Newly Diagnosed Childhood Brain Stem Glioma Treatment
Standard Treatment Options for Diffuse Intrinsic Pontine Gliomas (DIPGs)
Chemotherapy only (infants)
Treatment options under clinical evaluation
Standard Treatment Options for Focal or Low-Grade Brain Stem Gliomas
Surgical resection (with or without radiation therapy and chemotherapy)
Observation (with or without cerebrospinal fluid diversion)
Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors
Current Clinical Trials
Standard Treatment Options for Diffuse Intrinsic Pontine Gliomas (DIPGs)
While numerous clinical trials are available for children with newly diagnosed DIPGs, the utility of any therapy besides radiation therapy in the treatment of patients with newly diagnosed DIPG remains unproven.[1-6]; [7,8][Level of evidence: 2A]; [Level of evidence: 3iiiA]
Currently, no chemotherapeutic strategy—including neoadjuvant, concurrent, postradiation therapy, or immunotherapy—when added to radiation therapy has led to long-term survival for children with DIPGs.[10-12]; [Level of evidence: 2A] This includes studies utilizing high-dose, marrow-ablative chemotherapy with autologous hematopoietic stem cell rescue, which have also been ineffective in extending survival.
Standard treatment options for newly diagnosed DIPGs include the following:Radiation therapy
Conventional treatment for children with DIPGs is radiation therapy to involved areas. The conventional dose of radiation ranges between 54 Gy and 60 Gy given locally to the primary tumor site in single daily fractions. Such treatment will result in transient benefit for most patients, but more than 90% of patients will die within 18 months of diagnosis.
Radiation-induced changes may occur a few months after the completion of radiation therapy and may mimic tumor progression. When considering the efficacy of additional treatment, care needs to be taken to separate radiation-induced change from progressive disease.
Research studies evaluating the efficacy of hyperfractionated and hypofractionated radiation therapy and radiosensitizers have not demonstrated improved outcomes using these radiation techniques.
- Hyperfractionated (twice daily) radiation therapy techniques have been used to deliver a higher dose, and studies using doses as high as 78 Gy have been completed. Evidence demonstrates that these increased radiation therapy doses do not improve the duration or rate of survival for patients with DIPGs, whether given alone [1,17] or in combination with chemotherapy.
- Hypofractionated radiation therapy results in survival rates comparable to conventional fractionated radiation therapy techniques, possibly with less treatment burden.[15,18][Level of evidence: 2A]
- Studies evaluating the efficacy of various radiosensitizers as a means for enhancing the therapeutic effect of radiation therapy have been undertaken but to date have failed to show any significant improvement in outcome.[1,3-5,19,20]
Similar to the treatment of other brain tumors, radiation therapy is often omitted for infants with DIPGs, and chemotherapy-only approaches are utilized. However, published data supporting the utility of this approach is lacking.Treatment options under clinical evaluation
Early-phase therapeutic trials may be available for selected patients. These trials may be available via Children’s Oncology Group phase I institutions, the Pediatric Brain Tumor Consortium, or other entities.Standard Treatment Options for Focal or Low-Grade Brain Stem Gliomas
Standard treatment options for newly diagnosed focal or low-grade brain stem gliomas include the following:
- Surgical resection (with or without radiation therapy and chemotherapy).
- Observation (with or without cerebrospinal fluid diversion).
- Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors.
Patients with residual tumor may be candidates for additional therapy, including 3-dimensional conformal radiation therapy approaches, with or without adjuvant chemotherapy.Observation (with or without cerebrospinal fluid diversion)
Patients with small tectal lesions and hydrocephalus but no other neurological deficits may be treated with cerebrospinal fluid diversion alone and have follow-up with sequential neuroradiographic studies unless there is evidence of progressive disease.
A period of observation may be indicated before instituting any treatment for patients with neurofibromatosis type 1. Brain stem gliomas in these children may be indolent and may require no specific treatment for years.Radiation therapy, chemotherapy, and alternative approaches for inoperable focal or low-grade tumors
In selected circumstances, adjuvant therapy in the form of radiation therapy or chemotherapy can be considered in a child with a newly diagnosed focal or low-grade brain stem glioma.[25,26][Level of evidence: 3iDi] Decisions regarding the need for such therapy depend on the age of the child, the extent of resection obtainable, and associated neurologic deficits.
Alternative approaches for the treatment of inoperable brain stem gliomas include the following:
- Stereotactic iodine I-125 brachytherapy approaches, with or without adjuvant chemotherapy.
- The use of BRAF inhibitors for tumors harboring a V600E mutation.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with untreated childhood brain stem glioma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.References
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- Liu AK, Macy ME, Foreman NK: Bevacizumab as therapy for radiation necrosis in four children with pontine gliomas. Int J Radiat Oncol Biol Phys 75 (4): 1148-54, 2009. [PUBMED Abstract]
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