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Radiotherapeutic Management of Medulloblastoma

Radiotherapeutic Management of Medulloblastoma

ABSTRACT: Although craniospinal irradiation has been employed in children with medulloblastoma for the past 40 years, many issues concerning its use have been raised and examined, and some continue to be debated. Careful radiation technique includes adequate irradiation of the neuraxis with special attention to the cribriform plate region and termination of the thecal sac. Conventional-dose craniospinal radiation therapy, in combination with chemotherapy, is currently recommended for patients with high-risk medulloblastoma. The appropriate dose of radiation to the craniospinal axis when this modality is combined with chemotherapy for low-risk medulloblastoma remains to be defined. Long-term results of hyperfractionated radiation therapy are likewise awaited. In an effort to decrease late toxicity to the immature central nervous system, radiation therapy can be delayed in a proportion of infants by administering chemotherapy after maximal tumor debulking. [ONCOLOGY 11(6):813-823, 1997]

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 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.

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