bluuebunny/crossref_metadata_2025_split huggingface dataset:
How could improvement in the management of T-cell acute lymphoblastic leukemia be achieved? Experience of Princess Nourah Oncology Center, National Guard Hospital, Jeddah, Saudi Arabia
Authors: Khattab T. M. , Jastaniah W. A. , Felimban S. K. , Elemam N. , Abdullah K. , Ahmed B. 
Published: August 2020

10048 Background: T-cell acute lymphoblastic leukemia (T-ALL) is representing 10–15% of pediatric ALL. The use of more intensive treatments and risk adapted therapy have significantly improved the outcome of patients with T-ALL and event-free survival rate of 60–70% are now reported in children. Our published data showed that T-ALL phenotype patients fared poorly with 5 year survival of 27% versus 83% for precursor B-ALL (Recent Advances Research Update: 2006, 7; 1, P 51–56). Objectives: We reviewed all patients diagnosed with T-ALL to assess risk classification according to NCI criteria, type of therapy received, overall survival and causes of mortality. Methods: Retrospective review of all patients files diagnosed with T-ALL from 1989 until now with data collection including; sex, age, white cell count (WBCs), CNS disease, type of protocol used, length of survival, overall survival, cause of death (toxic, disease). Results: Over the last 20 years, T-ALL cases registered were 52/460 (11%) of all ALL cases, Male:Female ratio 42:10 (4.2:1), median age 7 year (range: 1.5–12 yrs). Median WBCs 50,000/Cmm (range: 1.500–619,000/Cmm) and positive CNS at diagnosis 10/52 (20%). NCI risk classification criteria showed SR 24/52 (46%) and HR 28/52 (54%). Protocols used were UKALL ( n = 21; 3 UKALL X-B, 4 UKALL X-D, 10 UKALL XI and 4 MRC-97 ). BFM (n = 8); and CCG 1961 (n = 23). Overall survival 27/52 (52%) and 25 pts. died (48%); 15 secondary to disease recurrence (9 on UKALL, 4 BFM, 2 CCG 1961); 4 during induction, 1 fulminant hepatic failure, 1 tumor lysis syndrome, and 4 due to toxicities (mucormycosis, staphylococcal toxic shock syndrome, CMV pneumonia, pseudomonas sepsis). Survival for different regimen; UKALL: 5/21=31%, BFM: 4/8=50%, CCG: 18/23=78%, while overall cohort survival 52%. Mean length of survivors 4 year (range 4–140 month) and mean length for non-survivors 1 year (range 0.1–40 months). Conclusions: This review showed the improvement of T-ALL survival from 27% to 56%. Using augmented therapy based on CCG1961 was associated with better outcome. Further risk and response stratification in addition to intensification of therapy for T-cell ALL in our center may prove to be beneficial. Therapy remains an important prognostic factor. No significant financial relationships to disclose.
Effect of selenium on anthracycline induced cardiotoxicity in children that treated for cancer: Correlation with pro-brain natriuretic peptide levels
Authors: Tacyildiz N. , Ucar T. , Ozyoruk D. , Yavuz G. , Unal E. , Atalay S. , Ozelci Kavas G. , Aribal P. , Dincaslan H. , Cavdar A. 
Published: August 2020

10061 Background: High cumulative doses of an anthracyclin (300–500 mg/m2) are used in the several treatment protocols of children with Cancer. Probrain natriuretic peptit (Pro-BNP), is relased by cardiac cells and elevated even before overt cardiac distress symptoms. Selenium, is an antioxidant which its’ absence cause cardiomyopathy in people living in the poor selenium soil area. Aim 1: Assesment of anthracycline-induced cardiotoxicity with Pro-BNP levels, correlated with echo-cardiographic (ECHO) findings. Aim 2: Determine possible effects of selenium levels and supplemantation on cardiac toxicity. Methods: Plasma levels of Pro-BNP have been measured in 58 pediatric cancer patients (leukemias, lymphomas,solid tumors; 38 boys, 20 girls; between 2–18 years, median:12) after completed their anthracycline containing regimens. Serum selenium levels examined in 12 patients (six patients were with high and other six with normal pro-BNP levels). Three of four Patients with low level of selenium showed cardiac failure according to ECHO and supplemanted with selenium besides digoxine, ACE inhibitors. Results: Eleven patients have found with high pro-BNP levels (120–8022 pg/ml; normal: lower than 120 pg/ml).Six of these patients (with 170–8022 pg/ml, median:798pg/ml pro-BNP) and other six patients with normal levels of pro-BNP (10–74pg/ml, median: 67pg/ml) examined for their serum selenium levels. All patients with normal pro-BNP levels have found in normal levels of selenium levels (71–150 μg/L,median:125 μg/L). Four patients in high pro-BNP group showed low levels of selenium (52–129 μg/L; median:67.5 μg/L). Since three of that four patients have cardiac failure, treated accordingly and supplemented with 100 μg/day selenium to maintain normal levels. During follow-up periods of 27; 8 and 2 months, all 3 patients are doing well with normal ECHO finding. Two patients reached normal Pro-BNP levels while one of them has 80 % decrease. Conclusions: Serum Pro-BNP levels can be used as a marker for anthracycline toxicity and as follow-up marker for protective agents. Selenium suplemantation may have a potential role to protect and/or overcome the difficulties related anthracyclin-induced toxicities. No significant financial relationships to disclose.
Endocrine complications in children treated for medulloblastoma or ependymoma using radiation therapy. Outcomes in the CT-planning era
Authors: Bahl G. , Urbach S. , Bartels U. , Hodgson D. C. , Millar B. , Parent A. , Le L. , Awrey S. , Laperriere N. 
Published: August 2020

10064 Background: The purpose of this study is to determine the frequency of late endocrine complications following radiation therapy (RT) in children treated for medulloblastomas or ependymomas. Methods: Seventy children with medulloblastoma or ependymoma were treated using RT from June 2000 to June 2005 at our institute. Median age at diagnosis was 6 years (range 1–17), and 52 (74%) were boys. Forty-eight patients (69%) had medulloblastomas and 22 (31%) had ependymomas. Twenty-two received highly conformal RT to the tumor bed alone (focal RT: median dose 54 Gy, range 54–59.4), 24 received low dose cranio-spinal RT (CSI: median dose 23.4 Gy) followed by a boost to the post fossa/tumor bed (median 30.6 Gy), and 24 patients received high dose CSI (median 36 Gy) followed by a boost (median 18 Gy). Only two of the 22 children with ependymomas received CSI. All patients underwent CT-based planning and were treated using conventional fractionation; 58 (83%) also received chemotherapy. None of the children had documented endocrinopathy prior to diagnosis. Results: After a median follow-up of 65.3 months, the 5-yr PFS and OS was 70% and 75% for children with medulloblastomas, and 54% and 84% for patients with ependymomas, respectively. Thirty-five children developed evidence of endocrinopathy (Growth hormone deficiency (GHD): 31, hypothyroidism (HPT): 23, precocious puberty (PP): 6, gonadotropin deficiency: 3, ACTH deficiency: 2, and diabetes insipidus: 2). The 5-yr cumulative incidence (CI) of endocrinopathy was 71% for the children treated with CSI vs. 18% for those treated with focal RT (Gray's test p-value = 0.004). The median time to development of endocrinopathy was 38 months for the patients who had CSI. For these children the 5-yr CI was 68% for GHD, 52% for HPT, and 16% for PP. There was no significant difference in the incidence of endocrinopathy for patients treated with low dose vs. high dose CSI. Conclusions: The 5-yr CI of endocrine toxicity in children treated with cranio-spinal RT is 71% (median time to development: 38 months), which is significantly higher than in children treated with focal RT. All children treated for medulloblastomas or ependymomas require long-term surveillance and close monitoring for the development of endocrinopathies. No significant financial relationships to disclose.
Safety and antitumor activity of 3-weekly anti-EpCAM antibody adecatumumab (MT201) in combination with docetaxel for patients with metastatic breast cancer: Results of a multicenter phase Ib trial
Authors: Sebastian M. , Hanusch C. , Schmidt M. , Marschner N. , Oruzio D. , Wolf C. , Reinhardt C. , Eiermann W. , Rüttinger D. , Schuler M. 
Published: August 2020

1009 Background: The fully human IgG1 antibody adecatumumab (MT201) binds to the epithelial cell adhesion molecule (EpCAM), which is expressed in over 90% of breast cancers and has been associated with poor prognosis. Data from a previous phase II study in metastatic breast cancer (MBC) indicated that single agent MT201 could prolong progression-free survival in a subset of patients with high EpCAM expression. This study tested safety and tolerability of MT201 treatment in combination with standard docetaxel. Methods: Relapsed or primary refractory, EpCAM-positive MBC patients were treated with docetaxel (100 mg/m2 q21d) in combination with MT201 (dose levels 180 mg/m2, and 550 mg/m2 q21d). A loading dose of 100 mg/m2 and 300 mg/m2, respectively, was administered on day 1 and 7. Patients were grouped into high- and low-level EpCAM expression. Primary objectives were safety and tolerability; anti-tumor activity according to RECIST was a secondary objective. Results: A total of 22 patients with a median of 3 prior chemotherapy lines were enrolled. Most frequent grade 3/4 adverse events (AE) in all patients were leucopenia (90%), neutropenia (77%), lymphopenia (68%), and diarrhea (23%). No evidence for aggravation of grade 3/4 toxicities typically associated with docetaxel was found. The dose level 550 mg/m2 q21d has been determined as MTD in combination with 100 mg/m2 q21d docetaxel. The overall response rate (CR/PR; RECIST) and clinical benefit rate (CR/PR and SD>24wks) in all evaluable patients was 24% and 41%, respectively. Patients with high EpCAM expression showed a response rate of 43%, whereas patients with low EpCAM expression had a response rate of 10%. Median time-to-progression (TTP) in all evaluable patients was 165 days. Conclusions: Combining MT201 with docetaxel for the treatment of MBC appears to be safe and feasible. The DLT of this combination were short and manageable episodes of grade 3 diarrhea. The response rate and TTP observed in this heavily pre-treated population is encouraging and warrant further development of MT201/chemotherapy combinations in patients with tumors of high EpCAM target level. [Table: see text]
Gemcitabine plus docetaxel versus docetaxel in patients (pts) with HER2-negative locally advanced or metastatic breast cancer (MBC): A randomized phase III study
Authors: Nielsen D. L. , Langkjer S. T. , Bjerre K. , Cold S. , Stenbygaard L. , Soerensen P. G. , Kamby C. 
Published: August 2020

1015 Background: Gemcitabine (G), either as a single agent or in combination with taxanes, has demonstrated efficacy in MBC in phase II and III studies. We conducted a phase III study to compare time to progression (TTP) of G plus docetaxel (T) versus (vs.) T alone. The secondary endpoints included overall survival (OS), overall response rate (ORR), and toxicity. Methods: Females with HER-2-negative locally advanced or MBC and a WHO performance status ≤ 2 were randomized to GT (G 1,000mg/m2 day 1 + 8; T 75mg/m2 day 1) or T (100mg/m2 day 1) every 21 days. Pts were previously untreated, had prior anthracycline-based (neo)adjuvant chemotherapy or had received a single prior anthracycline-bsed chemotherapy regimen for MBC. Time-to-event endpoints were estimated using the Kaplan-Meier method, and the log-rank test was applied for comparisons between regimens. The planned sample size was 254 evaluable pts with α I and β of 0.05 and 0.90, respectively. Results: A total of 336 pts were randomized (170 GT; 166 T), data from one centre are yet missing and the present evaluation is based on data from 306 pts (155 GT; 151 T). The pts had a median age of 58 years in both regimens; range 36–73 years and 30–74 years, respectively. The median TTP was 7.5 months for the GT regimen vs. 6.5 months for the T regimen. The GT arm demonstrated an ORR of 44% vs. 38% in the T arm with 4 and 3 % complete responses, respectively. The OS was 13.4 vs. 13.2 months in the GT and T arm, respectively. Hematologic toxicity was common, especially grade 3–4 neutropenia (GT = 69%; T = 61%); infection was reported in 22 and 20% of the pts, respectively (none of the pts received G-CSF). The most commonly reported non-hematologic toxicities of grade 3–4 included mucositis (GT = 2%; T = 5%), diarrhea (GT = 4%; T = 7 %), fatigue (GT = 6%; T = 11%), oedema (GT = 10%; T = 3%), and peripheral neuropathy (GT = 9%; T = 28%). Conclusions: Preliminary data of GT as first- or second-line chemotherapy demonstrates a TTP advantage among HER-2-negative pts with advanced breast cancer. Updated results and proper statistical analyses will be presented. No significant financial relationships to disclose.
Relevance of serum HER2 extracellular domain (sECD) in EGF30008, a study of letrozole ± lapatinib in patients (pts) with hormone-receptor positive (HR+) metastatic breast cancer (MBC)
Authors: Platek G. T. , Koehler M. , Gagnon R. , O'Rourke L. , Maltzman J. D. , Press M. , Johnston S. , Pegram M. 
Published: August 2020

1019 Background: Elevated baseline sECD (BsECD) correlates weakly with HER2 overexpression (HER2+). HR+ MBC. Lapatinib benefit was reported in pts with HER2+ tumors irrespective of BsECD status; BsECD status did not predict benefit for HER2- negative (HER2-ve) tumors. sECD levels and their predictive and prognostic value for progression-free survival (PFS) were further examined in a randomized, phase III trial of letrozole ± lapatinib. Methods: Pts (n=1286) with HR+ MBC were randomized to letrozole with placebo (P) or lapatinib (L). HER2 status was evaluated by FISH or IHC in archived tissue. sECD was measured by ELISA at baseline (n=1102 available samples), and every 4 wk. Pts were considered sECD+ if serum sECD was >15 ng/ml. Results: BsECD was positive in 14% (125/894) and 42% (87/208) of pts with HER2-ve and HER2+ tumors, respectively. Correlation between BsECD and FISH was weak but significant in HER2+ pts (R=0.35, p<0.0001) but not in HER2-ve pts (R=0.03, p=0.362). Unlike for HER2+ tumors, BsECD+ did not predict benefit in PFS from L in pts with HER2-ve tumors. HR: Hazard Ratio In pts with HER2- ve tumors, median ECD levels were stable in the P arm but increased slightly (4 ng/mL) in the L arm. In the HER2+ group, median levels in the P arm declined (3.5 ng/mL) but increased at 4 wk in L arm (3.4 ng/mL) and were stable thereafter. Conversion from sECD-ve to sECD+ was observed in both arms but did not correlate with outcome or provide predictive value. Data related to ECD status conversion will be reported. Conclusions: BsECD+ status correlates with HER2+ tumor status and may predict L benefit but BsECD+ status did not predict benefit in pts with HER2-ve tumors. On therapy changes in median sECD were small. Conversion from BsECD-ve to sECD+ did not predict L benefit and we could not confirm that evaluation of on treatment ECD status may help treatment decision. [Table: see text] [Table: see text]
Pertuzumab monotherapy following trastuzumab-based treatment: Activity and tolerability in patients with advanced HER2- positive breast cancer
Authors: Cortés J. , Baselga J. , Petrella T. , Gelmon K. , Fumoleau P. , Verma S. , Pivot X. , Ross G. , Szado T. , Gianni L. 
Published: August 2020

1022 Background: Pertuzumab binds to the dimerization epitope of the HER2 receptor, inhibits HER dimerization and signal transduction, and induces ADCC. In 2 cohorts of pts (n = 66) with HER2-positive metastatic breast cancer which had progressed during trastuzumab therapy after ≤3 lines of chemotherapy with or without trastuzumab, pertuzumab plus trastuzumab has been shown to be active (CR 7.6%, PR 16.7%, SD ≥6/12 25.8%) (Gelmon et al. ASCO 2008, Abs 1026). To assess the activity of pertuzumab monotherapy in this clinical setting, the protocol was amended to include a 3rd cohort of pts. Methods: Pt selection was not changed except that ≥1 month between the last dose of trastuzumab and study start was required. Pts received pertuzumab monotherapy. If the tumor failed to respond or responded and then progressed, trastuzumab could be added to pertuzumab. 27 pts were to be recruited to ensure that ≥24 were fully evaluable for objective response and stabilization of disease ≥6 months. Standard 21-day schedules of the antibodies were given. Results: 29 pts were recruited. Tolerability was good: the major adverse events were mild diarrhea and rash with no clinical cardiac events. To date, 2 responses have been reported, and several pts have ongoing stabilization of disease. 14 pts have received trastuzumab plus pertuzumab following inadequate response (or response then relapse) on pertuzumab monotherapy. Of these 14, 2, having progressed during trastuzumab, failed to respond to pertuzumab monotherapy but underwent confirmed response when trastuzumab was added to the pertuzumab –possibly the first report of such a phenomenon and providing good evidence of an enhanced effect when the antibodies are combined. Updated results will be presented. Conclusions: Pertuzumab monotherapy is active against HER2-positive breast cancer which has progressed during trastuzumab-based therapy. The combination of the two antibodies appears to be more active than either antibody alone. The combination is also active in patients that had failed both antibodies given separately. In clinical studies, the use of the two antibodies combined is justified. [Table: see text]
Tumor phenotype and characteristics of metastatic brain involvement in breast cancer patients: Potential clinical consequences
Authors: Palacova M. , Svoboda M. , Fabian P. , Ondrova B. , Grell P. , Jana G. , Princ D. , Radova L. , Slampa P. , Vyzula R. 
Published: August 2020

1026 Background: Central nervous system metastases (CNS) occur in about 20% of patients with breast cancer. Despite the fact that most of these patients die within a few months, substantial subgroup may survive a year or more. Methods: We performed this study on cohort of 187 breast cancer patients who developed CNS metastases to identify relations between the tumor phenotype and the incidence and characteristics of CNS dissemination, response to the local therapy and overall survival since the development of metastases in brain (OScns). Results: The incidence of monitored phenotypes and other data are included in the table. An unambiguous dependence between the tumor's phenotype and the following attributes has been proven: a) interval between the disease diagnosis and the 1st metastatic event (DFS); b) interval between the 1st metastatic event and the metastases in the CNS (TTPcns); c) characteristics of CNS dissemination. The CNS dissemination was the most extensive in patients with HER-2+ tumors in comparison with HER-2 negat. carcinomas. Surprisingly, patients with triple-negative tumors had the minimal metastatic involvement of CNS defined by size and number of lesions. Phenotype did not correlate with local response to therapy and OScns. The OScns has been significantly prolonged by neurosurgery (median 13,8 vs 2,4 months, p<0.0001) and when the effective local treatment was followed by system treatment (6,1 vs 1,9 months, p<0.0001). Conclusions: Our study has confirmed the dependence between primary tumor phenotype and the time of incidence of metastatic brain affection and character of their spread. Our results encourage the inclusion of CNS imaging examination (CT or MRI) into the regular restaging of patients with HER2 positive and triple-negative primary breast cancer, who are at high risk for early development of CNS dissemination. Especially in case of triple-negative tumors, there is higher probability for early detection of limited CNS metastatic involvement. [Table: see text] No significant financial relationships to disclose.
Complications associated with erythropoietin stimulating agents (ESAs) in patients with metastatic breast cancer: A surveillance, epidemiology, and end results (SEER)–Medicare study
Authors: Chavez-Macgregor M. , Fang S. , Srokowski T. P. , Hortobagyi G. N. , Giordano S. H. 
Published: August 2020

1034 Background: Results of recent clinical trials suggest that the use of ESAs is associated with adverse outcomes. ESAs increase the risk for thrombotic events and have the potential of decreasing survival. Guidelines recommend the use of ESAs in patients with chemotherapy-induced anemia being treated with non curative intent. In this population-based study, we sought to evaluate the thromboembolic effects associated with the use of ESAs in patients receiving chemotherapy for metastatic breast cancer. Methods: Retrospective cohort study using the SEER-Medicare linked database. Patients with stage IV breast cancer diagnosed from 1995–2002, who were 66 and older, were treated with chemotherapy, and had full coverage of Medicare A and B were identified. Patients with end stage renal disease were excluded. ICD-9 and HCPCS codes were used to identify the use of ESAs, chemotherapy, comorbidities, and complications of therapy. Analyses were conduced using descriptive statistics, logistic regression, and Cox proportional hazard models. Results: 1411 women were included, 519 (36.8%) received ESAs and 892 (63.2%) did not; median age was 73 and 74 years old respectively. Median time from diagnosis to first ESA dose was 6 months, median number of ESAs doses was 8.5. In univariate analysis, patients receiving ESAs had higher rates of MI/CAD (38% vs 32.9% p = 0.051), thrombosis (32.4% vs 23.2% p = 0.0002), phlebitis (21.4% vs 12.6% p < 0.0001), and transfusion (37.76% vs 19.4% p < 0.0001), with no difference in the rate of stroke or pulmonary embolism. Multivariate analysis showed HR for MI/CAD 1.29 (1.01–1.66); thrombosis 1.5 (1.116–1.93), phlebitis 1.79 (1.32–2.43), and transfusion 2.65 (2.05–3.43). Significant dose effect was evident for the thrombosis and phlebitis outcomes for patients receiving more than 5 ESAs doses. Conclusions: The use of ESAs in patients with metastatic breast cancer increases the risk of thrombosis and phlebitis, with evidence of a dose-dependent effect. Patients receiving ESAs were more likely to have blood transfusions. These data support current practice of using ESAs for minimum necessary time to reduce risk of complications. No significant financial relationships to disclose.