European Journal of Neurology 2002, 9: 201–205

CME ARTICLE

The position of the neurologist in neuro-oncology1

W. Grisolda, J. J. Heimansb, T. J. Postmab, R. Grantc, R. Soffiettid and The Neuro-oncology
Panel of the EFNS1
a
Ludwig Boltzmann Institute for NeuroOncology, Vienna, Austria; bDepartment of Neurology, Free University Hospital, Amsterdam,
The Netherlands; cDepartment of Clinical Neurosciences, University of Edinburgh, Western General Hospitals NHS Trust, Edinburgh, UK;
and dDepartment of Neuroscience, Section of Neurology, University of Torino, Torino, Italy

Keywords: Neuro-oncology is a growing new subspeciality with a strong interdisciplinary

brain tumours, neuro-
oncology, neurotoxicity,
quality of life, systemic
cancer
Received 11 January 2002
Accepted 11 January 2002
character. This position paper explains the role of neurology in the multidisciplinary
field of neurosurgeons, radiotherapists and general oncologists, dealing with
neuro-oncological patients. The paper delineates the varied spectrum of the field of
neuro-oncology which expands from primary brain tumours, to metastatic and non-
metastatic effects of systemic cancer on the central and peripheral nervous system,
neurotoxicity due to cancer treatment and issues of quality of life. It has been written
by the scientific neuro-oncology panel of the European Federation of Neurological
Societies (EFNS) to delineate the situation of neuro-oncology in Europe, and facilitate
the understanding and implementation of this subspeciality in the future.

sent to all members of the EFNS Scientific Panel on

Introduction
Neuro-oncology is emerging as a new subspeciality with
a strong interdisciplinary character involving neurolo-
gists, neurosurgeons, radiation oncologists, medical
oncologists and other closely related specialists. Its
scope is not only focused on primary brain tumours,
but also on metastatic and non-metastatic effects of
systemic cancer on the central (CNS) and peripheral
nervous system (PNS), neurotoxicity due to cancer
treatment and quality of life.
In the near future training facilities and improvement
of neuro-oncological services and institutions may be
expected.
This paper touches on the present situation of
neuro-oncology in Europe and the role of the neurol-
ogist in the treatment of patients with primary brain
tumours or in cancer patients with neurological
complications.
Questionnaire on neuro-oncology
In 1996 a small questionnaire was developed in order to
gain more insight into the role of neuro-oncologists in
Europe within the frame of the European Federation of
Neurological Societies (EFNS). The questionnaire was
Correspondence: Wolfgang Grisold, LBI for NeuroOncology, 1100
Vienna, Kundratrstr 3, e-mail: wolfgang.grisold@kfj.magwien.gv.at
1
This is a Continuing Medical Education article, and can be found
with corresponding questions on the Internet at http://www.blackwell-
science.com/ene. Certificates for correctly answering the questions will
be issued by the EFNS.
Neuro-oncology. The results of the enquiry were
presented at the EFNS Congress in Rome in November
1996. At that time 25 countries were represented in the
panel. Twenty-three of the 25 panel members respon-
ded. Seventeen of them were neurologists, six were
neurosurgeons. The majority of the representatives
worked in a university hospital.
The first part of the questionnaire addressed the
activities of the panel members themselves. The results
of this part of the inquiry were as follows.
Sixteen of the 23 panel members who responded
spent more than 50% of their time on patient care and
10 panel members reported that they spent more than
half of their time in neuro-oncology.
Fourteen of the 23 responders were, as a rule,
involved in the diagnosis and treatment of metastatic
and non-metastatic complications of cancer. Eighteen
were, as a rule, involved in the diagnosis and
treatment of primary brain tumours and most of
them reported that they were personally involved in
chemotherapeutic treatment of brain tumours. Six
participated actively in European Organization on
Research and Treatment of Cancer (EORTC) trials.
The vast majority (21/23) of panel members partici-
pated in neuro-oncological research, mainly clinical
brain tumour research.
The second part of the inquiry regarded the neuro-
oncological activities of neurologists in the respective
countries. In 16 of 23 countries there were neurologists
who were specialized in neuro-oncology. Most of these
neurologists spent less than 50% of their time on neuro-
oncological patient care. It was estimated that about 60
European neurologists spent more than 50% of their

ª 2002 EFNS 201

202 W. Grisold et al.
time on neuro-oncological patient care. Less than
10 European neurologists spent their time almost
exclusively (more than 90%) on neuro-oncology.
In 1996, there were active neuro-oncology working
groups in 9 of 23 countries. In almost all countries
neurologists are a minority in these working groups. The
primary aims of these working groups are: (i) develop-
ment of protocols for patient care, (ii) co-ordination of
joint research activities and (iii) organization of teaching
courses.
Systemic cancer and the nervous system
Neuro-oncology is not exclusively focused on primary
brain tumours, but has an important role in the
management of patients with systemic cancer.
Neurological complications are increasingly diag-
nosed in patients with systemic cancer. There are
several reasons for this: systemic treatment of cancer
increases survival, diagnostic methods are improving
and some treatment modalities are neurotoxic.
The causes of neurological symptoms in cancer
patients are not only metastases to the brain, spinal
cord and meninges but also metabolic, vascular and
paraneoplastic disorders. Moreover, cancer treatment
(surgery, radiotherapy and chemotherapy) may have
effects on the nervous system.
The analysis of large series of cancer patients with
regard to neurological symptoms has shown that
change of personality, seizures and back pain are the
most often encountered phenomena in cancer patients.
As these signs and symptoms may have various
aetiologies, neuro-oncological expertise is necessary
for further differentiation.
Traditionally, the role of the neuro-oncologically
trained neurologist is the detection and localization of
metastases in the nervous system, guided by symptoms
and signs. In addition to clinical knowledge, ancillary
investigations such as imaging methods, clinical neuro-
physiology and cerebrospinal fluid (CSF) analysis are
used and interpreted in this process. Results of the
investigations, however, should not be confined to a
mere topical localization, but should also involve the
neurologist in interdisciplinary treatment decisions
together with neurosurgeons, medical oncologists,
radiation oncologists and others.
Neoplastic involvement is not the only effect of
cancer on the nervous system. Metabolic changes,
infections, vascular causes and side-effects of therapies
need to be considered as a cause of neurological
symptoms and signs in cancer patients. Recent years
have also shown that paraneoplastic syndromes may
reveal an important interaction between systemic
tumours and the nervous system. In particular, the
discovery of antineuronal antibodies directed against
CNS antigens, often cross-reacting with systemic
tumour antigens, may shed some light on the inter-
action between the host’s defence and the CNS.
Primary brain tumours
Gliomas constitute the majority of primary brain
tumours in adult patients.
A neurologist by means of computed tomography
(CT) or magnetic resonance imaging (MRI) usually
makes the diagnosis of ‘brain tumour’, although the
definitive histological confirmation of the diagnosis by
the pathologist is only made after neurosurgical inter-
vention.
Equipped with modern image-guided techniques, the
neurosurgeon today will often be able to remove the
grossly visible part of the tumour without causing
additional neurological disability. Many authors
assume that maximal surgical resection prolongs the
duration of survival as well as the quality of survival,
although no controlled trials exist. However, despite
technical progress, surgery is never curative. Therefore,
in almost all cases where the diagnosis of high-grade
glioma is made, surgery is followed by radiation
therapy. This implies that a patient in whom the
diagnosis of glioma is made will be confronted with
three medical specialists within a couple of weeks. In
most centres, radiation treatment is delivered in
180 cGy fractions during a 6–7-week period. In some
centres exceptions are made for glioblastoma patients
who have a short life expectancy: in these patients
shorter treatment schedules are administered.
Neither surgery nor radiotherapy are likely to be
curative. High-grade glioma patients in most centres in
the US are prescribed adjuvant chemotherapy, usually a
nitrosourea-based regimen. In Europe there is no
consensus on the role of adjuvant chemotherapy in
high-grade gliomas. The opinion on the routine use of
adjuvant chemotherapy differs from one country to
another and, within countries, from one centre to
another. The main reason to refrain from adjuvant
chemotherapy is that it has only a modest advantage in
terms of survival and it may negatively affect quality of
life during a period when the patient is still in good
condition.
In those European centres where adjuvant chemo-
therapy is a routine part of the treatment of an high
grade glioma, the medication is usually prescribed by a
medical oncologist, adding a fourth specialist to the
medical team treating the patient, or by a neurologist-
neuro-oncologist (less frequently).
Meanwhile, there are several other palliative treat-
ment aspects after the diagnosis has been made.
ª 2002 EFNS European Journal of Neurology 9, 201–205

Dexamethasone is often routinely administered during
the first few days after surgery. Controversy exists on the
routine use of dexamethasone during radiation treat-
ment, but dexamethasone is the drug of choice in any
case where brain oedema causes neurological symptoms
or signs. Moreover, many glioma patients suffer from
epilepsy. Seizures may be the initial symptom, but
epilepsy may develop during the course of the illness as
well. It is recommended that prophylactic anticonvul-
sants are not used routinely in patients with newly
diagnosed brain tumours. However, in patients suffering
from seizures, anticonvulsant medication should be
prescribed. It is usually the neurologist who prescribes
anticonvulsant drugs to brain tumour patients.
Eventually, glioma will recur sooner or later after
initial treatment. Reoperation, reirradiation and che-
motherapy should be considered as treatment options
in recurrent tumours. A multidisciplinary approach is
highly desirable in this stage of the disease, because the
response rate is low and response duration is often
limited. Oligodendrogliomas, however, are an exception
to this rule. Most patients with anaplastic oligodendro-
gliomas respond to chemotherapy with procarbazine,
vincristine and CCNU (PCV), but it remains to be seen
if these tumours should be treated with adjuvant PCV
chemotherapy or if chemotherapy should be prescribed
at recurrence.
Primary central nervous system lymphomas
(PCNSL) are also chemosensitive tumours, with res-
ponse rates to high-dose methotrexate-based regimen as
high as 60–80%: survival time seems to be improved by
a combined treatment with upfront chemotherapy
followed by radiotherapy.
Neurotoxicity
Treatment of malignancies requires powerful therapies,
which also have side-effects. At present, therapy in
neuro-oncology is based on (i) surgery, (ii) radiotherapy
(conventional, stereotactic with Linac and gamma-knife
or brachytherapy), (iii) chemotherapy and related
therapeutic measures such as bone marrow and stem-
cells transplant, (iv) immunotherapy and biological
therapy (e.g. interferons), and (v) supportive measures,
including steroids and anticonvulsants.
Not withstanding broad awareness of toxicities, there
is the additional problem of time dispersion of toxic
effects (as seen in the late sequelae of radiotherapy), or
continuing, or even increasing toxic effects (‘coasting’)
in some toxic neuropathies, and it should be realized
that neurotoxicity is in many cases the limiting factor in
oncological treatment.
Presently, little is known about the cumulative effects
of combined treatment modalities [the best documented
ª 2002 EFNS European Journal of Neurology 9, 201–205
EFNS-neurooncology panel 203
interaction is the combination of radiation and intra-
thecally administered methotrexate (MTX)] or of drug
combinations. This issue, even if difficult to study
systematically, is of particular interest, because first,
second and third line therapies are increasingly used
according to patient’s need.
Detection of neurotoxicity and development of
effective countermeasures or even prophylactic drug
treatment are important tasks for future neuro-oncol-
ogists. Additionally, classification and grading of tox-
icity is important, World Health Organization (WHO)
classification will have to be replaced by precise
instruments being used in the CNS and peripheral
nervous system (PNS).
Management of patients in neuro-oncology
Patients with brain metastases, vertebral metastases or
primary malignant brain tumours are often affected by
many neurological signs and symptoms. The same
holds true for patients with paraneoplastic disease. (The
common factor in these diseases is that they are
incurable.) However, this does not mean that they are
untreatable. New technical developments in neurosur-
gery and radiotherapy have contributed to more
‘radical’ tumour treatment and to a decrease in treat-
ment related side-effects. PCV chemotherapy in ana-
plastic oligodendrogliomas and, to a lesser extent, in
anaplastic astrocytomas may prolong the duration of
survival considerably. Surgical treatment of single brain
metastases improves the duration as well as the quality
of survival in comparison with whole brain radiation.
Stereotactic radiotherapy has improved the therapeutic
possibilities in brain metastases.
It is of utmost importance that neuro-oncological
patients are treated by physicians with a basic know-
ledge of oncology as well as neurology. This holds true
for the four specialists who are generally involved
in the treatment of these patients, i.e. neurologists,
neurosurgeons, radiation oncologists and medical
oncologists. As can be concluded from the inquiry
we made among European neurologists in 1996, the
neurologist is not always involved in the treatment and
follow-up of brain tumour patients or patients with
neurological complications of cancer such as brain
metastases. However, neurologists are specially trained
to assess brain function and to treat neurological
symptoms such as headache and epilepsy. This makes
them indispensable for an optimal follow-up of neuro-
oncological patients.
It should be realized that the confrontation of a
patient, suffering from a fatal disease, with four
different specialists may be highly confusing. Neurolo-
gists should play a pivotal role in the co-ordination of
204 W. Grisold et al.
the treatment. Moreover, specially trained nurses and
multidisciplinary outpatient clinics could further
improve the medical, psychological and social coaching
of brain tumour patients and their partners.
Quality of life and neuro-oncology
Primary brain tumours and brain metastases are fatal
disorders. In contrast to other malignancies, these
tumours do not only affect the physical well being of
the patient but also affect cognitive and emotional
integrity. This places a heavy burden on patients and
proxies. Brain tumour treatment, such as surgery,
radiotherapy and different forms of chemotherapy
may, in the long run, severely affect the social and
emotional functioning of the patient. For that reason, it
is very important that Health Related Quality of Life
measurements are implemented in neuro-oncological
patients, especially when the patients are exposed to
new treatment modalities.
Immunotherapy, gene therapy, antiangiogenetic ther-
apy, boron neutron capture therapy (BNCT) and new
chemotherapeutic agents are all under investigation in
glioma patients. It is important that these investigations
take place, but it should be realized that neuro-
oncologists who are dealing with experimental treat-
ment are aware of the problems that may arise in
patients who undergo these therapies. Reliable meas-
urement of cognitive functions and different aspects of
quality of life make up one of the cornerstones of the
follow-up in neuro-oncological patients and should be
part of the diagnostic skills of any specialist dealing
with these patient groups.
Future aspects
As this outline has shown, neuro-oncology has several
tasks in the treatment of patients suffering from
primary brain tumours and from systemic cancer. The
role of neurology in neuro-oncology is crucial, but lacks
definition in most European countries. This can be said
for most Western European countries, but more so for
the countries in ‘transition’, where patients with neuro-
oncological problems are handled by neurosurgeons
and general oncologists exclusively.
The future aspects of neuro-oncology can be divided
into three categories:
Future therapeutic aspects
There is a broad range of new therapeutic modalities in
neuro-oncology: new drugs, new radiation modalities
such as BNCT and gene therapy. It will be an important
task for neurologists who are active in neuro-oncology
to be open to new ideas and treatments. It will be an
important task to set strict and solid criteria for
measuring the efficacy of these methods. This will be
of major importance in advising patients, who learn
about these methods from the Internet, and are hardly
able to weigh and judge what can be medically advised
and what may be at best experimental.
Another task for neurologists is an increased aware-
ness of the need of supportive and palliative care that
should be part of neuro-oncology. This also involves
pain therapy. Special attention should be given to
geriatric patients whose therapy tolerance is far lower
than that of younger patients. Supportive and palliative
care will often dominate in these elder patients.
Neuro-oncology and its position in neurology
and related fields
We encourage specialized training in neuro-oncology
for neurologists. This should involve special training in
the aspects of the diagnosis and treatment of primary
brain tumours, neurological complications of cancer,
neurotoxicity, and supportive and palliative care.
Training must also include enough basic knowledge
from related fields such as neuropathology, neurosur-
gery, medical oncology, and radiotherapy to enable
future neuro-oncologists to collaborate successfully
with the related fields in an interdisciplinary setting.
If neuro-oncology can be established as a neurolog-
ical discipline, training in neuro-oncology should be
given in a uniform pattern throughout Europe. A
European curriculum and guidelines should be devel-
oped and the establishment of neuro-oncology as a
subsection of neurology in the Union Europeene des
Medecins Specialites (UEMS) should be considered.
This would automatically increase awareness of neuro-
oncology and also facilitate its important role as a
neurological subspeciality.
Neuro-oncology and other institutions
Presently, several organizations are involved in neuro-
oncology. These are the multidisciplinary European
Association for Neuro Oncology (EANO), which
focuses on scientific presentations and biannual meet-
ings, and the EORTC. The latter organization has a
brain tumour group devoted to studies and trials of
primary and metastatic brain tumours. The EORTC
brain tumour group is also a multidisciplinary group,
in which a number of neurologists participate.
References
The following are recommended for further reading.
ª 2002 EFNS European Journal of Neurology 9, 201–205

Bauman GS, Cairncross JG (2001). Multidisciplinary man-
agement of adult anaplastic oligodendrogliomas and ana-
plastic mixed oligo-astrocytomas. Semin Radiat Oncol
11:170–180.
Chamberlain MC (2000). Neoplastic meningitis: a guide to
diagnosis and treatment. Curr Opin Neurol 13:641–648.
Clouston PD, DeAngelis LM, Posner JB (1992). The spectrum
of neurological disease in patients with systemic cancer. Ann
Neurol 31:268–272.
Davis FG, McCarthy BJ (2000). Epidemiology of brain
tumors. Curr Opinion Neurol 13:635–640.
De Angelis LM (2001). Brain tumors. N Engl J Med 344:114–
123.
De Angelis LM, Delattre JY, Posner JB (2001). Neurological
complications of chemotherapy and radiation therapy. In:
Aminoff MJ, ed. Neurology and General Medicine, 3rd edn.
Churchill Livingstone, Philadelphia, PA, pp. 437–458.
Gilbert MR, Grossman SA (1986). Incidence and nature of
neurologic problems in patients with solid tumors. Am J
Med 81:951–954.
Glantz MJ, Cole BF, Forsyth PA et al. (2000). Practice
parameter: anticonvulsant prophylaxis in patients with
newly diagnosed brain tumors. Report of the Quality
Standards Subcommittee of the American Academy of
Neuorlogy. Neurology 54:1886–1893.
Greenberg HS, Chandler WF, Sandler HM (1999). Brain
Tumors. Oxford University Press, New York, Oxford.
Hoskin PJ, Brada M (2001). Radiotherapy for brain meta-
stases. Clin Oncol 13:91–94.
Hovestadt A, Van Woerkom TCM, Vecht CJ (1990). Fre-
quency of neurological disease in a cancer hospital. Eur J
Cancer 26:766–767.
Jeyapalan SA, Batchelor TT (2000). Diagnostic evaluation of
neurologic metastases. Cancer Invest 18:381–394.
ª 2002 EFNS European Journal of Neurology 9, 201–205
EFNS-neurooncology panel 205
Jukich PJ, McCarthy BJ, Surawicz TS, Freels S, Davis FG
(2001). Trends in incidence of primary brain tumors in the
United States, 1985–94. Neuro-Oncol 3:141–151.
Kleihues P, Cavenee WK, eds. (2000). Pathology and Genetics
of Tumours of the Nervous System. World Health Organ-
ization Classification of Tumours. IARC Press, Lyon.
Klein M, Taphoorn MJB, Heimans JJ et al. (2001). Neuro-
behavioral status and health-related quality of life in newly
diagnosed high-grade glioma patients. J Clin Oncol
19:4037–4047.
Levin VA (1999). Neuro-oncology. An overview. Arch Neurol
56:401–404.
Peterson K, De Angelis LM (2001). Weighing the benefits and
risks of radiation therapy for low-grade glioma. Neurology
56:1255–1256.
Posner JB (1978). The role of the neurologist in the manage-
ment of cancer. Am J Med 65:4–6.
Posner JB (1995). Neurologic Complications of Cancer. FA
Davies, Philadelphia.
Posner JB (2001). Paraneoplastic syndromes involving the
nervous system. In: Aminoff, MJ, ed. Neurology and General
Medicine, 3rd edn. Churchill Livingstone, Philadelphia, PA,
pp. 417–436.
Rock JP, Rosenblum ML, Shaw EG, Cairncross JG (1999).
The Practical Management of Low-grade Primary Brain
Tumors. Lippincott, Williams & Wilkins, Philadelphia,
pp. 1–244.
Schlegel U, Schmidt-Wolf IGH, Deckert M (2000). Primary
CNS lymphoma: clinical presentation, pathological classi-
fication, molecular pathogenesis and treatment. J Neurol
Sci 181:1–12.
Vecht CJ (2000). Cancer pain: a neurological perspective. Curr
Opin Neurol 13:649–653.