bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical predictors and risk of optic pathway glioma (OPG) in Neurofibromatosis-1 (NF-1)
Authors: Mian A. R. , Schorry E. , Chakraborty R. , Chakraborty B. , Perentesis J. P. 
Published: March 2020

9016 Background: NF-1 is a progressive disease with wide spectrum of phenotype and unpredictability in clinical course. NF-1 patients are at significantly increased risk for development of a variety of neoplasms that cause morbidity and limited mortality, including OPG. There are limited data identifying risk factors predictive of subsequent OPG development. Objective: To identify key early clinical features which predict subsequent risk for development of OPG. Methods: Case-control study of NF-1 patients with and without OPG from Cincinnati Children’s Hospital NF-1 and Cancer Registries. Predictor variables were clinical risk factors (age at diagnosis of NF-1, race/ethnicity, gender, and history of familial NF-1, macrocephaly, plexiform neurofibroma, developmental delay, seizure disorder,), and the dependent variable was development of OPG by imaging. Patients received screening head MRI at the time of presentation with NF-1. Odds ratios (O.R.) were calculated with 75 cases (NF-1 and OPG) and 215 controls (NF-1 only) and statistically/clinically significant factors were further analyzed by logistic regression method. Results: Prevalence of OPG in NF-1 was 15.6%. Almost half had familial NF-1. Median age at diagnosis of NF-1 was 1.6 yrs (cases) and 2.4 yrs (controls). OPG was diagnosed at median age 4 yrs. Patients with T2 hyperintense lesions on imaging (UBOs) and age 4 years or less at diagnosis of NF-1 were at significantly increased risk of developing OPG (O.R=3.1, p=0.006 and O.R=3.1, p=0.002 respectively). In addition, presence of seizure disorder and developmental delay were borderline significant (O.R=2.8, p=0.07 and O.R=1.7, p=0.04 respectively). Race (Caucasian) appeared to have disease modifying effect on development and progression of OPG. Conclusions: Patients with T2 lesions on presentation MRI, developmental delay, seizures, and age 4 years or less at NF-1 diagnosis appear to be at an increased risk of developing OPG. Caucasian race appears to have a modifying effect on disease progression. Patients with these risk factors may be stratified as “high risk” and may benefit from close surveillance for early detection of OPG. The association of developmental delay and seizures may suggest a pathophysiologic relationship. No significant financial relationships to disclose.
Cardiac status predicts quality of life in Hodgkin’s disease survivors
Authors: Adams M. J. , Ng A. K. , Mauch P. M. , Lipshultz S. E. 
Published: March 2020

9029 Background: Long-term survivors of Hodgkin’s disease (HD) treated with mediastinal radiotherapy suffer from a variety of subclinical cardiac abnormalities including valvar defects and findings suggestive of restrictive cardiomyopathy. Their clinical importance has not been definitively demonstrated in longitudinal studies, but they may be related to the reduced quality of life reported by many HD survivors. Methods: The overlapping participants in two independent studies of HD survivors were identified in order to form a longitudinally studied cohort. In the first study, 48 survivors of childhood and young adulthood HD were evaluated by multiple cardiac testing modalities and quality-of-life assessment including the SF-36, a mean of 16 years after diagnosis. In the second performed about 5 years later, 511 survivors took part in a survey study, which also included the SF-36 instrument. A total of 23 patients participated in both studies and formed the current study population. Correlations were performed between key cardiac abnormalities uncovered during the first study and the physical component score (PCS) of the SF-36 measured in the second study, and the changes in PCS during the time between the 2 studies. Results: Average PCS was 44.05 at time of the second study, about 6.0 points lower than at time of cardiac testing. Maximum oxygen consumption correlated with PCS at time 2 (r=0.50, p=0.029). Univariate regression suggested that for every unit decrease in maximum oxygen consumption, the PCS decreased by 0.45 units. The higher the baseline PCS, the greater the negative change in PCS. Left ventricular fractional shortening correlated with PCS at time 2 (r=−0.579, p=0.0094) but not change in PCS. Conclusions: The study suggests that objective measures of reduced cardiac function are predictive of future quality of life in HD survivors. These results however need to be verified in a larger longitudinal study that allows for multivariate analysis. No significant financial relationships to disclose.
Immunological recovery in children with ALL at the end of intensive therapy, at the completion of therapy, and up to one year off therapy. A follow-up study
Authors: Kosmidis S. P. , Baka M. , Bouhoutsou D. , Kallergi C. , Doganis D. , Douladiris N. , Varvoutsi M. , Pourtsidis A. , Sotiropoulou A. , Papageirgiou P. S. , Kosmidis H. V. 
Published: March 2020

9031 Background: Children undergoing therapy for ALL are known to have impaired immune function. (ASCO 2005, abstract #8541). Methods: We prospectively evaluated the humoral and cellular immunity in children with ALL at the end of intensive therapy (Evaluation 1 -E1) and values were compared to those at the completion of therapy (E2), at 6 months (E3) and at 12 months thereafter (E4). Investigations among others included CBC, lymphocyte subpopulation by flow cytometry (CD3, CD4, CD8, CD16, CD19, CD3 DR, CD45RO and CD45RA), immunoglobulin levels by nephelometry, antibody titers to MMR immunization and skin tests to Candida, Trichophyton, diphtheria toxin and tetanus toxoid. Seventy three children with ALL, 48 boys, 25 girls (median age 4 years on diagnosis) treated according to BFM 95 protocol were evaluated. Of the 139 evaluations, 41 were E1, 43 E2, 37 E3, 18 E4 and data were analyzed with a non parametric Mann Whitney test. Results: Immunoglobulin levels at E1 were low in the majority of children and were increasing at E2 and E3 and E4 for IgA and IgM (median values of parameters studied are shown in the table in mg/dl for immunoglobulins and % for CD’s). Of the 70 children immunized with MMR only 11 had absent IgG antibodies. Also, skin tests were positive for tetanus toxoid in 93/139 evaluations, for candida in 41/139 and negative for trichophyton and diphtheria toxin. Conclusions: Children with leukemia experience severe immunological damage after intensive therapy which is gradually improving overtime although some values remain abnormal 6 months after the completion of therapy. It is worth mentioning that despite impaired immune function serious infections were not documented after the first six months of intensive therapy. [Table: see text] No significant financial relationships to disclose.
Metabolic syndrome traits in long-term survivors of pediatric sarcoma at a single institution
Authors: Hoffman K. E. , Derdak J. , Bernstein D. , Reynolds J. C. , Steinberg S. M. , Chrousos G. , Gerber L. , Mackall C. L. , Mansky P. J. 
Published: March 2020

9041 Multi-modality therapy (MMT) for pediatric sarcoma (SARC) may result in late endocrine abnormalities and increased cardiovascular morbidity. Metabolic syndrome (MS; NCEP ATPIII definition), a cluster of obesity, dyslipidemia, hyperglycemia and hypertension, conveys an increased risk of type 2 diabetes and cardiovascular disease. This cross-sectional study investigated the prevalence of the MS traits (MST) in long-term survivors of MMT for SARC. 32 survivors of SARC (predominantly Ewing’s; median age 36.5 years, range 17–54; f:m = 15:17; median age at MMT of 15 years, range 7–34; median time since completion of MMT 18 years, range 3–33) completed CT evaluation of abdominal obesity, DEXA scan for body mass composition, fasting serum lipid profile (FLP), the Human Activity Profile (HAP) and PAI and beta 2 microglobulin (B2M) analysis. Results, compared to appropriate controls were considered statistically significant if the p-value < 0.01. SARC survivors were more likely to have one or more MST (common OR 4.04, CI:[1.52, 13.55], p=0.0045). Subjects aged 20–39 had a higher pooled prevalence of the MS (common OR 4.29 [1.50, 11.21], p=0.0077), defined as 3 or more traits, compared to controls stratified by gender. Analysis of individual MST demonstrated higher prevalence of hypertension (common OR 2.61,[1.20, 5.59], p=0.015), hypertriglyceridemia (common OR 3.63, [1.75, 7.60], p=0.0006), and male abdominal obesity (common OR 4.52, [1.57, 13.39], p=0.0046). SARC survivors had a higher prevalence of hypercholesterolemia than healthy adults (p=0.012). PAI antigen (p=0.043), PAI activity (p=0.018) and B2M levels (p=0.043) increased with an increasing number of MST. In male subjects, total testosterone declined (p=0.008) as the number of MST increased. Average (p=0.028) and maximum (p=0.041) activity levels decreased as the number of MST increased. After a median follow up of 18 years, adult SARC survivors of MMT have an increased prevalence of MST, especially between ages 20–39 years. The development of MST may be associated with decreased testosterone and decreased activity level. Younger male adult SARC survivors may be at particular risk for type 2 diabetes and cardiovascular disease and should be monitored. No significant financial relationships to disclose.
Online pediatric oncology education: A novel teaching tool for oncology residents
Authors: Gfeller P. , Harrison R. , Goddard K. J. 
Published: March 2020

9048 Background: Deficiencies in pediatric oncology training for residents have been identified internationally. A lack of training in pediatric oncology during residency is correlated with impaired outcomes for pediatric patients. There is a clear need for novel teaching tools to supplement training in pediatric oncology. Purpose: The goal of this project was to develop a series of multimedia web-based learning modules for the interactive instruction and review of pediatric oncology. A needs-based assessment of pediatric oncology training in Canadian radiation oncology residency programs was used to guide web-site development. Methods: A needs-based analysis was conducted via a web-based survey sent to all Canadian radiation oncology program directors and residents. The survey was designed to identify the limitations of current training curriculum in pediatric oncology. A multidisciplinary team, including pathologists, radiologists, medical physicists, radiation and medical oncologists, developed the web site curriculum. The site was designed using teaching modules to focus on pediatric tumour sites. Modules were developed using a common format, divided into chapters detailing specific tumour types. Each chapter reviewed relevant epidemiology, anatomy, pathology, radiology, and treatment for the tumor type. A self-assessment tool was included at the end of the modules. User satisfaction surveys were used for feedback. Results: 100% (10/10) of Canadian radiation oncology program directors and 66% (69/106) of Canadian residents responded to the survey. 56% (59/106) of resident respondents felt that teaching in pediatric radiation oncology was inadequate and 56% (20/36) of senior residents felt unprepared for questions in pediatric oncology on qualifying board exams. 90% (105/116) of respondents felt that a web-based teaching tool would be useful. The first module, pediatric neuro-oncology, has been completed. Results indicate users find this module useful for supplementing traditional training. Conclusions: There are no other interactive teaching tools in pediatric oncology. This unique web-based educational program will allow self-directed study in the area of pediatric oncology, providing more effective learning of this challenging yet essential area of study. No significant financial relationships to disclose.
Micro-RNA deletion in neuroblastoma: A possible alternative mechanism of MYCN overexpression
Authors: Yaniv I. , Reshef-Ronen T. , Ash S. , Goshen Y. , Jeison M. , Stark B. , Nordenberg J. , Avigad S. 
Published: March 2020

9052 Background: Micro-RNAs (miRNAs) are small noncoding RNAs of 18 to 25 nucleotides that regulate protein expression. The biological functions of miRNAs are not yet fully understood. miRNA genes were recently found to be abnormally expressed in several types of cancer. By negatively regulating proto-oncogenes, miRNAs could act as tumor suppressors and conversely, by inhibiting tumor suppressors function as oncogenes. Neuroblastoma (NB) is the most common solid tumor in children under 5 years of age. Major adverse prognostic factors include: age over 1 year, advanced stages, adrenal primary site, MYCN amplification, diploid or tetraploid DNA content (DI), and chromosomal aberrations - including 1p deletions. We studied a possible involvement of miRNAs in neuroblastoma. Methods: The cohort consisted of 72 patients: 65% of them were above 1 year of age, 72% with advanced stages, 33% of the patients progressed. Median follow up was 60 months (ranging 1–221). Genomic DNA from 72 tumors were analyzed for the presence of 7 miRNAs located on chromosome 1p, ranging from 1p36.33 to 1p31.1 by PCR. Results: Deletion of one or more of the miRNAs was identified in 50% of the tumors.The most prevalent deletions were of two miRNAs: miR 30e located on 1p34.2 (29%) and miR 34a on 1p 36.23 (22%), accounting for 40% of the patients with a deletion of one or both of these miRs. Interestingly, miR 30e and miR 34a are known to negatively regulate the oncogene MYCN. MYCN protein expression is currently being evaluated in this cohort. Conclusions: The deletions of these miRNAs in neuroblastoma tumors suggest their involvement as tumor suppressor genes. This implies a new mechanism for the overexpression of MYCN. Discovery of the miRNAs and their targets involved in neuroblastoma has a therapeutic potential, for the development of new targeted therapies. No significant financial relationships to disclose.
Carboplatin hypersensitivity reaction in pediatric low grade glioma (LGG) patients: A national experience. On behalf of the Canadian Pediatric Brain Tumor Consortium
Authors: Lafay-Cousin L. , Hukin J. , Carret A. , Wilson B. , Zelcer S. , Strother D. , Odame I. , Silva M. , Johnson D. , Bouffet E. 
Published: March 2020

9053 Background: Carboplatin based regimens are widely used in the treatment of unresectable pediatric LGG. Carboplatin hypersensitivity reaction (CHSR) represents a main limiting factor. Objective: To analyse the incidence, characteristics, management and impact on outcome of CHSR. Methods: National retrospective review of children diagnosed with LGG between 1988 and 2004. Inclusion criteria were age <18 years, pathology proven diagnosis of LGG except in NF1 patients, and no chemotherapy or radiotherapy prior to carboplatin chemotherapy. Results: 105 patients (61F/44M) from 10 Canadian centers were included in the study. Median age at diagnosis was 3.5y (0.3–16.8). 33 patients had NF1, 75 had diencephalic tumor. Carboplatin was given monthly or weekly respectively in 46 and 59 patients. 44 (41.9%) patients developed carboplatin HSR at a median time of 6.5 months (0.4–15.4), after a median number of 10.5 (3–39) injections. CHSR occurred significantly earlier with the weekly schedule (p=0.016). Cumulative incidence of CHSR increased with the number of injections with no plateau. Female had significant higher risk to develop CHSR (p=0.02) whereas age, NF1 status and schedule of administration were not significant risk factors. First allergic reaction was rated grade I, II in 36 patients (82%). 34 patients were reexposed to carboplatin with desensitization/premedication, allowing 14 patients (41.2%) to complete their treatment. But the majority (58.8%) had recurrent allergic reaction with a significant worsening of their symptoms (p=0.039). The median number of additional Carboplatin injections delivered was 4 (0.5–34). After Carboplatin discontinuation, 18 patients were switched to another chemotherapy regimen. 5 years PFS was not significantly different in allergic and non allergic patients (53.9% and 45.6%). Conclusions: In our experience, the incidence of CHSR is high (41.9%). Female have higher risk of CHSR. Desensitization/premedication has limited efficacy and does not prevent worsening of CHSR. CHSR did not impact the PFS. However many patients did switch to another chemotherapy regimen and the total duration of treatment was comparable in both groups. No significant financial relationships to disclose.
Childhood nasopharyngeal carcinoma: A 4-year single institution experience
Authors: Patel A. A. , Shah P. M. , Patel K. M. , Shukla S. N. , Parikh B. J. , Anand A. S. , Shah S. A. , Talati S. S. , Panchal H. P. , Pandey R. 
Published: March 2020

9069 Background: Pediatric nasopharyngeal carcinoma (PNC) represents a locally advanced undifferentiated tumor. In this study, clinical experience and therapeutic results of 24 children with newly diagnosed PNC, treated in a single oncology institution in India over a period of 5 years, are analyzed. Methods: 24 patients (23 males and 1 female) 7–14 years old (median = 12) from Jan 2000 to Sep 2005 with PNC were retrospectively evaluated. 18/24 patients were evaluable. 16 patients received induction chemotherapy followed by radiotherapy while 1 patient was offered concurrent chemoradiotherapy, 1 patient received radiotherapy alone. 15/16 patients received postradiation chemotherapy. The agents used in induction and adjuvant therapy were cisplatin (100 mg/m2) on day 1 and 5-fluorouracil 750 mg/m2 for 5 days. The dose of radiotherapy used was 60 gray in 30 fractions. Results: The time of onset of symptoms to diagnosis ranged from 1 month to 9 months with a median of 5.5 months. Histopathology was lymphoepithelioma in 5 patients (27.7%) while 13 patients (72.2%) had poorly differentiated carcinoma. Disease extent was T2 (n = 7), T3 (n = 6), and T4 (n = 5); N1 (n = 5), N2 (n = 7), and N3 (n = 5). 7 patients had intracranial invasion. None had metastatic disease on presentation. 13 patients (72.2%) achieved major response which included 7 (38.8%) complete remission and 6 (33.3%) partial remission after the induction chemotherapy and radiotherapy. 4 (22.2%) had progressive disease. Another 3 (16.6%) attained complete remission after post radiation chemotherapy which consisted of two cycles of cisplatin and 5-flourouracil. The follow up ranged from 5 months to 84 months with a median follow up of 35 months. The disease free survival ranged from 10 months to 53 months with a median of 33 months. The patients who had a better response to induction chemotherapy had a better disease free survival. Out of 7 patients who attained complete remission 2 relapsed with a median time to first relapse of 9.5 months. Toxicity to therapy was modest. Only one patient had grade 4 neutropenia and mucositis. There was no therapy related mortality. Conclusion: Chemoradiotherapy for nasopharyngeal carcinoma in children is an effective treatment modality with minimal toxicity. No significant financial relationships to disclose.
Indication and results of surgery following imatinib treatment of locally advanced or metastatic GI stromal tumors (GIST)
Authors: Hohenberger P. , Langer C. , Pistorius S. , Iesalnieks I. , Wardelmann E. , Reichardt P. 
Published: March 2020

9500 Background: Imatinib mesylate efficiently induces tumor remission in advanced GIST however the curve of progression-free survival (PFS) in the large randomised trials does not reach a plateau. Surgery after achieving a PR is often recommended to remove tumor remnants or seems to be the treatment of choice to control tumor progression not or no longer controlled by drugs. The true impact of surgery is unclear and we analysed the indication and outcome of resective procedures including patients treated outside randomised trials. Patients: In a multi-institutional setting, we collected data from 113 patients after surgery for histologically confirmed GIST after imatinib treatment since April 2002. Primary tumor location: esophagus 3, stomach 23, small bowel 46, rectum 21, extraintestinal 20 pts. Indication for resection: to remove remnants of tumor sites responding well to imatinib 44 pts, resection of progressive lesions 55 pts, resection of a primary tumor after intended neadjuvant treatment 14 pts. Median duration of imatinib treatment prior to surgery was 11 (7–30) months for responding tumors, 14 months (4–28) for progressive lesions and 7 months (3–14) in the neoadjuvant group. Results: Median follow-up postoperatively is 16 months. Operative procedures: hepatic resection 13 pts., abdomino-perineal excision/anterior resection 27 pts, multivisceral resection 73 pts, peritoneal debulking 31 pts. An R0 resection could be achieved in 72% in the PR group, 86% in the neoadjuvant group, but only 26% in the progression group, postop. mortality was 1.7%. Median PFS in the R0 group is 16 (7-39) months and 7 months (2-25±) in the progressive group. In 14 pts imatinib treatment was not continued after R0 resection, 8 pts developed a recurrence. Conclusion: Progression-free survival after R0 resection of responding GIST is encouraging and the data could be used for planning a randomized trial of delayed vs. immediate resection in responding lesions after criteria ‘best response’ are agreed upon. Outside a trial, GIST patients developing a good PR with imatinib should be evaluated for resection as early as possible. However, even patients with a limited number of progressive lesions may benefit from surgery for a longer duration of time. [Table: see text]
A putative tumor suppressor role for Wnt-signaling in sarcomagenesis
Authors: Matushansky I. , Socci N. , Hernando E. , Singer S. , Schwartz G. , Cordon-Cardo C. , Maki R. 
Published: March 2020

9507 Background: We sought to elucidate the relationship between the human adult mesenchymal stem cell (hMSC), Wnt signaling and sarcomagenesis. Methods: In vitro hMSC differentiation, microarray gene expression analysis, distance correlation analysis, and standard molecular biology techniques were used to explore the role of Wnt in controlling the differentiation of both hMSCs and high grade undifferentiated sarcoma (HGUS; MFH, malignant fibrous histiocytoma), a common form of adult soft tissue sarcoma. Results: We determined that 1) hMSCs appear to be the progenitor cells of HGUS/MFH; 2) Dickkopf-1 (Dkk1), a specific inhibitor of Wnt signaling, is overexpressed in MFH as compared to other sarcoma subtypes and is involved in the proliferation of hMSCs; 3) in hMSCs, Dkk1 levels decline and nuclear β-catenin accumulates as hMSCs reach confluence, a prerequisite for initiation of in vitro differentiation, while in an MFH cell line Dkk1 levels do not decline and there is no nuclear β-catenin accumulation; 3) MFH cells appear to be primed for differentiation and express early markers of mesenchymal differentiation, then undergo apoptosis, if nuclear β-catenin is manipulated to enter the nucleus; 4) Wnt2 signals via the canonical β-catenin pathway and is responsible for “commitment” of hMSC and an MFH cell line to various differentiation pathways, while Wnt5a signals via the non-canonical JNK pathway in preventing apoptosis upon appropriate commitment toward differentiation. Conclusions: We identified the contribution of canonical and non-canonical Wnt signaling in the differentiation of hMSCs and showed that enhancing signaling via these pathways could be exploited as a potential target for therapy for high grade undifferentiated sarcomas. These data implicate Wnt-signaling as a mechanism of tumor suppression in early sarcomagenesis. No significant financial relationships to disclose.