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  • American Society of Clinical Oncology (ASCO)  (7)
  • 1
    Online Resource
    Online Resource
    Metastasis Stage, Adjuvant Treatment, and Residual Tumor Are Prognostic Factors for Medulloblastoma in Children: Conclusions From the Children's Cancer Group 921 Randomized Phase III Study
    American Society of Clinical Oncology (ASCO) ; 1999
    In:  Journal of Clinical Oncology Vol. 17, No. 3 ( 1999-03), p. 832-832
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 17, No. 3 ( 1999-03), p. 832-832
    Abstract: PURPOSE: From 1986 to 1992, “eight-drugs-in-one-day” (8-in-1) chemotherapy both before and after radiation therapy (XRT) (54 Gy tumor/36 Gy neuraxis) was compared with vincristine, lomustine (CCNU), and prednisone (VCP) after XRT in children with untreated, high-stage medulloblastoma (MB). PATIENTS AND METHODS: Two hundred three eligible patients with an institutional diagnosis of MB were stratified by local invasion and metastatic stage (Chang T/M) and randomized to therapy. Median time at risk from study entry was 7.0 years. RESULTS: Survival and progression-free survival (PFS) ± SE at 7 years were 55% ± 5% and 54% ± 5%, respectively. VCP was superior to 8-in-1 chemotherapy, with 5-year PFS rates of 63% ± 5% versus 45% ± 5%, respectively (P = .006). Upon central neuropathology review, 188 patients were confirmed as having MB and were the subjects for analyses of prognostic factors. Children aged 1.5 to younger than 3 years had inferior 5-year estimates of PFS, compared with children 3 years old or older (P = .0014; 32% ± 10% v 58% ± 4%, respectively). For MB patients 3 years of age or older, the prognostic effect of tumor spread (M0 v M1 v M2+) on PFS was powerful (P = .0006); 5-year PFS rates were 70% ± 5%, 57% ± 10%, and 40% ± 8%, respectively. PFS distributions at 5 years for patients with M0 tumors with less than 1.5 cm 2 of residual tumor, versus ≥ 1.5 cm 2 of residual tumor by scan, were significantly different (P = .023; 78% ± 6% v 54% ± 11%, respectively). CONCLUSION: VCP plus XRT is a superior adjuvant combination compared with 8-in-1 chemotherapy plus XRT. For patients with M0 tumors, residual tumor bulk (not extent of resection) is a predictor for PFS. Patients with M0 tumors, ≥ 3 years with ≤ 1.5 cm 2 residual tumor, had a 78% ± 6% 5-year PFS rate. Children younger than 3 years old who received a reduced XRT dosage had the lowest survival rate.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.1999.17.3.832
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 1999
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Ultrasensitive detection and monitoring of central nervous system tumors from plasma using personalized whole-genome ctDNA profiling.
    American Society of Clinical Oncology (ASCO) ; 2023
    In:  Journal of Clinical Oncology Vol. 41, No. 16_suppl ( 2023-06-01), p. 2064-2064
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 41, No. 16_suppl ( 2023-06-01), p. 2064-2064
    Abstract: 2064 Background: Patients with the central nervous system (CNS) tumors are largely followed up by imaging. Current plasma-based liquid biopsy techniques have limited utility in neuro-oncology due to a low circulating cell-free tumor DNA (ctDNA) burden, blood-brain barrier, and low number of mutations in coding regions. Whole genome sequencing (WGS)-derived patient specific mutational signature from a matched tumor-normal WGS can provide a personalized, highly sensitive and specific approach to detect mutations in ctDNA and provide blood-based monitoring in brain tumor patients. Furthermore, it can be performed on lower amount of peripheral blood since WGS requires less sequencing depth compared to targeted ctDNA panels. Methods: We have profiled a cohort of 28 extra- and intra-axial adult and pediatric brain tumors including adult and pediatric low- and high-grade glioma (9), meningiomas (11), medulloblastomas (5), ependymomas (2), neurocytoma (1). Tumor DNA was extracted from archival pathology tissue, normal DNA from unsorted white blood cells, and ctDNA from 1-2 mL of post-surgery plasma. WGS was performed with 40x coverage for Tumor-Normal DNA and 20x for ctDNA. Using WGS of matched Tumor-Normal and plasma samples, we derived a personalized mutational pattern using SNVs, indels, and copy numbers for quantification and ultra-sensitive detection of ctDNA in plasma samples. An AI-based error suppression model was implemented to filter out the noise in the cell-free DNA (cfDNA) while the personalized mutational signature was used to detect the ctDNA in the cfDNA and to amplify the somatic signal to determine the Tumor Fraction at the time of diagnosis, during the therapy or surveillance period. The ctDNA Tumor Fraction (TF) was compared to the clinical status and MRI-based imaging. Results: All subtypes of brain tumors contained enough mutations to derive personalized mutational signatures. Most mutations were distributed in the noncoding DNA. TF correlated with clinical status and with the disease course on imaging at given time points reaching a 10 -4 minimal residual disease detection sensitivity. We were able to detect ctDNA across all WHO grades ranging from WHO 1 meningioma to WHO 4 glioblastoma and medulloblastoma. Furthermore, we were able to detect tumor-specific copy number aberrations such as MYCN amplification in plasma samples and mutational signatures. Conclusions: Here we demonstrate that patient-specific WGS tumor signature in ctDNA from plasma can be used for sensitive monitoring of adults and children with primary low- and high-grade CNS tumors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2023.41.16_suppl.2064
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2023
    detail.hit.zdb_id: 2005181-5
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  • 3
    Online Resource
    Online Resource
    Cognitive and Adaptive Outcome in Extracerebellar Low-Grade Brain Tumors in Children: A Report From the Children's Oncology Group
    American Society of Clinical Oncology (ASCO) ; 2008
    In:  Journal of Clinical Oncology Vol. 26, No. 29 ( 2008-10-10), p. 4765-4770
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 26, No. 29 ( 2008-10-10), p. 4765-4770
    Abstract: To determine whether pediatric patients treated with surgery only for low-grade tumors in the cerebral hemispheres, supratentorial midline, and exophytic brainstem evidence neurocognitive, academic, adaptive, or emotional/behavioral sequelae. Patients and Methods Ninety-three patients from a natural history study of low-grade astrocytomas were tested an average of 111 days after surgery. Rates of below average (≤ 25th percentile) scores in this sample were compared with test norms, and performances were compared across anatomic sites. Finally, the relationships of pre-, peri-, and postsurgical complications to outcome were investigated. Results For the entire sample, there was a significantly elevated rate of below average scores across intelligence quotient, achievement, and adaptive behavior, but not behavioral/emotional adjustment measures. Patients with hemispheric, midline, and brainstem tumors did not differ significantly. Patients with left hemisphere tumors generally performed worse than those with right hemisphere tumors. Finally, neurobehavioral outcome was unrelated to pre-, peri-, or postsurgery complications. Conclusion After surgery for low-grade brain tumors, a significant number of patients was found to function below average, by as much as 55% compared with 25% in the normative population. Moreover, these results suggest greater risk for patients with lesions situated in the left cerebral hemisphere. Routine neuropsychological follow-up of children after treatment for low-grade tumors is recommended.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2008.17.1371
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2008
    detail.hit.zdb_id: 2005181-5
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  • 4
    Online Resource
    Online Resource
    Feasibility and Response to Induction Chemotherapy Intensified With High-Dose Methotrexate for Young Children With Newly Diagnosed High-Risk Disseminated Medulloblastoma
    American Society of Clinical Oncology (ASCO) ; 2004
    In:  Journal of Clinical Oncology Vol. 22, No. 24 ( 2004-12-15), p. 4881-4887
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 22, No. 24 ( 2004-12-15), p. 4881-4887
    Abstract: To evaluate the feasibility of and response rate to an intensified induction chemotherapy regimen for young children with newly diagnosed high-risk or disseminated medulloblastomas. Patients and Methods From January 1997 to March 2003, 21 patients with high-risk or disseminated medulloblastoma were enrolled. After maximal surgical resection, patients were treated with five cycles of vincristine (0.05 mg/kg/wk × three doses per cycle for three cycles), cisplatin (3.5 mg/kg per cycle), etoposide (4 mg/kg/d × 2 days per cycle), cyclophosphamide (65 mg/kg/d × 2 days per cycle) with mesna, and methotrexate (400 mg/kg per cycle) with leucovorin rescue. Following induction chemotherapy, eligible patients underwent a single myeloablative chemotherapy cycle with autologous stem-cell rescue. Results Significant toxicities of this intensified regimen, including gastrointestinal and infectious toxicities, are described. Among the 21 patients enrolled, there were 17 complete responses (81%), two partial responses, one stable disease, and one progressive disease. The 3-year event-free survival and overall survival are 49% (95% CI, 27% to 72%) and 60% (95% CI, 36% to 84%), respectively. Conclusion This intensified induction chemotherapy regimen is feasible and tolerable. With the majority of patients with disseminated medulloblastoma having M2 or M3 disease at diagnosis, the encouraging high response rate of this intensified induction regimen suggests that such an addition of methotrexate should be explored in future studies.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2004.12.126
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2004
    detail.hit.zdb_id: 2005181-5
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  • 5
    Online Resource
    Online Resource
    Cognitive and Adaptive Outcome in Low-Grade Pediatric Cerebellar Astrocytomas: Evidence of Diminished Cognitive and Adaptive Functioning in National Collaborative Research Studies (CCG 9891/POG 9130)
    American Society of Clinical Oncology (ASCO) ; 2005
    In:  Journal of Clinical Oncology Vol. 23, No. 22 ( 2005-08-01), p. 5198-5204
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 23, No. 22 ( 2005-08-01), p. 5198-5204
    Abstract: Clinicians often assume that children with posterior fossa tumors are at minimal risk for cognitive or adaptive deficits if they do not undergo cranial irradiation. However, small case series have called that assumption into question, and have also suggested that nonirradiated cerebellar tumors can cause location-specific cognitive and adaptive impairment. This study (1) assessed whether resected but not irradiated pediatric cerebellar tumors are associated with cognitive and adaptive functioning deficits, and (2) examined the effect of tumor location and medical complications on cognitive and adaptive functioning. Patients and Methods The sample was composed of 103 children aged 3 to 18 years with low-grade cerebellar astrocytomas, who underwent only surgical treatment as part of Children's Cancer Group protocol 9891 or Pediatric Oncology Group protocol 9130. The sample was divided into three groups based on primary tumor location: vermis, left hemisphere, or right hemisphere. Data were collected prospectively on intelligence, academic achievement, adaptive skills, behavioral functioning, and pre-, peri-, and postsurgical medical complications. Results The sample as a whole displayed an elevated risk for cognitive and adaptive impairment that was not associated consistently with medical complications. Within this group of children with cerebellar tumors, tumor location had little effect on cognitive, adaptive, or medical outcome. Conclusion We did not replicate previous findings of location-specific effects on cognitive or adaptive outcome. However, the elevated risk of deficits in this population runs contrary to clinical lore, and suggests that clinicians should attend to the functional outcomes of children who undergo only surgical treatment for cerebellar tumors.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2005.06.117
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2005
    detail.hit.zdb_id: 2005181-5
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  • 6
    Online Resource
    Online Resource
    Randomized Study of Two Chemotherapy Regimens for Treatment of Low-Grade Glioma in Young Children: A Report From the Children's Oncology Group
    American Society of Clinical Oncology (ASCO) ; 2012
    In:  Journal of Clinical Oncology Vol. 30, No. 21 ( 2012-07-20), p. 2641-2647
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 30, No. 21 ( 2012-07-20), p. 2641-2647
    Abstract: Surgery is curative therapy for pediatric low-grade gliomas (LGGs) in areas of the brain amenable to complete resection. However, LGGs located in areas where complete resection is not possible can threaten both function and life. The purpose of this study was to compare two chemotherapy regimens for LGGs in children younger than age 10 years for whom radiotherapy was felt by the practitioner to pose a high risk of neurodevelopmental injury. Patients and Methods Previously untreated children younger than age 10 years with progressive or residual LGGs were eligible. Children were randomly assigned to receive carboplatin and vincristine (CV) or thioguanine, procarbazine, lomustine, and vincristine (TPCV). Children with neurofibromatosis are reported separately. Results Of 274 randomly assigned patients who met eligibility requirements, 137 received CV and 137 received TPCV. The 5-year event-free survival (EFS) and overall survival (OS) rates for all eligible patients were 45% ± 3.2% and 86% ± 2.2%, respectively. The 5-year EFS rates were 39% ± 4% for CV and 52% ± 5% for TPCV (stratified log-rank test P = .10; cure model analysis P = .007). On multivariate analysis, factors independently predictive of worse EFS and OS were younger age and tumor size greater than 3 cm 2 . Tumor location in the thalamus was also associated with poor OS. Conclusion The difference in EFS between the regimens did not reach significance on the basis of the stratified log-rank test. The 5-year EFS was higher for TPCV on the basis of the cure model analysis. Differences in toxicity may influence physician choice of regimens.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2011.36.6054
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2012
    detail.hit.zdb_id: 2005181-5
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  • 7
    Online Resource
    Online Resource
    Growth Hormone Replacement Therapy in Children With Medulloblastoma: Use and Effect on Tumor Control
    American Society of Clinical Oncology (ASCO) ; 2001
    In:  Journal of Clinical Oncology Vol. 19, No. 2 ( 2001-01-15), p. 480-487
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 19, No. 2 ( 2001-01-15), p. 480-487
    Abstract: PURPOSE: Progress has been made in the treatment of medulloblastoma, the most common childhood malignant brain tumor: However, many long-term survivors will have posttherapy growth hormone insufficiency with resultant linear growth retardation. Growth hormone replacement therapy (GHRT) may significantly improve growth, but there is often reluctance to initiate GHRT because of concerns of an increased likelihood of tumor relapse. PATIENTS AND METHODS: This study retrospectively reviewed the use of GHRT for survivors of medulloblastoma in 11 neuro-oncology centers in North America who received initial treatment for disease between 1980 and 1993 to determine its impact on disease control. A Landmark analysis was used to evaluate the relative risk of relapse in surviving patients. RESULTS: Five hundred forty-five consecutive patients less than 15 years of age at diagnosis were identified. Six-year progression-free survival (mean ± SD) was 40% ± 5% in children less than 3 years of age at diagnosis compared with 59% ± 3% for older patients. Older patients with total or near-total resections (P = .003) and localized disease at diagnosis (P 〈 .0001) had the highest likelihood of survival. One hundred seventy patients (33% ± 3% of the cohort) received GHRT. GHRT use varied widely among institutions, ranging from 5% to 73%. GHRT was begun a mean of 3.9 years after diagnosis, later in children younger than 3 years at diagnosis (5.4 years). By Landmark analyses, for those surviving 2, 3, and 5 years after diagnosis, there was no evidence that GHRT increased the rate of disease relapse. CONCLUSION: This large retrospective review demonstrates that GHRT is underutilized in survivors of medulloblastoma and is used relatively late in the course of the illness. GHRT is not associated with an increased likelihood of disease relapse.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2001.19.2.480
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2001
    detail.hit.zdb_id: 2005181-5
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