Lecture 7: Brain tumors: Chapter 17 Flashcards
Why are more people getting cancer (2)?
- We live longer
- Cancer risk increases with age
What causes cancer?
DNA errors that accumulate in our cells throughout life
What percentage of people will be diagnosed with cancer in their life? How is the survival rate compared to the 1970s?
50%
Survival has doubled since 1970
What are 3 patient groups that can experience cognitive impairment as a complication of cancer/cancer treatment?
Which patient group does a neuropsychologist see most often?
- Primary brain tumors (2%)
- Secondary brain tumors (20%)
- Cancer outside the central nervous system, due to treatment
Most often patient group 3, simply because they’re the largest group
What is the difference between primary and secondary brain tumors?
Primary: tumor started in the brain
Secondary: tumor didn’t start in the brain, but there are metastases from another part of the body (e.g. lung cancer 20%)
What is the difference between intracranial and extracranial tumors?
Intracranial: originate in CNS/brain (primary or secondary)
Extracranial: originate outside of the CNS
What is an important aspect of treatment of tumors?
Cures are very limited, so treatment is mainly focused on better quality of life
What are the 2 main categories of primary brain tumors and what are the prevalences of each?
What is the most common name of tumor of each category?
- Non-malignant (benign): 68%
–> Meningioma’s - Malignant: 32%
–> Glioma’s
What are malignant tumors?
Tumors that are aggressive and often come back after removal. They often come back even more aggressive and in a higher grade
What is histopathology and what are the 4 grades? Which survival chance is there after 5 years?
How abnormal cells look
1: non-malignant: 90%
2: malignant: 50%
3: malignant: 20%
4: malignant: 2%
What are non-malignant/benign tumors?
Cells that don’t threaten to affect other tissues. They’re slow growing, non-cancerous and don’t spread
What are meningiomas?
Tumors arising from the meninges, rarely malignant
What are glioblastomas?
Malignant tumors developing from glial cells (the cells that surround and support neurons with myelin)
What are metastases?
Secondary brain tumors that have developed as a result of cancer elsewhere in the body
How can you know which type of tumor it is/on what is diagnosis of a tumor based?
Examination of tissue samples from tumors by staining and examination under the microscope by a pathologist
What is the difference between IDH gene mutant and IDH wildtype?
Mutant: better prognosis for survival
Wildtype: worse prognosis for survival
What are 3 molecular parameters the WHO classification of brain tumors is based on?
- Presence of mutation IDH gene
- 1p/19q codeletion
- MGMT promotor methylation
What is the impact of codeletion of 1p/19q gene?
Codeletion has better prognosis, because it responds better to treatment
What is MGMT promotor methylation?
If promotor of MGMT is methylated, the gene won’t be replicated anymore, which gives a better response to chemotherapy
What are the 3 main physical symptoms in clinical presentation in people with brain tumors? On what does this depend?
Headache - memory loss - cognitive change
Depends on location of tumor
What are the top 3 priorities for brain tumor treatments in the future for patients?
- Retain brain functioning
- Maintain ability to walk and perform basic tasks
- Reduce pain
What are 5 causes of cognitive impairment in brain tumor patients?
- Tumor itself
- Cancer treatment
- Other medication, metabolic impairments
- Distress, psychological state
- Fatigue
What can predict survival rate of someone with a brain tumor?
Molecular characteristics
What are 4 possible causes of cognitive impairment of the tumor itself?
- Affects healthy brain tissue (damage fiber tracts, local reorganization, neurotransmitters)
- Affects blood flow
- Edema/swelling
- If meningioma: pressure on nearby brain, nerves and vessels
Why is often multi-domain cognitive impairment observed in brain tumor patients?
Due to diaschisis caused by the brain tumor: tumor influence the brain across many regions which may affect the neural networks
In which 2 conditions is generally worse cognition found?
- Left-side brain tumors
- More aggressive brain tumors
What does an MEG show in brain tumor patients?
MEG measures nerve connections throughout the brain. In brain tumors these networks are disrupted
What are common complaints for people with temporal lobe tumors? What is the difference between left and right temporal lobe tumors?
Learning, memory and executive problems
Left: attention, language deficits
Right: no additional
What are 3 goals of surgery as treatment for brain tumors?
- Establish accurate diagnosis
- Decrease neurological symptoms
- Maximize survival
What are 4 different options for treating brain tumors?
- Surgery
- Radiotherapy
- Chemotherapy
- Immunotherapy
Why are patients often awake during brain tumor surgery?
To monitor functions of the brain that really shouldn’t be damaged by the surgery
What is the difference in surgery for people with meningioma vs. glioma?
Meningioma: better accessible tumors, often improvement of cognitive impairment
Glioma: infiltrates in the brain, so hard to reach
–> Permanent cognitive/neurological decline possible
–> Awake surgery is needed
What are eloquent areas?
Important area’s for cognition that have to be spared during brain surgery
What is the goal of radiotherapy?
Cause damage to DNA of cancer cells to overwhelm their ability to repair themselves, leading to cell death
What are 4 processes induced by radiotherapy that can lead to cognitive impaiment?
- Vascular damage
- Inflammation, glial dysregulation
- Oligodendrocyte injury (disturbed myelin production)
- Neuronal damage
What are the 3 phases of radiation toxicity in the CNS? What are the characteristics of each phase?
Phases after the radiotherapy
- Acute (1-3 weeks)
–> edema, focal deficits
–> treated with steroids: nausea - Subacute (1-6 months)
–> demyelination - Late (>6 months)
–> white matter injury, necrosis, irreversible cognitive impairment
What is the difference between focal and whole brain radiotherapy? Which treatment is preferred nowadays and why?
Focal: lower doses spread out over a period of a few weeks
–> preferred method, since stronger radiation kills cancer cells as well as healthy tissue
Whole brain: larger doses administered at a time
What is the relation between subcortical dementia and radiotherapy?
12% of people who received radiotherapy develop subcortical dementia
Atrophy + dilation of ventricles + severe white matter abnormalities –> explain the dementia
What are 2 factors determining the risk of developing diffuse white matter anomalies in radiotherapy?
- Dose of radiotherapy
- Size of radiation feeld
When could whole brain radiotherapy be an option?
Patients with lung cancer to prevent the development of metastases
How is the cognitive impairment among low-grade glioma patients? And in high-grade glioma patients?
Low: Cognitive impairment occurs frequently. This impairment is often not caused by late radiation damage
High: Cognitive impairment cause hard to find, because there are many more causes possible due to more treatment given. It’s estimated that the tumor itself plays the largest role, since it’s large and aggressive
The NKI initiative aims to predict which patients might be susceptible to the effects of radiation. What are 4 risk factors?
- Age <5 or >60
- Vascular risks
- Radiation dose
- Radiation therapy volume
What is the goal of chemotherapy?
Kill dividing cells (cancer cells divide more often than most normal cells, but it can still affect healthy cells as well)
When is chemotherapy extra neurotoxic?
If the blood brain barrier (BBB) is not intact. If the BBB is passed more easily, it damages the tumor more, but also more healthy cells
What are common cognitive complaints after chemotherapy?
Forgetfulness, difficulty focusing and generally having to exert more effort
In which type of tumor does epilepsy often occur and why? What helps against it and what are its downsides?
In gliomas –> because of the disruption in the entire brain
Use anti-epileptic medication –> side effects (fatigue, headache)
When are corticosteroids often prescribed? What are the short- and long-term effects?
When there is an increased intracranial pressure. The steroids diminish edema
Short term: better cognition
Long term: emotion problems, sleep disturbance, behavioral changes (mood disorders)
What are 4 types of interventions for cognitive impairment?
- Reversible contributions (comordities, mood, fatigue)
- Pharmacological interventions (radiotherapy, drugs)
- Technical interventions (avoid important brain regions)
- Behavioral interventions (cognitive training, strategy training)
What are 2 types of behavioral interventions for brain tumor patients?
- Cognitive training: often appealing to patients, but not effective
- Strategy training: teach strategies to compensate for and cope with cognitive impairment
What is the difference between external compensatory strategies and internal memory strategies?
External: to-do lists, organizers
Internal: re-teach the brain to retain info using rhyme/phrases to remember stuff
What is the evidence on ‘sparing’ the hippocampus in brain tumor patients?
Hypothesis: hippocampus is important for learning, so for cognitive reasons, you need to spare it as much as possible
Evidence: hippocampus doesn’t work on its own and needs connections with other regions as well. So it’s not very convincing
What is the role of a neuropsychologist in the field of brain tumors?
Educate about causes, diagnostics and treatment
What are 3 challenges with regard to diagnostics?
- Tests require clinical interpretation and absolute criteria (blood tests, imaging)
- Varied range of mechanisms of actions as well as behavioral and cognitive signatures, which are not available at individual level
- Weak correlation between actual experiences and scores on cognitive tests
