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  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2016
    In:  Neuro-Oncology Vol. 18, No. suppl 3 ( 2016-06), p. iii46.4-iii46
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 18, No. suppl 3 ( 2016-06), p. iii46.4-iii46
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
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  • 2
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 18, No. suppl 3 ( 2016-06), p. iii73.4-iii74
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2094060-9
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  • 3
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii297-iii298
    Abstract: There is no standard of care for cerebrospinal (CSF) diversion in children with diffuse intrinsic pontine glioma (DIPG), nor understanding of survival impact. We evaluated CSF diversion characteristics in children with DIPG to determine incidence, indications and potential impact on survival. Data was extracted from subjects registered in the International DIPG registry (IDIPGR). IDIPGR team personnel obtained clinical and radiographic data from the registry database and when appropriate, abstracted additional data from individual medical records. Univariable analyses were performed using the Fisher’s exact test or Wilcoxon rank sum test. Survival was estimated using the Kaplan-Meier method. Evaluable patients (n=457) met criteria for DIPG diagnosis by central radiology review. Ninety-two patients (20%) had permanent CSF diversion. Indications for permanent diversion were hydrocephalus (41%), hydrocephalus and clinical symptoms (35%), and clinical symptoms alone (3%). Those with permanent diversion were significantly younger at diagnosis than those without diversion (median 5.3 years vs 6.9 years, p=0.0002), otherwise no significant differences in gender, race, or treatment were found. The progression-free and overall survival of those with permanent CSF diversion compared to those without permanent diversion was 4.5 and 10.9 months vs 6.9 and 11.2 months, respectively (p=0.001, p= 0.4). There was no significant difference in overall survival in patients with or without permanent CSF diversion among a large cohort of DIPG patients. Patients without permanent diversion had significantly prolonged progression free survival compared to those with permanent diversion. The qualitative risks and benefits of permanent CSF diversion need to be further evaluated.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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  • 4
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii356-iii357
    Abstract: Optimizing the conduct of clinical trials for diffuse intrinsic pontine glioma (DIPG) involves use of consistent, objective disease assessments and standardized response criteria. The Response Assessment in Pediatric Neuro-Oncology (RAPNO) committee, an international panel of pediatric and adult neuro-oncologists, clinicians, radiologists, radiation oncologists, and neurosurgeons, was established to address unique challenges in assessing response in children with CNS tumors. A subcommittee of RAPNO was formed to specifically address response assessment in children and young adults with DIPG and to develop a consensus on recommendations for response assessment. Distinct issues related to the response assessment of DIPG include its definition and recent molecular classifications, dearth of imaging response data, the phenomena of pseudoprogression, and measuring response in the era of focal drug delivery. The committee has recommended response be assessed using magnetic resonance imaging (MRI) of brain and spine, neurologic examination, and use of supportive medication, i.e. steroids and anti-angiogenic agents. Clinical imaging standards and imaging quality control are defined. Unique recommendations for DIPG response include an eight-week response duration, a twenty-five percent decrease for partial response, and the distinction of pontine and extra-pontine response for trials that use focal drug delivery. The recommendations presented here represent an initial effort to uniformly collect and evaluate response assessment criteria; these recommendations can now be incorporated into clinical trials to assess feasibility and corroboration with patient outcomes.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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  • 5
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii332-iii332
    Abstract: Central nervous system (CNS) germinomas are radiotherapy (RT)-sensitive tumors with excellent survival. Current treatment strategies combine chemotherapy with RT to reduce the field and dose of RT. There is no standard treatment for germinomas originating in the basal ganglia/thalami (BGTG) given their rarity and poorly-defined imaging characteristics. Craniospinal (CSI), whole brain (WBI), whole ventricle (WVI), and focal RT have been previously utilized; however, the optimal strategy remains unclear. METHODS Retrospective multi-institutional analysis was conducted across 18 institutions in four countries. RESULTS For 46 cases with non-metastatic BGTG, the event-free survival (EFS) was 86.9% at both 5 and 10 years, while overall survival (OS) was 100%, and 95.7% respectively at 5 and 10 years. Median RT dose and range for the various treatment volumes were as follows: CSI (n=10): 2340 cGy (1980–3060 cGy), WBI (n=8): 2340 (1800–3000 cGy), WVI (n=14): 2340 cGy (1800–2550 cGy), focal (n=9): 3600 cGy (3060–5400 cGy). There was no statistically significant difference in the EFS based on RT modality (p=0.57), but EFS for subjects with CSI and WBI were both 100%. The three subjects who received chemotherapy alone had significantly lower EFS than those who received chemotherapy and RT (p=0.001), but were salvageable with RT. CONCLUSION In the largest study to date for BGTG, there were no significant differences in outcomes between patients who received CSI, WBI, WVI or focal RT. This group of patients should be included in future prospective clinical trials, and a more limited RT field may be considered.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
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  • 6
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 25, No. Supplement_1 ( 2023-06-12), p. i36-i36
    Abstract: Subsequent malignant neoplasms (SMNs) of the central nervous system (CNS) following childhood cancer are a frequently fatal late effect of cancer therapy. We used the CCSS (5-year childhood cancer survivors, diagnosed 1970-1999) to assess whether temporal changes in therapy have reduced CNS SMN risk. Twenty-year cumulative incidence rates (95% confidence interval) were estimated, and standardized incidence ratios (SIR, 95% CI) were calculated comparing observed to expected rates from SEER. Multivariable models assessed demographic and treatment-related risk factors for CNS SMN. Among survivors diagnosed between 1970-1979 (N=6223), 1980-1989 (N=9680), and 1990–1999 (N=8999) with median follow-up of 40.5, 32.2, and 22.6 years, respectively, 157 CNS SMNs (1970s, 52; 1980s, 63; 1990s, 42) were identified, excluding meningiomas. Malignant gliomas (N=131) were the most common SMNs. Cranial radiotherapy (CRT) exposure decreased by treatment decade, with the proportion of survivors receiving no CRT increasing from 23.0% (1970s), to 45.7% (1980s), and 66% (1990s). Decreases in & gt;0–10Gy exposure (39.0% to 14.1%) and 20.1–30Gy (19.2% to 2.4%) were observed while those receiving & gt;30Gy CRT has not substantially changed (12%, 11.1%, and 8.8%, respectively). Twenty-year cumulative incidence and SIR for development of SMN were 0.32% (0.18-0.46%) and 6.6 (5.0–8.7); 0.55% (0.41-0.70%) and 8.3 (6.6-10.4); and 0.43% (0.31-0.55%) and 9.2 (7.0–12.0), respectively, with no statistically significant differences between treatment eras, including when stratified by attained age. Multivariate analysis showed increased risk for all CRT dose levels & gt;10Gy and for primary diagnoses of medulloblastoma/PNET (HR 3.6, 2.0-6.6) and astrocytoma (HR 2.4, 1.4-3.9). Three-year cumulative incidences of death after SMN, by treatment decade, were 70%, 73%, and 69%, respectively. In conclusion, CNS SMN incidence has not decreased despite fewer survivors being treated with CRT, and CNS SMNs remain a significant source of mortality for affected patients.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2023
    detail.hit.zdb_id: 2094060-9
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_1 ( 2022-06-03), p. i150-i150
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_1 ( 2022-06-03), p. i150-i150
    Abstract: INTRODUCTION: Adult survivors of pediatric central nervous system (CNS) tumors are at the highest risk for morbidity and late mortality among all childhood cancers – owed in part to chronic health condition burden, which intersects with environmental and lifestyle factors. Their weight epidemiology has not been previously characterized. METHODS: An institutional, cross-sectional study was carried out amongst young adults ages 18-39 years, previously treated for pediatric CNS tumors and seen in our specialty survivorship clinic from January 2016 to December 2021. Sociodemographic, clinical, and treatment information was extracted from medical records and summarized by descriptive statistics. Anthropometric information extracted from clinical visit records was used to calculate body mass index (BMI) and weight status category according to CDC guidelines. RESULTS: We identified 200 survivors, 47% male and 53% female. Median age was 26 years (range 18-39); patients were median 16.5 years (range 1.5-34.2) from initial diagnosis. Most common primary diagnoses were low grade-glioma (51.0%) and embryonal tumor (20.5%.) One hundred and five (52.5%) survivors had received prior cranial radiation; 81 (40.5%) had an endocrinologic disorder at time of visit. Amongst the entire cohort, 39% were healthy weight, 5% were underweight, 27% overweight, 21% obese, and 8% severely obese. CONCLUSION: The majority of young adult survivors seen in our clinic were not healthy weight by BMI definition. The distribution of BMI groups appears comparable to contemporary studies of the general young adult U.S. population. For those with decreased muscle mass, a previously recognized issue in pediatric CNS tumor survivors, BMI may underestimate body fat. By abstract presentation, univariable analyses will be performed using the Fisher’s exact test or Wilcoxon rank sum test to assess for undernutrition and overnutrition risk factors. Our refined understanding of the nutritional epidemiology in this population will allow for more strategic diet and exercise interventions.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 79, No. 13_Supplement ( 2019-07-01), p. 3665-3665
    Abstract: Clinical use of gene-panel based sequencing has become increasingly common in the management of pediatric cancer patients. For many patients, gene-panel tests have identified clinically actionable findings. However, highly targeted approaches will miss unanticipated (but potentially clinically meaningful) or novel alterations. In diseases with unknown or complex etiologies, including many pediatric high-risk and solid tumors, an unbiased approach may yield more actionable findings. To accomplish this, we examined the feasibility and utility of whole genome sequencing (WGS) and RNA sequencing (RNAseq) in the management of high-risk pediatric oncology patients. Here we describe our experience with an expanded cohort of over 100 high-risk pediatric oncology patients, with a combination of solid tumors, brain tumors, and leukemia/lymphomas represented. The majority of patients were deemed high-risk due to relapsed/refractory disease. An additional group of patients were defined as high-risk at time of initial diagnosis due to metastatic disease, a rare tumor, prior history of another cancer type, an undifferentiated tumor, or less than 50% estimated overall survival. WGS (tumor/germline) and RNAseq were used to characterize available samples and compared to results from panel testing for each patient (performed as part of their clinical evaluation). When possible, multiple samples from an individual patient were collected (i.e. specimens obtained at biopsy, resection, relapse, and/or from metastatic sites). Somatic DNA samples were sequenced to an average depth of at least 60X and germline samples to at least 30X. RNAseq was performed to a depth of at least 20 million paired-end reads for each sample. WGS samples were analyzed for single nucleotide variants (SNVs), structural rearrangements (SV), and copy-number alterations (CNA). RNAseq samples were analyzed to identify known and novel gene-fusions, to measure allele specific expression of SNVs, and to perform gene-expression outlier analysis. Expression of variants (SNV/SV) identified using WGS were confirmed using RNAseq. For gene expression outliers detected using RNAseq, the WGS data was used to predict possible mechanisms for the aberrant expression (such as CNA, gene fusions, or promoter hijacking). This analysis suggests that WGS and RNAseq analysis is feasible in a clinical setting and can reliably identify variants reported on gene panel tests. However, the use of WGS/RNAseq resulted in additional clinically informative findings while also enabling novel research to further advance our understanding of these rare and highly aggressive pediatric malignancies. Citation Format: Marcus R. Breese, Avanthi T. Shah, Alex G. Lee, Bogdan Tanasa, Stanley G. Leung, Aviv Spillinger, Heng-Yi Liu, Inge Behroozfard, Phuong Dinh, Florette K. Hazard, Arun Rangaswami, Sheri L. Spunt, Norman J. Lacayo, Tabitha Cooney, Jennifer G. Michlitsch, Anurag K. Agrawal, E. Alejandro Sweet-Cordero. Integrative analysis of whole-genome and RNA sequencing in high-risk pediatric malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3665.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2019
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  • 9
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 31, No. 1_Supplement ( 2022-01-01), p. PO-116-PO-116
    Abstract: Background: Literature has shown that racial, ethnic, and gender disparities exist among clinical research participants and within the ranks of academic institutions. To assess this and develop solutions to potential disparities in pediatric neuro-oncology, the Pacific Pediatric Neuro-Oncology Consortium (PNOC) and Children's Brain Tumor Network (CBTN) Diversity, Equity, and Inclusion (DEI) working group distributed a survey to all members of the consortia regarding the state of DEI in our research environments. In parallel, the working group collated clinical data from a public CBTN dataset and a PNOC clinical trial patient cohort to assess racial, ethnic, and gender differences in clinical research participation and outcomes. Methods: This study consisted of two components: an electronically distributed REDCap survey of all PNOC and CBTN consortia members (distributed Fall 2020) and analysis of pediatric neuro-oncology patient cohorts from CBTN and PNOC. The survey collected demographic information of respondents and Likert opinions on DEI at the consortia- and institution level (e.g. “All team members are treated fairly”). Responses were then stratified based on self-identified race, ethnicity, and gender and by age and job title. Patient-level data from the CBTN and PNOC cohorts was collated to evaluate overall patient demographics and clinical outcomes stratified by race, ethnicity, and gender and including differences in survival and clinical research enrollment. Outcomes: Fifty-seven PNOC/CBTN members initiated survey responses, with 45 completing the entire survey (estimated 20-25% response rate). Responders were predominantly white, non-hispanic females with the most common age range of 35-44 years and with faculty or physician job titles, followed by clinical research staff. Statistically significant differences were identified in questions related to the DEI environment mainly at the institution-level. Regarding feelings of inclusion, acceptance, and fair treatment, distinctions were identified across self-reported race and gender with white race correlating with higher frequency of feeling included and respected and females most commonly reporting neutral or disagreement that all team members are treated fairly and that different cultures and backgrounds are valued and interact well. At the patient level, the CBTN and PNOC data pulls included 1711 and 463 patients, respectively, with analyses currently underway and to be aligned with data from the Central Brain Tumor Registry of the United States (CBTRUS) to assess for race, ethnicity, gender, and locoregional differences in our patient cohort and in the context of national registry data. Conclusions: The experiences and feelings of inclusion and treatment of clinical research members within the clinical research environment of pediatric neuro-oncology differ based on self-identified race and gender. Investigation is in process to extrapolate patient-level differences across race, ethnicity, and gender and in the context of larger registry data for pediatric neuro-oncology. Citation Format: Emily Marshall, Tom Belle Davidson, Jeffrey Stevens, Kristina Cole, Fatema Malbari, Tabitha Cooney, Lance Ballaster, Kaitlin Lehmann, Shannon Robins, Miguel Brown, Christopher Blackden, Christopher Friedman, Ammar Naqvi, Jonathan Waller, Ximena Cueller, Jennifer Mason, Jena Lilly, Phillip Jay B Storm, Adam Resnick, Michael Prados, Sabine Mueller, Angela Waanders, Cassie Kline. Identifying disparities across race, ethnicity, and gender in pediatric neuro-oncology clinical research - from patient to provider [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-116.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2022
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    detail.hit.zdb_id: 1153420-5
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  • 10
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 78, No. 13_Supplement ( 2018-07-01), p. 2075-2075
    Abstract: Several recent studies (including BASIC3, iCAT, INFORM, PEDS-MIONCOSEQ) have used whole exome sequencing (WES) and RNA-seq in order to identify targetable chromosomal alterations in a large variety of pediatric cancers. Few studies have attempted to evaluate whether a more comprehensive approach including WGS and RNA-seq could be used to identify novel events relevant to the pathogenesis of advanced pediatric cancer. We analyzed a total of 59 patients (37 solid tumors, 11 brain tumors, and 10 leukemia/lymphomas) to determine the feasibility of using whole-genome sequencing (WGS) technology in conjunction with RNA-seq in order to identify actionable/druggable alterations in the pediatric cancer genomes. WGS analysis has been performed on 75 samples, that were collected from 45 patients, either at diagnosis or at relapse. For WGS analysis of germline-tumor pairs, after performing the sequence alignment with BWA-MEM to gender-specific hg38 genomes, we have used and verified a set of computational methods: 1) MuTect2 for SNV calling, 2) cn.mops for CNV calling, 3) DELLY and LUMPY for SV calling. Here we present our findings on the sets of SNV, CNV, SV, and gene fusions that we have identified by WGSA and RNA-seq, respectively, with a particular emphasis on the druggable alterations, and on the tumor response in the murine PDX models of the pediatric cancers. Consistent with previous observations, the mutational burden across pediatric cancers was low. While common mutations were identified, there was a long-tail of mutations that occurred at a low frequency. As anticipated, samples obtained post-chemotherapy had a higher mutational burden than treatment naive samples. TP53 was the most commonly mutated gene, but we also identified SNVs in other genes commonly mutated in cancer, such as ASXL1, NOTCH2, and RB1. Other novel recurring variants were discovered, further analysis of which is ongoing. Our results indicate that integrated WGS and RNA-seq analysis is feasible in the clinical setting and can reliably identify variants reported on commercially available gene panel testing. However, this approach also resulted in additional clinically relevant findings and allows for novel discovery that will further advance our understanding of these rare and highly aggressive pediatric malignancies. Citation Format: Bogdan Tanasa, Alex Lee, Marcus Breese, Avanthi Shah, Stan Leung, Heng-Yi Liu, Aviv Spillinger, Kimberly Hazard, Arun Rangaswami, Sheri Spunt, Norm Lacayo, Tabitha Cooney, Eric Alejandro Sweet-Cordero. Whole genome sequence analysis informs precision medicine of pediatric cancers [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2075.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2018
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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