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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 variousaetiologies, 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 hosts 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 67-week period. In some

centres exceptions are made for glioblastoma patients

who have a short life expectancy: in these patientsshorter 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.

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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, butepilepsy 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 6080%: survival time seems to be improved by

a combined treatment with upfront chemotherapyfollowed 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

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 patients need.

Detection of neurotoxicity and development ofeffective 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

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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 dealingwith 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.

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