lntramedullary Spinal Cord Astrocytoma Versus Glioblas toma

The Prognostic Importance of Histologic Grade

GENE KOPELSON, MD AND RITA M. LINGGOOD, MD

Fourteen patients with intramedullary spinal cord astrocytoma (Grades I, 11) or glioblastoma (Grades 111, IV) were seen at a major referral center over a 19-year period. Although similar surgical and radio- therapeutic techniques were used for each group, the nine patients with astrocytoma had a five-year actuarial survival rate of 89% with five patients alive and well at least five years after treatment; none of the five patients with glioblastoma survived past three years. Histologic grade is the most important factor affecting prognosis for patients with intramedullary spinal cord astrocytomas or glioblastomas, and long-term survival can be achieved postirradiation for many patients with astrocytomas with im- proved neurologic functioning in most.

Cancer 50:732-735, 1982.

OST SERIES reporting on patients with intramed- M ullary spinal cord gliomas usually have separated these tumors into ependymoma or “astrocytoma” groups. Whereas the prognosis for patients with astrocytomas originating at other sites is clearly dependent upon the histologic grade, large and/or recent series of patients with intramedullary spinal cord astrocytoma have failed to distinguish the effect of histologic grade.’-7 This se- ries reports on 14 patients seen at a major referral center over a 19-year period in which the separation of these tumors into astrocytoma (Grade I, 11) or glioblastoma (Grade 111, IV) is the most important factor affecting survival.

Materials and Methods

At the Tumor Registry of the Massachusetts General Hospital from 1962-1980, 14 patients had biopsy- proven intramedullary spinal cord astrocytoma or glio- blastoma. The histologic material of older cases had been recently reviewed,6 and grading of the specimens was performed by one neuropathologist, as described elsewhere.6 Excluded were patients with prior or con- current intracranial lesions of the same histology, tu- mors of indeterminate grade, or patients seen here with recurrent disease. Several of these patients formed part

of a prior review of all intramedullary spinal cord tu- mors;6 however, this series specifically addresses the is- sue of grade (which was not discussed in the prior re- port), adds new patients, and provides long-term fol- low-up. The general clinical characteristics and initial management appears in Table 1. All patients had my- elograms and/or contrast (metrizamide) computed to- mography at initial evaluation and for irradiation treatment planning. Cytologic cerebrospinal fluid stud- ies were performed in one patient and the results were negative for malignant cells.

All irradiated patients were treated using techniques described elsewhere.6 Briefly, single posteroanterior and/or oblique wedge-pair fields were used to encom- pass the primary tumor site with at least 2-3 cm rostra1 and caudal margins. One patient had the entire spinal cord treated because of diffuse involvement (Table 1). Doses (corrected for roentgen-to-rad conversion for or- thovoltage and converted into time-dose-fractionation, TDF, to account for various fractionation schemes) appear in Table 1 . No patient received either neuraxis (craniospinal) irradiation or chemotherapy.

All recurrences were documented histologically at reexploration. Survival data were calculated from the date of initial histologic diagnosis using the actuarial method.8

From the Department of Radiation Medicine, Massachusetts Gen- eral Hospital, Boston, Massachusetts.

Present address and address for reprints: Dr. G. Kopelson, De- partment of Radiation Oncology, Salem Hospital, 8 1 Highland Av- enue, Salem MA 01970.

The authors thank Mindy and Barry Kopelson for their help in the preparation of this manuscript.

Accepted for publication June 8, 198 I .

Results

Astrocytomas

The five-year actuarial survival rate was 89% for these nine patients (Fig. 1). Three patients have had

0008-543X/82/08 15/0732 $1.00 0 American Cancer Society

732

No. 4 SPINAL CORD NEOPLASMS

relapses: two locally at the site of initial disease (one successfully salvaged with radiation after surgical fail- ure, and another successfully salvaged with surgery af- ter irradiation failure), and one intracranially (see be- low). Two died of intercurrent disease (one of a ruptured abdominal aortic aneurysm, not within the irradiation field, with autopsy negative for spinal cord, or any, tumor at five years, nine months; and the other of a myocardial infarction with autopsy negative for tumor at eight years, nine months).

Glioblastomas

There were no long-term survivors in this group (Fig. 1 ). No patient had clinical evidence of intracranial fail- ure. One patient died of multiple cerebrovascular ac- cidents documented arteriographically at ten months. No autopsies were performed in this group. One patient died of biopsy-proven local in-field tumor recurrence at 18 months. Two were lost to follow-up in the first year when they returned abroad posttreatment. The last pa- tient died at two years, one month of “liver cancer;” no autopsy was performed.

Long- Term Neurologic Sequelae

That long-term neurologic recovery can occur after radiation therapy to a relatively “injured” spinal cord (by tumor and operation) is demonstrated in Table 2, and will be discussed in more detail elsewhere.*’ Only

TABLE I , Patient and Tumor Characteristics in 14 Cases of Intramedullary Spinal Cord Astrocytoma/Glioblastoma

Astrocytoma Glioblastoma Characteristics (Grade I , 11) (Grade 111, IV)

No. ma1es:females 5:4 2: 3 Age at diagnosis (yr)

Range 6-69 17-70 Median 40 34

Cervical-thoracic 6 4 Thoracic-lumbar 2 1 Diffuse I * 0

Biopsy 6 5 Subtotal resection 3 0

Primary tumor + margins 7 5 Whole spinal cord 1 0 Craniospinal + boost 0 0

Anatomic location

Initial surgery

Irradiation fieldst

Spinal cord tumor dose (TDF)$ <70 4 4 > 70 4 1

* C,-L2 including conus medullaris. t One astrocytoma patient not irradiated; another astrocytoma pa-

tient irradiated after postsurgical recurrence. T D F = Time-Dose-Fractionation (see text): a T D F of 70 is equiv-

alent to 4500 rad in 180 rad fractions given five fractions per week. 4 Range for astrocytoma patients: T D F 55-77; for glioblastoma

patients: T D F 61-73.

- Kopelson and Linggood 7 3 3

I NTRAMEDULLARY SPINAL CORD

4009

9 7 7 6 5 3 I .---o-----.-m-u+-.+/--.

AST ROCY TOMA

c, 5 0 2

20

i o

0 I ’ /+--it-6 0 1 2 3 4 5 9

YEARS AF JER DIAGNOSIS

FIG. 1. Actuarial ( 8 ) survival related to histologic grade. Correction for intercurrent deaths has been made (two astrocytoma patients who died at five years, nine months and eight years, nine months, respec- tively, of autopsy-proven other causes-Table 2). Two successfully salvaged astrocytoma patients are also included as NED (alive NED at eight years, four months and I 5 years, ten months after retreatment, respectively).

the long-term survivors (Le., patients with astrocytoma alive at least five years after treatment, and the one patient with glioblastoma with a two-year minimum follow-up) were evaluated for chronic radiation effects. Marked improvement in neurologic functioning oc- curred in five of six patients. This, of course, was most evident in the patients with astrocytoma (the group with the longest survival); in the group with glioblastoma, uncontrolled tumor was the proven cause of neurologic deterioration in one patient, and presumed recurrent tumor in the other two patients (see above). However, the one long-term glioblastoma survivor (at two years, one month) had marked neurologic improvement and apparently died of a second primary although an au- topsy was not performed.

Discussion

Very few previously reported series distinguish spinal cord astrocytoma from glioblastoma (Table 3). The largest previous seriesI5 did report results by grade; patients with Grade I or I1 lesions had a mean survival of 90 months vs 15 months for patients with Grade 111 or IV lesions. However, this series is from the older

734 CANCER August 15 1982 Vol. 50

TABLE 2. Neurologic Status of Long-Term Surviviors

Neurologic changes

Patient Age TDF* Survival (mo) Last status Preirradiation Postirradiation

Patients with astrocytoma (minimum 5-yr follow-up)

RB 40 66

H C 69 59

T F 41 77

KN 6 56

BR 38 12

106 A, N E D Spasticity Weakness,

Quadriplegic.

Weakness, 1 70 A, N E D sensation

Paraplegic,

69 DID$ sensory level

105 DID§ sensory level

192 A, N E D sensory level

(Recurrent tumor)? Walked with cane,

normal sensation Normal strength,

normal sensation Normal strength,

normal sensation Walks with cane,

sensory level

Patient with glioblastoma (minimum 2-yr follow-up)

Normal strength, Paraplegic, improved

MS 34 61 25 DID" sensory level sensation

* TDF: Time-dose-fractionation. t Surgical treatment of irradiation failure. $ Ruptured abdominal aortic aneuyrsm; autopsy negative for re-

current/residual cervical spinal cord tumor.

Myocardial infarction; autopsy negative for tumor. I Died of liver cancer (see text). A, NED: Alive, no evidence of disease; DID: Dead of intercurrent

disease.

literature in which the details of surgery and irradiation technique, e.g., dose, field size, etc., were not described. Yet the marked difference in survival between these two histologic grade groupings (Fig. 1) suggests that even with modern surgical and irradiation techniques, his- tologic grade is the major factor affecting survival.

The five-year actuarial survival rate of 89% (Fig. 1 ) for low-grade lesions suggests that prior reports of rel- atively favorable survival for "astrocytoma" patients (in which the grade was unspecified) probably included low-grade lesions primarily. In addition, this high survival rate compared with the overall poorer long- term prognosis for patients with low-grade supraten- torial a s t r o ~ y t o r n a s ~ ~ ~ ~ ~ may be related to tumor size, i.e., a smaller tumor at diagnosis producing earlier

TABLE 3. Histologic Distribution of Intramedullary Spinal Cord Astrocytomas/ Glioblastomas

No. of No. of Author(s) (Ref.) astrocytomas glioblastomas

Grant and Austin" Guidetti er a/.' Iraci" Kopelson and Linggood (this report) Malis'' Marsa et d.I3 Rand and RandI4 Sloof el Woltmann et a/.''

Total (9%)

3 1 53 5

7 13 9 5

18 3 1 2 9 2

66 20 5 21 - -

187 (77) 56 (23)

symptomatology in the relatively smaller neuroana- tomic spinal cord compartment than a comparable su- pratentorial lesion. I t is also possible that these low- grade lesions in the spinal cord behave similarly to the juvenile pilocytic astrocytoma of the cerebellum, for which the prognosis is e ~ c e l l e n t . ~ ~ . ~ ~

Intrarnedullary spinal cord astrocytomas and glio- blastomas often appear cystic at s ~ r g e r y ~ . ~ , " and exhibit intramedullary infiltration both rostrally and cau- dally,3.4+l 1-21 thus often6." but not t ~ t a l l y ~ . ~ obviating a complete resection.

The major site of tumor spread and posttreatment failure is at the primary tumor site in the spinal cord.6 The issue of subarachnoid seeding from intramedullary spinal cord glioblastomas will be addressed elsewhere as part of a review of subarachnoid spread from all infratentorial glioblastomas.22 However, one of our pa- tients with a low-grade lesion failed intracranially (Ta- ble 4). It is interesting that two of the six reported patients with intracranial seeding from low-grade spinal cord astrocytoma had mixed oligodendrogliomatous ele- ments. Perhaps such mixed tumors have an increased propensity for subarachnoid seeding as others have re- ported in pure oligodendrogliomas.26

In conclusion, histologic grade is the most important factor affecting survival of intramedullary spinal cord astrocytoma or glioblastoma patients. Long-term sur- vival can be achieved for patients with low-grade lesions after irradiation with long-term neurologic recovery having been attained for five of six patients.

No. 4 SPINAL CORD NEOPLASMS - Kopelson and Linggood 135

TABLE 4. Reported Patients with Intracranial Seeding From Low-Grade Inramedullary Spinal Cord Astrocytomas

Time to diagnosis Year of Initial of intracranial Location of intracranial

Authors (ref.) report Age/sex management seeding (mo) seeding

Perese et Eade and UlrichZ4

Simonati et a].” Kopelson and Linggood

(current report)

1959 39/M Bx + RT 18 Cerebellum 1971 21/F Bx + RT 7 Pons, medulla

Brainstem, cerebellum,

Frontal lobe, cerebellum, 21/F Bx i RT 5 lateral ventricles

19/M* Bx + RT 5 lateral ventricles 1981 19/F RT < I Third ventricle

1982 32/F* Bx + RT 5 Midbrain

* Mixed astrocytoma-oligodendroglioma.

REFERENCES

1. Bloom HJG, Walsh LS. Tumors of the central nervous system. In: Bloom HJG, Lenerle J, Neidhardt MK, Voute PA, eds. Cancer in Children. New York: Springer-Verlag, 1975; 93-1 19.

2. Schwade JG, Wara WM, Sheline GE, Sorgen S, Wilcox CB. Management of primary spinal cord tumors. Int J Radiat Oncol Biol

3. Matson DD. Neurosurgery of Infancy and Childhood, 2nd ed. Springfield, IL; Charles C Thomas, 1969; 672-676.

4. Stein B. Surgery of intramedullary spinal cord tumors. Clin Neurosurg 1979; 26:529-542.

5. Bouchard J. Central nervous system. In: Fletcher GH, ed. Text- book of Radiotherapy, ed. 3. Philadelphia: Lea and Febiger 1980; 493-494.

6. Kopelson G, Linggood RM, Kleinman GM, Doucette J, Wang CC. Management of intramedullary spinal cord tumors. Radiology 1980; 135:473-479.

7. Wood EH, Berne AS, Taveras JM. The value of radiation ther- apy in the management of intrinsic tumors of the spinal cord. Ra-

8. Guidetti B, Mercuri S, Vagnozzi R. Long-term results of surgical treatment of 129 intramedullary spinal gliomas. J Neurosurg 1981; 54:323-330.

9. American Joint Committee for Cancer Staging and End Results Reporting (AJCC): Manual for Staging of Cancer, 1977. Chicago, IL: American Joint Committee, 1977; 18-21.

10. Grant FC, Austin GM. The diagnosis, treatment, and prognosis of tumors affecting the spinal cord in children. J Neurosurg 1956; 13:535-545.

1 1 . Iraci G. Intraspinal gliomas. J Int Coll Surg 1965; 44:159- 170.

12. Malis LI. Intramedullary spinal cord tumors. CIin Neurosurg 1978; 25:5 12-539.

13. Marsa GW, Goffinet DR, Rubenstein LJ, Bagshaw MA. Me- gavoltage irradiation in the treatment of gliomas of the brain and spinal cord. Cancer 1975; 36:1681-1689.

Phys 1978; 4~389-393.

diolog,v 1954; 63: 1 1-24.

BX: biopsy; RT: radiation therapy.

14. Rand RW, Rand CW. Intraspinal Tumors of Childhood. Springfield, IL: Charles C Thomas, 1960 xi.

15. Sloof JL, Kernohan JW, MacCarty CS. Primary Intramed- ullary Tumors of the Spinal Cord and Filum Terminale. Philadelphia: W. B. Saunders, 1964; 31-61.

16. Woltman HW, Kernohan JW, Adson AW, Craig W. Intra- medullary tumors of the spinal cord and gliomas of the intradural portion of the filum terminale. Arch Neurol Psychiatr 1951; 65:378- 395.

17. Fazekas JT. Treatment of Grade I and I1 brain astrocytomas. The role of radiotherapy. In1 J Radiat Oncol Biol Phys 1977; 2:66 1 - 666.

18. Leibel SA, Sheline GE, Wara WM, Boldrey EB, Nielsen SL. The role of radiation therapy in the treatment of astrocytomas. Cancer 1975; 35: 155 1 - 1557.

19. Marsa GW, Probert JC, Rubinstein LJ, Bagshaw MA. Ra- diation therapy in the treatment of childhood astrocytic gliomas. Can- cer 1975; 361646-655.

20. Griffin TW, Beaufait P, Blasko J. Cystic cerebellar astrocytoma in childhood. Cancer 1979; 44:226-280.

21. Salazar OM, Rubin P. The spread of glioblastomas as deter- mining factor in the radiation treated volume. Int J Radiat Oncol

22. Kopelson G, Linggood RM. Infratentorial glioblastoma: The role of neuraxis irradiation. Int J Radiat Oncol Biol Phys (In press).

23. Perese DM, Slepian A, Nigogosyan G. Postoperative dissem- ination of astrocytoma of the spinal cord along the ventrioles of the brain. J Neurosurg 1959; 16: 1 14- 1 19.

24. Eade OE, Urich H. Metastasizing gliomas in young subjects.

25. Simonati A, Mazza C, Rizzuto N. An unusual case of men- ingeal gliomatosis. Acta Neuropathol 198 1 ; S-7:97- 100.

26. Chen HW, Hazel JJ, Kim TH, Webster JH. Oligodendrogli- omas. Cancer 1980; 45:1458- 1466.

27. Kopelson G. Radiation tolerance of the damaged spinal cord: Long-term neurological improvement and time-dose-volume relation- ships after irradiation of intraspinal gliomas. Int J Radiat Oncol Biol Phys (in press).

Biol Phys 1976; 11627-637.

J Path01 1971; 103:245-256.