Radiotherapeutic Management of Medulloblastoma

Introduction

The most common solid tumors in children involve the brain, and medulloblastoma accounts for about 20% of all childhood brain neoplasms. Since Harvey Cushing and Percival Bailey's initial description of this posterior fossa tumor in 1925, numerous advances have been made in our understanding of medulloblastoma.

Medulloblastoma is a radiosensitive tumor; survival fraction after 200 cGy has been reported to be 27%.[1] The propensity of this tumor to disseminate along the neuraxis is well documented and is apparent in approximately 16% to 46% of cases.[2,3] Perhaps it was Edith Paterson's careful observation of this pattern of tumor spread that prompted her to deliver radiation to the whole neuraxis.

In 1953, Paterson and Farr reported a 41% 5-year survival rate for children treated with kilovoltage irradiation at the Christie Hospital.[4] Since that time, craniospinal irradiation has been a mainstay of treatment for this primitive neuroectodermal tumor. Many issues concerning the use of craniospinal irradiation in medulloblastoma remain, some of which continue to be the subject of controversy.

Radiation Technique

With the child immobilized and placed in the prone position, two lateral opposed fields are employed to treat the whole brain and a portion of the cervical spinal cord. These lateral fields are angled to match the divergence from a posterior spine field. In older children, two spine fields may be needed, and a skin gap between these two fields is maintained to avoid overdosing a portion of the cord secondary to the divergence of beams (Figure 1). In treating the spine, the inferior portion of the treatment table is "kicked," or angled, toward the gantry to correct for the divergence of the cranial fields (Figure 2).

During the course of radiation therapy, the junctions between the cranial and upper spinal fields and between the two spinal fields are moved, or "feathered," every 1,000 cGy to avoid overdosing or underdosing the spinal cord at the junction sites. Usually, the length of the cranial fields is decreased by 1 cm, the upper spinal field is moved cephalad to match the cranial fields, and the lower spinal field is moved superiorly, with its length increased to match the original inferior border of the lower spinal field. Children are usually treated with 1.25- to 6-MeV photons. In younger children, sedation may be needed to keep the patient immobilized.

In addition to adjusting the angle of the cranial field and kicking the treatment table, some radiation oncologists leave a 5-mm gap interposed between the cranial and upper spinal fields This gap is employed to minimize the possibility of radiation myelopathy at the feathered region. Tatcher and

Glickman demonstrated that when the cranial and upper spinal fields are directly abutted, the dose at the junction of the fields is relatively homogeneous. However, with a 5-mm gap, a "cold spot" on the order of 10% of the prescribed dose is created and may have clinical significance for tumor control.[5,6]

Radiation Volume

What Is the Optimal Treatment Volume?

Prior to the advent of craniospinal irradiation, virtually no child with medulloblastoma survived for more than a few years. At the University of Toronto, Jenkin noted that none of the 16 patients treated to volumes less than the craniospinal axis were alive at 5 years, as compared with 8 of 15 patients treated to the whole neuraxis.[7] Landberg and colleagues of the University Hospital in Lund, Sweden, found that the 10-year survival rate was related to the volume of the central nervous system (CNS) irradiated. When only the posterior fossa received radiation therapy, survival was 5%; if the spinal axis was irradiated in addition to the posterior fossa, survival rose to 25%. Children who underwent craniospinal irradiation had a survival rate of 53%.[8]

In an effort to reduce the late effects of radiation therapy on neurocognitive function, a French multi-institutional study (M4 protocol) was designed to determine whether supratentorial radiation could be omitted if two courses of "eight drugs in 1 day" chemotherapy followed by two courses of high-dose methotrexate(Drug information on methotrexate) were administered early after surgery. The rationale for the early use of chemotherapy was to exploit the surgically disrupted blood-brain barrier and enhance drug delivery to the CNS.

Of the 16 patients treated according to the M4 protocol, 3 (18%) were alive and disease-free at a mean follow-up of 6 years. The primary site of relapse was supratentorial in 9 (69%) of 13 patients The authors concluded that the chemotherapy regimen employed in the M4 protocol did not allow for omission of supratentorial radiation therapy.[9]

Thus, despite advances in chemotherapy, the whole craniospinal axis remains the standard volume that needs to be irradiated in children with medulloblastoma.

The Cribriform Plate

Multiple studies have documented the increased frequency of subfrontal brain relapses in patients in whom the cribriform plate region is not adequately treated.[10-13] Although the most frequent site of relapse in medulloblastoma is the posterior fossa, up to 15% of recurrences are subfrontal, according to a 1982 report from Memorial Sloan-Kettering Cancer Center.[14]

What accounts for these subfrontal recurrences? Some radiation oncologists underdose the cribriform plate region by using excessively generous eye blocks in an effort to minimize radiation effects to the ocular system. Alternatively, Donnal et al have hypothesized that tumor cells have a propensity to migrate to the subfrontal region because children with medulloblastoma are usually prone during surgical resection and craniospinal radiotherapy. Pooling of cells secondary to this gravitational effect and excessive eye blocks can potentiate recurrence in the cribriform plate region.[12]

To ensure that an adequate radiation dose is delivered to the cribriform plate region, Jereb et al have suggested that an anterior electron field be given as a boost.[10] Others have concluded that the brain can be irradiated without underdosing the cribriform plate region by using opposed lateral fields with careful eye blocking.[15]

Caudal Border and Width of the Spinal Field

Traditional thought holds that the thecal sac terminates at the S2 level. This presumption is based largely on autopsy studies in adults and may not necessarily reflect the caudal end of the spinal theca in children.[16,17] Furthermore, theoretically the presence of spinal metastases may displace the termination of the thecal sac more inferiorly. In an estimated 3% to 33% of children, the thecal sac terminates below the S2-3 level on MRI.[18-20] Placement of the caudal border of the spinal field should be individualized; routine placement of the inferior border at the S4 level may result in unnecessary irradiation to the gonads.

Another issue in the radiotherapeutic approach to medulloblastoma is how wide the spinal field should be at the level of the sacrum. Some radiation oncologists use a "spade" field, increasing the width of the sacral portion of the spine field to encompass the sacroiliac joints and cover the sacral nerve roots, whereas others feel that straight field borders throughout the whole spine are adequate.[21,22] In an anatomic study conducted at Duke University, Halperin noted that the caudal end of the craniospinal field needed to be widened by only 1.2 to 1.8 cm to encompass the increasing distance between nerve roots as one moved inferiorly down the spine, but not to the extent of covering the sacroiliac joints.[23] Thus, there is no anatomic basis for using a spade field to cover the sacroiliac joints.