What are intracranial and extracranial tumours? - Chapter 17

How often does cancer occur?

50% of all men and almost 40% of all women develop cancer (often at a later age) (Kiemeney and colleagues, 2008). The treatment of tumours may involve surgery, radiotherapy, chemotherapy, hormonal treatment, immunotherapy, or a combination of these. 

What are intracranial tumours?

Intracranial tumours can be divided into two groups; primary and secondary tumours. A primary brain tumour originates from the brain tissue itself, the cerebral nerves, the pituitary gland, or the meninges. Almost always, low-grade tumours (particularly gliomas) develop into high-grade tumours in the long term. Secondary brain tumours are metastases from the primary tumour located elsewhere in the body: the cause of brain metastasis can be found in 3 out of 4 cases in lung cancer, breast cancer or skin cancer. In approximately 50% of the annually additional cases with a primary brain tumour there is a glioma. In this patient group, approximately 20% have a low-grade tumour: in half of the patients, the glioma does not grow within the first five years and patients can live for decades with a glioma without serious cognitive impairments. Patients with a high-grade tumour live on average just twelve months.

Cognitive impairments

The cognitive impairment and diaschisis (the phenomenon in which distant brain areas function less well due to damage to the connecting lines) in less well-functioning brain areas may be due to the tumor itself, a tumor recurrence, but also to treatment (such as neurosurgery and radiotherapy). A tumor-related epilepsy and the psychological state in which the patient finds himself can also be a trigger for the generation of disorders.

When is the brain tumor the cause of the cognitive impairments?

In the case of rare tumours, cognitive impairment is the most important characteristic; in tumours that occur more frequently, symptoms are often an increased intracranial pressure and loss of neurological function. In 8 out of 10 cases of a slow-growing tumor (such as low-grade gliomas), the epileptic seizure is the first symptom. In the case of fast-growing (high-grade) tumors there is more neurological failure and high intracranial pressure. The memory disorders and problems with the word fluency that are present before the operation are often attributed to oedema formation, a larger tumour and a higher tumour degree (Talacchi, Santini, Savazzi & Gerosa, 2011). A left hemispheric tumour causes more explicit disorders than a right hemispherical tumor. Glioma patients usually have more diffuse cognitive impairments. The glioma can generate a cortical reorganization due to the high plasticity of the brain: the function recovers (in part). A meningioma (tumour from the meninges or meninges) is benign in 90% of the cases. Through this space-consuming process, 30% of this patient group experiences severe cognitive impairments in the long term.

When is neurosurgery the cause of cognitive impairment?

Neurosurgeons are reluctant to operate on patients with tumours in brain areas that are crucial for cognitive functioning (often referred to as eloquent brain areas). In these cases an awake resection may be considered (tumour surgery performed while the patient is awake). Meanwhile, the neuropsychologist conducts cognitive tests. If a glioma is surgically removed, any focal cognitive disorders will disappear in the short term.

When is radiotherapy the cause of cognitive impairments?

The amount of radiation that can be administered without inducing serious consequences for the surrounding tissue (therapeutic index) limits the use of radiotherapy (radiation). An irreversible, serious complication is the late radiation damage that can occur even years after the radiation. This complication can manifest itself as local radiation necrosis (healthy brain tissue in a particular location dies) or diffuse encephalopathy (attention disorders, working memory disorders, psychomotor slowness accompanied by subcortical dementia, executive dysfunction, memory disorders and behavioral changes). More than 10% of patients whose skull was radiated suffer from a subcortical dementia profile. The chance of this developing is partly determined by the dose of radiotherapy (in Gray) and the size of the radiation area (skull base). For this reason, only focal radiotherapy is used in glioma patients.

What does a low-grade glioma patient look like?

In low-grade glioma patients, mild cognitive impairment often occurs. There is no progression in the disorders during the first few years. These disorders are not the result of late radiation damage or focal radiotherapy, but rather of the tumour itself or other treatment factors. The chance that these disorders do occur due to late radiation damage is if patients have previously had a skull base radiation, a high fraction dose or experienced radiation therapy ten years ago. According to Douw and colleagues (2009), all low-grade glioma patients who have been irradiated are cognitively deteriorating in the long term compared to non-irradiated patients who remain stable.

What does a high-grade glioma patient look like?

The cause of cognitive impairment is more difficult to discover in high-grade glioma patients because of the polytherapy consisting of radiation and chemotherapy. The rapid cognitive decline can usually be attributed to the progression of the tumour, especially if it has remained stable for a period (Bosma et al., 2007). Before the treatment, at least moderate cognitive impairment has often been found which points to the tumour as the main culprit.

Which treatments are available?

The most commonly used treatment for patients with brain metastases is radiation. Focal radiation is increasingly being used in connection with the increased risk of late radiation damage with skull radiation. A form of skull radiation that is unlikely to result in late radiation damage is prophylactic brain radiotherapy (used to prevent metastasis in patients with lung carcinomas). It even seems that this radiation positively influences functioning. Patients with a primary CNS lymphoma often have late radiation damage. Factors that contribute to this are a higher age, the need to use skull radiation, and the increasing use of medicines. Nowadays, this CNS lymphoma is treated more often with chemotherapy alone. Patients with nasopharyngeal tumours also have a greater risk of late radiation damage. Patients who had surgery for a meningioma several years ago often still have disorders in the domains: memory, language, motor control, and executive functions. A meningioma at the base of the skull is an indicator of poorer cognitive functioning than a meningioma at the upper edge. Radiotherapy has no cumulative effect on cognitive impairment after surgery.

When are drugs the cause of cognitive impairment?

Epilepsy is a possible side effect of the intracranial tumor. Anti-epileptics can also induce cognitive impairment. In successfully treated low-grade glioma patients, disorders in working memory capacity, executive functions, speed of information processing and psychomotor speed were related to anti-epileptics or epilepsy. The neurotoxicity of central nervous system medication is noticeable during treatment or shortly after treatment. The chemotherapeutic agents that are often written for glioma patients are often non-toxic and do not lead to cognitive impairments (such as lomustine). Corticosteroids are given to reduce intracranial pressure (by reducing oedema). The biggest disadvantage of this type is the chance of mood disorders and the chance of psychoses. Other cognitive impairments are often temporary.

What are extracranial tumors?

Complaints common in chemotherapy

Chemotherapy is also toxic to healthy cells, because there is no difference in the survival capacities for cancer cells and healthy cells. The side effects mainly concern nausea, hair loss, fewer white blood cells or platelets and sometimes this affects fertility and menstruation. The medication easily crosses the blood-brain barrier, causing neurotoxic effects in nearly 50% of patients. The most frequently heard complaints are forgetfulness, problems in sustained and divided attention and maintaining an overview. Even long after the treatment is stopped the medication can still cause (heart) problems.

Cognitive impairments occur

Due to methodological differences and the different types of chemotherapy, the studies estimate the incidence of cognitive impairment in breast cancer patients between 13 and 64%. These disorders most closely resemble a frontal subcortical image (there are problems in learning and retrieving information, working memory, executive functions, the complex aspects of attention and the slower pace of information processing). There is almost never a cortical syndrome (such as aphasia, apraxia or agnosia).

Is there a mood disorder and fatigue following cancer?

The location of the brain tumor influences the degree of anxiety and depressive feelings experienced. Such feelings are particularly strong after diagnosis, although the patient often adjusts quickly. 20 to 30% also have mood complaints in the long term. Fatigue is one of the most subjectively reported symptoms in both patients treated with chemotherapy and patients who have not undergone chemotherapy (such as patients with primary brain tumors).