bluuebunny/crossref_metadata_2025_split huggingface dataset:
Process improvement in breast cancer care: Is mammography volume associated with a greater need for process improvement?
Authors: Dupuy Danielle , Weldon Christine B. , Trosman Julia R. , Marcus Elizabeth A. , Roggenkamp Betty , Schink Julian C. , Ansell David , Murphy Anne Marie 
Published: March 2020

6609 Background: Chicago Black women are 62% more likely to die from breast cancer than White women. Previous data from 39 Chicago hospitals suggested significant variation in mammography quality (Chicago Breast Cancer Quality Consortium, 2010). We developed process improvement recommendations for sites that participated in our care process assessment (Weldon CB, et al, ASCO-Abstract-6120-2012). This study was funded through a generous grant from the Susan G. Komen for the Cure Foundation. We compared improvement needs between high and low patient volume institutions. Methods: Using Deming’s PDCA cycle for continuous improvement, we created care process improvement recommendations for 25 Chicago institutions with the patient base averaging more than 50% minority patients (20 community, 3 academic and 2 public hospitals). Low mammography volume (< 5000 mammograms/ year) was reported by 12 of the 25 sites. Recommendations are based on analysis across sites, literature, and input from institution staff. Thematic and statistical analyses were performed using simple frequencies and Fisher's exact test. Results: Improvement recommendations are classified into nine areas, see table. We found that 100% (12/12) of low mammography volume institutions have specific improvement needs in 6 or more process improvement areas, as compared to 23% (3/13) of the high mammography volume institutions (pvalue > 0.0001). Conclusions: Lower volume mammography sites have a larger need for breast cancer care process improvements. [Table: see text]
Do clinical trial acronyms affect patients’ interest in clinical trials? A randomized survey.
Authors: Wiebe Meagan , Zhang Liying , Spiegle Gillian , Ko Yoo-Joung 
Published: March 2020

6639 Background: The use of acronyms in naming clinical trials has increased in recent years with minimal empirical examination of the effect that they have on research participants. The naming of trials is often a symbolic act; however, they may have a provocative origin that stimulates associations and influences perceptions of the research. No empirical evidence exists to confirm the supposition that certain trial acronyms may be coercive. The purpose of this study was to determine if a clinical trial title has an influence on a subject’s interest in a fictitious clinical trial. Methods: Two fictitious clinical trial scenarios (prevention and metastatic) for colon cancer were designed with the same three acronym titles (“CURE” a coercive, “RESCUE” a potentially coercive, and “COMET” a neutral acronym). An anonymous paper survey was randomly distributed to patients and caregivers at a comprehensive cancer center over a four-week period. Six different surveys were distributed and self-administered. Participants rated their interest in the clinical trial on a 5-point Likert scale and demographic information was collected. To determine the influence of acronym type on the Likert scale, univariate and multivariate ordinal logistic regression analysis was performed. Results: A response rate of 77.19% (1056/1368) was achieved. The specific acronym type (coercive and potentially coercive versus neutral) had no significant influence on the respondent’s interest in the clinical trial in either the preventive (p=0.787, OR=0.95) or the metastatic (p=0.284, OR=1.21) scenario. Only current (p=0.025, OR=1.56) or prior (p=0.038, OR=1.43) participation in a clinical trial positively influenced respondent’s interest in the fictitious clinical trials irrespective of the acronym title. Conclusions: Acronyms are commonly used in naming clinical trials and may facilitate clinician recall and familiarity. Although trial names may be perceived as potentially coercive, the results from this study suggest that coercive or potentially coercive acronym titles do not appear to influence patients’ or caregivers’ interest in the clinical trial.
Results of a phase I trial of the proteasome inhibitor carfilzomib in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic leukemia (SLL).
Authors: Woyach Jennifer Ann , Flynn Joseph M. , Jones Jeffrey Alan , Andritsos Leslie A. , Lucas Margaret , Chase Weihong , Yang Ying , Lucas David M , Sass Ellen , Waymer Sharon , Ling Yonghua , Jiang Yao , Phelps Mitch A. , Byrd John C. 
Published: March 2020

7077 Background: CLL is an incurable malignancy, and survival for patients (pts) with relapsed disease is limited. Carfilzomib (CFZ) has shown efficacy in multiple myeloma, and our group has shown significant in vitro activity in primary CLL cells. Therefore, we have undertaken a phase I trial of this agent in CLL. Methods: This is a single institution phase I trial of CFZ in pts with relapsed or refractory CLL. Primary endpoints were to determine maximal tolerated dose (MTD) and describe toxicity. Pts with CLL relapsed after at least one therapy were enrolled using a 3x3 design. CFZ was administered on the standard myeloma schedule. The first two doses were administered at 20 mg/m2 with remainder given at doses starting at 27 mg/m2 for dose level 1 with escalation to 56 mg/m2. Results: 17 pts received at least 1 dose of CFZ. 12 pts completed at least 1 cycle of therapy, with the remaining 5 experiencing PD during cycle 1. The MTD was not reached, with 3 pts accrued to each dose level to the maximal dose tested without dose limiting toxicity. Most adverse events (AE) were grade (G) 1 or 2. G3/4 AE were quickly reversible and included G3 neutropenia (4 pts), G4 neutropenia (2), G3 febrile neutropenia (1), and G3 thrombocytopenia (3). G1/2 toxicities observed in ≥ 20% of pts included anemia (10), thrombocytopenia (7), and hypocalcemia (8). Median number of cycles was 3, with 9 pts achieving stable disease after 2 cycles. Of 3 pts enrolled at maximal dose level, 2 remain on therapy after 5 and 7 months, with 1 achieving a clinical partial response. Of 5 evaluable pts, at least 50% proteasome inhibition was seen in all at 1 hour, with minimal recovery at 24 hours. PK was best characterized by a two-compartment model. Maximum plasma concentrations across all dose levels ranged from 0.81 to 8.1 uM. Across the evaluated dose range, area under the curve increased in an apparent dose-proportional manner. Conclusions: Despite relatively limited efficacy in this study, CFZ has acceptable toxicity in CLL, with no MTD identified up to 56 mg/m2. This suggests that CFZ may be better studied in CLL using a different schedule or in combination with other active agents. Clinical trial information: NCT01212380.
Apoptosis induction mediated through PI3-kinase/AKT/mTOR pathway using anti-ROR1 monoclonal antibody in chronic lymphocytic leukemia cells.
Authors: Daneshmanesh Amir Hossein , Hojat Farsangi Mohammad , Moshfegh Ali , Khan Salam , Österborg Anders , Mellstedt Hakan 
Published: March 2020

7087 Background: The PI3K/AKT/mTOR is a central pathway activated in many types of cancer. Mammalian target of rapamycin (mTOR) is a serine/threonine protein kinase regulating cell growth, proliferation and survival. In CLL cells PI3K pathway is constitutively activated leading to AKT activation with subsequent phosphorylation of other downstream signaling molecules. ROR1 is a type I transmembrane RTK, overexpressed and constitutively phosphorylated in CLL. A unique anti-ROR1 mAb directed against CRD region of ROR1 was capable of inducing direct apoptosis as well as dephosphorylating the ROR1 molecule. Here, we investigated the apoptotic effect of the anti-ROR1 mAb and effects on the PI3K/AKT/mTOR pathway using primary CLL cells. Methods: Apoptosis was detected by the MTT assay and Annexin V/PI methods in a 24 h assay. Antibody untreated and treated cell lysates were prepared and subjected to Western blot analysis for identification of the signaling molecules involved in apoptosis induced by the ROR1 mAb. We analysed total and phosphorylated levels of the following signaling proteins: AKT, p-AKT, PI3K, p-PI3K, mTOR, p-mTOR, ERK, p-ERK, PKC and p-PKC. Phosphoproteins were measured before incubation with the mAb and after 20 min-24 h. Results: ROR1 detection on surface of the CLL cells was 80-85% and apoptotic frequency 45-50%. Western blot analysis showed decreased levels of p-AKT, p85 isoform of p-PI3K and p-mTOR in treated compared to untreated samples. No changes in the phosphorylation levels of ERK and PKC proteins were seen. Conclusions: Incubation of CLL cells with the anti-ROR1 mAb induced apoptosis of CLL cells. Apoptosis was preceded by dephosphorylation of PI3K, AKT and mTOR proteins indicating deactivation of these proteins by the ROR1 mAb. In untreated CLL cells no effect was noted. Furthermore no dephosphorylation of PKC or ERK was seen. We suggest that activation of mTOR might occur via the PI3K/AKT pathway and may be a survival signal in CLL cells associated with the aberrant expression of ROR1. Further studies are warranted to understand better the signaling pathways associated with ROR1 and the downstream signaling effects of ROR1 targeting drugs.
Types, frequency, and adherence of molecular tests in chronic myelogenous leukemia at chronic phase (CML-CP) in the U.S. community setting.
Authors: Chen Clara , Chen Lei , Dhanda Rahul , Chung Hsingwen , Bhowmik Debajyoti , Ericson Solveig , DiBella Nicholas 
Published: March 2020

7096 Background: The objective was to evaluate the types, frequency and adherence of molecular tests utilized in patients (pts) with CML-CP who initiated 1st-line TKI therapy in the community practice (prac) setting. Methods: A retrospective study of newly diagnosed CML-CP pts; initiating 1st-line TKI during 06/2007 and 03/2011, with ≥18-mo follow-up was conducted. Data was collected from iKnowMed, various local & national labs to evaluate whether qRT-PCR test results was reported in International Scale (IS) or not (non-IS). The proportion (prop) of pts tested for molecular response in 3-mo intervals was tallied. Results: The study identified 189 pts (mean age 57 yrs, 53% male), 15% had no cytogenetic (cyto, FISH included) or molecular test (MT) recorded during 1st-line TKI therapy. The median number of MT was 6 (range: 1-28). In 3-mo intervals, the prop of pts tested for cyto responses were: 0-3 mos (24%), 3-6 mos (21%), 6-9 mos (24%), 9-12 mos (22%), 12-15 mos (10%), and 15-18 mos (7%). The prop of pts had MT in the 3-mo intervals were: 34%, 47%, 54%, 47%, 51% , and 55%. Regional patterns show the Northeast (defined by U.S. census regions) had a higher prop of pts for MT at almost all of these intervals. The number of physicians seeing CML pts correlated with the prop of pts monitored at each interval. Of the 1,226 MT ordered, 25% were reported on IS, 9% were unknown and 69% were on non-IS (Data reported: 48% log reduction, 45% BRC-ABL%, 7% other). Labs in the Midwest report on IS most often (61%), followed by the Northeast, Western (29% for both), and the South (13%). As the prac size increased, so did the utilization of IS. Conclusions: A low prop of CML pts were monitored for cyto and molecular responses. Only a quarter of the MT results were reported in IS. These results suggest gaps in CML management that could be closed with effective educational programs stressing the importance of monitoring and using IS reporting labs.
Influence of BMI on outcomes of high-dose cytarabine and mitoxantrone induction therapy for AML.
Authors: Burhani Mansoor , Dave Manish J. , Venugopal Parameswaran , Larson Melissa L. 
Published: March 2020

7106 Background: Acute Myeloid Leukemia (AML) affects thousands of Americans every year. With approximately 35.7% of the U.S. adult population being obese, it is important to understand how a patient’s BMI can affect their outcome with AML treatment. This study evaluates a high-dose cytarabine and mitoxantrone induction regimen, and the results are examined to determine the effect of BMI on outcome, in terms of induction response and survival. Methods: Eighty nine patients were treated with a High Dose Cytarabine and Mitoxantrone regimen from 2008-2012. Two doses of cytarabine 3 gm/m2 were given 12 hours apart followed by one dose of mitoxantrone 30 mg/m2on days 1 and 5. All patients were dosed based on their actual body weight. Before treatment began, the BMI for each of the patients was recorded. The outcome data was collected and analyzed. Results: Of the 89 patients, 22 patients were normal, 33 overweight, and 34 obese. The BMI readings are based on the definitions established by the WHO. The overall CR rate for all 89 patients was 65%. The CRR for normal patients was 77%, 55% for overweight patients, and 68% for obese patients. 62 (70%) patients remain alive: 73% of normal patients, 58% of overweight, and 79% of obese. 17 of patients never achieved remission, even after multiple induction courses: 2 (9%) in the normal group, 10 (30%) in the overweight group, and 5 (15%) in the obese group. Of the responders, 35% of normal patients had a relapse, 30% in the overweight group, and 21% in the obese group with median relapse free survival of 8 months, 10 months and 6 months, respectively. Conclusions: Patients with a healthier BMI were more likely to respond to induction therapy with high-dose cytarabine and mitoxantrone. However, there was no difference in relapses amongst the groups. Patients who did not respond initially were unlikely to respond to other treatments. Therefore, using actual weight to determine dosing in AML induction therapy is the appropriate strategy.
Epidemiologic study of myelodysplastic syndromes in a racially diverse inner-city population.
Authors: Jain Rishi , Sridharan Ashwin , Yu Yiting , Ramesh K H , Gundabolu Krishna , Friedman Ellen , Verma Amit 
Published: March 2020

7125 Background: The International Prognostic Scoring System (IPSS) and the revised IPSS (IPSS-R) are used to assess prognosis after diagnosis of myelodysplastic syndromes (MDS). They are based on cytogenetics, bone marrow (BM) blasts, and number and degree of cytopenias. This retrospective analysis examined racial disparities in the presentation and survival of MDS patients (pts) in Bronx, NY. Methods: MDS pts treated at the Einstein/Montefiore system between 1997-2011 were included. Diagnosis was confirmed by review of BM biopsy. Demographics, cytogenetics (for 135/161 pts), blood counts, and BM blasts at diagnosis were collected. The Kaplan-Meier method was used for median survival estimates. The two-sample t-test and chi-square analysis were used to compare clinical variables between groups. Results: 161 pts with MDS were identified. Mean length of follow-up was 3.66 years (yrs). There were significant differences between mean age at diagnosis between Hispanics and African-Americans (66.5 vs 72.3 yrs, p<0.05) and Hispanics and whites (66.5 vs 73.1 yrs, p<0.05). There was also significantly increased thrombocytopenia at diagnosis in Hispanics (p<0.05, when compared to non-Hispanics). Median survival decreased with higher risk among IPSS groups, however, the intermediate risk group in IPSS-R had a longer median survival (9 yrs) than all other risk groups. Conclusions: The cohort used to validate prognostic risk with IPSS and IPSS-R was primarily Caucasian. In our minority rich inner-city population, Hispanics presented with MDS earlier and with more thrombocytopenia. IPSS was a stronger predictor of survival than IPSS-R as the IPSS-R intermediate risk group had better survival than lower risk groups. Larger studies should be conducted to assess the applicability of IPSS-R in minority rich populations. [Table: see text]
Derivation and validation of the SEER-Medicare MDS risk score (SMMRS).
Authors: Uno Hajime , Cronin Angel , Schrag Deborah , Abel Gregory Alan 
Published: March 2020

7128 Background: The Surveillance Epidemiology and End Results (SEER) program has been collecting data on myelodysplastic syndromes (MDS) since 2001. These data, when linked to Medicare claims (SEER-Medicare), are an outstanding resource for MDS-related outcomes research. Unfortunately, in terms of prognostic factors at diagnosis, only morphologic subtype is available, and in about half of the registry cases, this is unclassifiable (MDS-U). We aimed to devise a prognostic risk score for use in the SEER-Medicare dataset, and compare it to the standard International Prognostic Scoring System (IPSS) using a granular MDS patient database at our institution (the DFCI/MDS CRIS). Methods: Borrowing from several validated MDS risk scoring systems, a set of candidate predictors that could be determined from claims was pre-specified. Cox proportional hazards models were then built for overall survival, using the 2001-2007 SEER-Medicare MDS dataset (n=9820). Different categorizations of each predictor were tested so that the final model would achieve the best predictive performance. The model was then validated independently using DFCI/MDS CRIS patient data (n=328). C-statistics were calculated to compare the performance of the new scoring system (SMMRS) with the IPSS. Results: The final model included cytopenias, MDS morphologic category, age at diagnosis, hospitalization at diagnosis, red cell or platelet transfusion dependence, and Charlson comorbidity score. The C-statistic for the final model in SEER-Medicare was 0.688. The table shows how the SMMRS performed in the DF/MDS CRIS database compared to, and in combination with, the IPSS. When the analyses were restricted to DF/MDS CRIS patients 65 or older (n=164), similar results were observed. Conclusions: Although missing some important clinical characteristics (eg, cytogenetics), the SMMRS can risk-stratify SEER-Medicare MDS patients with a precision similar to that of the IPSS. The SMMRS thus promises to make the large SEER-Medicare dataset much more useful for MDS clinical research. [Table: see text]
Correlation of epidermal growth factor receptor (EGFR) mutation profile with computed tomography (CT) imaging features in lung adenocarcinomas.
Authors: Chu Benjamin F. , Ozkan Efe , Erdal Selnur B , Zhao Weiqiang , Shilo Konstantin , Otterson Gregory Alan 
Published: March 2020

7542 Background: Imaging studies provide essential clinical information for lung cancer diagnosis, treatment and management. Features such as ground glass opacity (GGO) or internal air bronchogram (IAB), while commonly seen in early stage lung cancer, have minimal clinical implication. By examining a cohort at a single institution, we explored the hypothesis that radiographic characteristics correlates with the molecular signatures. Methods: Since 2009, our institution has prospectively characterized the EGFR status of all non-squamous lung carcinomas. Our inclusion criteria included tumor size < 3 cm and positive EGFR mutation. We randomly selected wild type (WT) patients matched by age and tumor size. The CT imaging of these patients was evaluated by a single radiologist (EO). Results: Imaging features were extracted from 20 WT and 19 EGFR-mutated tumors. Of the EGFR-mutated tumors, 7 had the exon 21 L858R point mutation and 12 had in-frame exon 19 deletion. There were 68% (13) solid nodules in EGFR-mutated and 90% (18) in WT tumors. While solid nodule was the primary feature seen in both WT and EGFR-mutated tumors, exon 21 mutation was associated with mixed ground glass/solid nodule (MGGS) (p = 0.005). This tendency, however, is not present in the exon 19 mutated tumors. No pure GGO was identified in either EGFR or WT group. IAB was present in 62% (24), pleural attachment (PA) in 87% (34), and spiculated (SP) as opposed to lobulated (LO) nodules in 90% (34) of the tumors, which do not differ significantly among groups. Conclusions: Early stage lung adenocarcinomas show a spectrum of imaging features that can be correlated with tumor’s genetic mutations. MGGS is a distinct imaging characteristic differentiating exon 19 and exon 21 EGFR-mutated tumors. [Table: see text]
Automated tumor size assessment: Consistency of computer measurements with an expert panel.
Authors: Brown Matthew S. , Kim Hyun J. , Lo Pechin , Barnoy Eran , McNitt-Gray Michael F. , Aberle Denise R. , Goldin Jonathan 
Published: March 2020

7566 Background: Manual tumor measurements for use in diagnosis and longitudinal assessment suffer from intra- and inter-observer variability. In practice they are also limited to 1-dimensional diameter measurements because manual contouring of 3D tumor boundaries is impractical. In this work we evaluated a fully automated tumor assessment system in the setting of lung nodules on CT by comparing its tumor size and density measurements against independent measurements made by an expert panel of radiologists. Methods: A new computer-aided detection (CAD) system has been developed that performs fully automated lung nodule detection and measurement. In order to identify the nodule boundary in 3D the system performs automated intensity thresholding, a Euclidean Distance Transformation, and segmentation based on watersheds. The system computes nodule diameter, volume, and mean density in Hounsfield Units (HU). The automated measurements were evaluated against data from the publically available Lung Imaging Database Consortium (LIDC), where each CT scan was reviewed and annotated (with volumetric tumor contours) by an expert panel of four radiologists. Nodule were included from consecutive subjects in the database that were ≥ 4 mm. The CT slice thickness ranged from 0.6 – 3.0 mm. For each nodule measure, the intra-class correlation coefficient (ICC) was computed among the four radiologists and then re-computed with CAD as a fifth observer. Results: 51 lung nodules from 44 subjects were analyzed. The ICCs were computed as shown in the table using a log transformation for volume and diameter. All nodule measures have similar ICCs and overlapping confidence intervals (CI). Conclusions: A new fully automated CAD system has been developed that provides CT lung nodule measurements that are consistent with an expert panel of radiologists. The automated computer system enables practical 3D tumor assessment and reduces measurement variability, which has implications for longitudinal studies. [Table: see text]