Cerebellar Glioblastoma

GENE KOPELSON MD

Eight patients with biopsy-proven cerebellar glioblastoma were seen at a major referral center over a 19-year period. Although patients with grade IV lesions did poorly, long-term survival can be achieved occasionally as demonstrated by one of four patients with grade I11 lesions who is alive and well more than eight years later. Local-regional contiguous invasiveness rather than subarachnoid dissemination appears to be the major pattern of tumor spread, and local-regional irradiation to the posterior fossa and adjacent areas at risk appears to be an acceptable form of management.

Cancer 50:308-311, 1982.

OST SERIES and multi-institutional trials of pa- M tients with intracranial glioblastoma have eval- uated only tumors of supratentorial primary site. Cer- ebellar glioblastomas are much less common. Since the initial report by Carmichaell in 1928, less than 50 cases have been reported Most of these re- ports emphasize histopathologic features of the tumor without much discussion of treatment. Of the reported patients who were irradiated, detailed information on field size and dose was usually not g i ~ e n ; ~ - ~ , ~ - ' I the use of chemotherapy has been reported very rarely.' The current report reviews the natural history and post- treatment failure patterns of these neoplasms based on eight patients seen at a major referral hospital over a 19-year period, and a review of the literature in order to form a rational basis for treatment.

Materials and Methods

During the period from 1962-1980, 745 patients with central nervous system astrocytoma (grade I, 11) or glioblastoma (astrocytoma grade 111, IV) were regis- tered at the Tumor Registry of the Massachusetts Gen- eral Hospital. Those eight patients with cerebellar glio- blastoma form the basis of this report. Excluded were patients with cerebellar astrocytomas of low grade (grade I, 11), those without biopsy, of mixed cell type, or of indeterminate grade.

It was elected to include lesions of grade I11 or IV as glioblastoma, although it is realized that certain in-

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

Address for reprints: G. Kopelson, MD, Department of Radiation Oncology, Salem Hospital, 81 Highland Ave., Salem M A 01970.

The author thanks Dr. George Kleinman for reviewing some of the pathological material, and to Mindy and Barry Kopelson for their help in the preparation of this manuscript.

Accepted for publication May 26, 1981.

vestigators believe that only the latter grade lesions should be classified as such.

Previously-reported patients from this hospital with cerebellar involvement as part of gliomatosis cerebri'* or those with malignant transformation of a prior be- nign cerebellar astrocytoma13 were excluded. All orig- inal pathologic material had been reviewed at this hos- pital at initial presentation, and an example is seen in Figure 1.

The clinical course of the eight patients appears in Table 1. Cerebrospinal fluid cytology was performed in three patients at presentation and was negative for malignant cells in each. All four irradiated patients were treated with supervoltage via 6oCo or a 10-MeV linear accelerator. The posterior fossa was treated via parallel-opposed fields; one patient in addition received treatment to the whole brain (Table 1). No patient re- ceived either craniospinal irradiation nor adjuvant che- motherapy.

Results

In this group of eight patients, there was one long- term survivor who had a grade I11 lesion; this patient (Patient 1, Table 1 ) is currently alive and well attending graduate school. A postirradiation computerized to- mogram (CT) showed no evidence of tumor (Fig. 2).

The most common pattern of tumor spread (Table 2) was local-regional extension into the brainstem and upper cervical spinal cord. Extension in the posterior fossa along the tentorium was also noted (Figs. 3A- 3D). Although local leptomeningeal invasion was pres- ent in one patient, no patient demonstrated clinical or autopsy cerebrospinal subarachnoid dissemination.

Discussion

Although there is much information in the literature on the clinical course and treatment results of patients

0008-543)</82/07 I5/0308 $0.70 0 American Cancer Society

308

No. 2 CEREBELLAR GLIOBLASTOMA Kopelson 309

FIG. I . (Patient 4; Pathol. No. 80-20890). Poorly differentiated grade 111 glioblastoma. Assign- ment to grade IV was not made because of lack of necrosis ( H & E. original magnification X 160).

with supratentorial glioblastoma, the natural history and management of patients with cerebellar glioblas- toma has received sparse attention. Indeed one classical paper states that “glioblastomas . . . never occur in the cerebel l~m.’”~ However, pooled data from recent series which reported glioblastomas from all sites and their relative incidence demonstrate that about 1 % of glio- blastomas occur in the cerebellum (Table 3).

Much attention has focused on the relatively favor- able prognosis of children with low-grade cerebellar as t ro~ytomas . ’~ , ’~ However, the clinician should be cog-

nizant that cerebellar glioblastomas have also been re- ported in indeed, in our series two of eight patients were in the pediatric age group. In adults, these lesions should be carefully distinguished from medul- loblastomas and other lesions with a markedly different prognosis and management.21

Six of our eight patients were male, confirming a prior observation.2

The natural history of these tumors as evidenced in Table 2 and prior reports indicates that local-regional invasiveness is c ~ m r n o n , ~ ~ ~ ~ ~ ” * ~ ~ ’ ~ characterized by exten-

TABLE I . Clinical Course of Eight Cerebellar Glioblastoma Patients

Irradiation Doses

(rad/fractions/elapsed days) Tumor Extent of Whole Primary Last

Patient Age/sex grade surgery brain site Survival status

Irradiated patients I 15/M I 1 1 PR - 5000/25/35 8 yr 10 mo A, NED 2 53/M IV C R - 4400/15/30 6 mo DID* 3 57/M IV PR 5400127139 5400/27/39 2 yr 5 mo A, N E D 4 60/M 111 Bx - S000/28/43 1 Yr A, N E D

Nonirradiated patients - I mo DC - 1 mo DOD

7 54/F IV B x - I mo DOD 8 67 /M I 1 1 Bx - I mo DOD

A, NED: alive, no evidence of disease; DOD: dead of disease; DID: dead intercurrent disease; DC: dead of postoperative complication; Bx: biopsy; PR: partial resection; CR: complete resection.

5 IO/F IV C R -

6 30/M 111 PR - - -

* Died of airway obstruction due to recurrent hypopharyngeal squa- mous cell carcinoma (histologically different than the glioblastoma) which had been treated prior to diagnosis of cerebellar primary.

310 CANCER July 15 1982 Vol. 50

Flc;. 2. (Patient I ) . Contrast-enhanced C T scan done 5 years after partial resection and SO00 rad/25 fractions/35 elapsed days to the posterior fossa. C T reveals no evidence of residual tumor. The fourth ventricle is slightly enlarged but normal in position. The lateral ven- tricles are normal, and surgical clips are present. The patient is doing well at eight years, ten months. No preirradiation C T is available because she was treated in the pre-CT scan era.

sion into the brainstem,* adjacent leptomeninges," up- per cervical spinal cord,' and occasionally into the soft tissues of the operative site.4

Overall survival for these patients has been poor as in glioblastomas originating elsewhere in the nervous system. Survival at three years has been reported for only four previously-reported cerebellar glioblastoma patient^^.'^.^*.^' plus the one patient in the current report. Prior series have not mentioned the importance of the histologic grade of the tumor; our long-term survivor had a grade 111 lesion. This latter patient was also in the pediatric age group, and it is possible that both the young age and a grade 111 lesion contributed to the long

T A H l I: 2 . I'atterns of Spread of Cerebellar Gliohlastoma

Local extension into brainstcm into cervical spinal cord leptomenigeal invasion

Subarachnoid spread intracranial intramedullary spinal cord*

Nonirradiated group

( 4 patients)

2 2 0

0 0

Irradiated

( 4 patients) group

I 0 I

0 0

survival in addition to the irradiation which was given after partial resection (Table 1 , Fig. 2).

Only brief mention has been made in prior reports of management. Of the few patients in modern case reports in whom radiation therapy was part of man- agement, information on dose and field size was usually not I n four other patients, however, small portals were used in which the posterior fossa received 4301 ad,^ 5000 rad,I6 5290 ad,^ and 6000 re- spectively. Of the four irradiated patients in the current report, the one long-term survivor had local field irra- diation to 5000 rad after partial resection. Such local field irradiation may be an acceptable form of treatment as evidenced by the local-regional spread patterns seen in Table 2 and briefly mentioned by other^.^.^.^.'.''

Subarachnoid seeding was not demonstrated i n any of the eight patients in Table 2. Three of the four ir- radiated patients survived at least one year, and sub- arachnoid seeding would probably have become evident by this time period. The subject of craniospinal irra- diation for all infratentorial glioblastomas will be dis- cussed elsewhere.24

In conclusion, cerebellar glioblastomas are uncom- mon. They should be distinguished carefully from other posterior fossa tumors such as the benign low-grade cerebellar astrocytoma of ch i ldh~od '~ , ' ' and from med- ulloblastomas in adults." Local-regional contiguous in- volvement appears to be the major method of spread of these tumors, and local-regional irradiation to the posterior fossa and adjacent areas at risk appears to be an acceptable form of management.

ADDENDUM

Since this article was accepted for publication. Salazar has updated the University of Rochester experience (Salazar OM, Primary ma- lignant cerebellar astrocytomas in children: A signal for postoperative craniospinal irradiation. Inr J Radior Onrol Biol Yhys 1981; 7:1661- 1665) and continues to advocate elective neuraxis irradiation for these patients. A detailed critique of that data (Kopelson G . Letter to the Editor. Inr J Radiar Onrol B i d Phys 1982, in press) suggests that more aggressive treatment to the primary site, rather than elective craniospinal irradiation, has accounted for their improved series. In - deed, another recent series (of analagous brain stem glioma patients) confirms a similar local-regional direct invasiveness, rather than sub-

TABLE 3. Incidence of Cerebellum as Primary Site of Glioblastorna in Recent Series

No. with cerebellar

Total no. patients with

Series, year (ref.) glioblastoma primary tumor

Kamsey and Brand, 1973" 60 2

1975'' I14 I Salazar er a1.,1976' 104 5 Onoyama er ol., 1976" 127 0 Luccarelli. 1980" 1206 3

Caldwell and Aristizabel,

* Spinal cord examined in all 3 autopsied patients. Total 161 I 1 1 ( I % )

No. 2 CEREBELLAR GLIOBLASTOMA - Kopelson 31 1

FIGS. 3A-3D. (Patient 3). Contrast-en- hanced C T scan done after partial resection reveals residual tumor with ring-enhance- ment (A) from the vermis extending up the tentorium (B) compressing the quadrige- minal cistern. Bilateral subdural hematomas are present anteriorly. He was then irradiated (Table 2 ) . and two months postirradiation. contrast-enhanced CT scan reveals decrease in sire of the ring-enhanced mass in the su- perior vermis ( C ) and resolution of the tumor- enhancement along the tentorium (D). Mod- erate dilatation of the third and lateral ven- tricles is unchanged from an interval C T scan (not shown). A subgaleal fluid collection in the region of the suboccipital craniotomy de- fect is noted, as is clip artifact. The patient is doing well at two years, five months.

arachnoid spread. as the major pattern of tumor spread and also advocates local-regional irradiation fields alone (Mantravadi RVP e f 01. Brain stem gliomas. Cancer 1982; 49:1294-1296).

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