bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic and medical consequences of myelodysplastic syndromes from a medical perspective
Authors: Goldberg S. , Mody-Patel N. , Warnock N. 
Published: March 2020

17534 Background: The myelodysplastic syndromes (MDS) are a heterogeneous group of bone marrow failure diseases affecting the elderly. The economic impact on Medicare of MDS is largely unknown. A retrospective analysis of total healthcare resource use and cost of MDS patients (pts) was conducted. Methods: The Medicare Standard Analytic File 5% (SAF5%) claims database was used to identify pts with a new primary MDS diagnosis code in first quarter (Jan-Mar) 2003 then followed through Dec 2005. Pts with myeloid leukemia or anemias of known causes in the previous year were excluded. Newly diagnosed MDS pts were descriptively characterized based on potential cause of MDS, MDS-related complications, and MDS therapies. Total healthcare costs and resource utilization for MDS pts were analyzed. Results: Of the 1,713,502 pts in SAF5%, 705 (4 per 10,000) developed MDS in first quarter 2003, including those with a previous history of unexplained anemia 159, (23%), chemotherapy or radiotherapy exposure 43, (6%), and de novo 503 (71%). Mean age was 76 (range 29- 98); 49% male, 90% Caucasian. 2003 median Medicare payment for MDS pts was $17,556, compared to $1,459 for the total SAF5% Medicare population (mean: $28,023.67 vs. $6,739.48; p< 0.001). Median Medicare payments for therapy induced were $34,271, prior anemia $17,191, and de novo MDS $16,493. 278 (39%) died; including 63% of the therapy-induced, 40% of the prior anemia and 37% of the de novo. 79% were hospitalized and 59% had at least one emergency room visit. Of 46% receiving blood transfusions 6% were coded with transfusional hemachromatosis. 314 (45%) received growth factor treatments and 108 (15%) chemotherapy. Of those at risk for MDS-related complications, 55%, 23%, and 2% experienced new onset cardiac complications, diabetes, and hepatic diseases, post MDS diagnosis. Additionally, 51% had pulmonary problems and 45% infections in the 3 year study. Conclusions: The majority of newly diagnosed MDS pts develop disease-related complications, resulting in significantly higher healthcare resource utilization and costs compared to non-MDS patients. No significant financial relationships to disclose.
The poor prognostic significance of deletions of derivative chromosome 9 in Chinese patients with chronic myelogenous leukemia
Authors: Li J. , Xu W. , Wu W. , Zhang S. , Zhu Y. 
Published: March 2020

17535 Background: Chronic myeloid leukemia (CML) is characterized by formation of the BCR/ABL fusion gene, usually as a consequence of the Philadelphia (Ph) translocation between chromosomes 9 and 22. Deletions of the derivative 9 chromosome [der(9)] in 10- 15% of CML patients with a standard Ph translocation and in >30% of CML patients with a variant Ph translocation. Subsequent studies demonstrated that CML patients who carry a der(9) deletion progress more rapidly to blast crisis and have a shorter survival than those without a deletion. The characteristics of Chinese patients with each hematologic malignancy compared with those in other countries have not yet been clarified. This prompted us to perform molecular and cytogenetic analyses on Chinese patients with CML. Methods: To study the incidence and the prognostic significance of the derivative chromosome 9 [der(9)] deletions in on Chinese patients with CML, a series of 48 BCR/ABL positive Chinese CML blast crisis (CML-BC) patients were investigated using dual colour dual fusion BCR/ABL probe and fluorescence in situ hybridization (FISH). Results: Eight (16.7%) cases showed der(9) deletions, and the deletions were also existed in chromosome preparations made at diagnosis. The estimated median length of chronic phase for patients with der(9) deletions was 18 months (range 4–38 months) compared to 48 months (range 0–204 months) for patients without deletions. Kaplan-Meier analysis revealed a striking difference in length of chronic phase between with and without der(9) deletions, and this difference was highly significant by log-rank analysis. Der(9) deletions are not associated with increased karyotypic instability. There was no difference in the probability of the der(9) deletions between the cases transformed to acute nonlymphocytic leukemia (ANLL) and those to acute lymphoid leukemia (ALL). Conclusions: The results indicate that FISH technique could effectively detect the der(9) deletions. Der(9) deletions occur at the time of Ph translocation. CML patients with der(9) deletions have more rapid process and poorer prognosis. Deletion status is a powerful prognostic factor for patients with CML. Der(9) deletions might not lead to transformation to specific type in CML. No significant financial relationships to disclose.
Rituximab, gemcitabine, vinorelbine, and methylprednisone (R-GVM), a hematopoietic cell (HC) mobilizing and salvage regimen for malignant lymphoma (ML)
Authors: Rezazadeh A. , Herzig G. , Herzig R. 
Published: March 2020

17537 Background: The prognosis of pts with recurrent ML remains poor. High-dose therapy (HDT) with HC rescue can cure a proportion of such pts. HC mobilization can be adversely affected by number and duration of prior treatments, interval from diagnosis to HC collection, prior radiotherapy and marrow involvement. There remains a need for more effective and less toxic salvage regimens, capable of mobilizing HCs. Methods: The mobilizing potential of R-GVM salvage regimen with hematopoietic growth factor (HGF) support (G- and GM-CSF) was evaluated in 6 pts with relapsed (n=5) or primary refractory (n=1) ML. Pts received R-GVM salvage therapy [rituximab (375 mg/m2, day 1), gemcitabine (1 g/m2, day 1, 8), vinorelbine (30 mg/m2, day 1, 8) and methylprednisone (1 g/m2, day 1, 8)] with HGF administration and subsequent HC collection. The HGF support was started on day 9 and was continued through apheresis which started when the CD34+ cell count ≥ 20/μl (median day of R-GVM cycle: 15, range 14–19). Pts had daily apheresis with continued HGF support until at least 5 x 106 CD34+ cells/kg were collected. The hematologic and non-hematologic toxicity were tolerable in all pts; no pt required hospitalization. Results: 6 pts (age range 20–45 years) with Hodgkin (n =3) and non- Hodgkin lymphoma (n =3) were evaluated in this study. Pts had received 1–3 previous treatment regimens. The median number of R-GVM courses given before HC collection was 2.5 (range 1–5). Effective HC mobilization (≥5x106 CD34+ cells/kg) was obtained in all ps. A single apheresis resulted in satisfactory HC collection in 4 pts (range 8.2–17.7 x 106 CD34+ cells/kg); 2 pts required 3 aphereses to collect an adequate number of cells (6.7 and 7.4 x 106 CD34+ cells/kg). One pt was heavily pretreated and had failed two previous attempts of HC mobilization (one with HGF alone and one with cyclophosphamide and HGF); the other pt was HIV+ treated with HAART and had prior marrow involvement. As a salvage regimen, one pt had progressive disease, 1 had stable disease, 1 had a partial response, and 3 had a complete response before proceeding with HDT with HC rescue. Conclusions: R-GVM regimen is feasible, tolerable and effective in mobilizing HPC in patients with relapsed and refractory lymphoma. No significant financial relationships to disclose.
Relapsed acute megakaryoblastic leukemia in Down syndrome (AMKL-DS) may be cured with chemotherapy alone, without stem cell transplantation (HSCT)
Authors: Jayabose S. , Sandoval C. , Levendoglu-Tugal O. , Ozkaynak M. F. 
Published: March 2020

17543 Background: Children with recurrent AMKL -DS have an extremely poor prognosis without HSCT. Methods: We report a case of a relapsed AMKL-DS cured with intensive chemotherapy alone, without HSCT. Results: A 19 month old boy with Down syndrome, who had transient leukemia as a newborn, developed AMKL-DS (GATA1 positive) and was treated with four cycles of CI-TAD: continuous infusion of cytarabine and daunorubicin, and oral thioguanine for four days, and intrathecal cytarabine; followed by two cycles of high dose cytarabine plus L-Asparaginase; and three weekly doses of intrathecal cytarabine. Although he achieved remission at the completion of first cycle of the induction chemotherapy, he relapsed within 6 weeks after the completion of therapy. He then received the following chemotherapy over the next six months: Cycle 1 and 2. High dose Ara-C ( 33. 3 mg/kg q 12 hours x 8 doses) on days 0 to 3 plus mitoxantrone 0. 4 mg/kg/day x 4 on days 3 to 6 Cycle 3. High dose Ara-C 33. 3 mg/kg q 12 hours x 8 doses Cycle 4 and 5 (FLAG): Fludarabine 0. 8 mg/kg/day x 4 plus Ara-C 67 mg/kg/d x 4 and G-CSF 10 mcg/kg/day x 4 all on days 0 to 3. He achieved complete remission after the 1st cycle of chemotherapy, and underwent further cycles of chemotherapy while waiting for HSCT from an unrelated donor. But after the 5th cycle of chemotherapy, he developed a pulmonary lesion of fungal etiology for which he received three months of therapy with liposomal amphotericin. Because of a persistent lung lesion on imaging, he was considered ineligible for HSCT, and no further therapy was given. His bone marrow aspirate after the 3rd cycle of therapy was negative for GATA1. He has been disease-free for 59 months after the completion of his last cycle of chemotherapy, and he is currently in good health without any evidence of pulmonary or cardiac dysfunction. Conclusions: Intensive chemotherapy alone, without HSCT, may be curative for relapsed AMKL- DS. No significant financial relationships to disclose.
Activity of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) in chemotherapy-pretreated non-small cell lung cancer (NSCLC) patients (pts) prospectively selected according to specific molecular predictive factors
Authors: Nuzzo C. , Marchetti A. , Mottolese M. , Cianciulli A. M. , Rinaldi M. , Cecere F. L. , Bria E. , Ceribelli A. , Milella M. , Cognetti F. 
Published: March 2020

18006 Background: EGFR TKIs are effective in a small proportion of chemotherapy-pretreated NSCLC pts. A number of molecular alterations along the EGFR pathway have been proposed as predictors of response to EGFR TKIs, but to date none of them has been prospectively validated. Methods: Advanced, chemotherapy-pretreated, NSCLC pts were screened for the following EGFR pathway alterations: EGFR gene mutations (by SSCP and sequencing) and/or increased copy number (by FISH), EGFR protein expression (by IHC), and HER-2, phosphorylated AKT (pAKT), and total AKT protein expression (by IHC). Upon progression, pts were then assigned to treatment with an EGFR TKI (Iressa™ or Tarceva™) according to one of the following groups: A) mutated (regardless of any other parameter); B) non-mutated, amplified (either true gene amplification or high-grade polysomy in > 40% of the tumor cells); C) non-mutated, non-amplified, EGFR positive (IHC score = 1+); D) Adk or BAC histology and no smoking history (non-mutated, non-amplified, EGFR-negative pts or unknown EGFR status). Results: From January 2005, 129 pts were screened for EGFR pathway alterations, while undergoing chemotherapy. Thirteen pts were identified in group A (6 with exon 19 deletions, 6 with exon 21 point mutations, 1 with both); 39 pts in group B (including 7 pts with true gene amplification); 32 pts in group C (including 19 pts with a pAKT IHC score = 1+); 7 pts in group D (including 2 pts with BAC histology). Treatment results in the different subgroups are reported in Table 1 . Conclusions: Based on the data available so far, there seems to be a continuum of response/ disease control rate that progressively declines from group A to group C. Accrual to the study will be continued in all 4 subgroups until computer simulations using a continual reassessment method will allow to confidently exclude a true response rate = 10% in any of the groups. [Table: see text] No significant financial relationships to disclose.
Analysis of the prognostic role of plasmatic K-ras mutations in advanced non-small cell lung cancer (NSCLC) patients
Authors: Sirera R. , Camps C. , Berrocal A. , Muñoz-Navarro M. , Garcia-Gomez R. , Viñolas N. , Artal A. , Guillot M. , Taron M. , Rosell R. 
Published: March 2020

18009 Background: Qualitative analysis of circulating DNA in blood is a promising non-invasive diagnostic and prognostic tool. Our aim was to study the association between the presence of K-ras mutations at codon 12 and several clinical variables in advanced NSCLC patients. Methods: We examined 451 NSCLC patients in stage IIIB and IV, treated with cisplatin and docetaxel. Blood samples were collected before chemotherapy, and circulating DNA was extracted from the plasma using commercial adsorption columns. K-ras mutational status was determined by a method based in allelic discrimination with RT-PCR. Results: Median age was 61 years [35–82] and 84% were males. 99% had performance status 0–1. 84% were in stage IV and 16% in stage IIIB. The histological subtypes were: 32% squamous cell carcinoma, 50% adenocarcinoma, 14% anaplastic large cell, and 4% undifferentiated. 41% of the patients received second line chemotherapy. 1% achieved complete response (CR), 36% partial response (PR), 35% had stable disease (SD) and 28% progressive disease (PD). Here we present the results of the analysis of K-ras mutations in the plasma of 165 samples. 17 patients presented K-ras mutations (10.3%), being codon 12 TGT in 16 patients and GTT in 1 case. Plasmatic mutations were found either in patients presenting squamous cell carcinoma (n=3) and in patients with adenocarcinoma (14). Patients with K-ras mutations in plasma had a median time to progression (TTP) of 2.3 months (m) [0.5- 4.6] while for wild type K-ras was 4.1 m [3.3–4.8], (p=0.9). Overall Survival (OS) in K-ras mutated patients was 10.1 m [4.1–15.8] and in wild type K-ras was 9.0 m [6.9–11.1], (p=0.6). Conclusions: In advanced NSCLC, there were no significant differences between patients with K-ras mutations and those with wild-type genotype with respect to baseline characteristics, response rates, TTP, or OS. Data from the rest of the cohort will be presented at the meeting. No significant financial relationships to disclose.
Gene expression levels of ribonucleotide reductase subunit M1 (RRM1), tyrosyl-DNA phosphodiesterase (Tdp1), nuclear factor of activated T-cells (NFAT), and BubR1 mRNA expression in completely resected chemo-naive non-small cell lung cancer (NSCLC) patients
Authors: Chaib I. , Jassem E. , Spkrzypski M. , Rosell R. , Taron M. , Perz-Roca L. , Szymanowska A. , Rzyman W. , Gulida G. , Jassem J. 
Published: March 2020

18016 Background: A relationship between gene transcripts and survival in operable NSCLC is now emerging. RRM1 is involved in DNA repair, Tdp1 is implicated in the repair of CPT-induced topoisomerase damage, and NFAT promotes cancer invasion. BubR1 is a key spindle checkpoint gene, and altered BubR1 mRNA levels are associated with lymph node metastasis and chromosome instability. Methods: In order to identify p with a high risk of relapse, we examined the expression of these four genes in frozen resected tumors from 126 resected NSCLC p by real-time quantitative PCR. Gene expression was normalized using β-actin expression as internal reference. Results: Adenocarcinoma (adeno), 33 p; squamous cell carcinoma (SCC), 93 p. Stage: IA, 18 p; IB, 53 p; IIB, 33 p; IIIA, 22 p. Tumor transcript expression: RRM1, 2.10; Tdp1, 1.77; NFAT, 0.56; BubR1, 16.40. Expression of RRM1, Tdp1 and BubR1 was higher in SCC than in adeno (P<0.001). Median time to relapse (TTR) was longer for p with low levels of RRM1 (P=0.11), Tdp1 (P=0.86), NFAT (P=0.29), or BubR1 (P=0.44) (Table). A significant trend towards longer survival was also observed in stage I p with low RRM1 P=0.06). In a multivariate Cox model, tumor size > 4 cm and stage III predicted shorter TTR and survival. Conclusion: Increased mRNA expression of these genes is associated with shorter TTR; this knowledge could be useful for customizing adjuvant chemotherapy. [Table: see text] No significant financial relationships to disclose.
Incidence of venous thromboembolic events and effect on survival in patients with lung cancer
Authors: Shah J. , Donegan S. , Wang D. , Robert F. 
Published: March 2020

18017 Background: Venous thromboemboli (VTE) is a known complication in patients with cancer, however the true incidence and effect on survival in patients with lung cancer is not clear. Methods: We retrospectively reviewed a cohort of 388 patients with lung cancer from 1997 to 2006 seen at the University of Alabama in Birmingham. Results: Median age was 62 and the male (n=227) to female (n=160) ratio was 1.41:1. Small cell lung cancer (SCLC) was the histology in 50 patients (13%) and non small cell lung cancer (NSCLC) in 331 patients (87%). Among NSCLC, the distribution of various subtypes was: 144 (37%) adenocarcinoma, 93 (24%) squamous cell, 7 (2%) large cells and 93 (24%) non-small cell, not otherwise specified(NOS). Metastatic disease was present in 29% (96/337) of NSCLC and extensive disease in 54% (27/50) of SCLC patients. 73% had a performance status of 0/1 and 29% had weight loss ( > 5% body weight). The overall incidence of VTE was 17 % (n=64); 9 patients prior to the diagnosis and 55 patients (86%) during the course of their disease. The incidence of VTE in SCLC was 10% (n=5) and in NSCLC 19% (n=59). VTE events in patients with non-small cell histologies were: 18% in adenocarcinoma, 25% in NSCLC-NOS, and 8% in squamous cell carcinoma. In patients with SCLC the incidence of VTE in limited stage disease (3/23) was similar to extensive stage disease (2/27). In NSCLC, patients with stage 1–3 disease had an incidence rate of 16% (39/241) compared to 21% (20/96) with metastatic disease. The median survival (MS) in SCLC patients with VTE was 21 months and without DVT was 17 months (P = 0.28). The MS in patients with NSCLC with VTE was 15 months and without VTE was 18 months (P = 0.12). Conclusions: There is a high incidence of VTE in patients with both NSCLC and SCLC with a trend to increased incidence in specific histologic subtypes and increased disease burden. Despite the potential anti-neoplastic benefit of anticoagulants there was a minimal difference in overall survival between cohorts, although this study was not designed to evaluate differences in survival. This data supports trials evaluating the role of prophylactic use of anticoagulants as a means to reduce the morbidity/mortality associated with VTE in this high risk population. No significant financial relationships to disclose.
Preoperative chemoradiotherapy in non-small cell lung cancer (NSCLC) patients with operable stage IIIB disease. A phase II trial of the Swiss Group for Clinical Cancer Research (SAKK)
Authors: Pless M. , Stupp R. , Kann R. , Zouhair A. , Mayer M. , Thierstein S. , Stahel R. , Betticher D. , Balmer Majno S. , Ris H. B. 
Published: March 2020

18021 Background and Methods: Outcome of patients (pts) with locally advanced NSCLC treated with radio- or chemoradiotherapy is poor. This two-stage phase II trial (planned sample size 46) aimed at evaluating feasibility and outcome of a tri-modality concept of neoadjuvant chemotherapy (CT), radiotherapy (RT) followed by definitive surgery in operable, stage IIIB NSCLC pts. Treatment consisted of 3 cycles of cisplatin (100 mg/m2) and docetaxel (85 mg/m2) followed by accelerated, concomitant boost RT (44 Gy/22 fx) and surgery. Primary endpoint is event-free survival at 1 year. Operable pts up to age 75 and a performance status of 0–1 with stage IIIB NSCLC (pleural effusion excluded) were eligible. Results: Forty-five eligible pts (46 accrued) with a median age was 60 years (range 28–70) were treated between September 2001 and May 2006. Tumor location was right-sided in 28 pts and left-sided in 17 pts. Histology was squamous cell 42%, large cell 11%, adeno-13% and undifferentiated carcinoma 33%. N3-disease was present in 29%, T4 stage in 78%. CT (45 pts) and RT (34 pts) were delivered as prescribed in >80% of cycles. The median time from enrollment to surgery was 3.7 months (2.8 - 5.2). The objective response rate after CT was 53% (95% c.i. 38–68%), after additional RT 67% (51–80%). Surgery (pneumonectomy in 17) was performed in 31 pts (69%), with an R0 resection in 24 pts. Median duration of hospitalization was 12 days (8–134). Two pts died in the perioperative phase due to ARDS and a cerebro-vascular event, respectively. Mature results of the primary endpoint and overall survival will be available at the ASCO meeting. Conclusions: Combined multimodality treatment strategy is feasible in a subgroup of patients, with acceptable toxicity. About two thirds of patients responded to the induction therapy, and were able to undergo subsequent surgery. No significant financial relationships to disclose.
Second-line therapy with irinotecan or gefitinib in docetaxel pretreated patients with non-small cell lung cancer: A new treatment strategy according to clinical predictors for response
Authors: Park S. , Park J. , Cho E. , Shin D. 
Published: March 2020

18026 Background: Retrospective analyses of previous trials have shown the clinical advantage of gefitinib in advanced non-small cell lung cancer (NSCLC) patients with certain favorable baseline factors (Asian ethnicity, female, adenocarcinoma, or no smoking history). This prospective phase II study was designed to test the hypothesis that higher response rates might be achieved if patients are selected according to these clinical predictors for response. Methods: Korean NSCLC patients who have failed after docetaxel-based first-line chemotherapy were consecutively accrued. Patients without any of the favorable clinical predictors (i.e., male smoker with non-adenocarcinoma) received irinotecan 100 mg/m2 on days 1, 8 and 15 every 4 weeks (irinotecan arm). Patients who had at least one of the predictors for response received gefitinib 250 mg/d orally from day 1 (gefitinib arm). Primary endpoint was response rate. With a two-stage phase II design, the required number of patients was at least 25 per each arm. Results: Of 68 patients accrued, 25 were treated with irinotecan and 43 with gefitinib. In the gefitinib arm, 22 patients were female, 20 were never-smoker, and 33 had adenocarcinoma. Treatment duration was significantly longer in the gefitinib arm (2.0 months for irinotecan arm v 4.4 months for gefitinib arm; p<0.01). Median number of chemotherapy cycles was 2 (range, 1–4) for irinotecan arm. Fewer drug-related toxicities were observed with gefitinib compared with irinotecan. In the irinotecan and gefitinib arm, 28% and 13% of patients, respectively, discontinued treatment because of toxicity. The objective responses of irinotecan and gefitinib arm were 16% (95% CI, 2–30) and 37% (95% CI, 21–51), respectively (p=0.07). Patients in the gefitinib arm had a longer, although statistically insignificant (p=0.11), progression-free survival (6.5 months; 95% CI, 3.8–9.2) than those in the irinotecan arm (3.2 months; 95% CI, 2.0–4.4). Conclusions: Gefitinib could be a reasonable second-line option in Korean NSCLC patients who had at least one favorable clinical predictor. Updated results, including an exploratory analysis of molecular characterization, will be presented. No significant financial relationships to disclose.