The radiotherapeutic management of optic nerve gliomas in children

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??Original Contribution THE RADIOTHERAPEUTIC MANAGEMENT OF OPTIC NERVE GLIOMAS IN CHILDREN BARBARA F. DANOFF, M.D.,’ SIMON KRAMER, M.D.’ and NOBLE THOMPSON. M.D.3 Thomas

Jefferson

University

Hospital,

Philadelphia.

Pa. 19 IO?.

Opticnerve gliomus

represent one to five percent of all intracranial tumors in children. Tbe management of these tumors remains controversial. From 1956 to 1977, 18 children with optic nerve gliomas were treated at Thomas Jefferson University Hospital using external beam radiotherapy. All children presented with decreased visual acuity and five of eighteen were blindin one eye. No patient was found to have involvement of a single optic nerve. In eight patients, the chiasm was involved, in ten patients. tumor had extended to the frontal lobes and/or hypothalamus. lnitial surgical management included biopsy only in seven patients, inspection of tumor in two patients and partial excision in seven patients. Two patients were treated with radiotherapy based on radiological findings. A tumor dose of 5OtW64Mhl rad was given in 5.5-6.5 weeks. Stabilization of visual impairment or improvement in vision was noted in 78 percent of patients who were evaluable. The ten year survival was 73 percent. Radiological evidence of tumor regression will be presented. It is our impression that radiotherapy is indicated in the treatment of children with optic nerve gliomas who have poor prognostic signs (i.e. chiasmal and/or hypothalamic involvement and progressive visual loss). Optic nerve glioma

Chiasmal

glioma,Cliomasof

the optic pathways.

INTRODUCIION Optic nerve gliomas comprise one to five percent of all intracranial tumors in children. Seventy-five percent occur in the first decade of life; 90% occur during the first two decades.” Histologically, the majority of these tumors are benign pilocytic astrocytomas. For prognostic and therapeutic considerations, gliomas confined to the optic nerve should be distinguished from those involving the chiasm and/or hypothalamus.” Considerable controversy still exists regarding the natural history and optimum treatment of optic nerve gliomas. The tumors are characterized by a slow but unpredictable growth pattern. Long survival, with stabilization or improvement of signs and symptoms has been reported following both incomplete excision or no therapeutic intervention.” “.I’ As a result, certain authors recommend only observation after initial diagnosis.6~‘o~z7 Others have recognized the potentially aggressive nature of these tumors especially with chiasmatic or hypothalamic involvement and have advocated total exci1. Assistant Professor Department of Radiation Therapy and Nuclear Medicine. 2. Professor and Chairman Department of Radiation Therapy and Nuclear Medicine. 3. Clinical Associate Professor Department of Radiology. *References 3-5. 7. 13. 14. 17, 18. 23. 24 Presented at the American Society of Therapeutic Radiologists’ Annual Meeting, Los Angeles. California. October 31November 4, 1978.

sion, 9.‘3.‘4.26subtotal excision and radiotherapy, or radiotherapy alone* for unresectable lesions. This report is a retrospective review of experience with the radiotherapeutic management of optic nerve gliomas over a 19 year period.

METHODS AND MATERIALS From 1958-l 977, 18 patients were irradiated for optic nerve gliomas. Eleven were females and seven were males. Ages ranged from 2 years to 12 years with a mean age of 5.9 years. The most frequent presenting symptoms were decreased vision, proptosis, and headache (Table 1). The average duration of symptoms prior to diagnosis was twelve months. The most frequent presenting signs were optic atrophy and decreased visual acuity (Table I ). Five patients presented with clinical hypothalamic involvement (diabetes insipidus. precocious puberty, somnolence, obesity). Neurofibromatosis was an associated finding in 33% (6/l 8) of the patients. Eight patients had chiasmal lesions with or without involvement of the optic This investigation was supported in part by Grant Number CA 11602. awarded by the National Cancer Institute. Depts. of Health. Education, and Welfare. Reprint requests to: Barbara F. DanoB. M.D., Dept. of Radiation Therapy and Nuclear Medicine. Thomas Jefferson University Hospital. I Ith and Walnut Sts.. Philadelphia, Pa. 19107. Accepted for publication I I September 1979.

Radiation Oncology 0 Biology??Physics

46

January 1980, Voiume 6, No. 1

Table I. Signs and symptoms Signs & symptoms

Table 3. Treatment of optic glioma

No. patients*

Percent

18

100

4

22 28 5 5 II 28 I7 22 83 28 33 33

Number of Patients Chiasm

Impaired Vision Proptosis Headache Seizure Vomiting Personality change Visual field defect Central scotoma Papilledema Optic atrophy Hypothalamic symptoms Hydrocephalus Neurofibromatosis

5 I

I 2 5

3 4 I5 5 6 6

*Total number of cases of optic glioma - 18.

nerve. Ten patients had lesions involving the chiasm and hypothalamus. In no case was the tumor confined to the optic nerve. Six of the ten patients with hypothalamic involvement had associated hydrocephaius. Only three of these patients required a shunting procedure. Radiologic findings (Table 2) included unilateral optic foramen enlargement in three patients and bilateral enlargement in six patients. Only three patients had the classic J shaped sella on skull X ray. Thirteen patients had a pneumoencephalogram and eleven were found to have a supraseliar mass lesion. Computerized tomography (CT) was performed in three patients and revealed bilateral optic nerve enlargement in one patient and a suprasellar mass lesion in two patients. Spinal fluid cytology and protein determinations were normal in the five patients so examined. Pretreatment endocrine evaiuation was performed in six patients. Two patients were found to have diabetes insipidus and four patients were normal. Table 2. Radidlogic findings No.

Radiologic findings Skull X ray J shaped sella Tomograms of the optic foramen Unilateral enlargement Bilateral enlargement Pneumoencephalogram Suprasellar mass Suprasellar mass extending to hypothalamus and/or anterior third ventricle Cerebral arteriogram Suprasellar mass Suprasellar mass with posterior extension Computerized tomography Optic nerve enlargement Suprasellar mass

patients*

Percent

18 3 I8 3 6 I3 6 5

100 I7 100 17 33 72 46 38

6 3 3

33 50 50

3 1 2

*Total number of cases of optic glioma - 18.

I7 33 67

Radiation alone Surgical inspection and radiation Biopsy and radiation Subtotal excision and radiation Total

Chiasm/hypothalamus

I

I

1 3

I 4

3 8

4 10

Seven patients underwent partial surgical resection followed by radiotherapy and seven patients had biopsy of the tumor and radiotherapy (Table 3). Six of these 14 patients (43%) had an increase in visual impairment after craniotomy. In two cases the diagnosis was based on neuroradiological findings and in two cases surgical inspection of the tumor without biopsy was followed by radiotherapy. Of the 14 patients whose tumors were verified on histologic examination, 12 were found to have a Grade I astrocytoma; one, a Grade II astrocytoma; and one, a Grade III astrocytoma. All patients received supervoltage radiotherapy with tumor doses of 5000-6000 rad in 5-6.5 weeks. Sixteen patients were treated at the time of initial diagnosis. In two patients treatment was delayed 1.5 years after initial diagnosis when signs and symptoms of progression became manifest. Sixteen patients received treatment to the primary tumor plus an adequate margin. Two patients received whole brain irradiation initially to 4000 and 5000 rad followed by a boost to the primary of 2000 and 1000 rad respectively. One of these patients had a Grade III astrocytoma. Patients were treated with parallel opposed fields, a three-field technique, or a rotational technique. RESULTS The follow-up period ranged from one to nineteen years; 15 of 18 patients remain alive at the time of this writing. Six patients have been followed for less than five years. The remaining 12 patients have achieved a fiveyear survival of 83% (lo/ 12) and a ten-year survival of 73% (8/l I) (Table 4). The five-year survival of patients with chiasmal gliomas is 100% (5/5) and the ten-year survival is 90% (4/S). The single death in this group occurred in a four-year-old boy with neurofibromatosis, five years post irradiation for a chiasmal glioma. He died of a fibrosarcoma of the left temporal lobe (outside of the Table 4. Survival optic nerve glioma Five years (B)

Ten years @)

Chiasm

5/5 (100)

Chiasm/hypothalamus Total

5/7 (71) IO/l2 (83)

4/5 (90) 4/6 (66) 8/l 1 (73)

Location

The radiotherapeutic management of optic nerve gliomas in children 0 B. F. DANOFF er 01.

irradiated field). Of the seven patients with hypothalamic and/or third ventricle involvement who were evaluable at five years, five are alive (71%) at this time. Two patients died of rapidly progressive disease within one year of treatment. The ten-year survival in this group is 4/6 (66%). Three patients developed a left hemiparesis within one to two years of completion of therapy and have subsequently experienced progressive deterioration suggestive of tumor extension into the middle cranial fossa. Two of these three patients are institutionalized in a semicomatose state at five and twelve years post treatment. The third patient remains stable at three years with a Grade 111astrocytoma. Two of six patients with hydrocephalus died of progressive disease within one year of treatment. There was no difference in survival among Table 5. Visual status post radiation optic glioma Vision No. of patients

Location Chiasm Chiasm/hypothalamus Total

Fig. 1.

8 IO 18

Improved

Stable

Worse

1

5 3 8

3 4

4 6

1

47

those patients with neurofibromatosis and those without this condition. Visual status was maintained or improved in 78% (14/ 18) of the patients (Table 5). Thirty-three percent (6/l 8) experienced improvement in vision post treatment. In four patients, vision decreased post treatment. Two of these patients died of disease within one year after treatment and one is alive at this time, with slowly progressive disease. In only a single patient did vision deteriorate without evidence of tumor progression. In five patients follow-up radiologic examinations demonstrated tumor regression post radiation. In one patient who originally had spongioblastoma polare involving the left optic nerve, suprasellar region, and base of the frontal lobe CT scan revealed no evidence of tumor thirteen years later. At the time of surgery only a biopsy was performed. A second patient had a Grade I astrocytoma involving both optic nerves, the chiasm, and hypothalamus two years post biopsy and radiotherapy, CT scan showed marked hydrocephalus without persistent tumor. In three patients with chiasmal and/or hypothalamic gliomas serial CT scans over a period of observation of one to three years have shown tumor regression. (Figure 1 and 2.)

Pneumoencephalogram demonstrates suprasellar extension

of an optic nerve glioma (arrowheads) both optic nerves. the chiasm. and right optic tract.

involving

Radiation Oncology 0 Biology 0 Physics

Fig. 2. CT scan (patient in Figure

I) two and a half

January 1980. Volume 6. No.

years post radiotherapy. persists.

Only

a small

I

area

of residual

disease

The conservative approach to treatment has been advocated by Hoyt and Baghdassarian” Wong and Lubow.” and Glaser et aL6 These authors as well as others”,“.‘5 have drawn attention to the benign character of optic nerve gliomas. They have recorded stabilization or improvement in vision for many years following incomplete excision or no therapy at all. They recommended observation only after initial diagnosis. However, the DISCUSSION number of spontaneous remissions remains small. Hoyt and Baghdassarian” reported spontaneous improvement The natural history and optimum treatment of optic in four eyes among 23 untreated patients and Tym” nerve gliomas remains controversial. For the most part. reported similar findings in two patients. these tumors are benign and slow growing; however. their growth can be unpredictable. Treatment must be directed Other authors recognize the potentially aggressive nature of these tumors.9.‘3.‘4.26 Housepian,’ Lloyd.” towards preservation or improvement of vision and mainMacCarty et alI4 and Walsh and Hoyt”’ advocate tenance of long-term survival. Therapeutic recommendacomplete surgical excision of all tumors confined to the tions have included observation alone, surgical resection optic nerve. Lloyd” noted deterioration of vision and (partial vs. total), and radiotherapy with or without general condition in 20 of 32 patients with optic nerve surgical resection. Certain aspects of therapy have achieved general gliomas involving the chiasm. Six of these patients are acceptance. Total excision cannot be performed on dead. tumors extending to chiasm and/or hypothalamus.” The Radiotherapy has generally been reserved for unrerole of surgery in this situation should be limited to sectable lesions involving the chiasm and/or hypothalamus. Throuvalas et al,24 Taveras et al,” Chutorian et al,’ exploration and inspection of the tumor, biopsy to confirm the neuroradiologic diagnosis, shunting ptoceChang and Wood.’ Montgomery et al,‘” and Harter et al,’ dures for hydrocephalus, and the removal of a grossly have reported stabilization or improvement of vision. proptosed blind eye.2.“.‘7~‘y~2s The following prognostic decrease in proptosis. and reduction in radiologic and factors may influence the decision for treatment: the gross tumor mass as well as long-term survival in patients anatomic location of the tumor, the presence or absence whose optic nerve gliomas were treated with radioof hydrocephalus, and the tumor grade. Lesions with therapy. posterior extension to the hypothalamus or third ventricle Tables 6-8 compare treatment results of several series tend to exhibit a more aggressive course.‘~4~5~‘o~‘2~‘7~‘9~22 for gliomas confined to a single nerve, chiasmal gliomas, Patients with hydrocephalus also have a poor prognoand optic nerve gliomas extending to the hypothalamus. sis.‘.” Malignant gliomas of the optic nerve, while rare in Uniformly good results are achieved with surgery, obserchildren, are associated with decreased survival.‘.’ vation, or radiotherapy in tumors confined to the optic

Of the 15 living patients, four are mentally retarded and two are institutionalized in a semicomatose state. One patient has developed a psychosis. Three patients have manifested endocrine dysfunction at 6, IO. and 13 years post treatment. All three were found to have decreased thyroid and adrenal function and two of the three have decreased gonadotrophin levels.

The radiotherapeutic

Table

6.

management

Treatment

of optic nerve gllomas in children 0 B. F. DAYOFF CI al

and results of lesions confined to the optic nerve Without

No. of patients

Series Hoyt and Baphdassarian’” Miller et al.” Chutorian et al.4 Wang and Lubow” Lloyd ” Oxenhandler and Sayers2” Taveras et al ” Heiskanen et al.” Harter et al.’

‘- Complete surgical resection

5 8 I9 7 72 8 9 4 3 2

49

W’ith radiotherapy

radiotherapy

G Decrease in vision

‘;I Complete surgical

‘T Survival*

_

80 100 100

40 0 0

I 00

45 100 100

* 0 0

IO0 100 100

‘/; Survival?

‘,T Decrease in vision

resection

_-- ---___

____--

100 IO0 *

25

100

‘5 IO0 0

25 0 0

100 100 100

*Information not available. *Follow-up period l-29 years. Table 7. Results of treatment Wtthout No. of

Series

patients

Hoyt and Baphdassarian” Myles and Murphy” Tym 2’ Wong and Lubow” Lloyd ” Oxenhandler

and Sayers’”

Chanp and Wood’ Miller et al.” Throuvalas et a1.24 Montgomery et al. ” Heiskanen et al.h Danoff et al.

9 4 8 7 9 8 IO 23 6 8 88 I5 I5 16 IO 8

chiasmal

radiotherapy

With

Survival:

II

100

*

37

0

radlotherap! -

<-

R Decrease

in vision

glioma

% Decrease in vision

YSurvlvai$

I’

100

I’

100

72

.

100

60

90

16

x.7

7

83

12 25

87 73 100 80 75 100 87

II

20 0 0 I’,.

*Information not available. tFollow-up period 6 months-20 years. SFollow-up period I -3O+ years. Table 8. Results of treatment

optic nerve glioma with hypthalamic Without

Series Hoyt and Baghdassarian” Miller et al.” Wonp and Lubow2’ Harter et al.’ Oxenhandler and Sayers2’ Heiskanen et al.” Taveras et al. 2’ Danoff et al. *Information not available. ?Follow-up period I-20 + years.

No. of patients 9 10 4 I 1 5 4 4 4 IO

%, Decrease in vision

radiotherapy

With radiotherapy

% Survivalt

33

87

100

25

*

involvement

R Decrease in vision

L” SurZvalt

25

15

40

71

20 25 * 17 30

60 75 20 25 80

Cl

50

Radiation Oncology 0 Biology ?? Physin

nerve (Table 6). No tumor related deaths are recorded. All patients undergoing complete resection have had stable vision in the contralateral eye. The results in chiasmal gliomas are less encouraging (Table 7). Mortality and morbidity (visual loss) related to progressive disease are apparent. The majority of the series reviewed have indicated the need for radiotherapy and survival rates of 73-100% are reported. Few authors other than Hoyt and Baghdassarian” advocate observation alone of optic nerve gliomas extending to the hypothalamus (Table 8). No other series has confirmed their results. The radiotherapy series (Table 8) have achieved stabilization or improvement in vision in the majority of patients as well as long-term survival. In the present series, visual status was maintained or improved in 78% of the patients. Eighty-three percent of the patients survived five years and 73%, ten years. Radiotherapy has been capable of producing definite tumor regression in five patients as documented by serial CT scans. Marks and Gado15 followed five patients with

January 1980, Volume 6, No. 1

optic nerve gliomas (treated with radiotherapy) with CT scans. In one patient the tumor had completely disappeared; in one it regressed; in three persistent disease remained. In our series, long-term effects of radiotherapy included three patients with endocrine deficiency manifesting at 6, 10, and 13 years post treatment. Four patients are mentally retarded although it is difficult to determine if this can be attributed to radiotherapy alone. Lloyd” noted that one-third of the patients in her series were mentally retarded pre treatment. Radiotherapy has been shown to be efficacious in the treatment of optic nerve gliomas. In gliomas confined to a single optic nerve, we recommend transcranial chiasmal inspection and prechiasmal resection if useful vision is not sacrificed. For lesions extending to the chiasm or hypothalamus, we recommend transcranial inspection and biopsy if vision will not be sacrificed followed by post operative radiotherapy. We recommend a tumor dose of 5500-6000

rad in 6 to 6.5 weeks.

REFERENCES 15. Marks, J.E., Gado,

1. Brooks, W.H., Parker, J.C., Jr., Young, A.B., Mortara, R.H.: Malignant gliomas of the optic chiasm in adolescents. C/in. Pediatr. IS: 557-56 1, 1976.

2. Bynke. treatment

H., Kagstrom, E., Tjernstrom, K.: Aspects on of gliomas of the anterior visual pathway. ACTA

Ophthalmologica 55: 269-280, 3.

4. 5. 6.

7.

1977.

Chang, C.H.. Wood, E.H.:

The value of radiation therapy for gliomas of the anterior visual pathway. In Conrroversy in Ophthalmology. R.J. Brockhurst, S.A. Boruchoff, B.T. Hutchinson, S. Lessell, Eds. Philadelphia, W.B. Saunders Company. 1977, pp. 878-886. Chutorian, A.M., Schwartz. J.F., Evans, R.A., Carter, S.: Optic gliomas in children. Neurology 14: 83-95, 1964. Fowler, F.D., Matson, D.D.: Gliomas of the optic pathways in childhood. J. Neurosurg. 14: 5 15-528. 1957. Glaser, J.S., Hoyt, W.F., Corbett, J.: Visual morbidity with chiasmal glioma. Arch. Ophthalmof. 85: 3-12, I97 I. Harter: D.J., Caderao, J.B., Leavens, M.E., Young, SE.: Radiotherapy in the management of primary gliomas involving the intracranial optic nerves and chiasm. Int. J.

Radiat. 0~01. Biol. Phys. 4: 68 l-686, 8.

1978.

Heiskanen, 0.. Raitta, C., Torsti, R.: Management and prognosis of gliomas of the optic pathways in children.

Mod. Probl. Paediatr. 1%: 216-219, 1977. 9. Housepian, E.M.: Surgical treatment of unilateral optic nerve gliomas. J. Neurosurg. 31: 604-607, 1969. IO. Hoyt, W.F., Baghdassarian, S.A.: Optic glioma of childhood: Natural history and rationale for conservative management. Br. J. Ophthalmol. 53: 793-798, 1969. 1 I. Hudson. A.C.: Primary tumors of the optic nerve. R. Ophthalmol. Hosp. Rep. 18: 3 17-439, 1912. 12. Klug, C.L.: Gliomas of the optic nerve and chiasm in children. Aust. NZ J. Surg. 47: 596-600, 1977. 13. Lloyd, L.A.: Gliomas of the optic nerve and chiasm in childhood. Trans. Am. Ophthalmol. Sot. 71: 488-535,

1973. 14. MacCarty,

C.S., Boyd, A.S., Childs, D.S.: Tumors of the optic nerve and optic chiasm. J. Neurosurg. 33: 439-444, 1970.

M.: Serial computed tomography of primary brain tumors following surgery, irradiation, and chemotherapy. Radiology 125: 119-123, 1977.

16. Martin, P.. Cushing. H.: Primary gliomas of the chiasm and optic nerves in their intracranial portion. Arch.

Ophthalmol. 52: 209-241, 17. Miller, N.R., Iliff, W.J., management

1923.

Green, W.R.: Evaluation and of gliomas of the anterior visual pathways.

Brain 97: 743-754. 1974. 18. Montgomery, A.B., Griffin, T.. Parker, R.G., Gerdes, A.J.: Optic nerve glioma: The role of radiation therapy. Cancer 40: 2079-2080,1977. 19. Myles, S.T.. Murphy, S.B.: Gliomas of the optic nerve and chiasm. Can. J. Ophthalmol. 8: 508-5 14. 1973. 20. Oxenhandler. D.C., Sayers. M.P.: The dilemma of childhood optic gliomas. J. Neurosurg. 48~ 34-4 I, 1978. 21. Posner, M.. Horrax, G.: Tumors of the optic nerve. Long survival in three cases of intracranial tumor. .4rch. Ophthalmol. 40: 56-76. 1948. 22. Schuster, G., Westberg, G.: Gliomas of the optic nerve and chiasm. Acra. Radiol. (Diagn.) (Stockh.) 6: 221-232, 1967. 23. Taveras, J.M.. Mount, L.A., Wood, E.H.: The value of radiation therapy in the management of glioma of the optic nerves and chiasm. Radiology 66: 5 18-528, 1956. 24. Throuvalas, N., Bataini, P., Ennuyer, A.: Les gliomes du chiasma et du nerf optique. L’apport de la radiotherapie transcutanee dans leur traitement. Bull. Cancer (Paris) 56: 231-264, 1969. 25. Tym. R.: Piloid gliomas of the anterior optic pathways. Br. J. Surg. 49: 322-331, 1961. 26. Walsh. F.B., Hoyt, W.F.: Clinical neuro-ophthalmology. Edition 3. Baltimore, Williams and Wilkins Company. 1969, pp. 2075-2097. 27. Wong, I.G., Lubow, M.: Management of optic glioma of childhood-a review of 42 cases. In Neuro-ophthalmology.

Symposium of University Miami and Bascom Palmer Eye Institute. Volume VI. St. Louis, C.V. Mosby. 1972, pp. 5 l-60.