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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- character. This position paper explains the role of neurology in the multidisciplinary
oncology, neurotoxicity, field of neurosurgeons, radiotherapists and general oncologists, dealing with
quality of life, systemic neuro-oncological patients. The paper delineates the varied spectrum of the field of
cancer neuro-oncology which expands from primary brain tumours, to metastatic and non-
metastatic effects of systemic cancer on the central and peripheral nervous system,
Received 11 January 2002 neurotoxicity due to cancer treatment and issues of quality of life. It has been written
Accepted 11 January 2002 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. The results of the enquiry were
Neuro-oncology is emerging as a new subspeciality with presented at the EFNS Congress in Rome in November
a strong interdisciplinary character involving neurolo- 1996. At that time 25 countries were represented in the
gists, neurosurgeons, radiation oncologists, medical panel. Twenty-three of the 25 panel members respon-
oncologists and other closely related specialists. Its ded. Seventeen of them were neurologists, six were
scope is not only focused on primary brain tumours, neurosurgeons. The majority of the representatives
but also on metastatic and non-metastatic effects of worked in a university hospital.
systemic cancer on the central (CNS) and peripheral The first part of the questionnaire addressed the
nervous system (PNS), neurotoxicity due to cancer activities of the panel members themselves. The results
treatment and quality of life. of this part of the inquiry were as follows.
In the near future training facilities and improvement Sixteen of the 23 panel members who responded
of neuro-oncological services and institutions may be spent more than 50% of their time on patient care and
expected. 10 panel members reported that they spent more than
This paper touches on the present situation of half of their time in neuro-oncology.
neuro-oncology in Europe and the role of the neurol- Fourteen of the 23 responders were, as a rule,
ogist in the treatment of patients with primary brain involved in the diagnosis and treatment of metastatic
tumours or in cancer patients with neurological and non-metastatic complications of cancer. Eighteen
complications. 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
Questionnaire on neuro-oncology
chemotherapeutic treatment of brain tumours. Six
In 1996 a small questionnaire was developed in order to participated actively in European Organization on
gain more insight into the role of neuro-oncologists in Research and Treatment of Cancer (EORTC) trials.
Europe within the frame of the European Federation of The vast majority (21/23) of panel members partici-
Neurological Societies (EFNS). The questionnaire was 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
Correspondence: Wolfgang Grisold, LBI for NeuroOncology, 1100 countries. In 16 of 23 countries there were neurologists
Vienna, Kundratrstr 3, e-mail: wolfgang.grisold@kfj.magwien.gv.at
who were specialized in neuro-oncology. Most of these
1
This is a Continuing Medical Education article, and can be found neurologists spent less than 50% of their time on neuro-
with corresponding questions on the Internet at http://www.blackwell-
oncological patient care. It was estimated that about 60
science.com/ene. Certificates for correctly answering the questions will
be issued by the EFNS. 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 discovery of antineuronal antibodies directed against
10 European neurologists spent their time almost CNS antigens, often cross-reacting with systemic
exclusively (more than 90%) on neuro-oncology. tumour antigens, may shed some light on the inter-
In 1996, there were active neuro-oncology working action between the host’s defence and the CNS.
groups in 9 of 23 countries. In almost all countries
neurologists are a minority in these working groups. The
Primary brain tumours
primary aims of these working groups are: (i) develop-
ment of protocols for patient care, (ii) co-ordination of Gliomas constitute the majority of primary brain
joint research activities and (iii) organization of teaching tumours in adult patients.
courses. A neurologist by means of computed tomography
(CT) or magnetic resonance imaging (MRI) usually
makes the diagnosis of ‘brain tumour’, although the
Systemic cancer and the nervous system
definitive histological confirmation of the diagnosis by
Neuro-oncology is not exclusively focused on primary the pathologist is only made after neurosurgical inter-
brain tumours, but has an important role in the vention.
management of patients with systemic cancer. Equipped with modern image-guided techniques, the
Neurological complications are increasingly diag- neurosurgeon today will often be able to remove the
nosed in patients with systemic cancer. There are grossly visible part of the tumour without causing
several reasons for this: systemic treatment of cancer additional neurological disability. Many authors
increases survival, diagnostic methods are improving assume that maximal surgical resection prolongs the
and some treatment modalities are neurotoxic. duration of survival as well as the quality of survival,
The causes of neurological symptoms in cancer although no controlled trials exist. However, despite
patients are not only metastases to the brain, spinal technical progress, surgery is never curative. Therefore,
cord and meninges but also metabolic, vascular and in almost all cases where the diagnosis of high-grade
paraneoplastic disorders. Moreover, cancer treatment glioma is made, surgery is followed by radiation
(surgery, radiotherapy and chemotherapy) may have therapy. This implies that a patient in whom the
effects on the nervous system. diagnosis of glioma is made will be confronted with
The analysis of large series of cancer patients with three medical specialists within a couple of weeks. In
regard to neurological symptoms has shown that most centres, radiation treatment is delivered in
change of personality, seizures and back pain are the 180 cGy fractions during a 6–7-week period. In some
most often encountered phenomena in cancer patients. centres exceptions are made for glioblastoma patients
As these signs and symptoms may have various who have a short life expectancy: in these patients
aetiologies, neuro-oncological expertise is necessary shorter treatment schedules are administered.
for further differentiation. Neither surgery nor radiotherapy are likely to be
Traditionally, the role of the neuro-oncologically curative. High-grade glioma patients in most centres in
trained neurologist is the detection and localization of the US are prescribed adjuvant chemotherapy, usually a
metastases in the nervous system, guided by symptoms nitrosourea-based regimen. In Europe there is no
and signs. In addition to clinical knowledge, ancillary consensus on the role of adjuvant chemotherapy in
investigations such as imaging methods, clinical neuro- high-grade gliomas. The opinion on the routine use of
physiology and cerebrospinal fluid (CSF) analysis are adjuvant chemotherapy differs from one country to
used and interpreted in this process. Results of the another and, within countries, from one centre to
investigations, however, should not be confined to a another. The main reason to refrain from adjuvant
mere topical localization, but should also involve the chemotherapy is that it has only a modest advantage in
neurologist in interdisciplinary treatment decisions terms of survival and it may negatively affect quality of
together with neurosurgeons, medical oncologists, life during a period when the patient is still in good
radiation oncologists and others. condition.
Neoplastic involvement is not the only effect of In those European centres where adjuvant chemo-
cancer on the nervous system. Metabolic changes, therapy is a routine part of the treatment of an high
infections, vascular causes and side-effects of therapies grade glioma, the medication is usually prescribed by a
need to be considered as a cause of neurological medical oncologist, adding a fourth specialist to the
symptoms and signs in cancer patients. Recent years medical team treating the patient, or by a neurologist-
have also shown that paraneoplastic syndromes may neuro-oncologist (less frequently).
reveal an important interaction between systemic Meanwhile, there are several other palliative treat-
tumours and the nervous system. In particular, the ment aspects after the diagnosis has been made.

ª 2002 EFNS European Journal of Neurology 9, 201–205


EFNS-neurooncology panel 203

Dexamethasone is often routinely administered during interaction is the combination of radiation and intra-
the first few days after surgery. Controversy exists on the thecally administered methotrexate (MTX)] or of drug
routine use of dexamethasone during radiation treat- combinations. This issue, even if difficult to study
ment, but dexamethasone is the drug of choice in any systematically, is of particular interest, because first,
case where brain oedema causes neurological symptoms second and third line therapies are increasingly used
or signs. Moreover, many glioma patients suffer from according to patient’s need.
epilepsy. Seizures may be the initial symptom, but Detection of neurotoxicity and development of
epilepsy may develop during the course of the illness as effective countermeasures or even prophylactic drug
well. It is recommended that prophylactic anticonvul- treatment are important tasks for future neuro-oncol-
sants are not used routinely in patients with newly ogists. Additionally, classification and grading of tox-
diagnosed brain tumours. However, in patients suffering icity is important, World Health Organization (WHO)
from seizures, anticonvulsant medication should be classification will have to be replaced by precise
prescribed. It is usually the neurologist who prescribes instruments being used in the CNS and peripheral
anticonvulsant drugs to brain tumour patients. nervous system (PNS).
Eventually, glioma will recur sooner or later after
initial treatment. Reoperation, reirradiation and che-
Management of patients in neuro-oncology
motherapy should be considered as treatment options
in recurrent tumours. A multidisciplinary approach is Patients with brain metastases, vertebral metastases or
highly desirable in this stage of the disease, because the primary malignant brain tumours are often affected by
response rate is low and response duration is often many neurological signs and symptoms. The same
limited. Oligodendrogliomas, however, are an exception holds true for patients with paraneoplastic disease. (The
to this rule. Most patients with anaplastic oligodendro- common factor in these diseases is that they are
gliomas respond to chemotherapy with procarbazine, incurable.) However, this does not mean that they are
vincristine and CCNU (PCV), but it remains to be seen untreatable. New technical developments in neurosur-
if these tumours should be treated with adjuvant PCV gery and radiotherapy have contributed to more
chemotherapy or if chemotherapy should be prescribed ‘radical’ tumour treatment and to a decrease in treat-
at recurrence. ment related side-effects. PCV chemotherapy in ana-
Primary central nervous system lymphomas plastic oligodendrogliomas and, to a lesser extent, in
(PCNSL) are also chemosensitive tumours, with res- anaplastic astrocytomas may prolong the duration of
ponse rates to high-dose methotrexate-based regimen as survival considerably. Surgical treatment of single brain
high as 60–80%: survival time seems to be improved by metastases improves the duration as well as the quality
a combined treatment with upfront chemotherapy of survival in comparison with whole brain radiation.
followed by radiotherapy. Stereotactic radiotherapy has improved the therapeutic
possibilities in brain metastases.
It is of utmost importance that neuro-oncological
Neurotoxicity
patients are treated by physicians with a basic know-
Treatment of malignancies requires powerful therapies, ledge of oncology as well as neurology. This holds true
which also have side-effects. At present, therapy in for the four specialists who are generally involved
neuro-oncology is based on (i) surgery, (ii) radiotherapy in the treatment of these patients, i.e. neurologists,
(conventional, stereotactic with Linac and gamma-knife neurosurgeons, radiation oncologists and medical
or brachytherapy), (iii) chemotherapy and related oncologists. As can be concluded from the inquiry
therapeutic measures such as bone marrow and stem- we made among European neurologists in 1996, the
cells transplant, (iv) immunotherapy and biological neurologist is not always involved in the treatment and
therapy (e.g. interferons), and (v) supportive measures, follow-up of brain tumour patients or patients with
including steroids and anticonvulsants. neurological complications of cancer such as brain
Not withstanding broad awareness of toxicities, there metastases. However, neurologists are specially trained
is the additional problem of time dispersion of toxic to assess brain function and to treat neurological
effects (as seen in the late sequelae of radiotherapy), or symptoms such as headache and epilepsy. This makes
continuing, or even increasing toxic effects (‘coasting’) them indispensable for an optimal follow-up of neuro-
in some toxic neuropathies, and it should be realized oncological patients.
that neurotoxicity is in many cases the limiting factor in It should be realized that the confrontation of a
oncological treatment. patient, suffering from a fatal disease, with four
Presently, little is known about the cumulative effects different specialists may be highly confusing. Neurolo-
of combined treatment modalities [the best documented gists should play a pivotal role in the co-ordination of

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204 W. Grisold et al.

the treatment. Moreover, specially trained nurses and to be open to new ideas and treatments. It will be an
multidisciplinary outpatient clinics could further important task to set strict and solid criteria for
improve the medical, psychological and social coaching measuring the efficacy of these methods. This will be
of brain tumour patients and their partners. 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
Quality of life and neuro-oncology
and what may be at best experimental.
Primary brain tumours and brain metastases are fatal Another task for neurologists is an increased aware-
disorders. In contrast to other malignancies, these ness of the need of supportive and palliative care that
tumours do not only affect the physical well being of should be part of neuro-oncology. This also involves
the patient but also affect cognitive and emotional pain therapy. Special attention should be given to
integrity. This places a heavy burden on patients and geriatric patients whose therapy tolerance is far lower
proxies. Brain tumour treatment, such as surgery, than that of younger patients. Supportive and palliative
radiotherapy and different forms of chemotherapy care will often dominate in these elder patients.
may, in the long run, severely affect the social and
emotional functioning of the patient. For that reason, it
Neuro-oncology and its position in neurology
is very important that Health Related Quality of Life
and related fields
measurements are implemented in neuro-oncological
patients, especially when the patients are exposed to We encourage specialized training in neuro-oncology
new treatment modalities. for neurologists. This should involve special training in
Immunotherapy, gene therapy, antiangiogenetic ther- the aspects of the diagnosis and treatment of primary
apy, boron neutron capture therapy (BNCT) and new brain tumours, neurological complications of cancer,
chemotherapeutic agents are all under investigation in neurotoxicity, and supportive and palliative care.
glioma patients. It is important that these investigations Training must also include enough basic knowledge
take place, but it should be realized that neuro- from related fields such as neuropathology, neurosur-
oncologists who are dealing with experimental treat- gery, medical oncology, and radiotherapy to enable
ment are aware of the problems that may arise in future neuro-oncologists to collaborate successfully
patients who undergo these therapies. Reliable meas- with the related fields in an interdisciplinary setting.
urement of cognitive functions and different aspects of If neuro-oncology can be established as a neurolog-
quality of life make up one of the cornerstones of the ical discipline, training in neuro-oncology should be
follow-up in neuro-oncological patients and should be given in a uniform pattern throughout Europe. A
part of the diagnostic skills of any specialist dealing European curriculum and guidelines should be devel-
with these patient groups. oped and the establishment of neuro-oncology as a
subsection of neurology in the Union Europeene des
Medecins Specialites (UEMS) should be considered.
Future aspects
This would automatically increase awareness of neuro-
As this outline has shown, neuro-oncology has several oncology and also facilitate its important role as a
tasks in the treatment of patients suffering from neurological subspeciality.
primary brain tumours and from systemic cancer. The
role of neurology in neuro-oncology is crucial, but lacks
Neuro-oncology and other institutions
definition in most European countries. This can be said
for most Western European countries, but more so for Presently, several organizations are involved in neuro-
the countries in ‘transition’, where patients with neuro- oncology. These are the multidisciplinary European
oncological problems are handled by neurosurgeons Association for Neuro Oncology (EANO), which
and general oncologists exclusively. focuses on scientific presentations and biannual meet-
The future aspects of neuro-oncology can be divided ings, and the EORTC. The latter organization has a
into three categories: brain tumour group devoted to studies and trials of
primary and metastatic brain tumours. The EORTC
brain tumour group is also a multidisciplinary group,
Future therapeutic aspects
in which a number of neurologists participate.
There is a broad range of new therapeutic modalities in
neuro-oncology: new drugs, new radiation modalities
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EFNS-neurooncology panel 205

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ª 2002 EFNS European Journal of Neurology 9, 201–205