Henson 1
MS# 199901439
Henson, J.W.; Thornton,A.F.; and Louis, D.N. Spinal cord astrocytoma:
Response to PCV chemotherapy. Neurology 2000 Jan 25;54(2):518-20.
Spinal cord astrocytoma: response to PCV chemotherapy
John W. Henson, M.D.1,4, Allan F. Thornton, M.D.1,2,4, David N. Louis, M.D.3,4
1
Brain Tumor Center and Spine Tumor Center, 2Department of Radiation Oncology,
3
Department of Pathology and Neurosurgical Service, Massachusetts General Hospital,
and 4Harvard Medical School, Boston, MA
Correspondence should be addressed to:
John W. Henson, M.D.
MGH Brain Tumor Center and Spine Tumor Center
Cox 315, 100 Blossom Street
Boston, MA 02114
Telephone (617) 724-8770
Fax (617) 724-8769
E-mail henson@helix.mgh.harvard.edu
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Key words: spinal neoplasm, astrocytoma, chemotherapy
Acknowledgments: This work was supported by the Brian D. Silber Memorial Fund for spine
tumor research at the Massachusetts General Hospital.
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Article Abstract
Information regarding the value of chemotherapy for spinal cord astrocytomas that
progress after irradiation is limited. We describe a patient whose conus medullaris
astrocytoma responded to PCV chemotherapy after failing radiation and cisplatin-based
chemotherapy. PCV should be considered in patients with progressive spinal cord
astrocytomas.
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Astrocytomas of the spinal cord are rare neoplasms, occurring with an incidence of
0.8 to 2.5 per 100,000 population per year.1 Surgery and radiation therapy are standard
treatments for patients with these tumors. Because of the rarity of this tumor, information
regarding the value of chemotherapy for spinal cord astrocytomas that progress after
irradiation is limited. We present a patient whose astrocytoma responded to PCV
chemotherapy, and review the literature on the subject.
Patient. An enhancing mass lesion in the conus medullaris was discovered by MRI in a 41
year old man with progressive bilateral lower extremity weakness. Biopsy revealed low-grade
astrocytoma (Figure 1). He received a total of 5040 cGy in 180 cGy fractions, with a return of
normal muscle strength. Two years later he developed progressive lower extremity symptoms
and MRI revealed new areas of contrast enhancement (Figure 2A). Cisplatin and etoposide
produced clinical stabilization, but after the fourth cycle the strength in both legs began to
deteriorate and MRI suggested progression of disease (Figure 2B). PCV chemotherapy
(procarbazine, CCNU, and vincristine) was administered, although without vincristine after
cycle 1 due to neurotoxicity. By the beginning of the 3rd cycle improvement in lower
extremity strength and function was apparent. An MRI scan after 7 cycles revealed a decrease
in size and degree of enhancement of the tumor (Figure 2C). Glucocorticoids were not
administered during either of the two chemotherapy regimens. After a total of 11 cycles he
again experienced progressive disease, having a time to progression of 23 months from the
start of PCV treatment. The patient died after failing to response to additional therapy with
topotecan or temozolomide. Overall survival was 6 years.
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Discussion. Spinal cord astrocytomas are devastating tumors which pose serious risks to
function and life. Histopathological grading, using the same criteria as for cerebral
astrocytomas, correlates well with clinical behavior and, together with location along the
spinal cord, is helpful in determining prognosis.2 Thus, patients with high-grade tumors in
the cervical cord have the worst prognosis with survivals measured in several months.3,4
Spinal cord astrocytomas usually progress locally, although dissemination throughout the
spinal cord and leptomeninges is not uncommon with high-grade tumors.
Surgery and radiation therapy are the first-line treatments for these tumors. The extent
of resection is usually limited by the infiltrative nature of spinal cord astrocytomas. With the
use of operating microscopes, however, partial surgical resection can lead to improvement in
the neurological deficits in patients with low-grade tumors. The value of aggressive resection
in high-grade spinal cord astrocytomas is unclear.
Radiation therapy is usually administered to spinal cord astrocytomas following
biopsy or surgery. Although it has been difficult to quantitate the value of radiation, there
may be a lower rate of progression among patients who receive radiation therapy.2,5
There is scant literature regarding the use of chemotherapy for spinal cord
astrocytomas. Of ten children treated with the “8-in-1” drug regimen prior to radiation for
high-grade spinal cord astrocytoma, five showed a response after two cycles of
chemotherapy.6 Bouffet et al. reported a complete clinical and radiographic response of a
low-grade astrocytoma of the spinal cord to carboplatin and vincristine without irradiation.7
Lindstadt et al. reported a 6-plus year response of a progressive spinal cord astrocytoma to re-
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irradiation plus BCNU.8 The present case showed a significant clinical and radiographic
response to PCV.
Thus, spinal cord astrocytomas can respond to chemotherapy. Although astrocytomas
of the cerebral hemispheres are not highly responsive to chemotherapy, recent evidence has
suggested that astrocytomas with 1p loss may also be sensitive to chemotherapy (manuscript
submitted for publication). Allelic loss of chromosome 1p is a powerful predictor of
chemosensitivity in patients with anaplastic oligodendroglioma 9. There was insufficient
tumor tissue available in the present case to determine the status of 1p. We conclude that
salvage therapy with PCV should be considered in patients with progression of spinal cord
astrocytoma after radiation therapy.
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Figure Legends
Figure 1. Biospy of the conus medullaris mass revealed moderate hypercellularity and nuclear
pleomorphism of astrocytic cells. Mitotic activity, vascular proliferation and necrosis were
not noted, although the biopsy was small. The tumor focally involved a sample of spinal
nerve root. (H&E, 400X)
Figure 2. Contrast-enhanced MRI scans of astrocytomas of the conus medullaris. A. Tumor at
the time of progression after irradiation. B. Clinical progression after four cycles of cisplatin
and etoposide. C. Radiographic and clinical response after 7 cycles of PCV.
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