Meningioma is a prime example of a tumor requiring a multimodality
approach. This tumor is usually benign and often grows slowly.
Under many circumstances, such a benign tumor would never attract
the attention of the oncologist or even require treatment at all.
However, a meningioma is a benign tumor in a malignant location.
In the closed space of the skull, there is no room for expansion
of even a benign lesion; thus, effective treatment of this potentially
neurologically devastating lesion is necessary. Neurosurgeons,
neuroradiologists, radiotherapists, and medical oncologists are
all directly involved in treatment decisions. Rapidly expanding
knowledge concerning the etiology and natural history of meningiomas
may now also involve epidemiologists, molecular geneticists, and
endocrinologists. Despite this concentration of expertise, numerous
questions remain unanswered or incompletely answered.
The epidemiology of meningiomas has always been of great interest
. Observations that meningiomas are twice as common in women
as in men, that they may wax and wane with pregnancy, and that
they are positively associated with breast cancer opened the door
to investigation of the role of sex hormone receptors in the growth
of meningiomas and to a greater understanding of the pathways
that control the expression and function of these receptors. However,
other risk factors have also been identified. Trauma may be a
factor in the induction of meningiomas; they may be the only tumors
associated with participation in a competitive sport (head trauma
from boxing) . Radiation may also play a role in the induction
of meningiomas, including either therapeutic radiation to the
brain or scalp  or possible risk from excessive dental x-rays
. Description of deletions of chromosome 22 as a possible marker
for meningiomas may help identify a common pathway of chromosomal
damage for these various risk factors .
Surgery remains the acknowledged mainstay for potentially curative
treatment of meningiomas. Surgical results have improved both
through technical advances and through the development of effective
multispecialty surgical teams, particularly in the area of skull-base
procedures. However, planning the extent of appropriate surgery
depends upon appreciation of the malignant potential of the tumor
in question, and this has been a special area of difficulty for
Some meningiomas may be obviously histologically malignant or
may present as malignant tumors by metastasizing to distant sites.
However, the description of an aggressive meningioma is often
based more on the clinical picture than on particular histologic
or cytologic features. In addition, there is a propensity for
meningiomas that intermittently recur over many years to demonstrate
increasingly aggressive behavior. More extensive surgery is therefore
finally needed at the time when previous interventions make such
an approach more difficult. Improvement of techniques for early
identification of malignant or aggressive potential through the
definition of appropriate markers of proliferation or through
metabolic imaging (such as the use of positron emission tomography)
is thus a major requirement for improvement in long-term results.
A significant literature now supports the use of radiotherapy
for the treatment of advanced meningiomas or for adjuvant treatment
after tumor resection . In much of neuro-oncology, the use
of aggressive cranial radiotherapy with potential delayed toxicity
can be justified, in part, by the poor expectations for long-term
outcome. In the case of meningiomas, where survival for a decade
or more can be expected in many cases, the question of persistent
or late toxicity becomes more important. Further work to identify
the subset of patients who may be at increased risk for deterioration
in cognitive function after cranial radiotherapy is required.
In addition, a greater appreciation of the possible delayed effects
of cranial radiotherapy, such as hypothalamic-pituitary dysfunction
resulting in hypothyroidism , is necessary for physicians involved
in the long-term care of patients with meningiomas.
Although isolated reports of success with cytotoxic chemotherapy
or embolization of meningiomas can be found, neither treatment
has become a significant part of general care. In contrast, the
role of various growth factors has been a fascinating area. The
epidemiologic association of meningiomas with female gender led
to the original description of female sex hormone receptors with
potential proliferative function on meningioma cells. Since then,
the realization that progesterone receptors on meningiomas may
be expressed independently of estrogen receptor stimulation has
led to potentially important insights into the regulation of these
receptors (including the possibilities of either totally independent
expression of progesterone receptors or expression induced by
a constitutively activated modified estrogen receptor) .
The suggestive results of early trials of antiprogesterone manipulation
of meningiomas (now being tested in larger phase III trials) have
introduced a new form of hormonal manipulation to the antineoplastic
armamentarium . This line of research has advanced the idea
that sex hormones and sex hormone receptors may function as growth
factors and growth factor receptors, even in the absence of an
obvious gender relationship of the organ in question. This concept
may have far-reaching implications for the management of numerous
medical conditions. Furthermore, the identification of additional
hormone receptors that could potentially serve as growth factor
receptors on meningiomas (including androgen and somatostatin
receptors) may suggest an increasingly important role for biologics
(rather than cytotoxics) in the medical management of meningiomas
Although treatment of benign tumors should be simple (ie, resection),
meningiomas, by virtue of their location and natural history,
have turned this simple question into a multifaceted research
and treatment challenge. In view of the expected long survival
of patients with meningiomas, superb surgical and radiotherapeutic
techniques for the avoidance of chronic and late toxicities are
needed. Meningiomas also have provided the opportunity to gain
greater insights into the role of hormonal and other growth factors,
which may have widespread implications for the understanding and
management of both malignant and nonmalignant conditions. Increased
knowledge of these signalling pathways may be the most important
contribution to emerge from the many ongoing avenues of meningioma
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