GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    MEDB-74. Serial assessment of measurable residual disease in medulloblastoma liquid biopsies
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_1 ( 2022-06-03), p. i123-i124
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_1 ( 2022-06-03), p. i123-i124
    Abstract: Nearly one-third of children with medulloblastoma, a malignant embryonal tumor of the cerebellum, succumb to their disease. Conventional response monitoring by imaging and cerebrospinal fluid (CSF) cytology remains challenging and a marker for measurable residual disease (MRD) is lacking. Here, we show the clinical utility of CSF-derived cell-free DNA (cfDNA) as a biomarker of MRD in serial samples collected from children with medulloblastoma (123 patients, 476 samples) enrolled on a prospective trial. Using low-coverage whole-genome sequencing, tumor-associated copy-number variations (CNVs) in CSF-derived cfDNA are investigated as an MRD surrogate. MRD is detected at baseline in 85% and 54% of patients with metastatic and localized disease, respectively. The number of MRD-positive patients decline with therapy, yet those with persistent MRD have significantly higher risk of progression. Importantly, MRD detection precedes radiographic progression in half who relapse. Our findings advocate for the prospective assessment of CSF-derived liquid biopsies in future trials for medulloblastoma.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac079.448
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    Patient-derived orthotopic xenografts of pediatric brain tumors: a St. Jude resource
    Springer Science and Business Media LLC ; 2020
    In:  Acta Neuropathologica Vol. 140, No. 2 ( 2020-08), p. 209-225
    Details
    In: Acta Neuropathologica, Springer Science and Business Media LLC, Vol. 140, No. 2 ( 2020-08), p. 209-225
    Abstract: Pediatric brain tumors are the leading cause of cancer-related death in children. Patient-derived orthotopic xenografts (PDOX) of childhood brain tumors have recently emerged as a biologically faithful vehicle for testing novel and more effective therapies. Herein, we provide the histopathological and molecular analysis of 37 novel PDOX models generated from pediatric brain tumor patients treated at St. Jude Children’s Research Hospital. Using a combination of histopathology, whole-genome and whole-exome sequencing, RNA-sequencing, and DNA methylation arrays, we demonstrate the overall fidelity and inter-tumoral molecular heterogeneity of pediatric brain tumor PDOX models. These models represent frequent as well as rare childhood brain tumor entities, including medulloblastoma, ependymoma, atypical teratoid rhabdoid tumor, and embryonal tumor with multi-layer rosettes. PDOX models will be valuable platforms for evaluating novel therapies and conducting pre-clinical trials to accelerate progress in the treatment of brain tumors in children. All described PDOX models and associated datasets can be explored using an interactive web-based portal and will be made freely available to the research community upon request.
    Type of Medium: Online Resource
    ISSN: 0001-6322 , 1432-0533
    URL: Article
    DOI: 10.1007/s00401-020-02171-5
    RVK:
    XA 10000
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 1458410-4
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    Patient-derived models recapitulate heterogeneity of molecular signatures and drug response in pediatric high-grade glioma
    Springer Science and Business Media LLC ; 2021
    In:  Nature Communications Vol. 12, No. 1 ( 2021-07-02)
    Details
    In: Nature Communications, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2021-07-02)
    Abstract: Pediatric high-grade glioma (pHGG) is a major contributor to cancer-related death in children. In vitro and in vivo disease models reflecting the intimate connection between developmental context and pathogenesis of pHGG are essential to advance understanding and identify therapeutic vulnerabilities. Here we report establishment of 21 patient-derived pHGG orthotopic xenograft (PDOX) models and eight matched cell lines from diverse groups of pHGG. These models recapitulate histopathology, DNA methylation signatures, mutations and gene expression patterns of the patient tumors from which they were derived, and include rare subgroups not well-represented by existing models. We deploy 16 new and existing cell lines for high-throughput screening (HTS). In vitro HTS results predict variable in vivo response to PI3K/mTOR and MEK pathway inhibitors. These unique new models and an online interactive data portal for exploration of associated detailed molecular characterization and HTS chemical sensitivity data provide a rich resource for pediatric brain tumor research.
    Type of Medium: Online Resource
    ISSN: 2041-1723
    URL: Article
    DOI: 10.1038/s41467-021-24168-8
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2553671-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Outcomes by Clinical and Molecular Features in Children With Medulloblastoma Treated With Risk-Adapted Therapy: Results of an International Phase III Trial (SJMB03)
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 7 ( 2021-03-01), p. 822-835
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 7 ( 2021-03-01), p. 822-835
    Abstract: SJMB03 (ClinicalTrials.gov identifier: NCT00085202 ) was a phase III risk-adapted trial that aimed to determine the frequency and clinical significance of biological variants and genetic alterations in medulloblastoma. PATIENTS AND METHODS Patients 3-21 years old were stratified into average-risk and high-risk treatment groups based on metastatic status and extent of resection. Medulloblastomas were molecularly classified into subgroups (Wingless [WNT], Sonic Hedgehog [SHH] , group 3, and group 4) and subtypes based on DNA methylation profiles and overlaid with gene mutations from next-generation sequencing. Coprimary study end points were (1) to assess the relationship between ERBB2 protein expression in tumors and progression-free survival (PFS), and (2) to estimate the frequency of mutations associated with WNT and SHH tumors. Clinical and molecular risk factors were evaluated, and the most robust were used to model new risk-classification categories. RESULTS Three hundred thirty eligible patients with medulloblastoma were enrolled. Five-year PFS was 83.2% (95% CI, 78.4 to 88.2) for average-risk patients (n = 227) and 58.7% (95% CI, 49.8 to 69.1) for high-risk patients (n = 103). No association was found between ERBB2 status and PFS in the overall cohort ( P = .74) or when patients were stratified by clinical risk ( P = .71). Mutations in CTNNB1 (96%), DDX3X (37%), and SMARCA4 (24%) were most common in WNT tumors and PTCH1 (38%), TP53 (21%), and DDX3X (19%) in SHH tumors. Methylome profiling classified 53 WNT (17.4%), 48 SHH (15.7%), 65 group 3 (21.3%), and 139 group 4 (45.6%) tumors. A comprehensive clinicomolecular risk factor analysis identified three low-risk groups (WNT, low-risk SHH, and low-risk combined groups 3 and 4) with excellent (5-year PFS 〉 90%) and two very high-risk groups (high-risk SHH and high-risk combined groups 3 and 4) with poor survival (5-year PFS 〈 60%). CONCLUSION These results establish a new risk stratification for future medulloblastoma trials.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.20.01372
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Outcome and molecular analysis of young children with choroid plexus carcinoma treated with non-myeloablative therapy: results from the SJYC07 trial
    Oxford University Press (OUP) ; 2021
    In:  Neuro-Oncology Advances Vol. 3, No. 1 ( 2021-01-01)
    Details
    In: Neuro-Oncology Advances, Oxford University Press (OUP), Vol. 3, No. 1 ( 2021-01-01)
    Abstract: Choroid plexus carcinoma (CPC) is a rare and aggressive tumor of infancy without a clear treatment strategy. This study describes the outcomes of children with CPC treated on the multi-institutional phase 2 SJYC07 trial and reports on the significance of clinical and molecular characteristics. Methods Eligible children & lt;3 years-old with CPC were postoperatively stratified to intermediate-risk (IR) stratum if disease was localized or high-risk (HR) stratum, if metastatic. All received high-dose methotrexate–containing induction chemotherapy. IR-stratum patients received focal irradiation as consolidation whereas HR-stratum patients received additional chemotherapy. Consolidation was followed by oral antiangiogenic maintenance regimen. Survival rates and potential prognostic factors were analyzed. Results Thirteen patients (median age: 1.41 years, range: 0.21–2.93) were enrolled; 5 IR, 8 HR. Gross-total resection or near-total resection was achieved in ten patients and subtotal resection in 3. Seven patients had TP53-mutant tumors, including 4 who were germline carriers. Five patients experienced progression and died of disease; 8 (including 5 HR) are alive without progression. The 5-year progression-free survival (PFS) and overall survival rates were 61.5 ± 13.5% and 68.4 ± 13.1%. Patients with TP53-wild-type tumors had a 5-year PFS of 100% as compared to 28.6 ± 17.1% for TP53-mutant tumors (P = .012). Extent of resection, metastatic status, and use of radiation therapy were not significantly associated with survival. Conclusions Non-myeloablative high-dose methotrexate–containing therapy with maximal surgical resection resulted in long-term PFS in more than half of patients with CPC. TP53-mutational status was the only significant prognostic variable and should form the basis of risk-stratification in future trials.
    Type of Medium: Online Resource
    ISSN: 2632-2498
    URL: Article
    DOI: 10.1093/noajnl/vdaa168
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2021
    detail.hit.zdb_id: 3009682-0
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    MEDB-29. Application of Rotterdam Post-Operative Cerebellar Mutism Syndrome Prediction Model to Patients Operated for Medulloblastoma in a Single Institution
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_1 ( 2022-06-03), p. i111-i111
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_1 ( 2022-06-03), p. i111-i111
    Abstract: BACKGROUND: Post-operative cerebellar mutism syndrome (CMS) develops in up to 30% of children. The Rotterdam model (RM) predicts a 66% risk of CMS in patients with a score ≥100. However, our findings suggested that surgical experience contributes to CMS risk. The aim of this study was to retrospectively apply the RM and report incidence of CMS in high-risk patients from our institution. METHODS: Participants had to have first tumor resection at our institution and be enrolled on SJMB12 protocol (NCT01878617). All participants got structured serial neurologic evaluations. CMS, when present, was categorized into type 1 (complete mutism) and type 2 (paucity of speech with an inability to string 3-word sentence). Rotterdam score is calculated based on pre-operative imaging parameters and study neurologist (RBK) obtained it while blinded to CMS status. RESULTS: Of the 40 (14 female, 26 male) study participants, 4 (10%) had CMS (3 CMS1, 1 CMS2). Median age at tumor resection was 11.7 years (range 3.5-17.8). Tumor location was midline in 30 (75%), right lateral 6 (15%) and left lateral 4 (10%). Median Evans index was 0.3 (0.2-0.4) and 34 (85%) were ≥0.3 (indicative of hydrocephalus); 5 participants needed ventricular shunt. Median tumor volume was 50 cm3 (2-180.6). Gross total resection was achieved in 35 (87.5%), near total in 4 (10%) and subtotal in 1. Twelve tumors were SHH, 7 WNT, and 29 NWNS. Median RM score was 90 (25 – 145). Eighteen participants had a score of ≥100 and 16.7% of these (n=3) had CMS. Scores for the 4 with CMS were 85, 125, 145 and 145. CONCLUSION: At our institution, the incidence of CMS in those that had RM of ≥100 was much lower than reported risk of 66%. This data supports our hypothesis that neurosurgical experience remains a significant risk factor in the development of CMS.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac079.403
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    RARE-12. VASCULOPATHY IN PEDIATRIC CRANIOPHARYNGIOMA PATIENTS TREATED WITH SURGERY AND RADIOTHERAPY
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii444-iii444
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii444-iii444
    Abstract: As much as 40% of pediatric brain tumor patients will experience varied levels of Vasculopathy (VS), however few predictive factors have been described. Here we describe the type and timing of VS and explore the relationship between treatment modality and the timing, location, and distribution of VS. METHODS 94 pediatric Craniopharyngioma patients underwent surgery and proton radiotherapy. Pre- and post-treatment imaging, cumulative physical and biological proton dose maps, clinical characteristics, and measures of dyslipidemia were evaluated. MR and MRAs were evaluated for pre- and post-radiotherapy VS (type, workup, location, and severity). VS events were segmented and described according to their normal brain region, and vascular territory. RESULTS 47 patients were found to have 154 confirmed VS of varying severity with a median time to event of 3.41 years 95% CI 3.08–3.88. 22% (N=21) of patients had ≥1 pre-existing instances of VS and 26.6% (N=25) had a dyslipidemia at diagnosis. Forty-six (48.9%) patients had evidence of VS post-RT with 9.5% (N=9) being clinically significant. Aspirin was recommended in 10.6% (N=10) patients. Only 4 (4.2%) patients required revascularization. Clinical characteristics were not predictive of VS. An increased frequency of VS were observed along the operative corridor and high-dose radiotherapy field. CONCLUSIONS VS often precedes radiotherapy necessitating appropriate baseline imaging. Surgery type and extent are interrelated to the risk for radiotherapy-induced VS. While the spatial radiotherapy dose distribution approximated most vascular injury events, it was not all-inclusive. Spatial modeling of biological and physical dose may offer insights into therapy related vascular injury.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa222.723
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    ATRT-22. Outcomes for children with recurrent atypical teratoid rhabdoid tumor: A single institution study with updated molecular and germline analysis
    Oxford University Press (OUP) ; 2022
    In:  Neuro-Oncology Vol. 24, No. Supplement_1 ( 2022-06-03), p. i8-i8
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 24, No. Supplement_1 ( 2022-06-03), p. i8-i8
    Abstract: BACKGROUND: Children with recurrent atypical teratoid rhabdoid tumor (recATRT) who fail frontline therapies have dismal outcomes. The association of ATRT molecular groups (SHH, TYR and MYC) and presence of underlying cancer predisposition with survival post-recurrence (postRD) is unknown. METHODS: We previously reported outcomes from a single-institution retrospective study of children & lt;21 years with recATRT treated at St. Jude Children’s Research Hospital from 2000 to 2020. Herein we report updated progression-free survival (PFS2: time from initial recurrence to subsequent first progression) and overall survival (OSpostRD: time from initial recurrence to death/last follow-up) outcomes by molecular groups determined by tumor DNA methylation and by germline SMARCB1/SMARCA4 alterations (GLA). RESULTS: Median age and time from initial diagnosis to recurrence for 64 eligible patients were 2.1 years (range: 0.5-17.9 years) and 5.4 months (range: 0.5–125.6 months), respectively. The 2- and 5-year PFS2 and OSpostRD were 3.1% (±1.8%)/1.6% (±1.1%) and 20.3% (±4.8%)/7.9% (±3.8%), respectively. PFS2 did not differ by molecular groups (p=0.210) for 42 participants with available data (MYC=11, SHH=21, TYR=10). Children with TYR group had a better 2-year OSpostRD [60.0% ±14.3% (TYR) vs. 18.2% ±9.5% (MYC) or 4.8% ±3.3% (SHH)] (p=0.018). In univariate analyses, OSpostRD was also better with older age at diagnosis (≥ 1 year vs & lt;1 year; p=0.03), female gender (p=0.008), and metastatic site of recurrence compared to local or combined sites of disease (p & lt;0.001). OSpostRD did not differ for those with positive GLA (n=12) compared to those without (n=21) (p=0.231). Only 6 children (9.4%) (TYR=4, SHH=1, NA=1) were alive at median follow-up of 7.7 years from recurrence. CONCLUSION: Children with recATRT have extremely poor outcomes. Older age at diagnosis, female gender, TYR group, and metastatic site of initial recurrence were associated with longer survival in our study. These results reinforce the dire need for better therapeutic options.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noac079.021
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2094060-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    EPEN-50. THE MANAGEMENT AND TREATMENT OF PEDIATRIC SPINAL CORD EPENDYMOMA: RESULTS FROM A COLLABORATIVE INTERNATIONAL MULTI-INSTITUTIONAL REVIEW
    Oxford University Press (OUP) ; 2020
    In:  Neuro-Oncology Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii317-iii318
    Details
    In: Neuro-Oncology, Oxford University Press (OUP), Vol. 22, No. Supplement_3 ( 2020-12-04), p. iii317-iii318
    Abstract: Pediatric Spinal cord ependymoma (SCE) is rare, and the management is often heterogeneous across centers. We evaluated the impact of clinical, pathologic, and treatment-related factors on outcomes in a multi-institutional, international cohort. METHODS SCE patients age & lt;21 years were reviewed across 5 institutions. We utilized nonparametric descriptive statistics, survival, and recursive partitioning analysis (RPA) to examine patient, tumor, histopathologic and treatment characteristics, failure pattern, and cause of death. RESULTS 125 patients were identified, 18 (14.4%) with metastases. Initial surgery was GTR, and STR in 44, 56% of patients respectively. Histology was grade 1, 2, and 3 in 55, 17.7 and 23.2% respectively. 55 patients with initial GTR were observed (52.7%) or irradiated (43.6%); 60 patients had STR and were observed (40%) or irradiated (60%). The 7-year event-free (EFS) and overall survival (OS) was 60% (95% CI 51.5–71.4) and 79% (95% CI 71.1–87.8) respectively. STR and metastasis increased the hazard for death [HR 1.87, 95% CI 1.02–3.57, p=0.05 (vs. GTR)] and [HR 2.28, 95% CI 1.1–5.2, p=0.048 (vs. localized)] respectively. Across 43 failures, local failure predominated (48.8%). Distant and combined failure occurred in 30.2 and 13.9% respectively. Adjuvant RT offered a 20% absolute improvement (vs. observation) in EFS at 5 years regardless of extent of resection. RPA identified thoracic (vs. non-thoracic), grade (1 & 3 vs. 2), STR (vs. GTR) and metastases as determinants of inferior EFS. CONCLUSIONS Tumor and treatment-related factors are predictive of EFS. OS is favorable despite diverse schema and frequent distant failures.
    Type of Medium: Online Resource
    ISSN: 1522-8517 , 1523-5866
    URL: Article
    DOI: 10.1093/neuonc/noaa222.183
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2094060-9
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...