scholarly journals The impact on outcomes by using thiotepa in tandem transplant for pediatric high-risk embryonal brain tumors

2019 ◽  
Vol 82 (2) ◽  
pp. 148-154
Author(s):  
Hsiu-Ju Yen ◽  
Ting-Yen Yu ◽  
Chih-Ying Lee ◽  
Giun-Yi Hung ◽  
Tzeon-Jye Chiou ◽  
...  
Keyword(s):  
High Risk ◽  
Brain Tumors ◽  
Embryonal Brain ◽  
The Impact

Concurrent cyclophosphamide and craniospinal radiotherapy for pediatric high-risk embryonal brain tumors

2012 ◽  
Vol 110 (2) ◽  
pp. 287-291 ◽  
Author(s):  
Cynthia J. Campen ◽  
Joanna Dearlove ◽  
Sonia Partap ◽  
Patricia Murphy ◽  
Iris C. Gibbs ◽  
...  
Keyword(s):  
High Risk ◽  
Brain Tumors ◽  
Craniospinal Radiotherapy ◽  
Embryonal Brain

Neurocognitive outcome in children with sensorineural hearing loss after treatment of malignant embryonal brain tumors.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 2029-2029
Author(s):  
Christine Dahl ◽  
Iska Moxon-Emre ◽  
Vijay Ramaswamy ◽  
Ute Katharina Bartels ◽  
Uri Tabori ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Brain Tumors ◽  
Sensorineural Hearing Loss ◽  
Sensorineural Hearing ◽  
Verbal Language ◽  
Intellectual Function ◽  
Embryonal Brain ◽  
Mild Hearing Loss ◽  
The Impact

2029 Background: Neurological side effects associated with childhood brain tumors and their treatments contribute to long term neurocognitive morbidity. The aims of this study were to identify the incidence of sensorineural hearing loss (SNHL) in a large sample of children treated for malignant brain tumors, and to evaluate the potential relationship between SNHL and intellectual functioning following the completion of treatment. Methods: We conducted a prospective follow-up study at a single center with review of 119 patients treated for embryonal brain tumors at the Hospital for Sick Children, between 1996-2015, to analyze the impact of significant SNHL (Chang > 2b) on intellectual function. Hearing was assessed post-treatment (median age: 13.5y (+4.5)) and the median age for neurocognitive testing was 12.8y (+ 4.1). The median interval from time of diagnosis was 5.8y (+ 3.7). Results: Severe SNHL was identified in half the patients (50.4%, n = 60/119). We identified a subset of patients (n = 61) who had assessments of intellectual function. In this cohort, intellectual function was significantly poorer in the group with severe SNHL, even after controlling for the effect of craniospinal radiation (severe SNHL 22.4 Gy + 13.3, no or mild hearing loss 20.4 Gy +12.8) and boost dose and volume. Children experiencing severe SNHL had lower overall IQ (severe SNHL 72.4 + 16.6; no/mild hearing loss 92.0 + 20.5) p < 0.001 and in significantly lower verbal comprehension (severe SNHL 78.7 + 15.9; no/mild hearing loss 94.7 + 13.8) p < 0.001, and working memory (severe SNHL 78.2+ 17.6; no/mild hearing loss 94.8 + 16.4) p < 0.001, scores. Conclusions: Hearing loss is a much more significant complication in children with embryonal brain tumors than previously estimated. We show the profound impact of hearing loss on intellectual deficit in children. Namely, patients with severe SNHL have difficulty using and understanding verbal language, and they have a reduced ability to concentrate and manipulate information in short-term memory. Our results have implications on future trial designs and follow-up of children treated for embryonal brain tumors.

scholarly journals PATH-24. MOLECULAR CLASSIFICATION OF HIGH RISK INFANT EMBRYONAL BRAIN TUMORS ENROLLED IN THE ACNS0334 TRIAL: A REPORT FROM THE CHILDREN’S ONCOLOGY GROUP

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii429-iii429
Author(s):  
Bryan K Li ◽  
Peter Burger ◽  
Alexander R Judkins ◽  
Ben L B Ho ◽  
Guolian Kang ◽  
...  
Keyword(s):  
High Risk ◽  
Brain Tumors ◽  
Significant Proportion ◽  
High Grade Glioma ◽  
Clinical Analysis ◽  
Phase Iii ◽  
High Risk Infant ◽  
Global Methylation ◽  
Molecular Features ◽  
Embryonal Brain

Abstract Young children with embryonal brain tumors including medulloblastoma (MB), supratentorial primitive neuro-ectodermal tumor, or pineoblastoma have historically been considered high-risk patients with poor outcomes despite the use of intensive radiation-sparing treatment. In the ACNS0334 phase III trial, 91 consented children &lt;36 months old with the above diagnoses were randomized to intensive induction chemotherapy with or without methotrexate followed by consolidation with stem cell rescue. Here we present the results of a centralized integrated molecular analysis including global methylation profiling (65/91), and whole exome sequencing of tumor (46/91) and germline (35/91) DNA. Unsupervised clustering analyses of methylation profiles using multiple orthogonal methods against a reference dataset of 1200 pediatric brain tumors, revealed known and new molecular entities. For tumors diagnosed as MB on central pathology review, 7.3% (3/41) had a non-MB molecular diagnosis (2 embryonal tumor with multiple rosettes/ETMR, 1 group MYC pineoblastoma), with the remainder as MB Group SHH (11/41), Group3 (25/41), and Group4 (2/41). Among histologic non-MBs, 3/24 (12.5%) were molecular entities not intended for trial inclusion (1 each for ATRT, pleomorphic xanthoastrocytoma, and high-grade glioma). ETMR, historically considered a rare entity, was molecularly identified in a significant proportion (14/65; 21.5%) of samples. Among MB-SHH, we detected deleterious PTCH1 mutations in 6/9 tumors but none among 5 germline samples tested; a germline SUFU frameshift mutation with tumor LOH was also observed in MB-SHH. Correlation of these and other molecular features to the parallel clinical analysis will yield important markers of risk stratification and predictors of treatment response.

Welfare Reform and the Delivery of Welfare-to-Work Programs to AAPIs: What Works?

2007 ◽  
Vol 5 (2) ◽  
pp. 77-97 ◽  
Author(s):  
Julian Chow ◽  
Grace Yoo ◽  
Catherine Vu
Keyword(s):  
High Risk ◽  
Welfare Reform ◽  
Asian American ◽  
Low Income ◽  
Personal Responsibility ◽  
Welfare To Work ◽  
Work Program ◽  
What Works ◽  
One Stop ◽  
The Impact

The passage of the Personal Responsibility and Work Opportunity Act (PRWORA) of 1996 has major implications for low-income Asian American and Pacific Islander (AAPI) populations. The purpose of this paper is to provide an overview of the research currently examining the impact of welfare reform on AAPI recipients and the welfare-to-work services available to this population. This article highlights AAPI participation and their timing-out rates in California’s CalWORKs program and their barriers to transitioning to work. Four welfare-to-work program models and recommendations are presented to illustrate strategies that can be used to address the unique needs of AAPI in order to alleviate their high risk for timing-out: one-stop-shops, transitional jobs programs, providing comprehensive and family focused services, and additional research and evaluation of programs specific to assisting the AAPI population on CalWORKs.

Decision Aids for Generating Analytical Review Alternatives: The Impact of Goal Framing and Audit-Risk Level

2002 ◽  
Vol 14 (1) ◽  
pp. 157-177 ◽  
Author(s):  
Jennifer M. Mueller ◽  
John C. Anderson
Keyword(s):  
High Risk ◽  
Cognitive Load ◽  
Information Search ◽  
Decision Aid ◽  
Decision Aids ◽  
Risk Level ◽  
Audit Risk ◽  
Goal Framing ◽  
Analytical Review ◽  
The Impact

An auditor generating potential explanations for an unusual variance in analytical review may utilize a decision aid, which provides many explanations. However, circumstances of budgetary constraints and limited cognitive load deter an auditor from using a lengthy list of explanations in an information search. A two-way between-subjects design was created to investigate the effects of two complementary approaches to trimming down the lengthy list on the number of remaining explanations carried forward into an information search. These two approaches, which represent the same goal (reducing the list) but framed differently, are found to result in a significantly different number of remaining explanations, in both low- and high-risk audit environments. The results of the study suggest that the extent to which an auditor narrows the lengthy list of explanations is important to the implementation of decision aids in analytical review.

scholarly journals Cisplatin +/− rucaparib after preoperative chemotherapy in patients with triple-negative or BRCA mutated breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Maitri Kalra ◽  
Yan Tong ◽  
David R. Jones ◽  
Tom Walsh ◽  
Michael A. Danso ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Therapy ◽  
Triple Negative ◽  
Residual Disease ◽  
Disease Free Survival ◽  
Parp Inhibition ◽  
High Risk Population ◽  
Risk Population ◽  
The Impact

AbstractPatients with triple-negative breast cancer (TNBC) who have residual disease after neoadjuvant therapy have a high risk of recurrence. We tested the impact of DNA-damaging chemotherapy alone or with PARP inhibition in this high-risk population. Patients with TNBC or deleterious BRCA mutation (TNBC/BRCAmut) who had >2 cm of invasive disease in the breast or persistent lymph node (LN) involvement after neoadjuvant therapy were assigned 1:1 to cisplatin alone or with rucaparib. Germline mutations were identified with BROCA analysis. The primary endpoint was 2-year disease-free survival (DFS) with 80% power to detect an HR 0.5. From Feb 2010 to May 2013, 128 patients were enrolled. Median tumor size at surgery was 1.9 cm (0–11.5 cm) with 1 (0–38) involved LN; median Residual Cancer Burden (RCB) score was 2.6. Six patients had known deleterious BRCA1 or BRCA2 mutations at study entry, but BROCA identified deleterious mutations in 22% of patients with available samples. Toxicity was similar in both arms. Despite frequent dose reductions (21% of patients) and delays (43.8% of patients), 73% of patients completed planned cisplatin. Rucaparib exposure was limited with median concentration 275 (82–4694) ng/mL post-infusion on day 3. The addition of rucaparib to cisplatin did not increase 2-year DFS (54.2% cisplatin vs. 64.1% cisplatin + rucaparib; P = 0.29). In the high-risk post preoperative TNBC/BRCAmut setting, the addition of low-dose rucaparib did not improve 2-year DFS or increase the toxicity of cisplatin. Genetic testing was underutilized in this high-risk population.

scholarly journals Polygenic burden has broader impact on health, cognition, and socioeconomic outcomes than most rare and high-risk copy number variants

2021 ◽  
Author(s):  
Elmo Christian Saarentaus ◽  
Aki Samuli Havulinna ◽  
Nina Mars ◽  
Ari Ahola-Olli ◽  
Tuomo Tapio Johannes Kiiskinen ◽  
...  
Keyword(s):  
High Risk ◽  
Educational Attainment ◽  
Household Income ◽  
Copy Number ◽  
Copy Number Variants ◽  
Well Being ◽  
Subjective Health ◽  
Polygenic Risk Score ◽  
The Impact ◽  
Health Cognition

AbstractCopy number variants (CNVs) are associated with syndromic and severe neurological and psychiatric disorders (SNPDs), such as intellectual disability, epilepsy, schizophrenia, and bipolar disorder. Although considered high-impact, CNVs are also observed in the general population. This presents a diagnostic challenge in evaluating their clinical significance. To estimate the phenotypic differences between CNV carriers and non-carriers regarding general health and well-being, we compared the impact of SNPD-associated CNVs on health, cognition, and socioeconomic phenotypes to the impact of three genome-wide polygenic risk score (PRS) in two Finnish cohorts (FINRISK, n = 23,053 and NFBC1966, n = 4895). The focus was on CNV carriers and PRS extremes who do not have an SNPD diagnosis. We identified high-risk CNVs (DECIPHER CNVs, risk gene deletions, or large [>1 Mb] CNVs) in 744 study participants (2.66%), 36 (4.8%) of whom had a diagnosed SNPD. In the remaining 708 unaffected carriers, we observed lower educational attainment (EA; OR = 0.77 [95% CI 0.66–0.89]) and lower household income (OR = 0.77 [0.66–0.89]). Income-associated CNVs also lowered household income (OR = 0.50 [0.38–0.66]), and CNVs with medical consequences lowered subjective health (OR = 0.48 [0.32–0.72]). The impact of PRSs was broader. At the lowest extreme of PRS for EA, we observed lower EA (OR = 0.31 [0.26–0.37]), lower-income (OR = 0.66 [0.57–0.77]), lower subjective health (OR = 0.72 [0.61–0.83]), and increased mortality (Cox’s HR = 1.55 [1.21–1.98]). PRS for intelligence had a similar impact, whereas PRS for schizophrenia did not affect these traits. We conclude that the majority of working-age individuals carrying high-risk CNVs without SNPD diagnosis have a modest impact on morbidity and mortality, as well as the limited impact on income and educational attainment, compared to individuals at the extreme end of common genetic variation. Our findings highlight that the contribution of traditional high-risk variants such as CNVs should be analyzed in a broader genetic context, rather than evaluated in isolation.

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