Ependymoma
Radiation Therapy (RT)
Some types of ependymoma may not benefit from postoperative RT. This depends on tumor location and histology.
Variants of ependymoma thought not to require RT:
| Subependymoma | Do well with surgery alone. Perhaps due to different biological nature of these tumors |
| Myxopapillary ependymoma of the spine | Good local control after surgery alone. |
| Supratentorial, low grade tumors | After gross total resection these patients can do well without adjuvant radiotherapy.
In the previous COG ACNS0121 study, after complete resection of a supratentorial low grade ependymoma, patients went on to an observation arm only |
For the great majority of posterior fossa ependymomas, post-operative radiotherapy (RT) is almost always given after surgical resection as RT reduces the risk of local recurrence.
Target Volume
- In the past most children received craniospinal RT, but the great majority of relapses were local and craniospinal RT was associated with significant morbidity.
- The standard of care is now high dose local RT after as complete a resection as possible (as long as any evidence of craniospinal metastatic disease has been excluded prior to therapy).
The previous COG ependymoma protocol was ACNS0121
- After a gross total resection all children (except for those with a gross total resection of a low grade, supratentorial tumor) went on to receive high dose local RT.
- Where it had not been possible to achieve a gross total resection, patients were given combination chemotherapy in an attempt to shrink disease and then had second look surgery to try to excise all gross residual disease.
- Conformal RT was standard practice to increase the dose to the primary site and at the same time decrease the side effects of treatment.
Guidelines from that protocol:
GTV = Gross Tumor Volume (GTV) = pre-operative tumor bed and residual tumor (based on initial MR imaging). Any anatomic changes that have resulted from the surgery must be taken into account.
NB. Sometimes ependymomas extend down through the foramen magnum to lie adjacent to the cervical cord. In these circumstances highly focused techniques such as proton therapy may be appropriate to spare the normal cervical cord.
CTV = the clinical target volume = added margin meant to treat subclinical microscopic disease - an anatomically defined margin of 1.0 cm surrounding the GTV and the planning target volume.
PTV = geometric margin of 0.3 - 0.5 cm to account for to account for uncertainty in immobilization, image registration and daily variability in patient positioning.
Dose - All patients were given a total dose of 59.4 Gy with 180 cGy fraction size per day.
Patients less than 18 months of age with a gross total resection received 54 Gy
Cord dose was limited to a maximum of 54 Gy using techniques such as field size reduction, conformal/stereotactic boost or protons.
Technique
- Immobilization devices are essential for planning. The immobilization technique used depends on the area being targeted. An aquaplast mask and vaculock bag will likely be required to reproduce set up daily.
- Many children will require anesthesia.
- The prone position is often the most effective for 4th ventricle tumors, while the supine position is mostly used for supratentorial tumors.
- Fusion of a preoperative MRI with a planning CT is essential for tumor bed delineation.
- 3D conformal treatment using multiple beams (4 MV or greater energy) should be used to cover the PTV with 95% isodose surface whilst minimizing the dose to critical structures and normal brain.
Off study, the above guidelines for treatment volumes would be regarded by many as standard of care in North America.
The current COG protocol is ACNS0831
This randomized phase III trial is studying maintenance chemotherapy to see how well this works compared to observation following induction chemotherapy and RT in treating young patients with newly diagnosed ependymoma.
For this study, the RT planning volumes are more complex and defined:
GTV = Gross tumor volume is based on the post-operative MR examination and includes gross residual tumor and the tumor bed at the primary site. In defining the GTV, the initial pre-operative imaging MR that defined the extent of tumor should be considered as well as the tissues involved anatomically. The GTV in most cases will be a contracted or collapsed tumor bed. Tissue defects resulting from surgical approaches are not included as part of the GTV when not previously involved by tumor. The pre-operative MR imaging sequence that demonstrated tumor and contour the structure to be identified as GTV_preop should be fused with the planning CT scan to assist in the delineation and evaluation of the GTV.
There are two phases to therapy:
GTV1 = Gross Tumor Volume 1
- Is the volume of tissue containing the highest concentration of tumor cells
- Includes the post-operative resection margin of tissues initially involved with disease and the entirety of residual tumor defined on post-operative MR with consideration given to the pre-operative imaging evaluation.
- In the setting of gross-total resection, the post-contrast T1-weighted MR sequence is generally the most useful. In the setting of non-enhancing residual disease, T2-weighted imaging may be required. GTV1 will take into account changes in brain anatomy resulting from tumor resection or CSF shunting.
The surgical corridor should not be included in the delineation of the GTV unless suspected to contain tumor.
When there is discrepancy between imaging studies or intra-operative findings, the larger volume will define GTV1.
GTV2 = Gross Tumor Volume 2.
The purpose of GTV2 is to administer radiation dose to the volume of tissue containing the highest concentration of tumor cells and allow the dose to the spinal cord and optic chiasm to be limited after the initial phase of treatment to 54 Gy.
There are several options to define GTV2:
- Option 1: GTV2 = GTV1. GTV2 may be the same as GTV1 when the composite plan dose distributions to the optic chiasm and spinal cord do not exceed tolerance
- Option 2: GTV2 = GTV1 minus GTV1 volume caudal to foramen magnum. When the recommended spinal cord dose distribution might exceed cord tolerance, GTV2 should be equal to GTV1 minus the any portion of GTV1 caudal to the intracranial
aspect of the foramen magnum. - Option 3: GTV2 = GTV1 minus (optic chiasm + PRV margin chosen for PTV). When the recommended optic chiasm dose distribution might be exceeded, GTV2 should be equal to GTV1 minus the optic chiasm with a planning organ at risk (PRV)
margin equal to the margin chosen for PTV1. - Option 4: GTV2 = combined procedure used for options 2 and 3. When both the spinal cord and optic chiasm dose distributions might be exceeded, both of the outlined procedures should be followed.
CTV = Clinical target volume (CTV) includes the GTV with an added margin that is meant to treat subclinical microscopic disease and is anatomically confined (i.e., the CTV is limited to the confines of the bony calvarium, falx and tentorium where applicable or extends up to but not beyond neuroanatomic structures through which tumor extension or invasion is certain not to have occurred); the CTV margin will be 5mm for all patients. When the GTV approaches the boundary of an anatomic compartment, the CTV will extend up to and include the boundary. The CTV margin chosen for this study requires treatment planning MR and/or diagnostic MR imaging data with image section thickness ≤ 5mm.
In keeping with the GTV1 and GTV2, there is a CTV1 and CTV2:
CTV1 for this protocol = GTV1 with an anatomically confined margin of 0.5 cm
CTV1 should be tailored at tissue interfaces where invasion/infiltration is not likely
CTV1 may be manually moved inward to the inner table of the bony calvarium
CTV2 = There is no CTV2
PTV = Planning target volume includes a margin which is added to the CTV in 3-5mm dimensions to create the PTV. It is geometric and not anatomically defined. The PTV has two components, the internal margin (IM) and the set-up margin (SM). The IM is meant to compensate for all movements and variations in size and shape of the tissues contained within the CTV. The SM is meant to account for set-up, mechanical and dosimetric uncertainties related to daily patient positioning, treatment equipment and software. For this study, the PTV margin should be 3 or 5mm
PTV1
- Option 1: 3mm (requires daily digital imaging and intervention or equivalent)
- Option 2: PTV1 = 5mm (no special requirements)
The total dose to the PTV1 prescription isodose surface is 54 Gy in 30 fractions of 180cGy.
PTV2
- will include GTV2 with an additional margin equal to the margin used to create PTV1.
- PTV2 may extend beyond bone margins and the skin surface.
- Option 1: PTV2 = 3mm (requires daily digital imaging and intervention or equivalent)
- Option 2: PTV2 = 5mm (no special requirements)
There is no PTV2 for children under the age of 18 months at the start of RT if their
extent of resection has been characterized as gross-total resection.
The total boost dose to the PTV2 prescription isodose surface is 540 cGy in 3 fractions of 180 cGy
Proton Therapy can be appropriate especially in:
- Young children (less than 5 years old) to limit damage to developing normal brain.
- If the disease extends through the foramen magnum to abut the cervical cord (at levels such as C3). In this case 59.4 Gy with conventional photons would be associated with a significant risk of damage to the upper cervical cord.
