Brain Metastasis

Disease/ Disorder

Definition

Intracranial neoplasms are abnormal growths within the cranial cavity that may be composed of benign (non-cancerous) or malignant (cancerous) cells. The tumor may be primary or a metastasis from another location. The most common primary malignancies that metastasize to the brain include lung, breast, renal, colon, and melanoma. The most common primary malignant brain tumor in adults is glioma.

Etiology

• Neuroepithelial origin from glial brain cells: gliomas
  • Astrocytoma: grade 1 (more common in children), grade 2 (diffuse and low grade), grade 3 (anaplastic astrocytoma), grade IV (glioblastoma)
  • Oligodendroglioma
  • Ependymoma can spread via cerebrospinal fluid leading to drop metastases
• Meningioma: slow growing, usually benign
• Primary central nervous system lymphoma
• Pituitary adenoma: functional type causes endocrine dysfunction, nonfunctional type causes problems through mass effect
• Schwannoma (benign, most commonly located at the cerebellopontine angle): hearing loss, tinnitus, impaired balance
• Cerebral metastases (secondary): Most commonly due to lung, breast, gastrointestinal (including colon), melanoma, renal cell

Epidemiology including risk factors and primary prevention

Risk factors may include genetics and ionizing radiation. The most common type of cancers that may metastasize to the brain or spinal cord include lung, breast, melanoma, and renal cell cancers. There is a higher risk of lymphoma in people with immune compromise, such as acquired immune deficiency syndrome or organ transplant.

The primary prevention is diagnosing and treating primary disease early.

Patho-anatomy/physiology

Brain tumor can cause various neurologic symptoms due to local invasion and mass effect with cerebral edema. Hemorrhage into the tumor may cause a sudden change in clinical presentation.

Metastatic tumors are usually at the gray/white junction where blood vessels narrow and trap cells and at terminal arterial watershed areas. Certain tumor types’ predilection for certain areas of the brain have not been elucidated.  Hematologic, lung, breast, melanoma, and gastric cancers can also spread to the leptomeninges.

Disease progression including natural history, disease phases or stages, disease trajectory (clinical features and presentation over time)

Symptoms may include:

• Headache
• Seizures
• Nausea
• Vomiting
• Focal deficits such as hemiparesis, visual field defects and aphasia depending on location
• Ataxia
• Dysphagia
• Impaired cognition and personality changes
• Fatigue and endocrine abnormalities may occur if the pituitary is involved.  

Specific secondary or associated conditions and complications

May include:

• Hydrocephalus (potentially requiring ventriculoperitoneal shunt),
• Pituitary abnormalities
• Seizures
• Muscle weakness
• Loss of coordination
• Urinary incontinence
• Deep venous thrombosis
• Paraneoplastic phenomena

Essentials of Assessment

History

One needs to ascertain symptoms, including the time course of onset of symptoms. Typically symptoms to ask about include headache, nausea/vomiting, motor changes such as weakness or coordination problems, sensory and/or visual changes. Headache may typically occur in the morning on awakening.  Other questions to ask may include “have there been any documented seizures or episodes of loss of consciousness” or “has there been shortness of breath?”

History should include details of how previously diagnosed cancer was treated.  Ideally one wants to know what doses of medications and radiation were used. It is important to note if there is a past personal or family history of cancer as well as a history of tobacco use. One should enquire as to the results of screening tests such as mammograms, pap smears, colonoscopies, digital prostate exams, and prostate specific antigen (PSA) tests. For functional history, one needs to get details of the recent past functional status and enquire as to current ability to ambulate, transfer, toilet, bath, light meal preparation, and driving skills. For social history, one needs details of the work and home duties.

Physical examination

The examination should include testing for strength, balance, gross and fine motor coordination, sensation, and reflexes. Gait evaluation should also be assessed. Cranial nerve exam should include visual fields, assessment for papilledema, assessment of palate symmetry, and tongue position. Cognitive and linguistic assessment should be done. Depending on the practice setting, one may consider also checking stool hemoccult.

Functional assessment

One needs to assess the ability for ADLS including transfers, ambulation, toileting, bathing, and cooking. Cognitive screening should be performed, and assessment of mood, judgement and decision-making completed.

Laboratory studies

Lab work-up should include electrolytes, liver function tests, blood urea nitrogen, creatinine, albumin, and complete blood count. Specialized tests for tumor progression/recurrence and pituitary function may be done depending on tumor type.

Imaging

Initial imaging will include brain magnetic resonance imaging, with gadolinium to assess the tumor itself, and depending on tumor type, chest imaging or spine imaging may also be ordered to assess other sites. Possible positron emission scan (PET) scan may also be ordered depending on clinical need to look for metastases, often in conjunction with computerized tomography scan. Imaging may need repeated if there is a change in clinical condition and in order to assess for edema, change in tumor size, or hydrocephalus.

Supplemental assessment tools

• Electromyography/nerve conduction velocities may be utilized to assess for possible peripheral neuropathy or paraneoplastic disease.   
• Brain biopsy to ascertain primary tumor type and to determine if recurrence or post treatment changes.
• Electroencephalogram if question of seizures.  
• Modified barium swallow to evaluate for dysphagia.

Early predictors of outcomes

Primary tumor prognosis depends most on histology, with glioblastoma having a significantly worse prognosis (mean lifespan of 18 months). Size and location may also predict outcome. For metastatic tumors, the primary tumor and tumor factors affect prognosis. Isolated metastasis can often be resected and have a better prognosis than multiple metastases.

Environmental

Identify what assistive devices and modifications are needed to move safely in the home and the community.

Social role and social support system

• Assess if the patient is cognitively and physically able to perform job duties. If unable to work, how does that affect insurance coverage?
• Identify how the patient wishes to spend his/her days if the end of life is near. Palliative care and hospice referral as appropriate.
• Assist family/friends in planning how to cope with day to day needs of patient as well as long term related to diagnosis.
• Identify support groups for the family as well as the patient.
• Identify financial resources in the community for care.
• Make patient/family aware of groups such as the American Cancer Society.

Professional Issues

Can the patient make their own decisions about finances, driving, and medical care or is she/he too cognitively impaired? Identify if there are different cultural and personal norms as to what the patient should be told if prognosis is dire. End of life decisions may need to be made depending on prognosis.

Rehabilitation Management and Treatments

At different disease stages

New onset/acute

• Potential curative interventions: Surgery and chemotherapy. Radiation therapy: whole brain, stereotactic radiosurgery.
• Symptom relief: Treatment of headache and nausea with medications, physical therapy, and pain management. Treat the side effects of drugs, such as constipation or peripheral neuropathy (which may develop later in course of treatment). Monitor surgical site. Watch for radiation therapy early reactions, such as nausea, vomiting, alopecia, tinnitus, and skin changes.
• Rehabilitation strategies that intend to stabilize or optimize function or prepare for further interventions at later disease stages: Physical therapy for mobility, occupational therapy for activities of daily living, speech therapy for cognitive problems, speech and language, and dysphagia. Adaptive equipment. For acute inpatient rehabilitation, cognitive deficits and weakness may be more common.¹ For fatigue, stimulants may be used. Functional gains for brain tumor patients during inpatient rehabilitation hospital stays were comparable with traumatic brain injury patients matched by age, sex, and admission functional status.² In a retrospective study, the tumor type did not affect efficiency of functional improvement in inpatient rehabilitation, though patients receiving concurrent radiation therapy made greater gains per day.³

Subacute

• Secondary prevention and disease management strategies: Radiation and chemotherapy. Monitor for radiation encephalopathy. Late delayed radiation can cause focal cerebral necrosis or diffuse injury. Minimize risk of other complications, such as osteoporosis leading to fracture. Promote adequate nutrition for skin integrity and muscle mass maintenance.
• Symptom relief: Treatment of headache and nausea with medications. Physical therapy; pain management including peripheral neuropathic pain due to chemotherapy. Treat side effects of drugs. Treat anxiety and/or depression if present.
• Rehabilitation strategies that intend to optimize function: Physical therapy, occupational therapy, and speech therapy. Neuropsychologic testing as needed for cognitive deficits. Orthoses if needed.

Chronic/stable

• Secondary prevention and disease management strategies: Late radiation encephalopathy may develop. Late delayed radiation can cause focal cerebral necrosis, or diffuse injury. Imaging to address growth/recurrence of primary tumor. If metastatic, it is necessary to follow what is occurring in the rest of body.
• Palliative strategies: Treatment of headache, nausea with medications, and physical therapy; pain management.
• Symptom relief: Treatment of headache, nausea with medications, and physical therapy; pain management. Fatigue is often multifactorial due to deconditioning, drugs including antiseizure meds, and anemia. Workup if needed for endocrine problems, especially if the pituitary gland is involved (tumor itself or in treatment field).
• Rehabilitation strategies that intend to optimize function: Physical therapy, occupational therapy, and speech therapy. Neuropsychologic testing as needed for cognitive deficits and the development of a behavioral plan.

End of life care

• Symptom relief:
  1. Pain management
  2. Treatment of anxiety by counseling and medications
  3. Meet family needs including more help in the home as mobility declines
  4. Decisions needed regarding fluid and nutritional intake

Coordination of care

Treatment of brain tumors need to take into account overall neurologic and cognitive functioning in assessing management options. This requires multidisciplinary coordination amongst neurosurgeons, oncologists, radiation oncologists, primary care physicians, and physiatrists. The inter-disciplinary rehabilitation team, including psychology, social work, and pastoral care, must work together to identify barriers to return to home. They must focus on the patients’ goals of improving quality of life, or in cases of limited life expectancy, of maintaining quality of life and dignity for as long as possible.

Patient & family education

It is important to work in tandem with oncology, radiation therapy, and neurosurgery to ensure there are no mixed messages, especially as far as life expectancy is concerned. If cognition is impaired, behavioral strategies may need to be elucidated to ensure safety.

Emerging/unique interventions

Impairment-based measurement

Functional Independence Measures (FIM)

• Studies have shown that inpatient rehabilitation can improve function which has been shown by improved FIM scores. Patients with primary brain tumors and metastatic tumors have shown equivalent improvement when compared. Those patients who have received radiation therapy during rehabilitation have shown significantly greater FIM scores while patients with recurrence of tumors had smaller strength/motor improvement noted (3).

Get Up and Go test

Berg Balance Scale

Timed 10-meter walk test

6-minute walk test to measure the distance walked indoor on a level surface in 6 minutes.

Measurement of patient outcomes

Karnovsky Performance Scale (KPS)

• 100 is normal, 0 is dead. On the KPSS, a score of 60 requires occasional assistance but can care for most needs; a score of 50 requires considerable assistance and frequent medical care; a score of 40 and the patient is considered disabled, requiring special care and assistance.
• KPS in studies has shown improvement after inpatient rehabilitation at both admission and three month follow ups (6).

Disability Rating Scale

• DRS in studies has shown improvement after inpatient rehabilitation at both admission and discharge (6).

Translation into practice: practice “pearls”/performance improvement in practice (PIPs)/changes in clinical practice behaviors and skills

Cognitive deficits are common in brain tumor patients; one needs to look for them as patients may not self-report. More work with oncologists is needed to address functional outcome measures, particularly for outpatients, and to address practical needs of patients and caregivers if the patient is being cared for at home. Palliative care programs need to include a functional component and integration of PMR into care plans for patients would be of benefit.

Cutting Edge/ Emerging and Unique Concepts and Practice

Proton therapy delivers a high level of focused proton beams to the tumor with the goal of limiting exposure to the neighboring brain tissues. New surgical technologies may include fluorescent imaging during surgery to help differentiate tumor tissue from healthy brain tissue as well as higher level MRI for greater resolution of the brain imaging for surgical planning. In addition, many academic medical centers have multiple clinical trials available for patient enrollment.

Gaps in the Evidence- Based Knowledge

There continues to be a lack of updated data on outpatient rehabilitation progress/efficacy.

References

1. Mukand JA, Blackinton DD, Crincoli MG, Lee JJ, Santos BB. Incidence of neurologic deficits and rehabilitation of patients with brain tumors. Am J Phys Med Rehabil. 2001;80:346-350.
2. O’Dell MW, Barr K, Spanier D, Warnick RE. Functional outcome of inpatient rehabilitation in persons with brain tumors. Arch Phys Med Rehabil 1998:79:1530-1534.
3. Marciniak CM, Sliwa J, Heinemann A, Semik PE. Functional outcomes of persons with brain tumors after inpatient rehabilitation Arch Phys Med Rehabil. 2001;82:457-463.
4. http://brain.mgh.harvard.edu/ChemoGuide.htm, accessed 2/16/2016
5. Robinson G, Bloggs V, and Walker DG. Front Oc Cognitive screening in brain tumors: short but sensitive enough? pub online 2015 Mar 2011:doi: 10.3389/fonc.2015.00060.
6. Huang ME, Wartella JE, Kreutzer JS. Functional outcomes and quality of life in patients with brain tumors: a preliminary report. Arch Phys Med Rehabil. 2001;82(11):1540-46.

Supplemental resources

Asher A. Cognitive dysfunction among cancer survivors. Am J Phys Med Rehabil. 2011;90(5 Suppl 1):S16-26.

Bell KR, O’Dell M, Barr K, Yablon, SA. Rehabilitation of the patient with brain tumor. Arch Phys Med Rehabil. 1998;79(3 Suppl 1):S37-46.

DeAngelis L. Brain Tumors. NEJM. 200;344:114-123.

Kirschblum S, O’Dell M, Ho C, Barr, K. Rehabilitation of persons with central nervous system tumors. CANCER. 2001; 92 (4 Suppl):1029-1038.8.

Omoro, A, DeAngelis, L. Glioblastoma and other malignant gliomas: a clinical review. JAMA. 2013;310 (17): 1842-1850.

Vargo, M. Brain tumor rehabilitation. Am J Phys Med Rehabil 2011;90(5 Suppl 1):S50-62.

Wen PY, Loeffler JS. Overview of the clinical manifestations, diagnosis, and management of patients with brain metastases. Available at: http://www.uptodate.com/contents/overview-of-the-clinical-manifestations-diagnosis- and-management-of-patients-with-brain-metastases. Accessed March 18, 2011.

Original Version of the Topic

Rina Bloch, MD. Intracranial Neoplasms. 11/11/2011.

Previous Revision(s) of the Topic

Rina Bloch, MD. Intracranial Neoplasms. 11/11/2011.

Author Disclosures

Whitney Luke, MD
State of Ohio, Billed hourly rate for Consulting, Consultant