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1. Joshi BH, Puri RA, Leland P, Varricchio F, Gupta G, Kocak M, Gilbertson RJ, Puri RK, US Pediatric Brain Tumor Consortium: Identification of interleukin-13 receptor alpha2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma. Neuro Oncol; 2008 Jun;10(3):265-74
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  • [Title] Identification of interleukin-13 receptor alpha2 chain overexpression in situ in high-grade diffusely infiltrative pediatric brainstem glioma.
  • Human malignant glioma cell lines and adult brain tumors overexpress high levels of interleukin-13 receptor alpha2 chain (IL-13Ralpha2).
  • Because the IL-13Ralpha2 chain is an important target for cancer therapy and prognosis for patients with brainstem glioma (BSG) remains dismal, we investigated the expression of this receptor in specimens of diffusely infiltrative pediatric BSG relative to normal brain tissue.
  • Twenty-eight BSG specimens and 15 normal brain specimens were investigated for IL-13Ralpha2 protein expression by immunohistochemical analysis (IHC) using two different antibodies in two different laboratories.
  • Highly sensitive Q-dot-based IHC and in situ hybridization (ISH) assays were also developed to identify IL-13Ralpha2 protein and RNA in these specimens.
  • By Q-dot IHC or a standard IHC assay, 17 of 28 (61%) tumor specimens showed modest to strong staining for IL-13Ralpha2, while 15 normal brain tissue samples showed weak expression for IL-13Ralpha2 protein.
  • High-level IL-13Ralpha2 RNA expression was detected in tumor samples by Q-dot ISH, but only weak RNA expression was observed in normal brain.
  • IL-13Ralpha2 protein and mRNA are expressed to significantly higher levels in BSG than in normal brain tissue.
  • Both IHC and ISH represent robust methods to detect expression of the IL-13Ralpha2 receptor in BSG that could represent an important new drug target for treatment of this disease.

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  • (PMID = 18430795.001).
  • [ISSN] 1522-8517
  • [Journal-full-title] Neuro-oncology
  • [ISO-abbreviation] Neuro-oncology
  • [Language] ENG
  • [Grant] United States / NCI NIH HHS / CA / U01 CA081457; United States / NCI NIH HHS / CA / U01 CA81457
  • [Publication-type] Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Interleukin-13 Receptor alpha2 Subunit; 0 / RNA, Messenger
  • [Other-IDs] NLM/ PMC2563049
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2. Thomale UW, Tyler B, Renard V, Dorfman B, Chacko VP, Carson BS, Haberl EJ, Jallo GI: Neurological grading, survival, MR imaging, and histological evaluation in the rat brainstem glioma model. Childs Nerv Syst; 2009 Apr;25(4):433-41
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  • [Title] Neurological grading, survival, MR imaging, and histological evaluation in the rat brainstem glioma model.
  • OBJECTIVE: Convection-enhanced delivery using carboplatin in brainstem glioma models was reported to prolong survival.
  • Functional impairment is of additional importance to evaluate the value of local chemotherapy.
  • We established a neurological scoring system for the rat brainstem glioma model.
  • In 38 animals survival time was recorded.
  • HE staining was used to evaluate tumor extension.
  • RESULTS: Neurological scoring showed significantly higher impairment in the high dose carboplatin group during the treatment period.
  • Overall neurological grading correlated with survival time.
  • MR imaging showed a focal contrast enhancing mass in the pontine brainstem, which was less exaggerated after local chemotherapy.
  • Histological slices visualized decreased cellular density in treatment animals versus controls.
  • CONCLUSION: Local chemotherapy in the brainstem glioma model showed significant efficacy for histological changes and survival.
  • Our neurological grading enables quantification of drug and tumor-related morbidity as an important factor for functional performance during therapy.
  • [MeSH-major] Brain Stem Neoplasms / pathology. Glioma / pathology
  • [MeSH-minor] Animals. Antineoplastic Agents / therapeutic use. Body Weight. Carboplatin / therapeutic use. Catheterization. Cell Line, Tumor. Disease Models, Animal. Dose-Response Relationship, Drug. Kaplan-Meier Estimate. Magnetic Resonance Imaging. Male. Neoplasm Staging. Random Allocation. Rats. Rats, Inbred F344. Severity of Illness Index

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  • (PMID = 19082613.001).
  • [ISSN] 1433-0350
  • [Journal-full-title] Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
  • [ISO-abbreviation] Childs Nerv Syst
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
  • [Chemical-registry-number] 0 / Antineoplastic Agents; BG3F62OND5 / Carboplatin
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3. Broniscer A, Gururangan S, MacDonald TJ, Goldman S, Packer RJ, Stewart CF, Wallace D, Danks MK, Friedman HS, Poussaint TY, Kun LE, Boyett JM, Gajjar A: Phase I trial of single-dose temozolomide and continuous administration of o6-benzylguanine in children with brain tumors: a pediatric brain tumor consortium report. Clin Cancer Res; 2007 Nov 15;13(22 Pt 1):6712-8
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  • [Title] Phase I trial of single-dose temozolomide and continuous administration of o6-benzylguanine in children with brain tumors: a pediatric brain tumor consortium report.
  • PURPOSE: To estimate the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of escalating doses of temozolomide combined with O(6)-benzylguanine in patients < or =21 years with recurrent brain tumors.
  • EXPERIMENTAL DESIGN: Treatment strata consisted of patients who had previously received no or local radiotherapy (Str1) and patients who had undergone craniospinal radiotherapy or myeloablative chemotherapy (Str2).
  • Treatment was repeated after recovery from toxicities at least 4 weeks apart for a maximum of 12 courses.
  • Predominant diagnoses were high-grade/brainstem glioma in Str1 and medulloblastoma in Str2.
  • Three patients with gliomas experienced centrally confirmed partial responses to therapy.
  • Four patients completed all planned therapy.
  • CONCLUSIONS: The current schedule of temozolomide and O(6)-benzylguanine is safe and showed modest activity against recurrent brain tumors in children.
  • [MeSH-major] Antineoplastic Agents / administration & dosage. Antineoplastic Combined Chemotherapy Protocols. Brain Neoplasms / drug therapy. Dacarbazine / analogs & derivatives. Enzyme Inhibitors / administration & dosage. Guanine / analogs & derivatives
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Female. Humans. Infant. Male. Treatment Outcome

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  • (PMID = 18006772.001).
  • [ISSN] 1078-0432
  • [Journal-full-title] Clinical cancer research : an official journal of the American Association for Cancer Research
  • [ISO-abbreviation] Clin. Cancer Res.
  • [Language] eng
  • [Grant] United States / NCI NIH HHS / CA / U01 CA 81457
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Enzyme Inhibitors; 19916-73-5 / O(6)-benzylguanine; 5Z93L87A1R / Guanine; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide
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4. Ronghe M, Hargrave D, Bartels U, Tabori U, Vaidya S, Chandler C, Kulkarni A, Bouffet E: Vincristine and carboplatin chemotherapy for unresectable and/or recurrent low-grade astrocytoma of the brainstem. Pediatr Blood Cancer; 2010 Sep;55(3):471-7
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Vincristine and carboplatin chemotherapy for unresectable and/or recurrent low-grade astrocytoma of the brainstem.
  • BACKGROUND: Radiotherapy remains a widely accepted postoperative treatment modality for unresectable or recurrent low-grade glioma (LGG).
  • However, there is increasing evidence to suggest that chemotherapy can delay and may obviate the need for radiotherapy in progressive/recurrent LGG.
  • The majority of the published experience is in children with hypothalamic/optic chiasmatic lesions and little information is available regarding its use in LGG of the brainstem.
  • PROCEDURE: We describe clinical characteristics and course of children with LGG of the brainstem who received carboplatin-based chemotherapy in two institutions over 10 years (1996-2006).
  • This was a retrospective review of consecutively treated children with LGG of the brainstem (midbrain, pons, medulla, and upper cervical cord).
  • Vincristine and carboplatin were first-line chemotherapy regimen used in all patients.
  • Eight children were treated at diagnosis while the remaining eight received chemotherapy after either radiological progression or clinical deterioration.
  • After a median follow-up of 57 months (range 20-136) from initiation of chemotherapy all children are alive and 11 remain progression free (1 complete response, 8 with partial response + minor response, and 2 stable diseases).
  • CONCLUSIONS: The efficacy of this chemotherapy regimen in this series supports its role in children with progressive unresectable LGG of brainstem.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Astrocytoma / drug therapy. Brain Stem. Brain Stem Neoplasms / drug therapy
  • [MeSH-minor] Carboplatin / administration & dosage. Child. Child, Preschool. Disease Progression. Female. Humans. Infant. Male. Neoplasm Recurrence, Local / drug therapy. Vincristine / administration & dosage

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  • [Copyright] 2010 Wiley-Liss, Inc.
  • (PMID = 20535831.001).
  • [ISSN] 1545-5017
  • [Journal-full-title] Pediatric blood & cancer
  • [ISO-abbreviation] Pediatr Blood Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 5J49Q6B70F / Vincristine; BG3F62OND5 / Carboplatin
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5. Broniscer A, Gajjar A: Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist. Oncologist; 2004;9(2):197-206
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Supratentorial high-grade astrocytoma and diffuse brainstem glioma: two challenges for the pediatric oncologist.
  • Pediatric high-grade gliomas represent a heterogeneous group of tumors that accounts for 15%-20% of all pediatric central nervous system tumors.
  • These neoplasms predominantly involve the supratentorial hemispheres or the pons, in which case the tumors are usually called diffuse brainstem gliomas.
  • Older children (>3 years) with supratentorial neoplasms undergo a multimodality treatment comprised of surgical resection, radiation therapy, and chemotherapy.
  • The addition of chemotherapy seems to improve the survival of a subset of these children, particularly those with glioblastoma multiforme.
  • The diagnosis of a diffuse brainstem glioma is based upon typical imaging, dispensing with the need for surgery in the majority of cases.
  • Radiation therapy is the mainstay of treatment for children with diffuse brainstem gliomas.
  • The role of chemotherapy for these children is not clear, and it is, in general, employed in the context of an investigational study.
  • Less than 10% of children with diffuse brainstem gliomas survive 2 years.
  • Because the outcome for patients with either type of tumor is poor when standard multimodality therapy is used, these children are ideal candidates for innovative treatment approaches.
  • [MeSH-major] Brain Neoplasms / genetics. Brain Neoplasms / therapy. Glioma / genetics. Glioma / therapy. Neoplasm Recurrence, Local
  • [MeSH-minor] Astrocytoma / physiopathology. Astrocytoma / therapy. Brain Stem Neoplasms / genetics. Brain Stem Neoplasms / physiopathology. Brain Stem Neoplasms / therapy. Child. Disease Progression. Humans. Prognosis. Treatment Outcome


6. Lashford LS, Thiesse P, Jouvet A, Jaspan T, Couanet D, Griffiths PD, Doz F, Ironside J, Robson K, Hobson R, Dugan M, Pearson AD, Vassal G, Frappaz D, United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study: Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study. J Clin Oncol; 2002 Dec 15;20(24):4684-91
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  • [Title] Temozolomide in malignant gliomas of childhood: a United Kingdom Children's Cancer Study Group and French Society for Pediatric Oncology Intergroup Study.
  • PURPOSE: To determine the response rate of the malignant gliomas of childhood to an oral, daily schedule of temozolomide.
  • PATIENTS AND METHODS: A multicenter, phase II evaluation of an oral, daily schedule of temozolomide (200 mg/m(2) on 5 consecutive days) was undertaken in children with relapsed or progressive, biopsy-proven, high-grade glioma (arm A) and progressive, diffuse, intrinsic brainstem glioma (arm B).
  • Evidence of activity was defined by radiologic evidence of a sustained reduction in tumor size on serial magnetic resonance imaging scans.
  • RESULTS: Fifty-five patients were recruited (34 to arm A and 21 to arm B) and received 215 cycles of chemotherapy.
  • Prolonged myelosuppression resulted in significant treatment delays and dose reductions (17% and 22% of cycles, respectively).
  • Stabilization of disease was also documented and was most noteworthy for brainstem gliomas, where two patients achieved both radiologic static disease and discontinued steroid medication.
  • CONCLUSION: Despite moderate toxicity, objective response rates to temozolomide have been low, indicating that temozolomide has minimal activity in the high-grade gliomas of childhood.
  • [MeSH-major] Antineoplastic Agents, Alkylating / therapeutic use. Brain Neoplasms / drug therapy. Dacarbazine / analogs & derivatives. Dacarbazine / therapeutic use. Glioma / drug therapy
  • [MeSH-minor] Adolescent. Bone Marrow / drug effects. Child. Child, Preschool. Female. Humans. Male. Thrombocytopenia / chemically induced

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  • (PMID = 12488414.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Clinical Trial, Phase II; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents, Alkylating; 7GR28W0FJI / Dacarbazine; 85622-93-1 / temozolomide
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7. Broniscer A, Leite CC, Lanchote VL, Machado TM, Cristófani LM: Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group. J Clin Oncol; 2000 Mar;18(6):1246-53
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  • [Title] Radiation therapy and high-dose tamoxifen in the treatment of patients with diffuse brainstem gliomas: results of a Brazilian cooperative study. Brainstem Glioma Cooperative Group.
  • PURPOSE: The efficacy of radiation therapy (RT) combined with tamoxifen (TX) was tested in patients diagnosed with diffuse brainstem gliomas in a multicenter trial.
  • RESULTS: Of 29 patients, 27 completed RT (median dose, 54 Gy).
  • Only three patients completed the entire course of treatment without tumoral progression or significant toxicity.
  • CONCLUSION: This treatment combination produced no significant change in the overall poor prognosis of these patients.
  • Most tumors responded initially to treatment but recurred as the study progressed.
  • Generally, treatment was well tolerated, with good patient compliance, but we recommend continuous close monitoring for side effects.
  • Based on our poor results, we recommend that alternative treatments be tested in patients with this type of tumor.
  • [MeSH-major] Antineoplastic Agents / therapeutic use. Brain Stem Neoplasms / drug therapy. Brain Stem Neoplasms / radiotherapy. Glioma / drug therapy. Glioma / radiotherapy. Tamoxifen / therapeutic use
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Combined Modality Therapy. Drug Administration Schedule. Female. Humans. Infant. Male. Radiotherapy, High-Energy. Survival Analysis

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  • (PMID = 10715294.001).
  • [ISSN] 0732-183X
  • [Journal-full-title] Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • [ISO-abbreviation] J. Clin. Oncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 094ZI81Y45 / Tamoxifen
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8. Wolff JE, Wagner S, Reinert C, Gnekow A, Kortmann RD, Kühl J, Van Gool SW: Maintenance treatment with interferon-gamma and low-dose cyclophosphamide for pediatric high-grade glioma. J Neurooncol; 2006 Sep;79(3):315-21
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  • [Source] The source of this record is MEDLINE®, a database of the U.S. National Library of Medicine.
  • [Title] Maintenance treatment with interferon-gamma and low-dose cyclophosphamide for pediatric high-grade glioma.
  • BACKGROUND: The prognosis of high-grade glioma in children is poor.
  • PURPOSE: Interferon-gamma may increase the immune surveillance of glioma cells.
  • METHODS: After induction treatment with simultaneous radiation and chemotherapy, patients were treated with individually increasing interferon-gamma (IFN-gamma) doses starting from 25 microg/m2/d s.c. increasing up to a maximum of 175 microg/m2/d within 7 weeks.
  • Forty pediatric glioma patients were enrolled (median age: 8.5 year, male: n = 22).
  • Tumor locations included cerebral cortex (n = 8), basal ganglia (n = 4), brainstem (n = 24), cerebellum (n = 3), spinal cord (n = 1).
  • Histologies were GBM (n = 14), AA (n = 14), LGG (n = 2, diffuse intrinsic pontine glioma).
  • There was grade IV toxicity for thrombocytopenia (10%) and leucopenia (2.5%), grade III toxicity for central nervous (2.5%) and hepatic (5%) side effects, no toxic death.
  • The observation time of the six surviving patients was: 1.2, 1.9, 4.2, 4.4, 4.6 and 4.7 years respectively.
  • CONCLUSION: Maintenance treatment with IFN-gamma and low dose CPM has no sufficient beneficial effect for the treatment of high-grade glioma.
  • [MeSH-major] Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Brain Neoplasms / drug therapy. Cyclophosphamide / administration & dosage. Glioma / drug therapy. Interferon-gamma / administration & dosage
  • [MeSH-minor] Adolescent. Child. Child, Preschool. Female. Humans. Male. Survival Analysis. Treatment Outcome

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  • (PMID = 16645718.001).
  • [ISSN] 0167-594X
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Clinical Trial; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
  • [Chemical-registry-number] 82115-62-6 / Interferon-gamma; 8N3DW7272P / Cyclophosphamide
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9. Hong S, Kim IH, Wang KC: Outcome and prognostic factors of childhood diffuse brainstem glioma. Cancer Res Treat; 2005 Apr;37(2):109-13
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  • [Title] Outcome and prognostic factors of childhood diffuse brainstem glioma.
  • PURPOSE: The outcome and prognostic factors of brainstem glioma were evaluated following radiotherapy methods.
  • MATERIALS AND METHODS: Between 1986 and 2001, 45 childhood patients with diffuse brainstem glioma were treated.
  • The histopathological diagnoses were confirmed in 13 patients, which revealed a low-grade glioma in four patients, and high-grade glioma in the other nine.
  • Before 1993, radiation therapy using a regime of 1.8 to 2.0 Gy once a day was performed in 16 cases; thereafter, a regimes of 1.1 or 1.5 Gy twice a day was given in 15 and 14 cases, respectively.
  • Nine patients were treated with adjuvant chemotherapy.
  • The response to the treatment was evaluated by the MRI findings 4 weeks after radiotherapy.
  • The MRI responses were as follows; partial response 22/39 (56%), minimal to no response in 16/39 (41%) and tumor progression in 1/39 (3%).
  • The median time to disease progression was 7 months, and the median survival was 12 months; the overall survival rate at 1 year was 41%.
  • The progression-free survival was influenced by the tumor histology (low grade vs. high grade, p=0.05) in those patients whose pathology was confirmed.
  • CONCLUSION: The radiation therapy fractionation schedule did not influence the survival.
  • Low grade histology was a possible favorable prognostic factor of progression-free survival in pediatric brainstem glioma patients.

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  • (PMID = 19956489.001).
  • [ISSN] 2005-9256
  • [Journal-full-title] Cancer research and treatment : official journal of Korean Cancer Association
  • [ISO-abbreviation] Cancer Res Treat
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Korea (South)
  • [Other-IDs] NLM/ PMC2785398
  • [Keywords] NOTNLM ; Brainstem glioma / Radiotherapy
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10. Bredel M, Pollack IF, Hamilton RL, Birner P, Hainfellner JA, Zentner J: DNA topoisomerase IIalpha predicts progression-free and overall survival in pediatric malignant non-brainstem gliomas. Int J Cancer; 2002 Jun 20;99(6):817-20
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  • [Title] DNA topoisomerase IIalpha predicts progression-free and overall survival in pediatric malignant non-brainstem gliomas.
  • Malignant non-brainstem glioma (MNBG) is a rare pediatric brain tumor.
  • Our current study examined the expression of nuclear DNA topoisomerase IIalpha (TIIalpha), a novel marker of cell cycle turnover and a determinant of tumor cell resistance to chemotherapy, in a series of 17 archival pediatric MNBGs.
  • In conclusion, considering that TIIalpha expression was not related to histopathologic grade, biological characteristics as assessed by TIIalpha labeling may complement the information obtained by tumor morphology as a means of improving the accuracy of patient prognosis prediction.
  • [MeSH-major] Antigens, Neoplasm / metabolism. Biomarkers, Tumor / metabolism. Brain Neoplasms / enzymology. DNA Topoisomerases, Type II / metabolism. Glioma / enzymology
  • [MeSH-minor] Adolescent. Cell Division. Child. Child, Preschool. Cohort Studies. DNA-Binding Proteins. Disease-Free Survival. Female. Humans. Immunoenzyme Techniques. Infant. Isoenzymes. Male. Prognosis. Retrospective Studies. Survival Rate

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  • [Copyright] Copyright 2002 Wiley-Liss, Inc.
  • (PMID = 12115482.001).
  • [ISSN] 0020-7136
  • [Journal-full-title] International journal of cancer
  • [ISO-abbreviation] Int. J. Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] United States
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / Biomarkers, Tumor; 0 / DNA-Binding Proteins; 0 / Isoenzymes; EC 5.99.1.3 / DNA Topoisomerases, Type II; EC 5.99.1.3 / DNA topoisomerase II alpha
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11. Lesniak MS, Klem JM, Weingart J, Carson BS Sr: Surgical outcome following resection of contrast-enhanced pediatric brainstem gliomas. Pediatr Neurosurg; 2003 Dec;39(6):314-22
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  • [Title] Surgical outcome following resection of contrast-enhanced pediatric brainstem gliomas.
  • BACKGROUND: The role of surgery in the management of gadolinium-enhancing pediatric brainstem lesions on magnetic resonance imaging (MRI) has been a matter of open debate.
  • METHODS: We retrospectively reviewed the charts of all pediatric patients admitted to the Johns Hopkins Hospital with a diagnosis of a brainstem tumor between January 1985 and December 2000.
  • Fifty-seven patients (64.0%) underwent surgical resection while 32 (36%) were treated with radiation and/or chemotherapy.
  • The remaining cases consisted of 10 patients (17.5%) with fibrillary astrocytomas, 3 (5.3%) with gangliogliomas, 1 (1.8%) with an oligodendroglioma and 1 (1.8%) with a primitive neuroectodermal tumor.
  • CONCLUSIONS: This case series illustrates that contrast-enhanced MRI has positive prognostic value in the management of pediatric brainstem gliomas.
  • Consequently, we recommend surgical resection and pathological diagnosis of all enhancing brainstem tumors with adjuvant therapy reserved for recurrent or unresectable cases.
  • [MeSH-major] Brain Stem Neoplasms / pathology. Brain Stem Neoplasms / surgery. Glioma / pathology. Glioma / surgery. Magnetic Resonance Imaging / methods
  • [MeSH-minor] Adolescent. Adult. Chemotherapy, Adjuvant. Child. Child, Preschool. Combined Modality Therapy. Contrast Media / administration & dosage. Female. Humans. Infant. Male. Prognosis. Radiotherapy, Adjuvant. Retrospective Studies. Sensitivity and Specificity. Survival Analysis. Treatment Outcome

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  • [Copyright] Copyright 2003 S. Karger AG, Basel
  • [CommentIn] Pediatr Neurosurg. 2004 Mar-Apr;40(2):99; author reply 100 [15292646.001]
  • (PMID = 14734866.001).
  • [ISSN] 1016-2291
  • [Journal-full-title] Pediatric neurosurgery
  • [ISO-abbreviation] Pediatr Neurosurg
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Switzerland
  • [Chemical-registry-number] 0 / Contrast Media
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12. Badhe PB, Chauhan PP, Mehta NK: Brainstem gliomas--a clinicopathological study of 45 cases with p53 immunohistochemistry. Indian J Cancer; 2004 Oct-Dec;41(4):170-4
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  • [Title] Brainstem gliomas--a clinicopathological study of 45 cases with p53 immunohistochemistry.
  • BACKGROUND: Brainstem tumors represent 10% of central nervous system tumors, accounting for 30% of pediatric posterior fossa tumors.
  • AIMS: The aim of this study was to clinicopathologically correlate 45 cases of brain stem gliomas and determine the occurrence and prognostic significance of p53 expression.
  • MATERIALS AND METHOD: 45 cases of brain stem gliomas encountered during a 19-year period.
  • The WHO brain tumor classification and Stroink's CT classification were applied.
  • Grade II astrocytomas were treated with excision and radiotherapy, while grade III and IV tumors were treated with radiotherapy and chemotherapy (CCNU).
  • The outcome was better in patients who were treated surgically. p53 is a frequently mutated gene in brain stem astrocytomas.
  • [MeSH-major] Biomarkers, Tumor / metabolism. Brain Stem Neoplasms / metabolism. Glioma / metabolism. Tumor Suppressor Protein p53 / metabolism
  • [MeSH-minor] Adolescent. Adult. Child. Child, Preschool. Female. Humans. Immunohistochemistry. India / epidemiology. Infant. Infant, Newborn. Male. Middle Aged. Retrospective Studies. Survival Rate

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  • (PMID = 15659871.001).
  • [ISSN] 0019-509X
  • [Journal-full-title] Indian journal of cancer
  • [ISO-abbreviation] Indian J Cancer
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] India
  • [Chemical-registry-number] 0 / Biomarkers, Tumor; 0 / Tumor Suppressor Protein p53
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13. Di Maio S, Gul SM, Cochrane DD, Hendson G, Sargent MA, Steinbok P: Clinical, radiologic and pathologic features and outcome following surgery for cervicomedullary gliomas in children. Childs Nerv Syst; 2009 Nov;25(11):1401-10
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  • RESULTS: Of 78 brainstem tumors, nine cervicomedullary tumors undergoing resection were identified: two pilocytic astrocytomas, two gangliogliomas, and five grade II astrocytomas.
  • Initial treatment was surgery in seven: biopsy (1), <25% resection (4), and 25-50% resections (2).
  • Bulbar worsening occurred in five of six patients with interposed areas of non-enhancement versus one of three patients without interposed non-enhancing tissue (P = 0.014).
  • Additionally, bulbar worsening occurred in five of five patients with a poorly defined tumor/brainstem interface and abnormal low T1 signal extending beyond obvious tumor into the brainstem versus one of four with a well-defined tumor margin (P = 0.008).
  • Following chemo- or radiotherapy, the definition of the brainstem/tumor interface improved.
  • CONCLUSION: A less aggressive initial surgical approach, supplemented by postoperative chemotherapy, designed to preserve brainstem function, is proposed for patients with interposed non-enhancing tissue continuous with normal cervical cord or medulla and/or a poorly defined ventral tumor/brainstem interface with abnormal low T1 signal extending beyond obvious tumor into the brainstem.
  • [MeSH-major] Brain Stem Neoplasms / pathology. Brain Stem Neoplasms / surgery. Glioma / pathology. Glioma / surgery
  • [MeSH-minor] Cervical Vertebrae. Chemotherapy, Adjuvant. Child. Child, Preschool. Cohort Studies. Female. Humans. Infant. Magnetic Resonance Imaging. Male. Medulla Oblongata / pathology. Medulla Oblongata / surgery. Neurons / pathology. Radiotherapy, Adjuvant. Retrospective Studies. Treatment Outcome

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  • (PMID = 19636567.001).
  • [ISSN] 1433-0350
  • [Journal-full-title] Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery
  • [ISO-abbreviation] Childs Nerv Syst
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Germany
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14. Benesch M, Lackner H, Sovinz P, Suppan E, Schwinger W, Eder HG, Dornbusch HJ, Moser A, Triebl-Roth K, Urban C: Late sequela after treatment of childhood low-grade gliomas: a retrospective analysis of 69 long-term survivors treated between 1983 and 2003. J Neurooncol; 2006 Jun;78(2):199-205
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  • [Title] Late sequela after treatment of childhood low-grade gliomas: a retrospective analysis of 69 long-term survivors treated between 1983 and 2003.
  • The aim of the present study was to evaluate the spectrum of late effects in a large cohort of pediatric patients with low-grade gliomas (WHO grade I and II) during an observation period of 20 years.
  • Eighty-seven patients with low-grade gliomas grouped according to tumor location (cerebellum: n=28; cerebral hemispheres: n=21; central midline: n=15; brainstem: n=12; tectum: n=5; other locations: n=6) were evaluated for tumor- and/or treatment-related late effects by analysis of medical and computer records, and personal interviews.
  • Seventy patients underwent neurosurgery, 29 patients received additional radiotherapy and 20 additional chemotherapy.
  • Median follow-up of survivors is 96 months with an overall survival of 79% (cerebellum: 89%; cerebral hemispheres: 95%; central midline: 80%; brainstem: 25%; tectum: 100%; other locations: 66%).
  • Chronic medical problems (mild ataxia to multiple severe neuroendocrine deficits) are observed in 100% of patients with brainstem/central midline tumors and in 40-50% of patients with low-grade gliomas of other locations.
  • Tumor- and treatment-related late effects are common in patients with low-grade gliomas with the most severe occurring in patients with brainstem or central midline tumors.
  • As long-term survival is excellent in patients with low-grade gliomas except for tumors located in the brainstem, future treatment studies should focus on avoiding long-term late effects.
  • [MeSH-major] Brain Neoplasms / therapy. Endocrine System Diseases / epidemiology. Glioma / therapy. Nervous System Diseases / epidemiology
  • [MeSH-minor] Adolescent. Adult. Antineoplastic Agents / adverse effects. Austria / epidemiology. Child. Child, Preschool. Cohort Studies. Combined Modality Therapy / adverse effects. Disease-Free Survival. Female. Follow-Up Studies. Hearing Disorders / epidemiology. Hearing Disorders / etiology. Humans. Infant. Male. Radiation Injuries / epidemiology. Retrospective Studies. Survivors / statistics & numerical data. Vision Disorders / epidemiology. Vision Disorders / etiology


15. Phillips NS, Sanford RA, Helton KJ, Boop FA, Zou P, Tekautz T, Gajjar A, Ogg RJ: Diffusion tensor imaging of intraaxial tumors at the cervicomedullary and pontomedullary junctions. Report of two cases. J Neurosurg; 2005 Dec;103(6 Suppl):557-62
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  • Brainstem gliomas are a heterogeneous group of lesions that account for 15% of all pediatric tumors of the central nervous system.
  • Diagnosis and treatment planning for these tumors is based on the observation of Epstein and Farmer that the growth of lesions with low malignant potential is limited by the anatomical structures of the brainstem.
  • Surgery is offered only to those patients with a high probability of harboring a low-grade tumor, because the attendant risk for significant morbidity outweighs the therapeutic benefit of debulking the tumor in cases of high-grade tumors.
  • The authors report two cases that highlight the potential of diffusion tensor (DT) imaging to identify local white matter tracts in the pons, medulla, and cervical cord and to improve the preoperative assessment of low-grade gliomas.
  • Preoperative DT imaging in both cases demonstrated that the white matter tracts were displaced by the bulk of the low-grade tumors but were structurally preserved.
  • Intraoperative and neurological findings were consistent with the preoperative interpretation of the DT images.
  • These cases demonstrate that DT imaging is a useful method for visualizing the relationship between tumor and normal brainstem white matter architecture, as well as for improving the surgical evaluation and management of pediatric brainstem tumors.
  • [MeSH-major] Central Nervous System Neoplasms / diagnosis. Diffusion Magnetic Resonance Imaging. Glioma / diagnosis
  • [MeSH-minor] Adolescent. Brain Stem Neoplasms / diagnosis. Brain Stem Neoplasms / surgery. Cervical Vertebrae. Child. Craniotomy. Fatal Outcome. Female. Humans. Laminectomy. Medulla Oblongata. Pons. Spinal Cord Neoplasms / diagnosis. Spinal Cord Neoplasms / surgery

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  • (PMID = 16383256.001).
  • [ISSN] 0022-3085
  • [Journal-full-title] Journal of neurosurgery
  • [ISO-abbreviation] J. Neurosurg.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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16. Bredel C, Lassmann S, Pollack IF, Knoth R, Hamilton RL, Volk B, Werner M, Bredel M: DNA topoisomerase IIalpha and Her-2/neu gene dosages in pediatric malignant gliomas. Int J Oncol; 2005 May;26(5):1187-92
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  • [Title] DNA topoisomerase IIalpha and Her-2/neu gene dosages in pediatric malignant gliomas.
  • Pediatric malignant non-brainstem glioma (PMNBG) is a rare tumor that accounts for only about five percent of childhood intracranial neoplasms.
  • DNA topoisomerase IIalpha (TIIalpha) is a novel marker of cell-cycle turnover and a target of high-risk chemotherapy in PMNBG.
  • Utilizing a combined approach of immunocytochemistry-based morphology guidance, laser-assisted microdissection and quantitative real-time PCR, we report a low-level co-amplification of the neighboring TIIalpha and Her-2/neu gene loci on chromosome 17q11-q22 in one of seventeen examined PMNBGs.
  • Analysis of both genes by real-time PCR in the crude tumor samples without prior tissue heterogeneity reduction via laser microdissection, resulted in loss of detection of amplification of the syngeneic Her-2/neu locus.
  • Gene dosage assessment in a microscopically distant tumor area revealed no amplification of either gene.
  • [MeSH-major] Antigens, Neoplasm / genetics. Brain Neoplasms / genetics. Chromosomes, Human, Pair 17. DNA Topoisomerases, Type II / genetics. DNA-Binding Proteins / genetics. Gene Amplification. Gene Dosage. Gene Expression Regulation, Neoplastic. Glioma / genetics. Receptor, ErbB-2 / genetics
  • [MeSH-minor] Child. Humans. Immunohistochemistry. Polymerase Chain Reaction

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  • (PMID = 15809708.001).
  • [ISSN] 1019-6439
  • [Journal-full-title] International journal of oncology
  • [ISO-abbreviation] Int. J. Oncol.
  • [Language] eng
  • [Publication-type] Journal Article
  • [Publication-country] Greece
  • [Chemical-registry-number] 0 / Antigens, Neoplasm; 0 / DNA-Binding Proteins; EC 2.7.10.1 / Receptor, ErbB-2; EC 5.99.1.3 / DNA Topoisomerases, Type II; EC 5.99.1.3 / DNA topoisomerase II alpha
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17. Wagner S, Warmuth-Metz M, Emser A, Gnekow AK, Sträter R, Rutkowski S, Jorch N, Schmid HJ, Berthold F, Graf N, Kortmann RD, Pietsch T, Sörensen N, Peters O, Wolff JE: Treatment options in childhood pontine gliomas. J Neurooncol; 2006 Sep;79(3):281-7
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  • [Title] Treatment options in childhood pontine gliomas.
  • BACKGROUND: Pontine gliomas are the subgroup of brainstem gliomas with the worst prognosis.
  • Controversial treatment approaches are discussed.
  • PATIENTS AND METHODS: Data of children with pontine gliomas treated in different prospective multi-center studies who were registered in the HIT-GBM database were pooled and analyzed addressing prognostic factors and the relevance of intensive treatment using contingency tables, Kaplan-Meier curves and Cox regression analyses.
  • Ninety children received chemotherapy according to the "HIT-GBM" protocols ("Hirntumor-Glioblastoma multiforme").
  • The one-year overall survival rate (1YOS) of all patients with pontine glioma was 39.9+/-4.3%.
  • None of the surviving patients had an observation time longer than 3.9 years.
  • Favorable prognostic factors seemed to be age younger than 4 years, low-grade histology and smaller tumor.
  • All three major treatment modalities including resection, irradiation and chemotherapy had prognostic relevance in univariable analysis.
  • Chemotherapy remained beneficial, even if the analysis was restricted to the subgroup of irradiated tumors (1YOS 45.8+/-5.4% vs. 34.4+/-13.5%, P=0.030).
  • CONCLUSION: Irradiation is an effective element for the treatment of pontine gliomas.
  • Intensive chemotherapy seems to be important in achieving a better OS.
  • [MeSH-major] Brain Stem Neoplasms / mortality. Brain Stem Neoplasms / therapy. Glioma / mortality. Glioma / therapy. Pons / pathology
  • [MeSH-minor] Age Factors. Antineoplastic Combined Chemotherapy Protocols / therapeutic use. Child. Clinical Trials as Topic. Female. Humans. Male. Multicenter Studies as Topic. Neurosurgical Procedures. Prognosis. Radiotherapy. Retrospective Studies. Survival Analysis

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  • (PMID = 16598416.001).
  • [ISSN] 0167-594X
  • [Journal-full-title] Journal of neuro-oncology
  • [ISO-abbreviation] J. Neurooncol.
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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18. Gilmer-Hill HS, Ellis WG, Imbesi SG, Boggan JE: Spinal oligodendroglioma with gliomatosis in a child. Case report. J Neurosurg; 2000 Jan;92(1 Suppl):109-13
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  • [Title] Spinal oligodendroglioma with gliomatosis in a child. Case report.
  • The authors present a rare case of oligodendrogliomatosis in a child, which they believe originated from a primary spinal cord tumor.
  • At 2.5 years of age this boy developed poor balance, neck stiffness, and a regression in developmental milestones.
  • A computerized tomography (CT) scan of the head initially revealed ventriculomegaly and multiple cystic cerebellar lesions.
  • A CT scan of the head and an MR image obtained 3 years later demonstrated diffuse small cysts on the surface of the brainstem, cerebellum, medial temporal and inferior frontal cortices, subcortical white matter, and corpus callosum suggestive of leptomeningeal tumor spread.
  • The cells appeared to migrate along the subpial space but no tumor cells were present in the subarachnoid space.
  • Despite having a complicated course, chemotherapy with carboplatin has provided the patient with long-term palliation and a high quality of life.
  • This case may represent the fifth report in the literature of oligodendrogliomatosis occurring in a child but only the third occurring with a spinal primary tumor.
  • [MeSH-major] Brain Neoplasms / pathology. Glioma / pathology. Neoplasms, Multiple Primary / pathology. Oligodendroglioma / pathology. Spinal Cord Neoplasms / pathology
  • [MeSH-minor] Child, Preschool. Combined Modality Therapy. Humans. Magnetic Resonance Imaging. Male. Palliative Care. Photomicrography. Tomography, X-Ray Computed


19. Siu IM, Tyler BM, Chen JX, Eberhart CG, Thomale UW, Olivi A, Jallo GI, Riggins GJ, Gallia GL: Establishment of a human glioblastoma stemlike brainstem rodent tumor model. J Neurosurg Pediatr; 2010 Jul;6(1):92-7
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  • [Title] Establishment of a human glioblastoma stemlike brainstem rodent tumor model.
  • OBJECT: Diffuse brainstem tumors are the most difficult type of pediatric CNS malignancy to treat.
  • These inoperable lesions are treated with radiation alone or in combination with chemotherapy, and the survival rate is less than 10%.
  • It is therefore essential to develop a reliable animal model to screen new therapeutic agents for the treatment of this type of tumor.
  • Ten female Fischer 344 rats received an injection of 75,000 F98 rat glioma cells and 10 female athymic nude rats received an injection of 75,000 060919 human glioblastoma stemlike cells in the pontine tegmentum of the brainstem.
  • A control group of 5 female Fischer rats received an injection of saline in the same location as the animals in the tumor groups.
  • Median survival of animals injected with F98 was 15 days, consistent with the authors' previous reports on the establishment of the brainstem tumor model using the F98 rat glioma line.
  • Histopathological analysis of the tumors confirmed the presence of brainstem lesions in animals that received brainstem injections of F98 and in animals that received brainstem injections of 060919.
  • The 060919 brainstem tumors histologically resembled glioblastoma.
  • CONCLUSIONS: Tumor take and median survival were consistent for animals injected in the brainstem with either the established F98 rat glioma cell line or the 060919 human glioblastoma stemlike neurosphere line.
  • Histopathological features of the 060919 brainstem tumors resembled glioblastoma.
  • Establishment of this human glioblastoma stemlike brainstem animal model will improve the evaluation and identification of more efficacious agents for the treatment of high-grade brainstem tumors.
  • [MeSH-major] Brain Stem Neoplasms / pathology. Disease Models, Animal. Glioblastoma / pathology. Multipotent Stem Cells / pathology. Neoplastic Stem Cells / pathology
  • [MeSH-minor] Animals. Brain Stem / pathology. Cell Line, Tumor. Child. Female. Glioma / pathology. Humans. Mice. Mice, Nude. Neoplasm Transplantation. Rats. Rats, Inbred F344. Rats, Nude. Spheroids, Cellular / pathology

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  • (PMID = 20593994.001).
  • [ISSN] 1933-0715
  • [Journal-full-title] Journal of neurosurgery. Pediatrics
  • [ISO-abbreviation] J Neurosurg Pediatr
  • [Language] eng
  • [Publication-type] Journal Article; Research Support, Non-U.S. Gov't
  • [Publication-country] United States
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20. Pollack IF, Jakacki RI, Blaney SM, Hancock ML, Kieran MW, Phillips P, Kun LE, Friedman H, Packer R, Banerjee A, Geyer JR, Goldman S, Poussaint TY, Krasin MJ, Wang Y, Hayes M, Murgo A, Weiner S, Boyett JM: Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: a Pediatric Brain Tumor Consortium report. Neuro Oncol; 2007 Apr;9(2):145-60
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  • [Title] Phase I trial of imatinib in children with newly diagnosed brainstem and recurrent malignant gliomas: a Pediatric Brain Tumor Consortium report.
  • This study estimated the maximum tolerated dose (MTD) of imatinib with irradiation in children with newly diagnosed brainstem gliomas, and those with recurrent malignant intracranial gliomas, stratified according to use of enzyme-inducing anticonvulsant drugs (EIACDs).
  • In the brainstem glioma stratum, imatinib was initially administered twice daily during irradiation, but because of possible association with intratumoral hemorrhage (ITH) was subsequently started two weeks after irradiation.
  • Twenty-four evaluable patients received therapy before the amendment, and three of six with a brainstem tumor experienced dose-limiting toxicity (DLT): one had asymptomatic ITH, one had grade 4 neutropenia and, one had renal insufficiency.
  • None of 18 patients with recurrent glioma experienced DLT.
  • After protocol amendment, 3 of 16 patients with brainstem glioma and 2 of 11 patients with recurrent glioma who were not receiving EIACDs experienced ITH DLTs, with three patients being symptomatic.
  • The recommended phase II dose for brainstem gliomas was 265 mg/m(2).
  • Three of 27 patients with brainstem gliomas with imaging before and after irradiation, prior to receiving imatinib, had new hemorrhage, excluding their receiving imatinib.
  • In summary, recommended phase II imatinib doses were determined for children with newly diagnosed brainstem glioma and recurrent high-grade glioma who were not receiving EIACDs.
  • Imatinib may increase the risk of ITH, although the incidence of spontaneous hemorrhages in brainstem glioma is sufficiently high that this should be considered in studies of agents in which hemorrhage is a concern.

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  • (PMID = 17293590.001).
  • [ISSN] 1522-8517
  • [Journal-full-title] Neuro-oncology
  • [ISO-abbreviation] Neuro-oncology
  • [Language] ENG
  • [Grant] United States / NCRR NIH HHS / RR / M01 RR000188; United States / NCI NIH HHS / CA / U01 CA081457; United States / NCRR NIH HHS / RR / M01 RR00188-37; United States / NCI NIH HHS / CA / U01 CA81457
  • [Publication-type] Clinical Trial, Phase I; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
  • [Publication-country] England
  • [Chemical-registry-number] 0 / Antineoplastic Agents; 0 / Benzamides; 0 / Piperazines; 0 / Pyrimidines; 8A1O1M485B / Imatinib Mesylate
  • [Other-IDs] NLM/ PMC1871662
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21. Thompson WD Jr, Kosnik EJ: Spontaneous regression of a diffuse brainstem lesion in the neonate. Report of two cases and review of the literature. J Neurosurg; 2005 Jan;102(1 Suppl):65-71
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  • [Title] Spontaneous regression of a diffuse brainstem lesion in the neonate. Report of two cases and review of the literature.
  • The authors present two cases of diffuse brainstem lesions that regressed without treatment.
  • Findings of clinical and imaging examinations were highly consistent with the characteristics of diffuse brainstem glioma.
  • After consultation with the parents of both infants, all parties agreed to forgo the treatment modalities available at the time.
  • Neither patient underwent surgery, radiation treatment, or chemotherapy; both underwent routine neurological and MR imaging examinations.
  • It must be stressed, however, that nearly all patients with diffuse brainstem lesions experience a poor outcome, regardless of tumor grade or treatment.
  • Brainstem gliomas, spontaneous regression of central nervous system tumors, and the differential diagnoses of brainstem lesions are discussed.
  • [MeSH-major] Brain Stem Neoplasms / pathology. Glioma / pathology
  • [MeSH-minor] Child. Child, Preschool. Cranial Nerve Diseases / etiology. Female. Follow-Up Studies. Humans. Infant, Newborn. Magnetic Resonance Imaging. Male. Remission, Spontaneous

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  • [CommentIn] J Neurosurg. 2007 Jul;107(1 Suppl):80-1; author reply 81 [17644928.001]
  • (PMID = 16206736.001).
  • [ISSN] 0022-3085
  • [Journal-full-title] Journal of neurosurgery
  • [ISO-abbreviation] J. Neurosurg.
  • [Language] eng
  • [Publication-type] Case Reports; Journal Article
  • [Publication-country] United States
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