bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disease response and survival outcomes in acute myeloid leukemia (AML) patients unfit for chemotherapy treated with 10-day decitabine as initial therapy.
Authors: Gourdin Theodore Stewart , Bhatnagar Bhavana , Duffy Alison P , Tidwell Michael , Ning Yi , Sausville Edward A. , Baer Maria R. 
Published: March 2020

6611 Background: AML is primarily a disease of older adults, with a median age of 67 years at diagnosis. Many patients are considered unfit for chemotherapy due to poor performance status and/or comorbidities, prompting investigation of less intensive approaches. A clinical trial in which 10-day courses of decitabine 20mg/m2 were given every 28 days as initial therapy demonstrated a promising complete remission (CR) rate and disease-free survival (DFS). We used this regimen to treat AML patients unfit for chemotherapy outside of a clinical trial. Methods: Charts of 32 newly diagnosed AML patients treated with 10-day courses of decitabine 20mg/m2 as initial therapy at the University of Maryland Greenebaum Cancer Center between September 2010 and November 2011 were retrospectively reviewed. If patients attained bone marrow blasts <5%, 5-day courses were administered subsequently and were continued until disease progression. Results: Median age at diagnosis was 74 years (range, 52-86). 18 patients were male and 14 female. 23 were Caucasian, 7 African-American and 1 Hispanic. 10 patients (31%) had performance status ≥ 2. All had significant cardiac, pulmonary and/or renal disease. Karyotype risk group was unfavorable in 17 patients, intermediate in 14 and unknown in one. There were 9 CRs and 1 partial remission, for an overall response rate of 31%, following a median of 2 (range, 1 to 4) courses. 21 patients did not respond to treatment following 1 to 6 courses, and one died within 29 days of treatment initiation. 21 patients (65%) were hospitalized at least once for fever or infection during treatment. Of the 9 patients who achieved CR, 5 had normal, 3 complex and 1 unknown karyotypes. Median DFS was 390 days (range, 87+-468+) and median OS 180 days (range, 15-623+). Six-month OS was 37.5% and 1-year OS 16.5%. Conclusions: AML patients unfit for chemotherapy treated with 10-day decitabine 20mg/m2 outside of a clinical trial had a higher response rate than reported for 5-day decitabine, but a lower response rate than in the reported clinical trial of the 10-day regimen. Additional novel treatment approaches are needed for these patients.
Time to ATRA in suspected newly diagnosed acute promyelocytic leukemia and association with early death rate at a non-cancer center institution: Are we meeting the target?
Authors: Manji Gulam Abbas , Khan Manji Samira , Karne Sheetal , Chao Jeff 
Published: March 2020

6615 Background: ATRA administration in suspected APL patients (sAPL) is thought to impact early death rate (EDR) (Tallman and Manji, Blood Cells Mol Dis. 2011). Delay in ATRA therapy at specialized centers was associated with EDR (Altman et al Blood 2011). EDR within this study was significantly lower compared to the SEER database (12% vs 17.3%) and hence may not reflect overall delay in ATRA therapy. We determined time to ATRA therapy in sAPL, and fraction of sAPL that did not have disease. Methods: Retrospective analysis of patients that received ATRA for newly diagnosed s APL between 01/01/98-12/31/11 at Albany Medical Center. Time to hematologist evaluation, ATRA ordered and administered, and mortality data was collected from cancer registry, medical record, and chemo-pharmacy database. Results: A total of 39 patients with newly diagnosed sAPL were administered ATRA (46% male, mean age 50y). APL diagnosis: 29/39 (75%) true APL (APL); 9/10 ATRA-treated non-APL (A-nAPL); and one patient for whom cytogenetic data unavailable. EDR amongst APL was 5/29 (17%) compared to 2/9 (22%) within A-nAPL. Time variables were compared between APL patients that died early (<30d) to those that survived 30 days, and included: time to hematologist response (0.9d vs. 0.4d); time to ATRA ordered (2.9d vs. 2.0d); time to ATRA administered (3.4d v. 2.2d); and time elapsed between hematologist response to ATRA administered (2.5d v. 1.9d), respectively. Cryoprecipitate was administered to 1/5 (20%) patients who expired within 30d compared to 10/23 (43%) who survived. Overall mortality for APL was 9/29 (31%) compared to 4/9 (44%) for A-nAPL group. Compared to recent reports, time to ATRA administration in our institution was later (2.0d vs. 2.4d). Conclusions: Our data indicate that APL patients who survived 30d received ATRA early. EDR at our institution is comparable to that reported by SEER database and may be attributed to delay in ATRA administration. Higher fraction of patients that survived 30d received cryoprecipitate. Hence aggressive blood product support may contribute to improved survival. Timing at which these products were administered is currently being evaluated.
The prognostic role of serum albumin in patients receiving induction chemotherapy for acute myeloid leukemia (AML).
Authors: Sadrzadeh Hossein , Brunner Andrew Mark , Drapkin Benjamin Jacob , Babirak Loren , Werner Lillian , Ballen Karen K. , Amrein Philip C. , Attar Eyal C. , Chen Yi-Bin Albert , Spitzer Thomas R. , McAfee Steven L , Neuberg Donna S. , Fathi Amir Tahmasb 
Published: March 2020

6618 Background: Serum albumin has been investigated as a prognostic tool in the care of patients with hematologic malignancies, including multiple myeloma and myelodysplastic syndromes. However, its prognostic utility in patients with AML is unknown. We hypothesized that a lower serum albumin is associated with worse outcomes following induction chemotherapy for AML. Methods: We conducted a retrospective medical record review of 166 adult, non-promyelocytic AML patients who had received induction chemotherapy at Massachusetts General Hospital from 1992 to 2007. Patient characteristics were summarized as numbers and percentages for categorical variables. The Kaplan Meier method was used to estimate median disease-free survival (DFS) and overall survival (OS). We dichotomized our patients by serum albumin ≥3 and <3, and determined the association of albumin with 60-day survival and complete remission (CR) rate using Fisher’s exact test. Association of albumin with DFS and OS was summarized using Cox regression in both univariate and multivariable analyses. Results: Of 166 patients, 125 (75%) achieved CR and 143 (86%) were alive at 60 days following diagnosis. After risk-adjusting for age and LDH, we found that a serum albumin level <3 mg/dL was associated with decreased 60-day survival (OR 0.30, p=0.015) and CR rate (OR 0.41, p=0.02) compared to patients with serum albumin ≥3. There was no association between serum albumin and DFS (p=0.88) or OS (p=0.31). As expected, younger age was associated with better induction outcomes. Conclusions: Serum albumin was negatively associated with short-term outcomes in patients receiving induction chemotherapy. A serum albumin level less than 3, clinically relevant to oncologic patients, was associated with a significantly decreased CR rate and lower 60-day survival after induction chemotherapy. This data suggests that serum albumin, a surrogate commonly used for nutritional status and suppressed in inflammatory comorbid states, has prognostic utility for AML patients undergoing induction chemotherapy.
Initial characterization of the toxicity and efficacy of elacytarabine (CP-4055), a novel antileukemic agent, using a multidimensional exposure-response relationship model.
Authors: Ducharme Murray P , Hagen Steinar , Hals Petter-Arnt , Jacobsen Tove Flem , Giles Francis J. , O'Brien Susan Mary , Dirven Hubert , Phillipe Colucci , Seng Yue Corinne 
Published: March 2020

6619^ Background: Elacytarabine (CP-4055), an elaidic acid ester of ara-C, is a novel antineoplastic agent developed to treat hematologic malignancies (HM). It is metabolized to active ara-CTP and inactive ara-U. In 3 studies, diverse elacytarabine monotherapy doses and regimens were given to patients with advanced HM and solid tumours. This analysis aimed to 1) describe the pharmacokinetics (PK) of elacytarabine in these patients and 2) investigate the relationship between PK and toxicity and efficacy in HM. Methods: Population PK analyses were run with ADAPT 5 (ITS) and included 146 patients given a 2h, 4h or 120h continuous infusion (CIV) of elacytarabine. Elacytarabine, ara-C and ara-U plasma concentrations (Cp) were simultaneously modeled and explained. Standard model discrimination criteria were used to select the best model. With the model, different dosing regimens were simulated to find average exposure and % of patients with efficacious or toxic exposure. A multi-dimensional exposure-response relationship (MDERR) was developed with pre-clinical and clinical data. Results: The best model was a 2-compartment (CPT) model with linear elimination and formation rates for the metabolism of elacytarabine to ara-C. Mean PK parameters were Vc = 4.12 L/m2, CL= 5.27 L/h/m2 and T1/2 = 7.57 h. Elacytarabine PK included a peripheral CPT with a non-linear distribution process to reflect saturable binding to red blood cells, otherwise its PK was linear. Ara-C and ara-U PK were described by 2- and 1-CPT linear models, respectively. The MDERR model related efficacy and toxicity thresholds to elacytarabine dosing regimens, and indicated that a 120 h CIV dosing regimen is preferable, allowing elacytarabine to exceed efficacious Cp for longer than the other investigated regimens. A minimum dose of 1000 mg/m2/day is needed for most patients to receive efficacious exposure. Conclusions: Elacytarabine is a promising anti-leukemic agent for patients with advanced HM. Its PK, toxicity and efficacy were characterized in patients given diverse dosing regimens. An MDERR model, which will be further refined or confirmed in upcoming clinical trials, was proposed.
Use of granulocytes concentrates from a single high yield apheresis to support more than one patient.
Authors: Aung Fleur M , Lichtiger Benjamin , Reddy Virgil , Hosing Chitra 
Published: March 2020

6622 Background: Allogeneic granulocyte transfusion therapy is sometimes the only therapeutic option in immunocompromised neutropenic leukemic/HSCT patients with life threatening bacterial and fungal infections. Collection of larger cell doses of granulocyte concentrates (GC) by automated apheresis following G-CSF/steroids administration has renewed interest and its use has grown steadily. Methods: Donors were recruited from family/friends of the patients and informed consent was obtained. GCs were collected via donor stimulation with a single subcutaneous dose of G-CSF (600 mcg). First time donors received an oral dose of dexamethasone (8 mg). GCs were harvested by Hetastarch-assisted leukapheresis 12 hours later via peripheral venous access with the continuous flow cell separator Spectra (COBE Caridian BCT, Lakewood, CO). Results: GCs were collected from 93 donors (67M: 26F; age median 40 (19-73 years) and 1 ½ x blood volume processed median 7048 (3212-8085 mL). The pre/post wbc were median 8.1 (4.1-22.8)/ 42.7 (22.4-77.5). The volume collected was based on the post G-CSF wbc count (> 35 K/UL - 800 mL; <35 K/UL between 600-700 mL). The original yield (10 x10e) was median 9.7 (5.1-17.2 units), volume median 718 (538-860 mL) and WBC median 132.7 (84.2 -241.6 K/UL per bag). The Split GCs were median 4.48 (2.70-7.72 units), with neutrophils median 87% (54-97% per bag). GCs were transfused to 51 patients (31M: 20F; age median 58 [19-83 years]) who received median 3.5 (1-18 split units), containing wbcs median 10734.69 [5778-42 -162698.09 (x10^3/uL)/unit) and achieved a WBC increment median 0.2 (0.0-8.3K/UL). Conclusions: The GCs were split due to the primary care team's reluctance to transfuse the entire volume of the product due to volume restrictions or for some other medical reason. The same rationale to split platelets from high yield single apheresis was used to split our GC products. We found that GCs from each donor was utilized maximally and also brought partial relief to other patients who lacked donors. We would like to make the case that when adequate numbers of GCs are collected it may be feasible to split the unit. This may offer a glimmer of hope to other patients in need of GCs who lack a donor network support.
Is consolidation chemotherapy after concurrent chemoradiotherapy beneficial for locally advanced non-small cell lung cancer? A pooled analysis of the literature.
Authors: Yamamoto Satomi , Tsujino Kazuyuki , Ando Masahiko , Kawaguchi Tomoya , Kubo Akihito , Isa Shunichi , Hasegawa Yoshikazu , Ou Sai-Hong Ignatius , Takada Minoru , Kurata Takayasu 
Published: March 2020

7000 Background: There is a growing interest on the efficacy of maintenance chemotherapy to metastatic non-small cell lung cancer (NSCLC) and adjuvant chemotherapy to early stage NSCLC. However, the role of consolidation chemotherapy (CCT) after concurrent chemo-radiotherapy in locally advanced NSCLC is undetermined. Methods: We systematically searched PubMed for phase II/III trials examining survival of locally-advanced NSCLC treated with concurrent chemo-radiotherapy between January 1, 1995 and October 31, 2011. Median overall survival (mOS) and corresponding 95% confidence interval (CI) were collected from each study and pooled. We extracted log-transformated hazards and its standard errors under the assumption that survival follows an exponential distribution, and computed a pooled mOS and its 95% CI using random-effect model. Collected trial arms were divided into two groups by the presence of CCT: Arm with CCT (CCT+) and without CCT (CCT-). Results: Forty-five studies were identified including 9 phase III studies and 36 phase II studies with 51 arms (CCT+: 29, CCT-: 22). Clinical data were comparable in clinical stage, performance status, cancer histology, gender, and median age between the two groups. I2 values for assessing heterogeneity were 15.3, 9.1 and 24.2% in overall, CCT+ and CCT- studies, respectively. There was no statistical difference in pooled mOS between CCT+ (18.5 month, 95%CI: 16.7-20.5) vs CCT- (18.1 month, 95%CI: 16.5-20.2). In regard to the ≥ grade 3 toxicities in pneumonitis, esophagitis, and neutropenia, there was no difference between the two groups throughout the whole treatment courses. In random effect models, predicted hazard ratio of CCT+ to CCT- was 0.98 (95%CI: 0.8-1.13, p=0.7574). These models estimated that addition of CCT could not yield more than 3 months of survival prolongation for patients with locally advanced NCSLC. Conclusions: The pooled analysis on publication basis failed to provide evidence that consolidation chemotherapy yields significant survival benefit for locally advanced NSCLC.
SWOG 0802: A randomized phase II trial of weekly topotecan with and without AVE0005 (aflibercept) in patients with platinum-treated extensive-stage small cell lung cancer (E-SCLC).
Authors: Allen Jeffrey Warren , Moon James , Gadgeel Shirish M. , Kelly Karen , Mack Philip C , Saba Hanna M. , Mohamed Mohamed K. , Gandara David R. 
Published: March 2020

7005 Background: Topotecan (T) (oral and IV) is the only FDA-approved second-line chemotherapy for patients with SCLC. Weekly T is associated with less toxicity than the daily x 5 regimen. AVE0005 (aflibercept) (A) is a novel recombinant human fusion protein which binds to circulating VEGF, thereby inhibiting its interaction with cell surface receptors. We sought to evaluate the efficacy and toxicity of weekly IV T (4 mg/m2) with or without A (6 mg/kg Q21D) in patients with relapsed SCLC following one line of platinum-based chemotherapy for E or limited-stage (L) SCLC. Methods: Patients were randomized 1:1 to T or A+T. Eligible patients had adequate organ function, ECOG PS 0-1, and no recent bleeding or cardiac events. Patients with brain metastases stable for ≥ 3 months prior to study entry were allowed. Primary endpoint was 3-month PFS. Patients were stratified as platinum-sensitive (PS) or platinum-refractory (PR). PR patients had progressed within 90 days of last chemotherapy for E and 6 months for L. This report is limited to the PR stratum. Results: 98 patients were registered. 1 was ineligible and 1 withdrew consent, leaving 96 evaluable for the primary endpoint (91 for toxicity (see Table for characteristics)). 3-month PFS was 26% for A+T versus 9% for T (P=0.01). Overall survival was similar in each arm (4.6 mos (A+T) versus 3.9 mos (T) (P=0.25)). There was 1 partial response with A+T. Disease control rate (DCR) was 28% with A+T and 12% with T. Toxicity was mainly hematologic with 14% and 19% of patients experiencing a Grade 4 event with T and A+T, respectively. There was one treatment-related death with T (renal failure). Conclusions: This study met its primary endpoint of improved 3-month PFS with A+T (p=0.01), warranting further study in the PR setting. Clinical benefit with A+T was achieved primarily through improved DCR. Toxicity was manageable and less than is seen with standard dose T. Accrual to the PS cohort is ongoing. [Table: see text]
Comprehensive genomic characterization of squamous cell carcinoma of the lung.
Authors: Govindan Ramaswamy , Hammerman Peter S. , Hayes David N. , Wilkerson Matthew D , Baylin Stephen , Meyerson Matthew ,   on behalf of the Cancer Genome Atlas (TCGA) Group
Published: March 2020

7006 Background: A third of patients with non-small cell lung cancer are diagnosed with squamous cell carcinoma (SCC) histology. This report describes findings from the comprehensive genomic analyses of 178 SCC samples. Methods: The Cancer Genome Atlas (TCGA) is conducting DNA, RNA, and miRNA sequencing along with DNA copy number profiling, quantification of mRNA expression and promoter methylation on surgically resected samples from previously untreated patients with stage I-III SCC of the lung. Results: The demographics of 178 patients enrolled in the study: median age 68 years (range: 40-85); female 47 (26%) and history of tobacco smoking 171 (96%). Over 30 sites of significant somatic copy number alteration (SCNA) were identified. Exome sequencing of 178 lung SCC and matched normal samples revealed 13 significantly mutated genes with a False Discovery Rate (FDR) of <0.01 and high expression levels, including TP53, CDKN2A, PTEN, KEAP1, and NFE2L2. Apart from the near universal loss of TP53 and CDKN2A, alterations in the NFE2L2/KEAP1 and PI3K/AKT pathways were found in 35% and 43% of tumors analyzed. mRNA expression profiling revealed four distinct expression subtypes, each one enriched with distinct mutations and SCNAs - classical (37%): NFE2L2 and KEAP1 mutations, FGFR kinase alterations, increased global methylation and the highest rate of tobacco use; basal (24%): alterations in FGFR kinases; secretory (24%): PDGFRA alterations; primitive (15%): RB1 mutations. Rearrangements involving several known tumor suppressors were detected by whole genome shotgun sequencing of 20 tumor/normal pairs and confirmed by RNA sequencing including PTEN, RB1, NOTCH1, NF1 and CDKN2A. CDKN2A loss by one of several mechanisms (deletion, mutation, rearrangement with loss of function and methylation) was observed in 72% of specimens. Potential therapeutic targets for clinical trials with currently available drugs were identified in 127 patients (75%). Conclusions: SCC of the lung is a distinct molecular subtype of lung cancer potentially amenable to distinct molecularly targeted therapies.
Feasibility trial of adjuvant chemotherapy with docetaxel (DOC) plus cisplatin (CDDP) followed by maintenance chemotherapy of S-1 in completely resected non-small cell lung cancer (NSCLC): Thoracic Oncology Research Group (TORG) 0809.
Authors: Niho Seiji , Suzuki Kenji , Sakai Hiroshi , Kaburagi Takayuki , Koike Teruaki , Minato Koichi , Kato Terufumi , Okamoto Hiroaki , Seto Takashi , Hosomi Yukio , Shimizu Kimihiro , Oshita Fumihiro , Tsuchida Masanori , Yamashita Motohiro , Kawashima Osamu , Kishi Kazuma , Kunitoh Hideo , Takeuchi Masahiro , Watanabe Koshiro , Ikeda Norihiko 
Published: March 2020

7012 Background: Maintenance chemotherapy could prolong overall and/or progression-free survival in advanced NSCLC. S-1 is an oral anticancer agent comprised of tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate. The TORG 0809 study was conducted to evaluate the feasibility and efficacy of maintenance chemotherapy of S-1 following DOC+CDDP in patients (pts) with curatively resected stage II and IIIA NSCLC. Methods: Pts received 3 cycles of DOC (60mg/m2 d1) plus CDDP (80mg/m2 d1), q3-4w, and subsequently S-1 at 40mg/m2 twice a day for 14 consecutive days, q3w, for more than 6 months (max 1 year). The primary endpoint was determination of feasibility, which was defined as the proportion of pts who had completed maintenance for 8 cycles of S-1 or more. If the lower confidence interval (CI) of this proportion was 50% or more, the feasibility of the treatment was considered confirmed. The sample size was set to be 125. Results: Between Jun 2009 and Nov 2010, 131 pts were enrolled, of whom 129 pts were eligible and assessable. The median age was 63 (23-74 years); PS 0: 107, 1: 22; p-stage IIA: 19, IIB: 30, IIIA: 80; adenocarcinoma: 99, non-adenocarcinoma: 30. Of 129 pts, 109 pts (84.5%) completed 3 cycles of DOC+CDDP. 106 pts initiated the maintenance S-1 and 66 pts (51.2%, 95% CI: 42.5-59.8) completed 8 cycles or more S-1 treatment; this percentage was less than our previously defined criterion for treatment feasibility, since 32 pts terminated maintenance S-1 at 3 cycles or less. Grade 3/4 toxicities during the maintenance S-1 included anemia (7.3%), neutropenia (3.7%), anorexia (3.7%), dyspnea (1.8%), infection with neutropenia of grade 0 to 2 (1.8%). Febrile neutropenia was not observed. One pt developed interstitial pneumonia and sepsis, resulting in treatment-related death. Recurrence-free survival data will be presented. Conclusions: The toxicity level was acceptable, although the results did not meet our criterion for feasibility. Modification of the treatment schedule of maintenance S-1, such as a 2-week rest period rather than 1-week, might improve treatment compliance.