Management of Low-Grade Gliornas of the Optic Nerve

and Chiasm

JOHN C. FLICKINGER, MD, CARLOS TORRES, MD, AND MELVIN DEUTSCH, MD

Thirty-six patients were evaluated between 1965 and 1983 for glioma of the optic nerves and/or chiasm.
Median follow-up was 10.2 years. Pathologic verification was obtained in 32 patients. Tumor initially
confined to the optic nerve recurred in one of five patients after complete resection. The actuarial
survival for 25 patients irradiated for biopsy-proven glioma of the optic chiasm was 96%,90%,and 90%
at 5, 10, and 15 years, respectively, and the progression-free survival was 87%at 5, 10, and 15 years.
Vision stabilized or improved in 86% of patients after radiotherapy. Patients irradiated to a dose greater
than a NSD of 1385 ret had a significantly improved progression-freesurvival (P= 0.015). One serious
complicationoccurred after a dose of 1533 ret. The recommended radiation dose for optic glioma is 45 to
50 Cy with 1.8 Gy fractions.
Cancer 61:635-642, 1988.

G LIOMAS of the optic nerve and chiasm are rare

tumors which occur most commonly in child-
hood.02 The majority these tumors are low-grade astro-
cytoma~.~- The clinical course of these tumors is not
benign in all patients and may lead to blindness or death
from tumor progression in a significant number of pa-
tients. Tumors involving the optic chiasm and particu-
larly extending outside the chiasm into the hypothala-
mus tend to be more aggressive than tumors involving
the optic nerve alone and are less able to be managed by
surgery without serious m ~ r b i d i t y . Radiation
~.~ therapy
has been reported to be effective in controlling gliomas
of the optic nerve and ~hiasrn.~- The long natural his-
tory and slow course of this disease in some patients
makes the effectiveness of radiation therapy difficult to
evaluate and some authors have doubted its effective-
ness.. This report analyzes the experience at our in-
stitution in the management of glioma of the optic nerve
and/or chiasm.
Materials and Methods
From 1965 to 1983, a total of 38 patients were evalu-
ated at the University of Pittsburgh for the diagnosis of
glioma of the optic nerve and/or chiasm. In Table 1,
Presented at the 69th Annual Meeting of the American Radium
Society in London, England, April 7, 1987.
From the Joint Radiation Oncology Center, University of Pitts-
burgh, Pittsburgh, Pennsylvania.
Address for reprints: John C. Rickinger, MD, Joint Radiation On-
cology Center, University of Pittsburgh, 230 Lothrop Street, Pitts-
burgh, PA 15213.
Accepted for publication August 25, 1987.
these patients are listed in groups according to surgical
and radiation treatment. Biopsy confirmation of the
diagnosis was obtained in 32 of the remaining 38 pa-
tients (Group la, 2a, and 2b in Table l). All were low-
grade astrocytomas. In four patients from group lb, Ic,
and 2c, the diagnosis was based upon clinical findings as
well as skull x-ray, arteriogram and radioisotope brain
scan. One patient also underwent craniotomy and oper-
ative exploration without biopsy. There were two pa-
tients (group 3a, 3b) that received radiation therapy for
the diagnosis of optic glioma based upon skull x-ray,
arteriogram, and radioisotope brain scan followed by
operative exploration without biopsy. After failing to
respond to radiation therapy, they were later found not
to have optic glioma. One of these patients had a tumor
involving the optic nerve which was found to be an
inflammatory sclerosing pseudotumor of the right orbit.
The other patient had a tumor involving the optic
chiasm which was later found to be a craniopharyn-
gioma. These two patients are excluded from further
analysis in this series.
The tumor appeared to be confined to the optic nerve
in seven patients (group la, ib, lc). Five underwent
surgical resection, one received radiotherapy without
biopsy, and one patient was observed without biopsy.
Twenty-nine of the 30 patients in groups 2a, b, and c,
had tumors initially involving the optic chiasm. One
patient listed in both groups 1a and 2b presented with a
tumor confined to the optic nerve that was resected,
later recurred in the optic chiasm and received radia-
tion. Fifteen patients in groups 2a, 2b, and 2c, had
tumor extension outside of the optic chiasm into the

635
636 CANCERFebruary 15 1988 Vol. 61

TABLE1 . Therapy of Optic Nerve and Chiasm Tumors NSD for these patients ranged from 1253 to 1639 ret
(median, 1415 ret). Equivalent dose, which may more
1 Optic glioma 7 patients
a Resected 5 accurately reflect the tolerance of normal neural tissue,2
b Observed I ranged from 955 to 1258 ret (median, 1081 ret).
c No biopsy, radiation I The clinical characteristics of the 32 patients with
2 Optic chiasm glioma 30 patients
a Partial resection 3 biopsy confirmation of their tumors (groups la, 2a, 2b)
b Biopsy. radiation 25 are shown in Table 2. Age ranged from 8 months to 17
c No biopsy, radiation 2 years with a mean of 7.4 years. Nine patients were male
3 Other irradiated tumors 2 patients
a Pseudotumor of the orbit I and 23 were female. There was evidence of neurofibro-
b Craniooharvnaioma 1 matosis (cafe au lait spots), in ten of the 32 patients
(3 1%). The duration of symptoms before diagnosis
ranged from 1 month to 7 years (median, 6 months).
hypothalamus, optic tract, or temporal lobe. The tumor Follow-up of the patients ranged from 2 to 21 years.
appeared to be confined to the optic nerves and chiasm Median follow-up was 10.3 years. Follow-up was greater
in the other 15 patients. A total of 25 patients received than 5 years in 84% of the patients, greater than 10 years
radiotherapy for biopsy-proven glioma involving the in 69% of the patients, greater than 15 years in 28%,and
optic chiasm (group 2b). The results of radiotherapy are greater than 20 years in 10%. No patient was lost to
analyzed in detail in this group of patients. One of these follow-up. Eight patients were included in a previous
patients received chemotherapy with vincristine and report by Deutsch. Recent follow-up was obtained on
dactinomycin 6 months before radiotherapy. Three pa- the two patients that were reported as lost to follow-up at
tients with chiasm involvement underwent subtotal re- that time.
section without radiotherapy (group 2a). One died post- Actuarial survival and progression-free survival were
operatively of infection. Two patients with chiasm in- calculated according to the method of Kaplan and
volvement received radiation therapy without biopsy M e i e ~ -The
. ~ ~ differences in survival between groups of
(group 2c). patients were examined using the method of Mantel24
Radiotherapy was administered with a cesium tele- with a two-tailed significance test. This was checked
therapy unit in six patients, cobalt 60 in seven, 6-MeV using the log-rank test25and the larger (less significant)
linear accelerator in eight, and 8 MeV in seven. A total of the two P value calculations was reported in each
of 17 patients were treated with parallel opposed lateral case.
fields, eight with multiple portals and two with rota-
tional treatment plans. All the radiation doses were re- Results
ported at the 95% isodose line. The radiation treatment
dose ranged between 38.0 and 56.86 Gy with a mean of The actuarial survival for the entire group of 36 pa-
47.0 Gy. Dose per fraction ranged from 143 to 200 cGy tients was 94% at 5 years and 9 l % at 10 and 15 years.
with a mean dose per fraction of 174 cGy. Treatment Three patients died of disease. One patient died of a
field sizes ranged from 4.5 X 4.5 cm to 1 1 X 12 cm postoperative infection. Two patients died with central
(median size, 6 X 6.5 cm). Computed tomographic (CT) tumor progression 2.5 years and 6.5 years, respectively,
scans were used in treatment planning for 56% of the after receiving radiotherapy. The patient who died 2.5
patients. Calculations of the nominal standard dose years after radiotherapy developed a complete left
(NSD) and equivalent dose (ED) were performed to hemiparesis followed by further neurologic deteriora-
analyze the results of radiotherapy in the 25 cases with tion and was considered to have undergone a tumor-re-
biopsy-proven glioma involving the optic chiasm. The lated death. The other patient first experienced deterio-
ration of vision 2 months after radiotherapy requiring
placement of a shunt, and later died with central tumor
progression 6.5 years after radiotherapy. No patient died
TABLE2. Clinical Characteristics of intercurrent disease. As shown in Figure 1, the ac-
~~

Age
tuarial survival for patients with tumor confined to the
Range 8 mo- 17.7 yr optic nerve was 100% at 5 , 10, and 15 years and for
Median 7.4 yr tumors involving the optic chiasm 93%, 88%,and 88%,
Sex
Male 28% at 5 , 10, and 15 years, respectively.
Female 72%
Neurofibromatosis 31% Oplic Nerve Gliomas
Duration of symptoms
Range 0-7 yr Seven patients were found to have gliomas that ap-
Median 6 mo
peared to be confined to the optic nerve. Five of these
No. 4 OF THE OPTIC
GLIOMAS AND CHIASM
NERVE . Flickinger et a/. 637

patients underwent what was described as a complete

resection of their tumor (group la in Table I). Four of
these five patients are free of disease after complete re-
section with follow-up of 4.3, 7.5, 1 1.1, and 16.9 years,
respectively. One patient developed recurrent disease in -1
the optic chiasm with headaches and decreased vision -3> .a-
2.7 years after surgery. He received radiotherapy at that I
u)
time and is free of disease progression 12 years later. -
.40
One patient (in group lb) with a diagnosis based upon
CT scan findings was followed without treatment or
biopsy 10 years after diagnosis with only a moderate -
.20

decrease in vision in one eye and no significant change

in tumor size on follow-up CT scans. The final patient
2 6 8 10 12 14 16 18 20
(group lc) was referred for radiation therapy without 4

biopsy. She was almost blind in one eye at that time and YEARS

surgery was thought to be contraindicated because she FIG. 1. Actuarial survival of patients with gliorna confined to the
optic nerve (solid line) and involving the optic chiasrn (dashed line).
belonged to a religious group prohibiting blood transfu-
sions. She has stable vision 13 years after radiotherapy
with no evidence of disease progression.
poor tolerance and no evidence of response on CT scan.
Radiotherapy was started at 19 months of age because of
Gliomas Involving the Optic Chiasm
visual deterioration documented by visual evoked re-
sponses and an increase in size of the tumor on CT scan.
Surgery: Biopsy confirmation was obtained in 28 of
The actuarial survival and disease progression-free
the 30 patients with the diagnosis of glioma involving
survival for the 25 patients in group 2b (Table 1) are
the optic chiasm. One patient died postoperatively after
shown in Figure 2. The actuarial survival at 5 , 10, and
a partial resection. The two other patients in group 2a
15 years was 9670, 90%, and 90%, respectively. The dis-
(Table I ) had partial resections of glioma involving the
ease progression-free survival was 87% at 5 , 10, and 15
optic chiasm with posterior extension into the optic
years. As previously mentioned, two patients experi-
tracts. One patient was noted to have enlargement of the
enced central disease progression 0.2 and 2.5 years after
tumor on CT scan 1 year after surgery but has not yet
radiotherapy, respectively, and died 6.5 and 2.5 years,
had any change in vision a total of 2.5 years after sur-
respectively, after radiation. A third patient who devel-
gery. The other patient required placement of a ventric-
oped central disease progression 2.9 years after radiation
uloperitoneal shunt 6.9 years after surgery and now has
therapy and underwent a subtotal resection is presently
stable but poor vision 16.8 years after the partial resec-
alive with stable vision 5.0 years after radiation.
tion. In group 2b subtotal resections were performed in
ten patients and biopsies in 15 before radiotherapy.
Radiation therapy: There were 27 patients who re-
ceived radiation therapy for glioma involving the optic
chiasm. The two patients with tumors that did not un-
dergo biopsy both have stable vision with no evidence of
tumor progression at 10.3 and 18 years after radiother-
apy, respectively. The remaining 25 patients who did
undergo biopsy (group 2b) were analyzed for factors in-
fluencing survival and tumor control.
The age at the start of radiation treatment for the
patients in group 2b ranged from 19 months to 17.7
years. The only patient treated younger than age 2 years
was a 19-month-old girl with a tumor involving the
optic chiasm with extension into the right optic tract
and hypothalamus which was partially resected at age 10 2
1
4
1
6
I
8
1 I
I 0 1 2 1 4
1 1
16
I 1
1 8 2 0
months. The child's vision deteriorated 2 months later YEARS
and she received two courses of vincristine and dactino-
FIG. 2. Overall survival (S)and disease progression-free survival
mycin with the hope of delaying radiotherapy until the (DFS) for patients irradiated for biopsy proven optic glioma involving
child was older. Chemotherapy was stopped because of the optic chiasrn.
638 CANCERFebruary I5 1988 Vol. 61

TABLE3. Vision Before Radiation
Normal
Decreased, one eye
Moderately impaired. both eyes
Severely impaired. both eyes
Blind
TABLE4. Response to Radiotherapy
Vision improved
Vision stable
Vision worse
The visual status before radiotherapy for the patients
in group 2b is shown in Table 3. Before radiotherapy,
vision was normal in two patients. There was a signifi-
cant decrease in the vision in one eye in ten patients with
three of them being essentially blind in that eye. Six
patients had moderately impaired vision in both eyes
with four patients being completely blind in one eye.
Four other patients were legally blind from severe bilat-
eral visual impairment but did have a little useful vision.
Three patients were blind in both eyes. Changes in vi-
8% sion after radiotherapy are shown in Table 4. Follow-up
40% examinations demonstrated clear improvement in two
24% patients (9%) documented by visual field and visual
I690
12% acuity tests. Vision was stable in 17 patients (77%). Vi-
sual deterioration from tumor progression occurred in
three patients ( 14%). Vision stabilized following repeat
subtotal resection in one of the three patients, the other
two died of disease progression. Change in vision could
not be evaluated in the three patients who were com-
9%
77% pletely blind before radiation therapy.
14% Dose response: Death due to tumor progression oc-
curred in two patients. One was treated to a dose of 3899
rad in 22 fractions over 29 days with cesium teletherapy
and the other received a dose of 4275 rad in 25 fractions
over 35 days with cobalt 60. These doses correspond to
NSD of 1281 and I335 ret and ED of 1000 and 1034 ret.
The patient who recurred and is alive with stable disease
after subtotal resection received a dose of 4760 cGy in
30 fractions over 45 days which corresponds to a NSD of
1385 ret and an ED of 1059 ret. A plot of both NSD and
ED for each patient is shown in Figure 3. As shown in
Figure 4, a statistically significant (P = 0.045) improve-

DOSE EWIVALENCE 1.8 Gy/Fr

I I 1 1 1 L I I I 1 I I I
c 59.4
1250 - 0 - 57.6

- s5.e
1200 - 0 - 54.0

- 0
- 522
a
-
W
8*O - 50.4
8
#
w 1150-
In O0 m
0
a 0 -46.6 0
E
+
2 0 -46.8
s
W
2 1100- 0 z
a 0 .-DEAD OF DISEASE fl
1. -43.0 m
a
a
0
u
0 m -ALIVE WITH DISEASE PROGRESSION -
-43.2 0
o@
I050 - 0 - ALIVE, TVYOR CONTROLLED
WITH >SYR FOLLOW-UP
0
\
.
I

-41.4 2
a - ALIVE, TUMOR CONTROLLED

CQ
WITH <SYRS FOLLOW-UP - 39.6
1000 - d *-
a
ALIVE, TUMOR CONTROLLED
WITH RADIATION COMPLICATIONS -31.8

r 36.0
I
I I I 1 1 I I I
1250 I300 1330 1400 14% I500 I550 1- I650

NOMINAL STANDARD DOSE (NSD)

FIG.3. Tumor control and complications with respect to Nominal Standard Dose (NSD) and Equivalent Dose (ED) for patients irradiated for
biopsy-proven glioma involving the optic chiasm. The scales opposite the ordinate and abcissa (dose equivalence 1.8 Gy/fr) represent the doses
delivered at 1.8 Gy/fraction that correspond to the NSD or ED on the corresponding opposite scale.
No. 4 GLIOMAS A N D CHlASM
OF THE OFTIC NERVE * Flickinger et a/. 639

ment in overall survival was found in patients treated to

a dose greater than or equal to a NSD of 1385 ret or an
ED of 1059 ret. The improvement in disease progres-
sion-free survival also was statistically significant ( P NSD <I385
= 0.0 15) in the patients irradiated to a NSD of greater I51 (51

than 1385 ret NSD and 1059 ret ED (Fig. 5). The dose of
1385 ret NSD and 1059 ret ED was chosen for analysis
since it represented the highest dose at which tumor P = .045
recurrence developed.
Complications of radiation therapy: One serious radi-
ation complication occurred. A 10-year-old girl with no
evidence of neurofibromatosis developed recurrent bi-
lateral transient ischemic attacks and two major strokes
two years after being irradiated at age 8 years with cobalt
'20 1
1
2
I
4 6
I I
8
I
10
I
12
I
14
I
16
I
18
I
20
YEARS
60 to a dose of 5216 cGy at the 95% isodose line in 30
FIG.4. Overall survival of biopsy optic chiasm gliorna patients irra-
fractions over 41 days (NSD 1533, ED 1167). A four- diated to a dose greater than or equal to a NSD of 1385 ret compared to
field treatment technique was used with anteroposterior patients irradiated to a dose less than 1385 ret.
and posteroanterior fields measuring 6 X 8 cm and two
lateral fields measuring 6 X 7 cm which were designed to
include all of the tumor seen on CT scan within the 95%
who is alive with disease after recurrence did not have
isodose line. Arteriography demonstrated occlusion of
tumor extending outside of the optic chiasm. There was
the right carotid and severe stenosis of the left carotid
no statistically significant influence detected for sex, age,
artery within the previous radiation field. The clinical
the presence of neurofibromatosis, or biopsy versus sub-
and radiological findings fulfilled the criteria for a diag-
total resection. There was no clear effect of radiation
nosis of moyamoya syndrome.26This patient is left with
field size detected. A 4.5 X 4.5 cm field size was used in
severe, right sided, spastic hemiparesis, slight left sided
weakness as well as difficulty speaking. Less serious one of the patients who died of tumor progression. Since
this patient and the other tumor death occurred in pa-
complications included sunken temples noted in one
tients who were treated before CT scanning was avail-
patient irradiated at age 2 years. Growth hormone defi-
able, it is possible that a portion ofthe tumor could have
ciency was noted after treatment in two patients.
been underdosed. The other patient who is alive with
Another patient developed precocious puberty at age
tumor progression did have a CT scan used in the radia-
9.5 years, 1.5 years after radiotherapy. Since one other
tion treatment planning. No significant difference in
patient had developed precocious puberty before radio-
survival or disease progression-free survival was de-
therapy, the relationship to the radiation is unclear. Re-
tected between the 12 patients with tumor extension
sults of endocrine tests in other patients were not avail-
able. As shown in Figure 3, four patients were safely
treated to a dose above that received by the patient who
developed strokes. Two of these patients were treated
with larger field sizes using multiple fields, one with
smaller lateral fields, and one with multiple smaller
fields. Considering both tumor control and complica-
tions, the optimum treatment dose in this series is be-
tween an NSD of 1400 and 1520 ret, or an ED of 1080
to 1155 ret. If 180 cGy fractions are used, this would
correspond to a dose of 4500 to 5040 cGy.
P= .014
Influence of other clinical factors: The influence of
several clinical factors besides radiation dose were in- .2o
vestigated and not found to show any statistically signifi-
cant influence upon survival or progression free sur-
vival. Although both tumor deaths did occur in patients 2 4 6 8 10 12 14 16 18 x)

in whom the tumor extended outside of the optic YEARS

chiasm, it was not possible to show a statistically signifi- FIG. 5. Disease progression-free survival of biopsied optic chiasm
cant decrease in the survival or progression-free survival glioma patients irradiated to a dose of greater than a NSD of 1385 ret
of patients with this feature (P = 0.49). The one patient compared to patients irradiated to a dose less than or equal to I385 ret.
640 CANCERFebruary 15 1988
outside of the optic chiasm into the hypopharynx. optic
tract. or temporal lobe and 13 patients without tumor
extension.
Conservative management: Five patients with gliomas
involving the optic chiasm were clearly managed with a
conservative approach consisting of initial observation,
biopsy, or subtotal resection without radiotherapy. The
two younger sisters of the patient who died of a postop-
erative infection after subtotal excision of her optic
chiasm both initially were managed conservatively with
observation and visual testing. One patient was mentally
retarded and was followed for 5 years 3 months from the
time she developed a seizure and the tumor was docu-
mented on a CT scan at age 12 years. She was totally
blind by the time she underwent subtotal excision and
radiation therapy. Her younger sister was followed 6
months for decreasing vision beginning at age four years
and was almost blind by the time she underwent biopsy
and radiation therapy. She is still able to perceive light
but has little useful vision. Another patient underwent
partial excision at age I 1 months and chemotherapy was
given to try to delay radiotherapy until after age two
years. Unfortunately, the patient's tolerance was poor
and no clear benefit was seen. Ten months after the
partial excision, deterioration in vision documented by
visual evoked response and increase in size of the lesion
on CT scan led to the end of conservative management
and the patient received radiotherapy with resulting sta-
bilization of her vision. Two patients with chiasmal
gliomas were managed conservatively with a greater de-
gree of success. One patient, an 18-month-old girl, was
found to have an enlarged tumor on CT scan 1 year after
subtotal resection but vision remained unchanged with
follow-up 2.5 years after resection. The other patient
was a 7-year-old girl who required a ventriculoperito-
neal shunt 6.9 years after subtotal resection. She is alive
with stable vision 16.8 years after her subtotal resection.
She is barely able to see fingers with her right eye but has
fair vision in her left eye although a left hemianopsia is
present.
Discussion
There is presently some controversy in the manage-
ment of glioma of the optic nerve and chiasm, particu-
larly in the role of radiotherapy. A conservative ap-
proach to therapy has been advocated by Hoyt and
BaghdassarianI8 in their series of 36 patients later u p
dated by Imes and H ~ y t In . ~their
~ initial report, Hoyt
and BaghdassananI8 recommended against transcranial
operations, stating there was a lack of evidence that they
prolong life and that modern neuroradiologic proce-
dures permit accurate diagnosis and assessment of the
extent of tumor. Surgery was recommend only for relief
Vol. 61
of severe proptosis of a blind eye. They did not find any
evidence for benefit from radiotherapy and attributed
favorable visual responses to spontaneous visual im-
provement. The findings in our series and several others
recently reported in the literature take issue with many
of these recommendations.
The need for biopsy confirmation to be certain one is
dealing with a low-grade glioma of the optic chiasm has
not been totally eliminated. One of the patients in the
original series of Hoyt and Baghdassarian" was ex-
cluded from the recent update by Imes and be-
cause reevaluation cast doubt on the original diagnosis.
The series of 22 patients with chiasmal gliomas reported
from the same institution by Fletcher et af." included
two patients who were found to have anaplastic astrocy-
tomas involving the chiasm. Excluded from our series
were two patients who received radiotherapy for a diag-
nosis based upon operative exploration of their tumors
without biopsy who were later found not to have optic
glioma. One patient was found to have a craniopharyn-
gioma and the other an inflammatory pseudotumor of
the orbit. Dosoretz er a/.'' reported one patient not in-
cluded in the analysis of their series with a preoperative
diagnosis of optic glioma was found to have a cranio-
pharyngioma. Harter ef al.," Danoff et and Brand
and Hoover" reported one patient with anaplastic as-
trocytoma in each of their series containing 6, 18 and 16
optic glioma patients respectively. Miller and associates6
reported a series of 5 1 cases of gliomas of the optic nerve
and/or chiasm of whom 40 underwent biopsy and two
were found to be lymphomas. Tenny et aLZ9found four
of 83 patients in their series with biopsy of optic glioma
to have grade 111 anaplastic astrocytomas. They reported
that no patient in their series experienced any loss of
vision after biopsy of a posteriorly situated tumor. We
therefore recommend the biopsy of all patients with sus-
pected optic glioma.
It is clear that optic glioma does not follow a benign
course in all patients, particularly when the optic chiasm
is involved or there is extension beyond the optic chiasm
into the hypothalmus or optic tracts. This is very well
illustrated by the large series in two reports from the
Mayo The report of Rush et al.' analyzed their
patients seen between 1919 and 1973, and found a
long-term survival of 85% in 33 patients with tumors
confined to the optic nerve compared to a survival of
44% in 52 patients with tumors involving the optic
chiasm. Ninty-three percent of the deaths in patients
with chiasmal tumors were from tumor progression. All
ten of the patients with extension outside of the chiasm
died compared to 17 of 42 patients with limited chias-
ma1 involvement.
There is very good reason not to dismiss radiation
therapy as being ineffective. There are several possible
No. 4 GLIOMAS
OF THE OPTIC NERVEA N D CHIASM
explanations for the apparent ineffectiveness of radia-
tion in the series of Hoyt and Baghdassarian." Since the
treatment was not randomized, selection factors may
have led to the inclusion of patients with more aggres-
sive tumors in the radiotherapy group. Biopsy confir-
mation was not obtained in all patients. No patients
were irradiated with the benefit of CT scans to insure
that the entire tumor was irradiated.
Information on radiation doses but not field sizes was
given in only ten patients in the later report by Glaser et
al. l9 One patient received three courses of radiotherapy
with a total dose of 65 Gy, and it is unlikely that any of
these courses alone were to a high enough dose to con-
trol the tumor. Horwich and Bloom" reported a benefi-
cial effect of radiotherapy in their series of 29 patients
treated with radiotherapy for optic glioma for progres-
sive disease. Twenty-six of 29 (90%) remain free from
disease progression with a median follow-up of 10 years.
The probability of survival at 5 , 10, and 15 years was
loo%, 93%, and 93%, respectively. Visual acuity im-
proved after treatment in 43%of patients, was stable in
48% and deteriorated in 9%. They also presented an
excellent summary of the collective results of several
recent series including their own and found improved
vision after radiotherapy in 28 of 96 patients (29%).
Spontaneous improvement of vision without treatment
has been reported, but does not seem to occur nearly as
often.''s30
The recent series of Tarbell el a1.16 reported visual
improvement after radiotherapy in nine of 14 patients
and stabilization of vision in the remaining five patients.
Twelve of 12 patients were alive without tumor progres-
sion after primary radiotherapy as were two of four pa-
tients undergoing repeat radiotherapy. Survival and pro-
gression-free survival of the patients reported in our
series are similar to those in recent literature. Stabiliza-
tion or improvement of vision was found in 86% of
patients in our series, although the number of patients in
whom visual improvement was clearly documented
(9%) is slightly less than other series. Overall, there is
substantial evidence in our series and in the recent litera-
ture that radiation therapy is effective in controlling
optic glioma.
We did not have a favorable experience with using an
initial conservative approach to therapy patients with
glioma of the optic chiasm. Five patients with chiasmal
tumors in our report were managed with initial conser-
vative approach. Only two of these patients were fairly
successfully managed without radiotherapy after subto-
tal resection, one for only 2.5 years and the other did
experience deterioration of vision which stabilized after
a ventriculoperitoneal shunt was performed. In the re-
maining three patients, radiotherapy was required be-
cause of tumor progression accompanied by decreased
- Flickinger et a/. 64 1
vision. Two patients paid a high price for conservative
therapy with complete blindness in one and near total
blindness in the other before being referred for radio-
therapy. In the remaining patient, radiotherapy was
successfully delayed for 10 months until the child was
closer to 2 years of age and radiotherapy was required
because of declining vision and increasing size of the
tumor on CT scan.
Several series have demonstrated a poor outcome in
patients with chiasmal tumor managed conservatively
without radiation. The report of the Mayo Clinic series
from 1919 to 1972 by Tenny et ~ 1included. ~ 58~ patients
with chiasmal gliomas. Only three of 14 (2 1%) survived
who were managed with only biopsy or exploration
compared to 28 of 44 (64%)surviving with the radio-
therapy administered of that time. The series reported
by Tym3' contained seven patients with chiasmal
tumors managed without radiation therapy. This series
is sometimes referred to because of two patients with
spontaneous improvement in their vision, but despite
this, two other patients died of disease and three others
were blind in one eye. It would now appear unwise to
indefinitely withhold radiotherapy from patients with
either rapidly declining vision or slowly deteriorating
vision and little vision remaining when radiotherapy
can be administered with a relatively low morbidity and
reasonable evidence exists that it is effective in prevent-
ing deterioration of vision, preventing tumor death from
tumor progression and sometimes improving vision.
An attempt was made in our series to define an opti-
mum radiation treatment dose for gliomas involving the
optic chiasm. A dose of 4500 to 5040 rad to the 95%
isodose line with 180-rad fractions (or treatment to bio-
logically equivalent doses using smaller fractions) was
the optimum for tumor control and avoiding late com-
plications in our series.
Dosoretz et a1." also have recommended a dose of 45
to 50 Gy in 4.5 to 5 weeks. Horwich and Bloom'5 rec-
ommended a dose of 50 Gy in 30 to 35 fractions for
patients older than 3 years and 45 Gy in 6 weeks for
patients younger than 3 years. Montgomery et a1.' found
no tumor deaths occurring in their series in patients who
received more than 50 Gy. Harter et a/.'' did report
three patients in their series that had tumor recurrence
after doses of 50 Gy in 26, 50 Gy in 25 fractions, and
55.7 Gy in 35 fractions. Tarbell et a1.I6 have recom-
mended doses of 5000 to 5400 Gy in 180 cGy fractions.
Slightly higher doses of 5500 to 6000 Gy in 6 to 6.5
weeks have been recommended by Danoff et al. l4 Vas-
cular occlusion of the internal carotid artery within the
radiation field was found in one patient in our series
after a dose of 52 I6 cGy in 30 fractions over 4 I days
(NSD 1533, ED 1167). Painter et ~ 1 . reported
~' one pa-
tient in whom this occurred 4.5 years after the second of
642 February 15 1988
CANCER
two courses of radiotherapy. The first course of radia-
tion was given at age 8 months to a dose of 25 Gy in 4
weeks and the second at age 4 years to a dose of 35 Gy in
4 weeks, both through lateral fields. Well-documented
cases of this complication were reported by Rajakula-
singam et a/.26in two patients irradiated to a dose of 48
Gy at ages of 6 and 9 months. respectively, for optic
glioma. Bilateral carotid artery occlusion developed 3
years later in the first and severe stenosis of the carotid
artery was documented the other 4 years after radiother-
apy. Unfortunately, no information regarding fraction
size was given either of these reports. As further series
are reported with modern radiotherapy with CT or
nuclear magnetic resonance (NMR) scans used for
treatment planning, the optimum dose for controlling
gliomas of the optic nerve and avoiding normal tissue
damage should be more clearly defined.
Chemotherapy has been used in the treatment of
young children with optic glioma with some success.
Rosenstock et demonstrated tumor control in eight
of 12 children with newly diagnosed optic glioma and
shrinkage oftumor on CT scan in six of 12 children.32It
is not possible to draw any reasonable conclusion from
the use of chemotherapy in one child in our series. An
initial trial of chemotherapy may be the best treatment
approach in young children, particularly younger than 2
years that have progressing glioma of the optic chiasm.
In summary, there is convincing evidence that radio-
therapy is effective in preventing deterioration of vision,
preventing tumor progression, and sometimes improv-
ing vision in patients with glioma of the optic chiasm.
Conservative management with observation and no ra-
diotherapy is unsuccessful in many if not the majority of
patients with glioma involving the optic chiasm. The
optimum dose for controlling glioma involving the optic
chiasm and avoiding serious complications appears to
be 45 to 50 Gy to the 95% isodose line using 180-cGy
fractions or a biologically equivalent dose using smaller
fraction sizes.
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