant financial relationships to disclose.
Phase II study of vorinostat (V) in combination with idarubicin and high-dose cytarabine (IA) as front-line therapy in patients (pts) with high-risk myelodyplsatic syndrome (MDS) or acute myeloid leukemia (AML)
Authors: Jabbour E. , Faderl S. , Ravandi F. , Konopleva M. , Verstovsek S. , Cortes J. , Wierda W. , Newsome W. M. , Yang H. , Kantarjian H. , Garcia-Manero G. 
Published: August 2020

7004 Background: Standard induction therapy for pts with AML has not changed over the last 2 decades nor has the outcome of these pts. We demonstrated in vitro and ex vivo that the combination of an histone deacetylase inhibitor with anthraycline is synergistic (Blood 2006;108:1174); an effect that could be mediated by activation of DNA damage/repair pathways, and found that such combination is safe in phase 1 trial (Blood 2007;110:1842). We designed a phase II study of V with IA as front-line therapy for MDS/AML. Methods: Pts with untreated int-2/high-risk MDS or AML ages 15–65 with adequate liver and renal functions and PS, and EF ≥ 50% were eligible. Pts with CBF were excluded. Initial dose of V was 500 mg orally TID for 3 days followed on day 4 by IA (I:12 mg/m2/dx3; A:1.5g/m2/dx4 over 24 hrs). After induction and if in CR, pt can receive 5 cycles of consolidation with V at the same dose and IA (I:8 mg/m2/dx2; A:0.75g/m2/dx3 over 24 hours) followed by 1 year of maintenance with V. The study was powered to demonstrate improvement in PFS at 7 months and acceptable toxicity. Prior to formal initiation of the phase II, the study had a “run-in” phase to confirm the safety of the triple combination. Correlative studies include analysis of DNA repair/damage pathways. Results: 22 pts have been registered. 3 pts with relapsed/refractory AML were treated in the run-in phase. No excess toxicity was observed; 2 achieved CR and 1 CRp. Following these, 19 pts were enrolled on the phase 2 portion. 17 pts were evaluable. Median age was 49 years. Median WBC at presentation was 12.75 x 109/L. Cytogenetic analysis were abnormal in 12 (71%), complex in 10 (59%). 8 (47%) had secondary disease. 4 (23%) were Flt-3 positive. No unexpected grade 3/4 toxicities have been observed. The CR rate was 82%. 1 pt acheived a marrow CR and 2 pts died during induction. CR were universally associated with CG response. All Flt-3+ pts achieved a CR. Only 2 pts (14%) have relapsed (4 and 5 months). The median PFS has not been reached. Conclusions: The combination of IA and V is safe and active in AML/MDS. No stopping rule has been met. Results will be compared with those of a parallel IA study at MDACC. Correlative analysis are ongoing. [Table: see text]
Randomized phase II trial of the nucleolin targeting aptamer AS1411 combined with high-dose cytarabine in relapsed/refractory acute myeloid leukemia (AML)
Authors: Stuart R. K. , Stockerl-Goldstein K. , Cooper M. , Devetten M. , Herzig R. , Medeiros B. , Schiller G. , Wei A. , Acton G. , Rizzieri D. 
Published: August 2020

7019 Background: Aptamers are small synthetic oligonucleotides that form stable nuclease-resistant 3D structures and bind target proteins with specificity and affinity similar to antibodies. These “chemical antibodies” represent a new class of therapeutics. The AS1411 aptamer binds nucleolin on the surface of cancer cells and induces apoptosis. AS1411 has synergistic effects in combination with cytarabine on AML cell lines in vitro and in vivo. A phase I trial of AS1411 monotherapy in 30 patients with advanced cancer showed objective responses without serious toxicities. Methods: This open-label randomized phase II trial compared AS1411 plus high-dose cytarabine (HiDAC) with HiDAC alone in patients with primary refractory or relapsed AML who had received up to 3 previous lines of chemotherapy. Patients in cohort I were randomized 2:1 to receive AS1411 10 mg/kg/day as continuous IVI on days 1–7 + HiDAC 1.5 g/m2/ twice daily on days 4–7 or HiDAC alone for 4 days. Following safety assessment, a second cohort was randomized in a similar manner, with AS1411 escalated to 40 mg/kg/day. Objectives were comparison of response rates (CR+CRp), safety and tolerability between treatment groups. Results: Accrual has been completed, with 71 patients randomized: 22 to AS1411 10 mg/kg/day + HiDAC (AS1411–10), 26 to AS1411 40 mg/kg/day + HiDAC (AS1411–40) and 23 to HiDAC alone (control). Safety findings are currently available for 44 patients (AS1411–10, 21; AS1411–40, 9; control, 14). The main grade 3/4 toxicities were hematologic, notably febrile neutropenia, neutropenia, and thrombocytopenia; and infections. Safety findings were similar across groups, except that grade 3 hypokalemia was more frequent with AS1411–40. Deaths within 28 days of treatment were: AS1411–10, 1/21; AS1411–40, 1/9; and control, 2/14. Response data are currently available for 39 patients; response rates were: AS1411–10, 16% (3/19); AS1411–40, 14% (1/7); and control, 0% (0/13). Conclusions: Data from this first phase II trial of an aptamer in oncology are encouraging. The combination of AS1411 at 10 or 40 mg/kg/day with HiDAC appears well tolerated and shows promising signs of activity in patients with relapsed/refractory AML. [Table: see text]
Vancomycin resistant enterococci (VRE) infections in hematopoietic stem cell transplant (HSCT) recipients
Authors: Rosko A. E. , Arfons L. M. , Barr P. M. , Cooper B. W. , Kindwall-Keller T. , Laughlin M. J. , Gerson S. , Creger R. J. , Fu P. , Jacobs M. R. , Lazarus H. M. 
Published: August 2020

7036 Background: VRE blood stream infections (BSI) pose significant hazards to HSCT patients. Risk factors predisposing patients for a relatively nonpathogenic organism to become bacteremic include immune suppression, neutropenia, renal failure, antibiotic exposure, indwelling catheters, and VRE colonization. Some studies suggest that a VRE BSI is simply a marker of primary disease severity or an indicator of poor outcome, while other data demonstrate VRE BSI as an independent predictor of mortality. Methods: We performed a retrospective chart analysis of HSCT patient data using the electronic medical record and written charts using a standard data collection tool from February 1994 to October 2008. Vancomycin susceptibility was determined using the Dade Berhing panel. Results: We noted 625 infections in 385 HSCT patients; 26 patients developed 27 VRE infections over the course of 15 years. All isolates were Enterococcus faecium and not polymicrobial. Host characteristics included mean age of 49.5 yrs, all had central venous catheters, and 26 received linezolid treatment. Persistent infection was identified in 11 patients with central access removal in 4. VRE colonization was identified in stool (18 patients) and urine (5 patients) and 4 patients had a prior VSE BSI. 16 patients received vancomycin within 30 days of developing VRE BSI. 21 patients were neutropenic (mean duration15 days). 8 patients were not receiving immunosuppressants during time of bacteremia. Gastrointestinal endoscopy was identified in 6 patients prior to BSI. 16 patients died during the hospitalization. Conclusions: VRE accounted directly or indirectly for 13 of 16 deaths during incident hospitalization. In this population, blood, urine, stool surveillance is warranted to prevent morbidity/mortality related to developing a VRE BSI. Prolonged neutropenia was associated with development of a VRE BSI prophylactic granulocyte transfusion might be useful to prevent BSI. In contrast to prior studies, many patients were not receiving immunosuppressants and did not undergo GI instrumentation. VRE BSI prevention should include identifying patients with urinary or stool colonization, appropriate isolation and early central venous catheter removal if a VRE BSI is identified. No significant financial relationships to disclose.