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Disorders
We Treat
Glioma / Glioblastoma
Incidence: Of the estimated 17,000 new brain tumors diagnosed each year
in the United States, about half are malignant gliomas. With improvemens
in diagnosis, surgery, radiotherapy, and chemotherapy, the prognosis has
gradually improved. Glioblastomas are highly malignant; most arise in
the upper brain (cerebrum; not cerebellum or back of the brain), but they
may occur anywhere in the brain or spinal cord, including the cerebellum,
brain stem, or optic chiasm.
Low-grade gliomas account for 25% of all
primary brain tumors and have a better prognosis. Over time, most of these
low-grade tumors dedifferentiate into more malignant gliomas. Low-grade
gliomas include astrocytomas, oligodendrogliomas, pilocytic astrocytomas.
Evaluating Treatment Results: Comments
about treating malignant gliomas are relevant to all malignant brain tumors.
Although it might seem straightforward to determine whether or not a treatment
is effective, this is not the case. Problems include tumor measurement,
assessment of response, and selection bias.
Clinical changes are susceptible to factors
other than changes in the tumor. For example, steroid dosage, anticonvulsants,
or antibiotics can affect the clinical performance. Time to progression
is used to determine the efficacy of treating recurrent tumor, but the
definition of both recurrent tumor and progression may be quite difficult.
Even survival, seemingly an unambiguous end point, is influenced by the
aggressiveness of treatment and supportive care in the terminal stages.
With CT and MRI, it is possible to measure
tumor dimensions. Brain tumors, however, are not as easy to measure as
lung neoplasms, in which the diameter can be measured accurately on CT.
For enhancing lesions, the tumor is considered to include the entire area
that enhances, but there is no consensus about how to deal with cystic
lesions with a rim of enhancement, or nonenhancing lesions, multifocal
lesions, or the zone of increased T2 signal on MRI that may be either
tumor or edema. The most widely used method is to measure the largest
diameter on a CT or MRI section and the dimension perpendicular to that,
multiplying the two to obtain a cross-sectional area. What happens if
the tumor enlarges in the third (unmeasured) direction? Other investigators
measure tumor volume, but this is not widely available.
Response Criteria : "Partial"
responses were reported if there was any tumor shrinkage, even if it did
not fulfill the standard criterion of at least 50% decrease in size. Some
investigators have proposed uniform tumor response criteria that would
be based solely on imaging as follows: complete response--disappearance
of all tumor, with stable or improving neurologic examination; partial
response--at least 50% decline in tumor, with stable or improving neurologic
examination; progressive disease--at least 25% increase in tumor size;
stable disease--all other conditions. For complete or partial response
categories, the dose of corticosteroids should be the same or lower than
that in earlier assessment.
Selection Bias: In evaluating reports of
new treatments, it is important to consider how patients were selected.
Patients with malignant gliomas treated with external radiotherapy plus
a high dose of local radiation (brachytherapy or radiosurgery) seem to
have a far better survival rate than those treated with conventional external
beam radiotherapy. Retrospective analysis of patients referred for treatment,
however, reveals that patients who would have been eligible for brachytherapy
protocols fared just as well as the patients who actually received the
therapy. These patients tend to have small polar, easily approached tumors.
Therefore, even among patients with high-grade astrocytomas, there may
be differences within selected groups, and unless that bias is controlled,
results will be skewed.
Conventional Therapy: Cooperative studies
have shown that patients with glioblastoma or anaplastic astrocytoma survive
longer if they are under age 40, have a good performance status (Karnofsky
score), and have had gross total resection of the tumor. Overall, the
survival of patients with glioblastoma after surgery alone is 14 weeks.
With surgery plus radiotherapy, median survival increases to 40 weeks,
justifying the time and effort involved in administering radiotherapy.
The median survival of patients with anaplastic astrocytoma is about 1.5
years. Although tumor cells often infiltrate far into adjacent brain,
the tumor burden is relatively localized, and recurrence in 90% of cases
occurs within 2 cm of the original tumor margins (Fig. 51-2) . Thus, whole-brain
radiotherapy has been supplanted by extended local field irradiation;
4000 cGy is now given to the area of visible tumor and edema plus a 2-cm
margin, and a 1500 to 2000 cGy boost is given to the field of the tumor
itself.
Chemotherapy: Adjuvant chemotherapy, usually
the nitro-sourea BCNU (1,3-bis (2-chlorethyl)-1-nitrosourea), increases
survival slightly but significantly. Attempts to administer BCNU by arterial
injection have been complicated by irreversible encephalopathy and ipsilateral
visual loss owing to retinal toxicity.
Radiotherapy: Experimental: Because radiotherapy
remains the best single mode of therapy for malignant astrocytomas, many
attempts have been made to improve on radiobiologic tumor killing. Hyperfractionation,
the delivery of multiple doses of radiation per day, theoretically permits
higher total tumor doses to be given without additional risk to normal
tissue. Small tumors may be treated by implantation of high-energy radioactive
seeds of iodine-125 or iridium-192, a procedure called interstitial brachytherapy.
Radiosurgery: The radiosurgery is a useful
option for treatment for the smaller malignant gliomas. The fractionated
stereotactic radiotherapy (FSR) offers sparing of toxicity and higher
tumor doses.
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