Support Care Cancer (2002) 10:322328

DOI 10.1007/s00520-001-0333-0

Christina Hempen
Elisabeth Weiss
Clemens F. Hess

Published online: 9 February 2002

Springer-Verlag 2002

C. Hempen () E. Weiss C.F. Hess

University of Gttingen,
Department of Radiotherapy, Gttingen,
Germany
e-mail: chempen@gmx.de
C. Hempen E. Weiss C.F. Hess
Klinik und Poliklinik fr Strahlentherapie
und Radioonkologie,
Georg-August-Universitt Gttingen,
Robert-Koch-Strasse 40, 37075 Gttingen,
Germany
C. Hempen
Stdtisches Krankenhaus Gtersloh,
Ansthesiologische Klinik,
Reckenberger Strasse 19, 33332 Gtersloh,
Germany

O R I G I N A L A RT I C L E

Dexamethasone treatment in patients with

brain metastases and primary brain tumors:
do the benefits outweigh the side-effects?

Abstract In order to minimize neurological symptoms and treatment-related side-effects, patients with primary or secondary brain tumors receive dexamethasone. The goal of
this study was to analyze dosage and
duration of dexamethasone intake and
to compare the advantages and disadvantages of this medication during the
course of radiation therapy (RT). Data
from 138 consecutive patients were
therefore analyzed retrospectively.
During the course of therapy, the dosage of dexamethasone was evaluated,
as were the indications for and duration of this treatment, its side-effects
and any clinical changes reported during dexamethasone intake. The dosage of dexamethasone was higher at
the outset and during RT (median
712 mg/day) than at the end of RT
(median 16 mg/day). The average
duration of dexamethasone intake
was 23 weeks for patients with primary, and 7 weeks for patients with
secondary brain tumors. The most
frequent side-effects were a rise
in serum glucose level, peripheral
edema, psychiatric disorders, and

Introduction
Brain metastases develop in 2040% of all cancer patients
[22]. They are the main cause of central neurological deficiencies in patients with intracranial neoplasms [10]. Malignant gliomas account for half of all primary brain tumors
[20]. Among these, glioblastoma multiforme is the most
malignant, treatment-resistant, and frequent tumor [19].

Cushings syndrome. Life-threatening

complications remained rare. Initially,
dexamethasone led to good clinical
improvement with few side-effects of
RT, whereas by the end of RT the
symptom relief was slight and toxicity increased. In a group of 13 patients
who received no dexamethasone during RT, 12 showed neither RT-related
side-effects nor of neurological impairment. Dexamethasone effectively
minimizes neurological symptoms
and RT-related side-effects in patients
with primary and secondary brain tumors. Nevertheless, the side-effects of
dexamethasone itself increase over
time. For this reason, a generalized
dose scheme should not be used. Instead, dosage should be adapted to
each patients individual needs. Future prospective studies will have to
determine whether dexamethasone is
advantageous on balance or not.
Keywords Brain metastases
Primary brain tumor
Dexamethasone Radiotherapy
Side-effects

Routine treatment consists in neurosurgery and RT for

malignant gliomas and RT for brain metastases (plus surgery for a limited number of metastases). Benefits of
chemotherapy have not yet been unequivocally demonstrated [1]. Dexamethasone reduces the tumor-associated
edema in patients with brain metastases or primary brain
tumors. Considering the gravity and the poor prognosis
of this disease, this effect is impressive. A marked im-

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provement is often seen within the first 24 h after dexamethasone has been administered [9]. For this reason, an
initial dexamethasone treatment in patients with symptomatic intracranial neoplasms has become a standard
therapy. However, high-dosage dexamethasone treatment
can also have a multitude of side-effects, which in some
cases not only reduce the quality of life (e.g. muscular
weakness, increased blood sugar level or Cushings syndrome), but can also become life threatening (e.g. gastrointestinal ulcer or thromboembolism) [8, 22].
There are few analyses concerning the benefits and
risks of administering dexamethasone to patients with
primary and secondary brain tumors. The aim of this retrospective study was to evaluate the duration of dexamethasone treatment and to compare the advantages and
disadvantages of this medication in patients with brain
metastases and primary brain tumors. We also discuss
whether it is necessary to give dexamethasone in each
individual patient.

deterioration, and no change in their symptoms were determined.

In this study, the terms improvement or deterioration are not
based on a fixed scale such as the Karnofsky Index, as their use in
the charts was not consistent. Rather, the state recorded with either
of these terms was based on neurological examination and each
patients subjective perception documented by the physician during a follow-up interview. In the case of prophylactic use of dexamethasone the percentage of patients showing neurological deterioration (signs of high intracranial pressure, headache, nausea and
vomiting) was determined. The incidence of side-effects was researched for both symptomatic and prophylactic dexamethasone
intake. The effects of dexamethasone treatment, both beneficial
and detrimental, were evaluated separately for different stages of
treatment (beginning of treatment, during and after RT). In the
case of patients with primary brain tumors the interval between
surgery and RT was also taken into account.
Finally, we analyzed how the patients not receiving dexamethasone had fared during RT.

Results
Dexamethasone dosage at diagnosis, during RT
and at the end of RT

Patients and methods

Two groups of patients were evaluated retrospectively: 91 patients
with brain metastases newly diagnosed during the period from
1992 to 1997, and 47 patients with primary brain tumors newly diagnosed during the period from 1991 to 1997. Information was
collected by chart evaluation and consultation with the patients
family doctors.
Among the 91 patients with brain metastases, 44% were women and 56%, men. Their mean age at the time of diagnosis was
58 1/2 years. Solitary brain metastases were found in 41.8%, while
58.2% had multiple lesions. The most frequent primary tumor was
lung cancer (43%), followed by breast cancer (26%) and others.
Surgery was performed in 28 (30.8%) of 91 patients, most of
whom had single brain metastases. All patients with brain metastases received whole-brain RT using either a Co-60 machine or
6-MV photons from a linear accelerator. The doses administered
varied within a range of 3035 Gy, 452.53 Gy per week.
Among the 47 patients (100%) with primary brain tumors,
45% were women and 55%, men. Their mean age was
56 1/2 years. The most frequent primary brain tumor was malignant glioblastoma in 72%, followed by malignant astrocytoma in
26% and oligodendroglioma in 2%. All 47 patients underwent primary surgery. Total excision was performed in 53%, subtotal excision in 30%, and a biopsy in 17%. RT was applied to the tumor
bed including a 2 cm safety margin. Doses of 59.460 Gy,
51.82 Gy per week were given using either a Co-60 machine or
a 6-MV linear accelerator.
As a steroid drug we always used dexamethasone. First, the
initial dexamethasone dosage (mg/day, given orally), the maximum dosage during RT, and the dosage at the end of RT were determined. In addition, the duration of dexamethasone intake was
ascertained. Secondly, acute and late sequelae related to dexamethasone medication in patients who had taken dexamethasone
for at least 1 week were analyzed, such as an increased blood sugar level, peripheral edema, Cushings syndrome, thromboembolism, muscular weakness, gastrointestinal bleeding, and psychiatric disorders.
Whether dexamethasone was given because of neurological
symptoms or prophylactically was also determined. Both the benefits and the side-effects of dexamethasone in these patients were
analyzed. To evaluate the effect of dexamethasone on neurological
symptoms, the percentages of patients who showed improvement,

At the time of diagnosis all patients received dexamethasone (324 mg). The exact dose depended on the physicians decision. Higher doses were prescribed in patients
with pronounced edema or neurological symptoms.
Some patients who did not have any neurological symptoms or extensive edema and who appeared to be able to
assess their own symptoms critically, started RT without
dexamethasone.
Figures 1 and 2 show that the majority of patients, not
only those with cerebral metastases, but also those with
primary brain tumors, were receiving 712 mg dexamethasone per day at diagnosis and during RT.
A subgroup of 13 patients (9.4%) did not receive
dexamethasone during RT.

Fig. 1 Dexamethasone dose of patients with brain metastases: initial dose / maximum dose during radiotherapy (RT) / dose at the
end of RT

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dexamethasone until the beginning of RT was 6.8

(249) weeks, and the subsequent mean duration of
dexamethasone intake from the beginning to the end of
RT or death was 13.9 (352) weeks. Summing up, dexamethasone was taken for a mean of 17.3 weeks in the
second group.
In 19% of cases, the patients with primary brain tumors continued taking dexamethasone until their death.
Side-effects of dexamethasone treatment

Fig. 2 Dexamethasone dose of patients with primary brain tumors:

initial dose / maximum dose during RT / dose at the end of RT

Duration of dexamethasone treatment

The mean duration of dexamethasone treatment in patients with brain metastases was 6.9 (150.5) weeks, and
17.6% of the patients continued taking dexamethasone
until their death.
The patients with primary brain tumors had to be divided into two groups. In the first group, dexamethasone
was administered continuously from the time of diagnosis until the end of RT or death. In this group, the mean
duration of dexamethasone intake amounted to 23.3
(7.552) weeks.
In the second group, dexamethasone medication was
administered from the time of diagnosis, stopped after
surgery, and then started again at the beginning and continued until the end of RT or death. The mean duration
of dexamethasone intake from the time of diagnosis
until the time it was stopped after surgery was 3.4
(1.57) weeks. The mean postoperative interval without

Table 1 Side effects of dexamethasone treatment

Side-effects of dexamethasone treatment in patients with

primary and secondary brain tumors were peripheral
edema, Cushings syndrome, a rise in the blood sugar
level, thromboembolism, infections, delayed wound
healing, muscular weakness, gastrointestinal disorders,
and psychiatric problems (Table 1).
Patients with brain metastases mostly complained of a
rise in the blood sugar level, peripheral edema or psychiatric disorders, whereas in patients with primary brain
tumors, raised blood sugar levels, Cushings syndrome
and psychiatric disorders were the most frequent sideeffects.
Life-threatening complications, such as embolism or
gastrointestinal bleeding, remained rare in both groups.
To prevent gastrointestinal ulcers and bleeding, patients
were routinely given antacids and H2-blockers.
These results do not prove a causal connection between dexamethasone intake and the aforementioned
side-effects, since patients who suffered from side-effects did not receive dexamethasone in higher doses or
for a longer time than those who had none. Muscular
weakness, for example, might also have been caused by
the disease itself. However, patients in this study who
complained about side-effects had taken dexamethasone
for at least 1 week.

Side-effect

Hyperglycemia (>100 mg/dl)

Of these, known to have diabetes mellitus
(Pulmonary) embolism
Thrombosis
Oropharyngeal candidosis
Pneumonia
Gastritis
Gastrointestinal bleeding / ulcer
State of anxiety, depressive disorder, insomnia,
other psychiatric disorders
Peripheral edema
Cushings syndrome
Muscular weakness
Delayed wound healing

Brain metastases
(N=91)

Primary brain tumors

(N=47)

43
3
2
1
6
1
3

47.3
3.3
2.2
1.1
6.6
1.1
3.3

9.9

34
6
1
2
4
1
3

72.3
12.8
2.1
4.3
8.5
2.1
6.4

10.6

10
4
4

11
4.4
4.4

1
7
4
1

2.1
14.9
8.5
2.1

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Table 2 Dexamethasone administration in patients with brain metastases: indications, clinical response and side-effects (HIP high intracranial pressure, s symptomatic, p prophylactic)
Time

At diagnosis
During RT
After RT

Indication for
dexamethasone
(n)
s (64)
p (2)
s (59)
p (15)
s (18)
p (5)

Clinical response (%)

Improvement
32.8

No
change

No sign
of HIP

6.3
100

44.1

17
66.7

11.1

11.1
40

Deterioration

Unknown

0
0
23.7
6.7
16.7
0

60.9
15.2
26.6
61.1
60

Side-effects
(%)

No
side-effects
(%)

12.5
50
15.2
26.7
83.3
40

87.5
50
84.8
73.3
16.7
60

Table 3 Dexamethasone administration in patients with primary brain tumors: indications, clinical response, and side-effects
Time

At diagnosis
After surgery/
before RT
During RT
After RT

Indication for
dexamethasone
(n)
s (30)
p (0)
s (18)
p (4)
s (30)
p (12)
s (16)
p (4)

Clinical response (%)

Improvement

No
change

36.7

10

No sign
of HIP

22.2

50
100

40

26.7
100

6.3

25
100

Indications, clinical change and side-effects

of dexamethasone administration during treatment
At the time of diagnosis, 94 patients in the two groups
(68.1%) received dexamethasone because of symptoms
and 2 patients (1.4%) received it for prophylactic reasons
(Tables 2, 3). There were 14 patients (10.1%) who did
not receive dexamethasone initially. During RT, 89 patients (64.5%) received dexamethasone because of neurological symptoms and 27 (19.6%) prophylactically.
There were 13 patients (9.4%) who had no dexamethasone during RT. After the completion of RT, 34 patients
(24.6%) were known to receive dexamethasone because
of symptoms and 9 (6.5%) to receive it prophylactically.
In the group with brain metastases, the percentage of
patients with side-effects of dexamethasone increased after RT, whereas in the group with primary brain tumors
the side-effects increased even during RT, which usually
lasted 6 weeks in these patients, as against 23 weeks in
those with brain metastases. Especially patients who had
received dexamethasone because of symptoms deteriorated after RT despite the medication.

Deterioration

Unknown

3.3

22.2
0
33.3
0
37.5
0

50
5.6

31.2

Side-effects
(%)

No
side-effects
(%)

33.3
0
63.3
33.3
62.5
50

100

66.7
100
36.7
66.7
37.5
50

Patients without dexamethasone during RT

Among the 138 patients with primary or secondary brain
tumors, 14 (10%) were known not to have received
dexamethasone at the time of diagnosis. Eight of them
received dexamethasone during the subsequent RT, 5 because of deterioration, which improved after dexamethasone administration, and 3 for prophylaxis. None of the
last was seen to have any problems.
The remaining 6 patients, and a further 7 patients who
had dexamethasone only in the perioperative period, did
not have this medication during RT. The RT was tolerated well by 12 of these 13 patients, without RT-related
side-effects or neurological impairment. However, 1 patient with lung cancer complained of brain stem symptoms caused by metastases and died of unknown causes.

Discussion
The use of dexamethasone for treatment of neurological
symptoms caused by primary brain tumors or brain metastases and the administration of dexamethasone for the
prevention or attenuation of treatment-related sequelae is
generally accepted. However, there is no detailed analy-

326

sis of the indications for and duration of dexamethasone

intake referred to improvements in neurological symptoms and side-effects. It must also be mentioned that it is
often difficult to estimate whether the side-effects are
due to the tumor, to dexamethasone or to RT.
About 70100% of patients with brain metastases receive dexamethasone during RT [2, 3, 5, 17, 26]. In this
study, 32% of the patients did not receive dexamethasone, because they were free of neurological symptoms,
had no edema, or did not undergo surgery. Concerning
the percentage of patients receiving dexamethasone after
completion of therapy, those reported in the literature
range from 8.4% to 55%, as opposed to 25.3% in this
study at the time of the first follow-up [3, 26].
Few reports have dealt with the duration of dexamethasone treatment during RT. It has been shown, however,
that more patients receive dexamethasone during therapy
than at the time of diagnosis, which is in keeping with
the findings of this study [6, 12, 18].
Many study reports state an initial daily dose of dexamethasone of 16 mg [4, 5, 16, 22]. This was not apparently taken as standard in this study, where the dose
ranged from 7 mg to 12 mg. The initial dosage rather depended on each patients condition. A low dose could be
administered initially and then increased if necessary.
As a rule, attempts were made to reduce or discontinue dexamethasone preferably during RT but at the latest at the end of it [3, 5, 16, 23, 24, 26]. This is also
shown in the present study.
Nevertheless, the high percentage of patients receiving
dexamethasone after completion of RT (45% in brain metastases; 70% in primary brain tumors) demonstrates that
most patients also still required this medication after RT.
The results of a dexamethasone treatment with a median duration of 7 weeks in patients with brain metastases in this study are comparable to the results of treatments of similar duration reported in the literature (4 and
8 weeks, respectively) [17, 23].
Hirschl [11] has shown a median perioperative duration of 2.2 weeks for dexamethasone intake in patients
with primary brain tumors, which is about 1 week shorter than in this study (3.4 weeks). In a study by Shenouda
et al. [21], 28.6% of the patients with primary brain tumors received steroids with a median duration of
12.3 weeks from the time of surgery up to 5 weeks after
completion of RT. The difference from the prolonged
median steroid intake in the present study (23.3 weeks)
can be explained by a longer interval between surgery
and the beginning of RT and the longer course of RT in
this study. Beyond that, in the remaining 71.4% of patients in Shenouda et al. [21] it was not possible to taper
off steroids after the completion of radiation. The duration of steroid intake was longer than 19.3 weeks and
therefore comparable to that in this study.
Corticosteroid intake leads to a wide range of sideeffects [7]. In the literature, side-effects of corticoste-

roids include endocrine disorders such as Cushings syndrome and disturbances of the blood sugar level ranging
up to diabetes mellitus, muscular weakness, an increasing risk of infectious diseases, gastrointestinal complications such as ulcers or bleeding, atrophic changes of the
skin, and hematological and psychiatric disorders [7,
22]. In addition, corticosteroid intake can also cause
thromboembolism [8].
The side-effect of dexamethasone most frequently reported in this study was a rise in the serum glucose level
to over 100 mg/dl (in 47% of patients with brain metastases and in 72% of those with primary brain tumors). In
3 patients (3.3%) with cerebral metastases and 6 patients
(12.8%) with primary brain tumors, pre-existing diabetes
mellitus was known. The serum glucose level was higher
than 300 mg/dl in 3.3% of the patients with brain metastases, as against 10.6% of those with primary brain tumors. In this retrospective analysis, patients were not
been assumed to have had their serum glucose levels
checked on an empty stomach.
Psychiatric problems such as anxiety states, depressive disorders and insomnia were reported in 9.9% of patients with brain metastases and 10.6% of patients with
primary brain tumors. Although a correlation is seen between psychiatric symptoms and corticosteroid intake,
the precise mechanism of emergence of these symptoms
is as yet unknown [14]. In view of the gravity of primary
and secondary brain tumors and the hopeless prognosis
the patients are confronted with, such psychic changes
are surely not attributable solely to the dexamethasone
medication but also to the patients reaction to the diagnosis or to the disease itself.
Peripheral edema was also noted in many cases, especially among the patients with brain metastases (11%). In
a study by Vecht et al. [25] peripheral edema was one of
the most frequent side-effects of dexamethasone. This is
particularly surprising, as dexamethasone is preferred
because of its minimal mineral-corticoid effect, and peripheral edema should therefore be rare [13].
Cushings syndrome is also a known side-effect of
dexamethasone treatment. It was one of the most frequent complications in patients with malignant gliomas
in this study (14.9%) [24].
Life-threatening complications such as gastrointestinal ulcers and bleeding were not noted, and thromboembolism remained rare in this study. Gastric disorders
such as stomach ache were reported by 3.3% of the patients with brain metastases and 6.4% of the patients
with primary brain tumors, proportions comparable to
the 4.8% published by Shenouda et al. [21]. In a study
by Messer et al. [15] it was concluded that steroids increased the incidence of peptic ulcers and gastrointestinal bleeding, even if they were given for less than
30 days and in a prednisone-equivalent dose of less than
1,000 mg in total. Prophylactic administration of antacids or H2-blockers made it possible to avoid gastrointes-

327

tinal complications in several studies [22, 25]. This

could also be the reason for the low frequency of gastric
problems in this study.
This study shows that in patients with brain metastases who take dexamethasone over a prolonged period
there is a pronounced decrease in clinical improvement
and an increase in the frequency of dexamethasone complications after RT. This tendency is seen even during RT
in patients with malignant gliomas. In any consideration
of whether dexamethasone is more beneficial or more
detrimental to patients with intracerebral neoplasms, the
opinion put forward by Cairncross and Posner [4] seems
reasonable: they suggest that dexamethasone shows a
positive effect in the acute treatment of patients with
brain metastases and can attenuate the acute complications of RT, so that the advantages outweigh the disadvantages. However, if possible it should be given at a
lower dose or stopped altogether after the completion of
radiotherapy.
Despite the benefit that can accrue from dexamethasone intake, it should be mentioned that 48% of the patients in this study initially underwent neurosurgery and
that a certain benefit must be assumed from this.
For this study in particular it must also be mentioned
that data from only a few patients were analyzed and that
some of these were incomplete. As this was a retrospective analysis, there was no fixed protocol for the dosage

of dexamethasone and no scale was used to define improvement or deterioration of neurological status. In addition, it was often not possible to distinguish unequivocally whether complications were due to dexamethasone,
the tumor itself, to the RT, or a combination of all of
these.
Nevertheless, despite these shortcomings, a similar
conclusion to that reached by Cairncross and Posner [4]
can be drawn from this study. Because life-threatening
complications remained rare and, in view of the short
survival time, a neurological improvement is important
for the quality of life, dexamethasone should not be
withheld from patients with primary or secondary brain
tumors. However, the dosage should be adapted to each
patients individual needs. For symptomatic patients the
rule should be: as high as necessary, as low as possible.
The observations that up to 50% of the patients who
took dexamethasone prophylactically suffered from sideeffects and that 13 out of 14 patients tolerated RT well
without dexamethasone justify attempting to start RT
without dexamethasone initially and only starting to administer it in the case of neurological deterioration. Lack
of neurological symptoms, good general condition or
minimal cerebral edema could be possible reasons for
not giving dexamethasone at first. This aspect will have
to be examined in a prospective study with special emphasis on the evaluation of quality of life criteria.

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