Surgery
Treatment of brain stem tumors is highly dependent on the location of the tumor, imaging studies and clinical symptoms.
Diffuse disease:
- Surgery is not generally used to obtain an initial pathological diagnosis in diffuse brain stem gliomas because of the risk of brain stem damage.
Low grade, dorsally exophytic tumors in the cervicomedullary junction:
- “Debulking” and resection of cystic components is often of value.
- Total resection of these tumors is often avoided in favor of sparing the surrounding normal structures.
- When performed, gross total resection of small focal low-grade tumors is associated with 5-year progression-free survival rates near 100%.
Chemotherapy
Diffuse disease:
- Multiple pilot and phase I and II studies assessing the addition of chemotherapy to radiation therapy for diffuse brainstem gliomas have not been able to show any benefit.
- A phase II Children’s Oncology Group study, ACNS0126, investigated the use of temozolomide, a DNA methylating agent, given concurrently with radiation therapy in children with diffuse intrinsic brainstem gliomas and other high grade astrocytomas after surgical resection. There did not appear to be a significant survival benefit.
- Future approaches will focus on new chemotherapeutic agents, small molecules and radiosensitizers. Targeted biologic therapies may be aimed at epidermal growth factor receptor (EGFR) and mutations of p53.
- Currently the Pediatric Brain Tumor Consortium (PBTC) is conducting a phase II study of capecitabine and concomitant radiation therapy PBTC-030
Low grade, dorsally exophytic tumors in the cervicomedullary junction:
- In low grade, focal brainstem gliomas chemotherapy has been shown to have some benefit. This strategy is often employed in young children in whom delay of radiation therapy is required to avoid devastating neurocognitive sequelae.
- In young children (<5y) with newly diagnosed or recurrent low grade gliomas, weekly vincristine and carboplatin resulted in ~55% objective response as assessed by neuroimaging.
Children’s Oncology Group (COG) regimen A9952 was designed to compare standard weekly vincristine / carboplatin with a combination of thioguanine, lomustine (CCNU), procarbazine and vincristine in children < 10 years with progressive low grade astrocytomas. The rationale was based of reports of efficacy of this combination in hypothalamic and chiasmal astrocytomas. Follow up is not sufficiently mature for conclusions at this point.
Radiation Therapy (RT)
RT is generally the standard of care for these tumors. For diffuse intrinsic brain stem gliomas, the results are very disappointing.
The tumor responds to RT in at least 70% of patients, but then usually recurs locally in a matter of months. In an attempt to increase the RT dose given, studies were performed using hyperfractionated RT (up to 78 Gy in 100 cGy fractions twice daily). No survival benefit was found.
Radiotherapy Planning
Immobilization shell is made – to ensure accurate, reproducible set up and for the placement of reference marks.
Treatment is planned using a CT simulator and scanning the child in the shell.
The tumor volume is then identified by CT/MR image fusion (achieved by fusing the diagnostic MR image to the planning CT using the bony landmarks of the base of skull).
Different volumes are then outlined:
- GTV = Gross tumor volume identified using the MR scan.
- CTV = Clinical Tumor Volume. This is the GTV plus 1 - 1.5 cm.
- PTV = The Planning Target Volume = CTV + 5 mm.
The prescribed dose is generally 54 Gy in 30 fractions (180 cGy size fractions).
The PTV should be encompassed within the 95% isodose surface.
Multiple beams are used to treat the tumor in a 3D conformal fashion.
