Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies

Frazier, James L.; Lee, James; Thomale, Ulrich W.; Noggle, Joseph C.; Cohen, Kenneth J.; Jallo, George I.

doi:10.3171/2008.11.peds08281

Cited by 124 publications

(111 citation statements)

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“…Brainstem tumors (BST) comprise 10-15% of pediatric brain tumors [1,2]. Over the last 2 decades the outcome of patients diagnosed with the most common pediatric brain tumors has improved significantly (3)(4)(5)(6).…”

Section: Introductionmentioning

confidence: 99%

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Favorable outcome with conservative treatment for children with low grade brainstem tumors

Fried¹,

Hawkins²,

Scheinemann³

et al. 2011

Pediatric Blood & Cancer

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BackgroundPediatric brainstem tumors (BST) comprise a heterogeneous group of entities. Data regarding treatment options and outcome of BST, specifically brainstem low grade tumors (BSLGT) are limited. In order to better define risk groups and evaluate treatment options for pediatric BST, we performed a comprehensive analysis of all BST patients treated in our hospital during the MRI era.ProceduresWe retrospectively analyzed clinical, imaging, and pathology data at presentation, treatment, and outcome of all BST patients followed at the Hospital for Sick Children in Toronto over the last 25 years.ResultsOf 1,801 children with brain tumors, 223 (12%) had a brainstem primary location. Tumors without pontine involvement were BSLGT in 98.3%, whereas 75% of tumors involving the pons were high grade (P = 0.0001). Patients with BSLGT had 5‐year progression‐free survival (PFS) and overall survival (OS) of 57 ± 3% and 89 ± 5%, respectively. Upfront observation of tumor residual conferred no survival disadvantage with 5‐year PFS and OS of 57 ± 5% and 93 ± 3%, respectively. In the group of patients requiring further treatment, 5‐year PFS and OS were comparable between chemotherapy and radiotherapy with 53 ± 12% and 93 ± 4% and 66 ± 11% and 83 ± 6%, respectively (P = 0.26 and 0.3, respectively).ConclusionBST without pontine involvement are almost invariably BSLGT. Children with BSLGT have an excellent outcome even with careful initial observation. No clear benefit was observed for radiotherapy over chemotherapy when adjuvant treatment was needed. A conservative approach may be warranted for children with non‐pontine brainstem lesions. Pediatr Blood Cancer 2012; 58: 556–560. © 2011 Wiley Periodicals, Inc.

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Section: Introductionmentioning

confidence: 99%

“…DIPG carries a dismal prognosis regardless of pathological diagnosis [6]. Patients are treated with radiation with short-term responses and a median OS of 9-12 months [1,7,8].…”

Section: Introductionmentioning

confidence: 99%

Favorable outcome with conservative treatment for children with low grade brainstem tumors

Fried¹,

Hawkins²,

Scheinemann³

et al. 2011

Pediatric Blood & Cancer

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“…The mutations of IDH1 and K27M-H3F3A exclude each other, and they have opposite effects, and the brainstem glioma patients with IDH1 mutation have better prognosis [36]. Most brainstem gliomas do not have the MGMT promoter methylation, thus explaining why they are resistant to temozolomide and other alkylating agents [41,42], and the mutations of PPM1D and TP53 would explain the reason for radiation resistance [36,43]. The tumors with the same pathological types have distinct gene mutations between the brainstem and cerebral hemisphere.…”

Section: The Treatment Of Brainstem Glioma Promoted By Molecular Pathmentioning

confidence: 99%

The historical change of brainstem glioma diagnosis and treatment: from imaging to molecular pathology and then molecular imaging

Zhang

Pan

2015

Chin Neurosurg Jl

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Understanding a process from shallow to deep is necessary for controlling and even curing diseases. The history of diagnosis and treatment of brainstem gliomas vividly reflects this process. The development of neuroimaging plays a great role in tumor treatment at different periods, including the period when brainstem gliomas were regarded as an homogenous incurable disease, and currently it is considered as an entity with high heterogeneity. Presently, it is not enough to just rely on the conventional neuroimaging techniques to determine the anatomic location of a tumor and its relationship with normal tissues. The development of molecular genetics and molecular imaging further promotes the progress of individualized and precision diagnosis and treatment in brainstem gliomas. In this paper, we summarize the evolution of brainstem glioma radiological classification mainly focusing on the aspects of imaging and surgical treatment. In the meanwhile, we reviewed the recent progresses in the fields of molecular genetics and molecular imaging.

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“…The association of Chemotherapy (ChT) and radiotherapy (RT) have not improved survival 1,[6][7][8]10,11 and now biologics are combined with RT in clinical trials. 9,12,13 We investigated the association of RT with Nimotuzumab, a humanized monoclonal antibody developed at the Center of Molecular Immunology, Havana, Cuba and testing the hypothesis that this combination will improve survival in these tumors.…”

Section: 9mentioning

confidence: 99%

“…Radiation treatment response rates show low degrees of efficacy, with short-term responses and a median overall survival less than one year; [2][3][4][5][6][7][8] Diffusely infiltrating pontine glio-mas must be distinguished from other subsets of diffuse intrinsic pontinegliomas, such as focal tumors, which are described with better prognosis and longer term survival.…”

Section: Introductionmentioning

confidence: 99%

Radiation Therapy and Nimotuzumab in Children and Adolescents with Brainstem Gliomas: A 5-Year Institutional Experience

Jose¹,

Chon²,

Cabanas³

et al. 2015

Neuro Open Journal

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CitationUp to now chemotherapy has not shown to improve survival in these patients. The outcome of Radiation Therapy (RT) in combination with Nimotuzumab is shown in the present report. Material and Methods: 28 children and adolescents were included between Jan/2009 and Dec/2012 with the diagnosis of BSG and follow-up till January 2015. All patients had Diffuse infiltrative Pontine Gliomas (DIPG) and were irradiated with a dose ranging from 54 to 59.6 Gy at the National Oncology and Radiobiology Institute in Havana, Cuba. Three patients were planned with IMRT and 25 with 3D Conformal RT. Nimotuzumab was indicated at the dose of 150 mg/m 2 weekly during the time of RT treatment, then every 15 days during 8 weeks and finally monthly for 1 year. Univariate and multivariate Cox regression models and Kaplan Meier survival were analyzed to evaluate the survival. Results: Median age at diagnosis was 7 years (range 3-18 years old), median overall survival was 17.3 months (95% CI 14.0-20.5 ) since the beginning of the treatment and the accumulated survival at 5 years of treatment was 42,9%. There was balance in sex, age and dosage of RT in the population. Addition of Nimotuzumab to RT was safe. Conclusions: The combination of Radiotherapy and Nimotuzumab were well tolerated in this brainstem tumours patient's series.

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Treatment of diffuse intrinsic brainstem gliomas: failed approaches and future strategies

Cited by 124 publications

References 122 publications

Favorable outcome with conservative treatment for children with low grade brainstem tumors

Favorable outcome with conservative treatment for children with low grade brainstem tumors

The historical change of brainstem glioma diagnosis and treatment: from imaging to molecular pathology and then molecular imaging

Radiation Therapy and Nimotuzumab in Children and Adolescents with Brainstem Gliomas: A 5-Year Institutional Experience

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