Henson 2
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
1Brain Tumor Center and Spine Tumor Center, 2Department of Radiation Oncology, 3Department 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
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.
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.
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.
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-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.
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.
References
1. Alter M, Statistical aspects of spinal cord tumors. In: Klawans, H.L. ed. Tumours of the Spine and Spinal Cord: Part I. Handbook of Clinical Neurology. Vinken, P.J. & Bruyn, G.W. eds. New York: American Elsevier, 1975:1-22.
2. Kopelson G, Linggood RM, Kleinman GM, Doucette J Wang CC. Management of intramedullary spinal cord tumors. Radiology 1980;135:473-479.
3. Garcia DM. Primary spinal cord tumors treated with surgery and postoperative irradiation. Int J Rad Onc Biol Phys 1985;11:1933-1939.
4. Guidetti B, Mercuri S Vagnozzi R. Long-term results of surgical treatment of 129 intramedullary spinal gliomas. J Neurosurg 1981;54:323-330.
5. Shirato H, Kamada T, Hida K, et al. The role of radiotherapy in the management of spinal cord glioma. Int J Rad Onc Biol Phys 1995;33:323-328.
6. Allen JC, Aviner S, Yates AJ, et al. Treatment of high-grade spinal cord astocytoma with "8-in-1" chemotherapy and radiotherapy: a pilot study of CCG-945. J Neurosurg 1998;88:215-220.
7. Bouffet E, Amat D, Devaux Y, Desuzinges C. Chemotherapy for spinal cord astrocytoma. Medical and Pediatric Oncology 1997;29:560-562.
8. Linstadt DE, Wara WM, Leibel SA, Gutin PH, Wilson CB Sheline GE. Postoperative radiotherapy of primary spinal cord tumors. Int J Rad Onc Biol Phys 1989;16:1397-1403.
9. Cairncross JG, Ueki K, Zlatescu MC, et al. Specific genetic predictors of chemotherapeutic response and survival in patients with anaplastic oligodendrogliomas. J Nat Cancer Inst 1998;90:1473-1479.