Brain tumor, malignant glioma, surgery, radiation therapy, chemotherapy
Many patients diagnosed with malignant
gliomas
between 1997 and 2000 received
treatment that did not conform with established practice guidelines for the
care of adults with this type of brain tumor, according to a new study.
Journal of the American Medical Association, February 2, 2005 (see the journal abstract).
Malignant gliomas are the most common
primary
brain tumor, accounting for more
than half of the more than 18,000 primary malignant brain tumors diagnosed each
year in the United States. These tumors are the second-most common cause of
cancer death in the 15 to 44 age group.
The outlook for patients with malignant gliomas is poor.
Median survival
for
patients with moderately severe (grade III) malignant gliomas is three to five
years. For patients with the most severe, aggressive form of malignant glioma
(grade IV glioma or
glioblastoma multiforme), median survival is less than a
year.
Surgery is recommended for all operable brain tumors and is usually followed by
radiation therapy. Several studies have shown that adding chemotherapy to
radiation can improve patients' survival. In June 2004, after the completion of
the current study, researchers announced that adding the drug temozolomide
(Temodar®) to radiation therapy increased median survival in patients with
glioblastoma multiforme by about two months
(see related story). This approach
is now considered the standard of care for the initial treatment of these
tumors.
The Glioma Outcomes Project is a study that tracked how patients with grade III
or IV malignant gliomas were treated and what the outcomes of that treatment
were. A total of 565 patients with newly diagnosed malignant gliomas were
enrolled in the study between 1997 and 2000; 74 percent of these patients had
grade IV gliomas.
Patients were treated both at academic medical centers and by
community oncologists. Information about their care and its outcomes was collected when
patients enrolled, immediately after they had surgery, and at three-month
intervals thereafter for two years or until the patient's death, whichever
occurred sooner.
The study's lead author is Susan M. Chang, M.D., of the University of
California, San Francisco.
The treatment patients received conformed with practice guidelines in some
respects and departed from them in others. For example, most patients underwent
contrast-enhanced
magnetic resonance imaging
(MRI) at diagnosis. This imaging
test is almost universally accepted as the test of choice for diagnosing
malignant glioma.
Also in keeping with practice guidelines, most patients had surgery to remove
as much of the tumor as possible, followed by postoperative radiation therapy.
However, only 54 percent received chemotherapy, despite the fact that
chemotherapy has been shown to improve survival.
Other aspects of patients' care conflicted with best practice recommendations.
For example, the American Academy of Neurology (AAN) recommends treating glioma
patients with anti-epileptic medications only if they have seizures as a
symptom when their tumor is diagnosed. Because these drugs can have severe side
effects, the AAN advises against prescribing them routinely to all patients
with newly diagnosed malignant gliomas. Nevertheless, nearly 90 percent of
patients in this study received anti-epileptic medications, although only 32
percent had seizures.
Several areas of patients' care reflected a lack of agreement on best practice.
For example, studies of the safety and effectiveness of giving low-dose
anticoagulants
to prevent post-surgical blood clotting in glioma patients have
produced conflicting findings. In this study, only 7 percent of patients
received preventive anticoagulants, although as many as 60 percent developed
blood clots within six weeks of surgery.
Thirteen percent of newly diagnosed patients reported symptoms of depression.
However, only 28.6 percent of these patients received antidepressant
medications. Patients' doctors may have been concerned about the possible side
effects of giving antidepressants to patients who were also taking
anti-epileptic medications, the study authors say. The likelihood of such
adverse effects is not known.
Almost all patients received corticosteroid medications to reduce neurologic
symptoms, although these medications may cause significant adverse effects such
as diabetes, high blood pressure, muscle pain, and increased susceptibility to
infections.
This was an observational study, not a prospective clinical trial.
(See Which
Study Results Are the Most Helpful in Making Cancer Care Decisions? for an
explanation of how observational studies differ from clinical trials.)
Patients in this study were diagnosed between 1997 and 2000, a time when there
was little consensus about the best approach to treating newly diagnosed
malignant gliomas, comments Howard Fine, M.D., Chief of the Neuro-Oncology
Branch at the National Cancer Institute's (NCI's) Center for Cancer Research
and the National Institute of Neurological Disorders and Stroke.
That situation has changed, particularly since the release of the temozolomide
findings in 2004, he says. Surgery plus radiation therapy plus temozolomide
chemotherapy is now the established standard of care in the United States for
all patients with newly diagnosed grade III or IV malignant gliomas.
"The data presented [in this study] suggest that current clinical practice does
not follow guidelines or evidence," write Paul Graham Fisher, M.D., and
Patrician A. Buffler, M.D., in an accompanying editorial.
What's more, note the study's authors, "Variations in patterns of care were
associated with differences in survival." Additional practice guidelines may
help to reduce this variability, they suggest. Further research is needed to
clarify the value of anticoagulants, antidepressants, and corticosteroids in
the treatment of glioma patients, they add.
To ensure that they receive care consistent with current best practices,
patients with a diagnosis of malignant glioma should always obtain a second
opinion from a brain tumor specialty center, advises Fine. NCI supports brain tumor specialty centers around the country; some centers specialize in treating adults while others specialize in treating children.
Patients should also consider enrolling in a clinical trial, adds Fine. The
Neuro-Oncology Branch offers free consultations and can provide information
about NCI-directed and NCI-supported clinical trials around the country that
are currently accepting patients.
To obtain information about clinical trials or treatment for glioma patients, call NCI's Cancer
Information Service at 1-800-4-CANCER (1-800-422-6237) or call the
Neuro-Oncology Branch directly at 301-402-6298.
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