bluuebunny/crossref_metadata_2025_split huggingface dataset:
Concordance between abstracts, virtual meeting (VM) presentations, and final publication of phase III clinical trials presented at the Annual Meeting of the American Society of Clinical Oncology.
Authors: Khanna Suneil Kumar , Boyko Matthew John , Heng Daniel Yick Chin , Vickers Michael M. , Tam Vincent Channing 
Published: March 2020

6622 Background: Phase III clinical trial results described in abstracts in the ASCO Annual Meeting Proceedings often differ from final results seen in publication. We hypothesize that the abstracts may act only as place holders, while the results presented at the ASCO Annual Meeting are more highly concordant with the final publication. Methods: A retrospective review of all abstracts submitted to the ASCO Annual Meeting in 2005 to 2007 was conducted. Inclusion Criteria: randomized, prospective phase III clinical trials of greater than 200 patients with at least one quantitative primary endpoint such as OS or PFS. For each abstract, we viewed the VM presentation and searched Pubmed and Medline for the corresponding publications. Data regarding the clinical trials was extracted from all three sources and statistical comparisons were made. Results: A total of 7,900 abstracts were screened from the ASCO 2005 and 2007 Annual Meetings, of which 124 met the inclusion criteria. An additional 43 studies were excluded due to absence of either a VM presentation or publication. The majority (96%) of these trials were presented as either an oral presentation or poster discussion. Key comparisons of the concordance between the abstract or VM presentation and the final publication are shown in the Table below. Conclusions: While the statistical significance of the primary endpoint and conclusions from all three sources are very similar, the results reported in VM presentations at ASCO Annual Meetings are a better representation of the final publication compared to the abstract. When relying on clinical trial results from these meetings to change clinical practice, physicians should refer to the VM presentation rather than the abstract. [Table: see text]
The use of routine surveillance imaging scans in women with early breast cancer (EBC) treated in Ontario, Canada.
Authors: Enright Katherine , Ghannam Mohammed , Yun Lingsong , Taback Nathan , Booth Christopher M. , Trudeau Maureen E. , Krzyzanowska Monika K. 
Published: March 2020

6628 Background: Over use of routine surveillance imaging to detect recurrence in women with EBC was recently identified as one of the top five opportunities to improve the quality of cancer care by the American Society of Clinical Oncology. We undertook a population level assessment of the current practice of surveillance imaging in EBC women treated in Ontario Canada. Methods: Incident early breast cancer patients diagnosed 01/07 – 12/09 in Ontario, Canada were identified from the Ontario Cancer Registry. Patient records were linked deterministically to provincial health care databases to provide comprehensive medical follow-up. Basic (chest x-ray, abdominal x-ray and abdominal ultrasound) and advanced (computed tomography [CT] or bone scans) surveillance imaging scans completed during the first and second year of follow-up care (starting 6 months after surgery or upon completion of adjuvant chemotherapy) were identified. Logistic regression models were used to identify covariates associated with advanced surveillance imaging. Results: 16,981 EBC patients were included in the analysis of which 7,907(46.6%) received chemotherapy. In the first year of follow up care, 8,311 (48.9%) had at least 1 basic imaging test, while 4,916 (29.0%) had advanced imaging. This fell to 45.7% (basic) and 25.1% (advanced) in the second year of follow-up. Bone scans were the most common advanced imaging test (14.5%), followed by CT thorax (10.8%). On multivariable analysis age, stage, the use of chemotherapy and comorbidity were associated with increased use of advanced surveillance imaging (Table). Significant geographic variation was also demonstrated. Conclusions: Surveillance imaging was common in the first two years of follow-up for EBC patients. While appropriate for symptom driven investigation, attention should be paid to the routine use of surveillance imaging in EBC women during follow-up care. [Table: see text]
Baseline bone mineral density testing among breast cancer patients prescribed aromatase inhibitors (AIs).
Authors: Charlson John A. , Smith Elizabeth , Laud Purushottam , Smallwood Alicia , Neuner Joan 
Published: March 2020

6642 Background: Because of the adverse effects of AI’s on bone mineral density (BMD) and fracture risk, current guidelines recommend baseline BMD testing when initiating adjuvant AI’s. Methods: We used a validated breast cancer algorithm of Medicare claims to identify older US female breast cancer patients starting adjuvant AI therapy and to examine baseline BMD testing rates. The cohort included all US non-HMO Medicare D-enrolled women age ≥67 years who initiated AI therapy within one year after a 2006-2007 initial breast cancer surgery. Women receiving IV bisphosphonates consistent with metastatic breast cancer treatment (interval <90 days)were excluded. We examined BMD testing between 24 months prior and 6 months after AI initiation, adjusting for demographic and fracture risk factors, and comparing to a duration-adjusted testing rate for a 5% random sample of all cancer-free women enrolled in Medicare in 2008. Results: A majority of the cancer cohort (67.7%) had baseline BMD testing. This was substantially higher than the 2008 BMD testing rate for the non-cancer sample (15.4%, which translates into a 38.5% 30-month rate). Women of higher age and co-morbidity, as well as women of black race or lower income were less likely to be tested (see Table). Empiric use of oral bisphosphonates increased slightly with age, but this did not fully account for the testing differences by age. Conclusions: Although baseline BMD testing is high among women initiating AIs, approximately one-third do not receive guideline-recommended testing. Furthermore, those with greater risk fracture risk based on age and higher co-morbidity are less likely to have appropriate bone care. [Table: see text]
Impact of a decision support tool on quality measures.
Authors: Ellis Peter G. , Lokay Kathleen 
Published: March 2020

6643 Background: UPMC CancerCenter received their ASCO QOPI certification after the Spring 2011 measurement period with a QOPI Certification Overall Quality Score of 78.2%. The results, however, demonstrated a number of metrics performing below QOPI mean scores. Physicians and staff performed an analysis of root causes for these underperforming metrics and identified a combination of steps to improve these metrics and the overall score. Methods: Interventions to ensure high capture of Core Metric #9 (staging within 30 days of diagnosis), #10 and #11(treatment intent and discussion with patient) were imbedded into the clinical pathways program (Via Oncology Pathways) used by the UPMC CancerCenter physicians beginning in February 2011. These data points were charted by physicians when utilizing the Via Pathways Portal and automatically displayed on the regimen order sets that are generated by that Portal. These order sets were used as official orders and therefore placed into the patient charts. Results: UPMC CancerCenter’s QOPI Certification Overall Quality Score improved by 7 percentage points to 85.39% for the Fall 2012 measurement period (as compared to Spring 2011). All of the 24 certification metrics for Fall 2012 were similar or improved as compared to Spring 2011. Core Metrics #9 and #10 improved by 18 and 22 percentage points, respectively Conclusions: Improvements in quality measures such as ASCO QOPI can be gained through targeted analysis of root cause and application of new interventions such as clinical pathways decision support. We feel that decision support tools such as pathways programs may be an important source of data for e-QOPI type programs and should be considered.
A phase II study of the selective phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor idelalisib (GS-1101) in combination with rituximab (R) in treatment-naive patients (pts) ≥65 years with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).
Authors: O'Brien Susan Mary , Lamanna Nicole , Kipps Thomas J. , Flinn Ian , Zelenetz Andrew David , Burger Jan Andreas , Holes Leanne , Johnson David Michael , Gu Jessie , Dansey Roger D. , Dubowy Ronald L. , Coutre Steven E. 
Published: March 2020

7005 Background: PI3K-delta is critical for activation, proliferation and survival of B cells and plays a role in homing and retention in lymphoid tissues. PI3Kδ signaling is hyperactive in many B-cell malignancies. Idelalisib is a first-in-class, selective oral inhibitor of PI3Kδ. When combined with R in 19 relapsed/refractory patients with CLL, the ORR was 78% (Coutre, ASH 2012). Methods: Treatment-naive pts ≥65 yrs with CLL or SLL were treated with R 375 mg/m2 weekly x 8 and idelalisib 150 mg bid continuously for 48 weeks (primary study). Pts completing 48 wks w/o progression could continue to receive idelalisib on an extension study. Responses and progression were based on investigator assessment using IWCLL criteria (Hallek, Blood 2008). Results: Data is presented here on the first 50 of 64 pts enrolled, 48 CLL/2 SLL, median age 71 yrs (range: 65-89), M/F 70/30 (%), Rai stage III/IV 10/32 (%), nodes ≥5 cm in 16%, WHO 0/1/2 in 34/64/2 (%); del(17p) in 6 pts and del(11q) in 13 pts. 32 pts completed 48 wks (18 discontinued, 11 due to AE, 4 due to death and 3 other); 30 pts entered the extension study and 26 remain on treatment. The median time on treatment was 16 months (range 0.8-27.5). The ORRwas 96% with 4% nonevaluable; median time to response was 1.9 mos (range 1.0-6.5). There have been no on-study relapses. The Kaplan-Meier estimated PFS is 91% at 24 mos. Of note, 6/6 pts with del(17p) responded (1 CR, 5 PR) and 3 remain on treatment for more than 21 months. 13/14 (93%) pts with thrombocytopenia and 12/12 (100%) pts with anemia at baseline responded. Of 20 pts with B symptoms at baseline, 13 (65%) were asymptomatic by 8 wks. Most frequent AEs (total%/ ≥G3%) were diarrhea (including reported as colitis) (46/16), pyrexia (42/4), chills (34/0), fatigue (34/2), rash (34/10), pneumonia (30/20) and nausea (28/0). Elevated ALT/AST was seen in 60%, Gr ≥3 in 22%. Conclusions: Idelalisib + R is highly active, resulting in durable disease control in treatment-naïve older pts with CLL. These results support the further development of idelalisib in frontline CLL. Clinical trial information: NCT01203930.
Long-term safety and survival outcomes after TK-expressing donor lymphocyte infusion (TK-DLI) in allogeneic hematopoietic stem cell transplantation (HSCT).
Authors: Ciceri Fabio , Lupo-Stanghellini Maria Teresa , Oliveira Giacomo , Greco Raffaella , Vago Luca , Bondanza Attilio , Lambiase Antonio , Bordignon Claudio , Bonini Chiara 
Published: March 2020

7007 Background: Suicide gene therapy (SGT) was firstly applied to allogeneic HSCT, addressing the need for modulation of graft vs host disease (GvHD) reactions while preserving graft vs leukemia (GvL) effect of alloreactive T cells. HSV-TK gene insertion in donor T-cells modulates alloreactivity by selectively destroying dividing alloreactive cells involved in GvHD. Methods: Long-term safety and survival was assessed in 128 pts entering worldwide 10 phase I-II trials that used TK-DLI to improve GvL, immune reconstitution (IR) and GvHD control. In all, 57 pts received TK DLI at our Institution: 23 to treat relapse after HLA-identical HSCT (Ciceri, 2007) and 34 to improve IR after haploidentical HSCT (Ciceri, Bonini, 2009). Results: SGT was feasible, safe and effective in promoting a dynamic and specific modulation of alloreactivity. TK-DLI clinical benefit, defined by chimerism, tumor response and/or IR, was achieved by 65 pts (51%). Grade 2 to 4 GvHD (n=28, 22%) was fully controlled by SGT. TK-DLI engrafted in 51 pts (90%) and, being detectable at low frequency up to 14 yrs, no SGT-related adverse events occurred. In HLA-identical setting (n=23; median follow-up, 15 yrs), 11 pts (48%) had disease response and 2 pts (9%) were alive in complete response (CR). In haploidentical setting (n=34; median follow-up, 7 yrs), 25 pts (73%) had IR and 9 pts (26%) were alive in CR. All pts were monitored according to guidelines on long-term survivors (Majhail, 2012). There were no major infections, while 3 pts had a second tumor. Immunity against TK-DLI was reported exclusively after HLA-identical allo-HSCT indicating that TK-DLI is not limited by SGT-specific immunity after haploidentical HSCT. Conclusions: Long-term follow-up confirms the high benefit to risk ratio of TK-DLI. A phase III trial is ongoing in haploidentical HSCT (NCT00914628). Clinical trial information: NCT00423124.
Use of tumor genomic profiling to reveal mechanisms of resistance to the BTK inhibitor ibrutinib in chronic lymphocytic leukemia (CLL).
Authors: Chang Betty Y , Furman Richard R. , Zapatka Marc , Barrientos Jacqueline Claudia , Li Daniel , Steggerda Susanne , Eckert Karl , Francesco Michelle , Woyach Jennifer Ann , Johnson Amy J , James Danelle Frances , Versele Matthias , Byrd John C. , Stilgenbauer Stephan , Buggy Joseph J. 
Published: March 2020

7014 Background: Ibrutinib interacts covalently with cysteine 481 of Bruton tyrosine kinase (BTK), resulting in targeted inhibition of B cell receptor signaling. Early trials of ibrutinib mono- or combination therapy enrolled 246 CLL patients receiving a median of 14 months of ibrutinib. 20 patients (8%) experienced progressive disease (PD), including 8 patients with Richter's transformation. Here we examine changes to the CLL genome in 3 patients that acquired resistance to ibrutinib. Methods: Ibrutinib resistance was defined as patients achieving partial response (PR) or better lasting ≥ 6 months, then developing PD without Richter’s transformation. RNAseq and whole exome sequencing (WES) followed by comparative genome analysis was performed at baseline and after PD and confirmed by Sanger sequencing. RNAseq and WES data were aligned using TopHat and BWA software. Single nucleotide variations (SNVs) were identified using SAMtools mpileup. Results: Compared to patients who relapsed from conventional chemotherapy, minimal genomic changes were acquired in ibrutinib resistant patients, reflecting relative genomic stability. SNVs were discovered in 3 patients specific to the relapse sample (Table). 2 out of 3 patients had distinct SNVs that each encode a cysteine-to-serine substitution at position 481of BTK (C481S). Homologous cysteine residues in BMX, ITK, TEC and BLK were wild-type (WT). Ibrutinib inhibited recombinant C481S 25 fold less potently than WT, and could not covalently bind C481S expressed in cells. The third patient had WT BTK, but acquired a potential gain-of-function mutation encoding a R665W substitution in PLCg2, a substrate of BTK, consistent with constitutive PLCg2 activation. Conclusions: Although rare, the acquisition of C481S BTK and R665W PLCg2 mutations in the setting of resistance confirms BTK as an important pharmacologic target of ibrutinib, and suggests mechanisms of ibrutinib resistance. [Table: see text]
Updated results of a phase I first-in-human study of the BCL-2 inhibitor ABT-199 (GDC-0199) in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).
Authors: Seymour John Francis , Davids Matthew Steven , Pagel John M. , Kahl Brad S. , Wierda William G. , Miller Thomas P. , Gerecitano John F. , Kipps Thomas J. , Anderson Mary Ann , Huang David C.S. , Darden David E. , Gressick Lori A. , Nolan Cathy E. , Yang Jianning , Busman Todd A. , Graham Alison M. , Cerri Elisa , Enschede Sari H. , Humerickhouse Rod A. , Roberts Andrew Warwick 
Published: March 2020

7018 Background: Targeting BCL-2 is a promising strategy for treating CLL, including disease refractory to fludarabine (F), or with (del(17p). ABT-199 is a selective BCL-2 inhibitor with >500-fold higher affinity for BCL-2 (Ki<0.10 nM) than for BCL-XL (Ki=48 nM). Methods: Objectives of this Ph I dose-escalation study include evaluations of safety, pharmacokinetics and preliminary efficacy of ABT-199 in patients (pts) with R/R CLL. A single oral dose was given followed by 6 days off drug, before continuous once daily dosing. After cohort 1, the initial dose was reduced and daily dosing modified to include a 2 or 3 step dose-escalation to the target dose for each cohort. Results: As of January 11, 2013, 56 pts have been enrolled; median age 67 y (range 36-86); 41 males; median 3.5 prior therapies (range 1-10). 16 (29%) had del(17p) and 18 (32%) F-refractory CLL. Median follow up is 6.3 months (range 0.03-16.5); 7 pts have been on study for more than 1 yr. 13 pts discontinued; 7 due to PD, 6 for other reasons: tumor lysis syndrome (TLS; 2), other illness (2), thromboembolic event (1), consent withdrawal (1). The most common non-hematological AEs (>15% pts) were nausea (36%), diarrhea (30%), fatigue (25%), upper respiratory tract infection (23%), and cough (16%). Grade 3/4 AEs occurring in > 5 pts were neutropenia 21(38%), thrombocytopenia 6 (11%) and TLS 5 (9%). TLS occurred in 3/3 pts in cohort 1 and 2/53 pts with the modified stepped dosing schedule (DLTs). Additionally, 1 fatal AE occurred within 48 hrs of dose-escalation to 1200 mg in a pt with laboratory evidence of TLS (DLT). 46 of 54 pts (85%) evaluable for efficacy achieved a response to ABT-199; 7 (13%) a CR or CR with incomplete count recovery and 39 (72%) a PR (30 confirmed by consecutive scans). 14/16 (88%) and 12/16 (75%) of pts with del(17p) and F-refractory CLL, respectively, achieved at least a PR. Conclusions: ABT-199 is highly active achieving a 85% overall response rate in R/R CLL, independent of high risk markers such as del(17p) and F-refractory disease. Additional dosing and scheduling modifications are currently being explored to minimize the risk of TLS. Clinical trial information: NCT01328626.
SWOG S0919: A phase II study of idarubicin and cytarabine in combination with pravastatin for relapsed acute myeloid leukemia (AML).
Authors: Advani Anjali S. , McDonough Shannon , Copelan Edward , Willman Cheryl L. , Mulford Deborah A. , List Alan F. , Sekeres Mikkael A. , Othus Megan , Erba Harry P. , Appelbaum Frederick R. 
Published: March 2020

7028 Background: Inhibition of cholesterol synthesis and uptake sensitizes AML blasts to chemotherapy (Blood 104: 1816, 2004). A prior Phase 1 study demonstrated the safety of high dose pravastatin given with idarubicin and cytarabine in patients with AML and also reported an encouraging response rate (Blood 109: 2999, 2007). SWOG S0919 therefore evaluated the complete remission (CR) rate in a larger number of pts with relapsed AML treated with the pravastatin dose arrived at in the Phase 1 trial. Methods: Pts were treated at SWOG institutions from Aug 2009 through Nov 2012. Pravastatin was supplied by Bristol-Meyers Squibb. The protocol was approved by each institution’s review board. Eligibility: age ≥ 18 yrs, relapsed AML, cardiac ejection fraction ≥ 45%, CR/ CR with incomplete count recovery (CRi) following most recent chemotherapy lasting ≥ 3 months, no prior hematopoietic cell transplant. Treatment: oral pravastatin 1280 mg Days 1-8, idarubicin 12 mg/m2/d IV Days 4-6, and cytarabine 1.5 g/m2/d continuous IV infusion Days 4-7. Pts achieving a CR could receive 2 cycles of consolidation. CR and CRi were defined by IWG criteria. Fifty eligible pts were to be accrued. If ≥ 21 pts achieved CR or CRi, the regimen would be considered sufficiently effective (critical level = 4.8% if true CR rate = 30% and power of 90% if true CR rate = 50%). Results: The study closed to accrual on Nov 1, 2012 after meeting the defined criterion for a positive study. Thirty-six pts with a median age of 59 yr (range 23-78) were enrolled. Seventeen pts (47%) were male and the median WBC was 2800/ uL (range 700-110,600). The median time from initial dx to registration was 18 mo (range 5-136). Relapse status: 1st: 17 pts (47%), 2nd: 15 (42%), 3rd: 2 (5.5%), and 4th: 2 (5.5%). Eighteen pts have died, 3 during treatment. The response rate was 75% (95% CI 58-88%; 20 CR, 7 CRi); and the median overall survival was 10 mo. The p-value comparing 75% to 30% (null response rate) is 3.356 x 10-8. Duration of last CR (≤ 6 months) and prior high dose cytarabine exposure did not affect response to protocol treatment. Conclusions: The CR/ CRi in this relapsed population is encouraging. We plan to evaluate the efficacy of this regimen in higher-risk patients. Clinical trial information: NCT00840177.
Exploratory analysis of the effect of ruxolitinib on bone marrow morphology in patients with myelofibrosis.
Authors: Kvasnicka Hans-Michael , Thiele Juergen , Bueso-Ramos Carlos E. , Hou Kevin , Cortes Jorge E. , Kantarjian Hagop M. , Verstovsek Srdan 
Published: March 2020

7030 Background: Myelofibrosis(MF) is characterized by splenomegaly, burdensome symptoms, progressive bone marrow (BM) fibrosis, and shortened survival. Ruxolitinib (Rux), an oral, FDA-approved JAK1/JAK2 inhibitor, has demonstrated improvements in spleen volume, symptoms, and survival in patients (pts) with MF. This study was conducted to explore possible effects of long-term Rux treatment on BM morphology in MF. Methods: Trephine biopsies were obtained at baseline, 24 (67 pts), and 48 (17 pts) months (mo) from the cohort of MF patients treated at MD Anderson Cancer Center who participated in a phase I/II trial of Rux (NCT00509899). The clinical outcomes from this trial have been published previously [Verstovsek, NEJM 2010]. Two of the authors (JT and HMK) independently evaluated the World Health Organization (WHO)-defined BM fibrosis grade (0-3). Reviewers were blinded to pts characteristics and outcomes and consensus decided discordant scores. For demonstrative purposes, WHO BM fibrosis grading was also determined for a control cohort of pts treated with hydroxyurea (HU) for 24 (31 pts) and 48 (20 pts) mo. Changes in BM fibrosis grade vs. baseline were calculated for 24 and 48 mo, and categorized as improvement, stabilization, and worsening for each patient. Results: A higher percentage of Rux-treated pts showed stabilization or improvement of BM fibrosis at both 24 and 48 mo than the HU-treated pts. Worsening was greater in the HU-treated cohort at both time points. Conclusions: This exploratory analysis of long-term exposure to Rux in MF provides the first indication that JAK inhibitor therapy may be able to meaningfully retard advancement of BM fibrosis. A comparable effect was not seen with long-term HU therapy. Additional research is needed to further elucidate these findings. Clinical trial information: NCT00509899. [Table: see text]