bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilization of positron emission tomography scans (PET) in the management of NSCLC at a center with limited access to this imaging modality
Authors: Nair B. P. , Safar A. M. 
Published: March 2020

6140 Background: PET is recommended as an important diagnostic aid in the initial evaluation of patients with lung cancer, according to the NCCN guidelines. The aim of this study is to estimate the proportion of NSCLC patients receiving PET, its impact on staging, and its utilization by different treating specialties, in a facility with limited access to PET. This is a situation comparable to several community medical centers. This study was done at the Veterans Hospital, Little Rock (VALR), where the requested PET scans were done at an outside facility, due to its unavailability within this center. Methods: All patients with NSCLC who were diagnosed or treated at VALR between 01/01/03 and 06/30/05 were retrospectively identified from the tumor registry, and details of PET were obtained. Subsequently electronic patient records at VALR were reviewed and the best estimate of pre-PET and post-PET stage was made. The details of the requesting specialty were also obtained. Then frequency distributions relevant to the aims of the study were calculated. Results: 444 patients with diagnosis of NSCLC were identified in this time period, of which 48 (10.8%) had PET scans. Overall 10 (21%) patients were down staged and 4 (8.3%) patients were upstaged. PET helped establish stage among 13 of 15 patients with unknown stage. Details are provided in the table . The number of PET scans requested by treating specialties are as follows: medical oncology 44% (21), pulmonary 40% (19), cardiothoracic surgery 13% (6), and others 3% (2). Conclusions: In this study 10.8% of patients with NSCLC had PET. There was establishment of, or change in stage among 27 (56%) patients. These numbers are comparable to studies from larger centers with ready availability to PET, reflecting its adequate utilization in this setting with limited access. Medical oncology and pulmonary services initiated majority of the PET requests, possibly because of their involvement in the early diagnostic work-up in this patient population. [Table: see text] No significant financial relationships to disclose.
How conversations about adjuvant hormonal therapy differ from ‘typical‘ oncology discussions: Results of an observational linguistic study
Authors: Davidson B. , Vogel V. , Wickerham L. 
Published: March 2020

6141 Background: Adjuvant hormonal therapy in breast cancer presents a conversational challenge for oncologists. Oral medications are a relatively new therapeutic paradigm, and many aspects of typical oncology communication, e.g., risk-benefit presentation, goal of therapy, and the role of patient in selecting/continuing therapy, require a different approach in this setting. An observational linguistic study was undertaken to capture how oncologists and patients discuss adjuvant therapy, and to develop recommendations to improve communication. Methods: Letters of invitation were mailed to 800+ community-based oncologists; of these, 14 met the screening criteria and agreed to participate in this study. 28 postmenopausal, early breast cancer patients on or initiating hormonal therapy were recorded during their regularly scheduled visits. Results: Adjuvant hormonal therapy discussions differ from infusional chemotherapy-focused oncology discussions in several ways: Selection of therapy is based on more than efficacy (e.g., cost, side effects); Chance of recurrence is discussed directly, without significant hedging; Disease name (“cancer”) is discussed openly–the word “cancer” is notably absent from other types of oncology discussions; Visits are routine–patients’ lives are no longer “on hold” (unlike other treatment discussions, where chemotherapy is assumed to be at the center of the patient’s life); Time between visits often moves from every three months to every six months after being on hormonal therapy for a year (unlike other therapies, where patients are seen frequently). Conclusions: Analysis of conversations shows that these patients are seen as, in some way, “cured” (goal of therapy is to prevent recurrence) and that patients are “given their lives back.” The conversational frame displays a lack of urgency and emotion, similar to that of discussions of dyslipidemia management and not like other chemotherapy discussions where the emotional content is very high. New models of therapy require new conversational approaches, e.g., where issues like adherence should be addressed directly, and longer-term therapeutic goals take on primary importance. [Table: see text]
Development of a model emergency oncology response system (EORS): The California oncology emergency master plan (COEMP)
Authors: Moss R. , Yu P. , Presant C. , Gonzalez J. , Lamb M. , Tucker S. 
Published: March 2020

6142 Background: Hurricane Katrina displaced patients (PT) and physicians (MD). Time & resources were needed to match displaced PT with oncology (ONC) practices (PRC) for ongoing care. Disruption of care can be life-threatening to ONC PT who need to adhere to schedules & monitoring. California (CA) is particular risk for natural disaster. In order to better support PT in a future emergency (E) MOASC & ANCO created a model EORS with pilot implementation of select elements. Methods: MOASC & ANCO prepared a multi-component COEMP. Joint calls & meetings yielded a draft EORS approved by both society boards. Initial & long-term funding is expected via granting mechanisms. Pilot implementation of specific elements began in 11/2005. Results: Goals of the COEMP are: Establish dedicated E ONC MD network; Create a voluntary ONC-specific PT medical record (MR) template & secure data repository; Create & test a functional E MD responder system for CA ONC MD; Develop liaison with relief providers (Homeland Security, FEMA, Red Cross); Strengthen existing role with Bio-Pharma (BP) for delivery of medicine (Rx) to displaced PT and PRC; Develop specific educational materials for the EORS (PT, MDs, Insurers, BP); Create & distribute an EORS “PT Wallet Card” with PT national digital record (NDR) and E responder contacts. To prioritize components of the COEMP, a needs assessment, reviewing past E experience, response, and current capacity, has been initiated. The specific active components of the EORS include: 1-E ONC MD support network: ONC MDs have been invited to volunteer via email and at regional meetings. 2-Secure PT MR repository: MDs and PT will coordinate relevant MR, insurance, and E contact data, in locations (home of PT, w/relatives, NDR). 3-E coordinator MDs & staff will respond to E calls from PT/MD via phone & email. 4-Open dialogue with BP for E access to Rx for displaced PT. 5-Educational & training for PRC and PT in printed & electronic form. Conclusions: COEMP provides an initial E model for ONC. It may be applicable for state societies or national ONC groups. At ASCO 2006, MDs will be invited to participate and expand COEMP capabilities. Although we hope COEMP/EORS need never be used, its development will enable ONC practices to be more prepared for loco-regional E. No significant financial relationships to disclose.
Clinical activity and safety of the histone deacetylase inhibitor MGCD0103: Results of a phase I study in patients with leukemia or myelodysplastic syndromes (MDS)
Authors: Garcia-Manero G. , Minden M. , Estrov Z. , Verstovsek S. , Newsome W. M. , Reid G. , Besterman J. , Li Z. , Pearce L. , Martell R. 
Published: March 2020

6500 Background: MGCD0103 is a novel inhibitor of human histone deacetylases (HDACs), with selectivity for the cancer-associated isoforms of class I HDACs. Deacetylation of histones by HDACs is postulated to inactivate tumour suppressor genes leading to neoplastic transformation, and therefore inhibition of this enzyme may result in antineoplastic activity. Methods: To study the safety and activity of MGCD0103, we have developed a phase I open-label dose escalation study of MGCD0103 administered orally, three-times weekly in patients with leukemia or MDS, with the primary endpoints being the determination of the maximum tolerated dose (MTD) and the pharmacokinetic (PK) and pharmacodynamic (PD) characteristics of MGCD0103. Eligibility criteria included appropriate performance status and renal and hepatic functions. Patients with relapsed/refractory leukemia or MDS and older patients with untreated AML/MDS were eligible. Results: Twenty patients have been enrolled at four dose levels (20, 40, 80 and 60 mg/m2) so far. Their characteristics are: median age 60 years (range 33–76); the majority of patients so far treated have AML; median number of prior therapies is 1 (range 0–3). Most patients had complex cytogenetics. MGCD0103 has been well tolerated at doses below 80 mg/m2. The MTD has been reached, with 3 out of 4 patients at a dose of 80 mg/m2 developing grade 3 toxicity, mainly fatigue, nausea, vomiting or diarrhea. Grade 2 toxicities include anorexia, constipation, dehydration. The median number of courses is 1 (range 1 to 6). As of January 2006, 7 patients are on study. PK evaluations show dose-dependent exposure. Analysis of peripheral blood cell HDAC activity indicates that HDAC inhibition occurs in all patients in a dose-dependent manner. Two patients with multiple relapsed/refractory acute myelogenous leukemia, and one with MDS have achieved a complete marrow response (blasts less than 6%). Of importance, maximal HDAC inhibition was observed in those patients at the time of best response. Conclusions: Single-agent MGCD0103 has clinical activity and is well tolerated at doses below 80 mg/m2 orally three times a week in patients with advanced leukemia. No significant financial relationships to disclose.
High expression of the transcription factor ERG predicts unfavorable outcome in acute T-lymphoblastic leukemia (T-ALL) in adults
Authors: Baldus C. D. , Burmeister T. , Martus P. , Schwartz S. , Goekbuget N. , Bloomfield C. D. , Hoelzer D. , Hofmann W. K. , Thiel E. 
Published: March 2020

6505 Background: In adult T-ALL long-term survival remains limited to 32–46%. Transcription factors are frequently targeted by chromosomal translocations resulting in disruption of hematopoietic proliferation and differentiation. The oncogenic ETS transcription factor ERG is expressed during early T-cell development and shut off once T-cell commitment is complete. We hypothesized that due to its specific involvement in T-cell maturation and oncogenic potential, ERG might contribute to leukemogenesis. Thus we have determined the prognostic impact of ERG expression in T-ALL. Patients and Methods: ERG mRNA expression was analyzed by real-time RT-PCR in pretreatment marrow samples of 105 adults with T-ALL treated on German ALL protocols. Patients (pts) were dichotomized at ERG’s median expression into low (n=52) and high (n=53) expressers. HOX11 and HOX11L2 expression was determined by real-time RT-PCR. Immunophenotyping was performed differentiating T-ALL into 3 subtypes: pre-T (CD2-), thymic (CD1a+), and mature (sCD3+). Results: High ERG expression was associated with a higher relapse rate (45%) compared to pts with low ERG expression (20%; P=0.01). High ERG expressers compared to low ERG expressers had an inferior overall survival (OS, P=0.02; 5-year OS: high ERG 26% vs low ERG 58%) and relapse-free survival (RFS, P=0.003; 5-year RFS: high ERG 34% vs low ERG 72%). On multivariable analysis high ERG expression (P=0.005), immunophenotypic subgroups (pre-T vs mature vs thymic; overall P=0.04), HOX11L2 positivity (P=0.055) and absence of HOX11 expression (P=0.017) were independent adverse risk factors predicting RFS. Patients with high ERG expression had a hazard ratio (HR) for relapse of 3.2. Within the good prognostic subgroup of thymic T-ALL (n=57) high ERG (HR 4.1; P=0.02) and presence of HOX11L2 (HR 6.6; P=0.008) were independent adverse factors for RFS. Conclusion: High expression of the oncogene ERG is an adverse factor in adult T-ALL. Within thymic T-ALL otherwise classified as standard risk, high ERG expression identified pts that were more than four times likely to fail long-term RFS. The prognostic impact of ERG may assist treatment stratification and suggest the need of more intensive regimens for these high risk thymic T-ALL pts. No significant financial relationships to disclose.
Dasatinib (D) in patients (pts) with chronic myelogenous leukemia (CML) in myeloid blast crisis (MBC) who are imatinib-resistant (IM-R) or IM-intolerant (IM-I): Results of the CA180006 ‘START-B’ study
Authors: Cortes J. E. , Kim D. W. , Rosti G. , Rousselot P. , Bleickardt E. , Zink R. , Sawyers C. 
Published: March 2020

6529 Background: Dasatinib (D) (BMS-354825) is an oral, multitargeted tyrosine kinase inhibitor of Bcr-Abl and SRC with activity against IM-R cell lines. In a phase I study, there was preliminary evidence that D was active in MBC-CML patients (pts). Methods: START B is an open-label study of D in IM-R or IM-I MBC carried out in 46 sites worldwide. From December 2004 to May 2005, 124 MBC pts were accrued. D was given orally at 70 mg twice a day (BID) with dose escalation to 100 mg BID for poor initial response or dose reductions to 50 mg and 40 mg BID for toxicity. Pts had weekly blood counts and monthly bone marrow evaluations, including cytogenetics. The primary endpoint was confirmed (minimum 4 weeks duration) major hematologic response (MaHR). Results: Data are currently available on the first 74 pts (68 IM-R, 6 IM-I). Median age was 55 years, 55% were male. Other prior therapy included interferon in 55% of pts and bone marrow transplant (BMT) in 12%. Prior IM dose was >600 mg/day in 49% of pts and 47% of pts received IM for > 3 years. At baseline, the WBC count was ≥20 × 103/mm3 in 46%, the platelet count was < 100 × 103/mm3 in 72% of pts and 35% of pts had ≥ 50% bone marrow blasts. Mutations in the BCR-ABL domain were found in 27/63 (43%) pts. Median duration of therapy was 3.5 months. D doses were reduced in 35% pts, temporarily interrupted in 58% pts, and escalated in 41% pts. With a minimum of 6-month follow-up, hematologic response was seen in 39 (53%) pts: confirmed MaHR in 24 (32%) pts, Complete in 18 (24%) and No Evidence of Leukemia in 6 (8%). Major cytogenetic responses were documented in 22 (30%) pts and was complete in 20 (27%). The median time to MaHR was 56 days. There was no loss of response in pts with MaHR; the duration of MaHR ranged from 1.2+ to 7.8+ months. The median PFS had not been reached. Severe myelosuppression was very common. Non-hematologic toxicities were usually mild to moderate. Most common Grade 3–4 toxicities included diarrhea in (7%), pleural effusion (9%), nausea (4%). Peripheral edema was reported in 14% of pts (0% Grade 3–4), and rash in 11% of the pts (0% Grade 3–4). Conclusions: Dasatinib was highly effective in IM-R pts with MBC with durable MaHR. Data on all 124 pts will be presented at the meeting. [Table: see text]
A phase II study of AMN107, a novel inhibitor of Bcr-Abl, administered to imatinib resistant and intolerant patients (pts) with chronic myelogenous leukemia (CML) in chronic phase (CP)
Authors: Kantarjian H. M. , Gattermann N. , O’Brien S. G. , Bhalla K. , Hochhaus A. , Cervantes F. , Alland L. , Ottmann O. , Giles F. , Le Coutre P. 
Published: March 2020

6534 Background: AMN107 is a potent, highly selective, aminopyrimidine inhibitor which in vitro is 30-fold more potent than imatinib and active against 32/33 imatinib resistant Bcr-Abl mutations. Methods: This open-label study was designed to evaluate the safety and efficacy of AMN107 (400 mg bid) defined by hematologic/cytogenetic response (HR/CyR) rates in imatinib resistant or intolerant CP pts. Results: For this study which remains open to enrollment, preliminary data are reported for 67 pts including 39 (58%) with imatinib-resistant and 27 (40%) imatinib-intolerant CML (1 pt unknown). The median age was 62 (range 31–80) yrs and the median time from first diagnosis to treatment was 52 (range 5–279) mos. BCR-ABL mutations associated with imatinib resistance were detected in 11/17 (65%) pts at baseline. The median duration of AMN107 exposure was 129 (range 3–225) days. Treatment is ongoing for 50 (75%) pts with 17 (25%) pts discontinued (9 adverse events, 2 disease progression, 6 other). Major CyR was observed in 13 (19%) pts (6 complete, 7 partial), minor CyR was observed in 4 (17%) pts, and minimal CyR in 5 (7%) pts. Complete HR was reported in 35 of 42 (83%) pts without a baseline CHR. AE’s in ≥ 10% of pts were headache in 24 (36%) pts, fatigue in 21 (31%) pts (Gr 3/4 in 2 (3%)), pruritus in 19 (28.4%) pts (Gr 3/4 in 1 (2%)), rash in 18 (27%) pts (Gr 3/4 in 2 (3%)), nausea in 18 (27%) pts, diarrhea in 18 (27%) pts (Gr 3/4 in 1 (2%)), constipation in 11 (16%) pts, vomiting in 10 (15%) pts, thrombocytopenia in 10 (15%) pts (Gr 3/4 in 9 (13%)), anemia in 10 (14.9%) pts (Gr 3/4, 1 (2%)), neutropenia in 9 (13%) pts (Gr 3/4 in 8 (12%)), bone pain, muscle spasms, arthralgia, peripheral edema in 8 (12%) pts each, abdominal pain and myalgia in 7 (10%) pts each (Gr 3/4 in 1 (2%) each), and dyspnea in 7 (10%) pts. No deaths occurred. Conclusions: AMN107 has clinical activity and an acceptable safety and tolerability in pts with imatinib-resistant or intolerant CML-CP. [Table: see text]
High-dose imatinib mesylate treatment in patients (Pts) with untreated early chronic phase (CP) chronic myeloid leukemia (CML): 2.5-year follow-up
Authors: Aoki E. , Kantarjian H. , O’Brien S. , Talpaz M. , Giles F. , Garcia-Manero G. , Wierda W. , Verstovsek S. , Jones D. , Luthra R. , Cortes J. 
Published: March 2020

6535 Background: The standard dose (SD) of imatinib for CP CML is currently 400 mg daily, but higher doses (HD) may be more effective. We conducted 2 consecutive trials using HD imatinib (i.e., 400mg twice daily) in previously untreated early CP CML pts. This is an updated analysis of the longer follow-up. Methods: A total of 175 previously untreated pts received HD imatinib. We compared the results with a previous study using SD imatinib (400mg/day) in untreated pts with early CP CML (N=50). Results: Cytogenetic and molecular responses were evaluable in 222 pts (N=49 at SD, 173 at HD) and 217 pts (N=46 at SD, 171 at HD), respectively. In HD group, Sokal risk classification was good in 69%, intermediate in 29%, and poor in 11% of pts. There were no differences in pre-treatment characteristics between two groups. The median age was 48 years in both groups. Median follow-up is 53 months for SD and 30 months for HD group. Patients treated with HD had a higher rate of complete cytogenetic responses (90% vs 78% with SD, p=0.03) and these occurred earlier, with 69% achieving this response after 6 months of therapy vs 45% with SD (p=0.001). The cumulative incidence of major molecular response was significantly better in HD group (p=0.03), and this response was also observed earlier in HD group: at 12 months 54% in HD and 24% in SD group had achieved this response (p=0.001). At 24 months, 19/70 (27%) evaluable pts with HD versus 3/31 (10%) of pts in SD group achieved complete molecular remission. Four pts (2%) in HD group and 4 pts (8%) in SD group have progressed to advanced phases (p=0.05). There was a trend in favor of the HD group for transformation-free-survival but it was not statistically significant (p=0.07). Overall survival is excellent in both groups (24 month survival, 99% with HD vs 98% with SD; p=0.24). Grade 3 or 4 hematologic toxicity was more frequent in HD group whereas extramedullary toxicity was similar in two groups. The median actual dose in HD group was 800 mg at 12 months, with 39% patients requiring dose reduction at some point. Conclusions: High-dose imatinib provides higher rates of complete cytogenetic responses and earlier molecular responses with some increase myelosupression. The long-term benefit of earlier responses remains to be demonstrated. [Table: see text]
Ibritumomab tiuxetan combined with high-dose chemotherapy and autologous stem-cell transplantation (SCT) in patients with chemo-refractory aggressive non-Hodgkin’s lymphoma
Authors: Shimoni A. , Zwass T. , Oksman Y. , Hardan I. , Shem-Tov N. , Yerushalmi R. , Nagler A. 
Published: March 2020

6538 Background: High-dose chemotherapy and autologous SCT have an established role in the treatment of patients with first chemo-sensitive relapse of aggressive lymphoma. However, autologous SCT has only limited success when performed in refractory or progressive stage of the disease and the expected 1-year progression-free survival (PFS) in this setting is < 20%. Methods: This study was designed to explore the safety and outcome following inclusion of ibritumomab tiuxetan (IT) in the conditioning regimen given prior to autologous SCT. Patients were eligible for this study only if they had refractory lymphoma and a positive PET-CT prior to SCT. The primary end-point was 1-year PFS. Rituximab 250 mg/m2 followed by IT 0.4 mCi/kg were given on day -14. Chemotherapy according to standard BEAM was started on day -6. Results: The study included 20 pts, median age 55 years (range, 35–66). Histology was diffuse large cell (n=14), transformed follicular (n=5) and mantle cell lymphoma (n=1). Patients had active lymphoma at SCT, either primary refractory (n=11) or refractory relapse (n=9) and 12 had bulky disease at SCT. The median number of prior therapies was 3 (range, 1–6). There were no early infusion reactions associated with IT. Fourteen patients achieved CR, 4 achieved PR and 2 died early after SCT. With a median follow-up of 9 months (range, 1–20), 14 patients are alive and 6 have died with an estimated 1-year survival of 58% (95% C.I., 31–85). All surviving patients are progression-free. Only 2 patients relapsed with a 1-year cumulative incidence of only 14% (5–51). Two patients died of multi-organ toxicities and 2 of late occurring infections. These rates of non-relapse mortality are expected in heavily pretreated patients with refractory lymphoma and there was no additional toxicity related to IT. Conclusions: The inclusion of IT in the conditioning regimens given prior to autologous SCT may reduce the risk of relapse following autologous SCT and improve the poor outcome of patients with refractory lymphoma given SCT with standard conditioning regimens. This observation merits further study in larger comparative trials. No significant financial relationships to disclose.