Metastatic Brain Tumor Case File

Metastatic Brain Tumor Case File

Eugene C. Toy, MD, Ericka Simpson, MD, Pedro Mancias, MD, Erin E. Furr-Stimming, MD

CASE 53

A 59-year-old retired bartender presents to his primary care physician (PCP) complaining of headaches over the past 6 weeks. He has been healthy all of his life and takes no medications. He says the headaches are located primarily over the right frontal and temporal region, and the headaches are described as “dull and aching” in nature. He has experienced occasional nausea but no vomiting with the headaches. The headaches are worse in the morning upon waking. Additionally, he has had difficulty focusing and concentrating on tasks at hand, such as reading the newspaper or playing cards. His wife states that he has been more irritable, moody, and “not himself” for 1 month. There is no history of alcohol abuse or exposure to toxins. He admits to a 30-pack-year smoking history. The review of systems is significant for weight loss and a productive cough.

His examination reveals that he is afebrile with a blood pressure of 124/72 mm Hg and a heart rate of 78 beats/min. His general examination is normal. He is oriented to person, time, location, and situation, although he becomes upset during the examination. Cranial nerve and sensory examination findings are unremarkable. Motor strength testing is normal except for questionable weakness in the left finger extensors. The deep tendon reflexes are normal except for a Babinski sign present on the left. With ambulation, he has decreased arm swing on the left.

▶ What is the most likely diagnosis?

▶ What is the next diagnostic step?

▶ What is the next step in therapy?

ANSWERS TO CASE 53:

Metastatic Brain Tumor                                                       

Summary: A 59-year-old previously healthy man presents with a 6-week history of right frontal temporal headaches associated with difficulty concentrating, weight loss, and productive cough. His headaches are often associated with nausea, are dull in nature, and are predominantly present upon waking in the morning. His wife reports he has experienced a mild personality change, and the patient himself recognizes mood disturbances. His examination is notable for decreased arm swing on the left, questionable weakness of the left finger extensors, and a left Babinski sign.

• Most likely diagnosis: Metastatic brain tumor affecting the right cerebral hemisphere.
• Next diagnostic step: Magnetic resonance imaging (MRI) of the brain with and without gadolinium and chest x-ray.
• Next step in therapy: Corticosteroids and anticonvulsants should be started immediately while waiting for surgical evaluation.

ANALYSIS

Objectives

1. Know the clinical presentation and diagnostic approach to metastatic brain tumor.
2. Be familiar with the differential diagnosis of metastatic brain tumor.
3. Describe the treatment for metastatic brain tumor.

Considerations

This 59-year-old otherwise healthy man with a 30-pack year tobacco history presents with unilateral dull headaches worse upon waking and associated with nausea and personality changes. Additionally, there is a history of difficulty concentrating, weight loss, and cough. His physical examination suggests mild left-sided weakness that is most likely from an upper motor neuron lesion in the right hemisphere, given the left Babinski sign. Based on the history and examination, the most likely diagnosis is a right hemispheric mass lesion. The history of weight loss and cough are concerning for possible primary lung cancer. With this in mind, metastatic lung cancer should be considered. A primary brain tumor is also on the differential. A chest x-ray reveals that he has a large right upper lobe mass lesion highly suggestive of lung cancer. An MRI of the brain shows a right frontal-temporal well-circumscribed lesion at the gray-white junction with hemorrhage and surrounding edema. Evidence of midline shift or impending herniation should be evaluated. Corticosteroids such as dexamethasone should be initiated, as this reduces cerebral edema and capillary permeability. Anticonvulsant prophylaxis in individuals with metastatic tumors who have not experienced a seizure is controversial. Approximately 40% of patients with metastatic brain tumors will experience a seizure. Only 20% of patients with metastatic brain tumors present with seizures as the first symptom. In this particular case, the patient has a hemorrhagic metastatic lesion, which is known to be epileptogenic. Most physicians would begin or at least strongly consider anticonvulsants. Caution should be taken in patients who receive both anticonvulsants and corticosteroids, as the latter can significantly reduce anticonvulsant levels. Neurosurgical consultation should be obtained, as should an oncology consultation.

APPROACH TO:

Metastatic Brain Tumors                                               

DEFINITIONS

METASTATIC BRAIN TUMORS: Tumors that arise from the metastasis of systemic neoplasms to the brain parenchyma.

BABINSKI SIGN: Extension of the great toe followed by abduction of the other toes when the lateral sole of the foot is stimulated. Stroking the foot at the heel and moving the stimulus toward the toes elicit this reflex. It is a sensitive and reliable sign of corticospinal tract disease. It is also known as the plantar extensor reflex. The normal plantar reflex is flexor.

MIDLINE SHIFT: Movement of a cerebral hemisphere to the contralateral side secondary to intracranial swelling. This can cause compression of the lateral ventricles and contribute to further elevated intracranial pressure.

HERNIATION: Downward displacement of the cerebral hemisphere from increased intracranial pressure.

CLINICAL APPROACH

Epidemiology

Metastatic brain tumors can arise from primary systemic cancers that spread to the leptomeninges, brain parenchyma, calvaria, or dura. Brain metastases are 10 times more common than primary brain tumors. In the United States, roughly 150,000 new cases of metastatic brain tumors are reported each year. Men have a slightly higher incidence than females with a ratio of 1.4:1. Approximately, 66% of metastatic brain tumors involve the parenchyma, with almost 50% of these being a solitary lesion. The most common tumors that metastasize to the brain are listed in Table 53–1, with lung cancer being most common.

Tumors metastasize to the brain most commonly by entering the systemic circulation through hematogenous spread. The distribution of tumor parallels arterial blood flow to the brain, with approximately 82% metastasizing supratentorially, 15% spreading to the cerebellum, and 3% affecting the brainstem. Metastatic brain tumors are commonly located at the gray-white junction and arterial border zones, locations that have narrowed blood vessels that can trap tumor cells. Venous embolization of tumor cells through the vertebral venous plexus of Batson has also been proposed as an alternative route of the spread of pelvic and retroperitoneal tumors.

Clinical Evaluation

Clinical features of metastatic brain tumors are varied and depend on their location. Neurologic symptoms occur from direct tumor infiltration, hemorrhage, edema, or even hydrocephalus. Table 53–2 illustrates the most common clinical features of brain metastases. The differential diagnosis for metastatic brain tumors includes brain abscess, demyelinating diseases, radiation necrosis, cerebral vascular accidents, intracranial bleed, and primary brain tumors. Approximately 60% of those without any known primary tumor who present with brain metastasis have a primary lung cancer. Of these, 25% to 30% of non–small cell cancer patients will have brain metastasis.

The clinical evaluation in patients with an unknown primary cancer is focused and includes an MRI of the brain with gadolinium. Gadolinium or contrast is critical, as it will show enhancement around the lesions suggestive of vasogenic edema. A chest x-ray followed by a computed tomography (CT) scan of the chest should be performed since lung cancer is the most common type of cancer to metastasize to the brain. If these studies are unrevealing, an abdominal or pelvic CT scan should be performed. Careful attention should be paid to the prostate, testicles, breasts, and rectum during clinical examination. Stool examination should be performed to evaluate for occult blood as a screening tool to evaluate for gastrointestinal cancers. A positron emission topography (PET) may be helpful in identifying the primary tumor and the degree of metastatic spread.

Unfortunately, an MRI of the brain cannot diagnose the type of tumor in patients with an unknown primary malignancy. One exception to this is malignant melanoma, which is typically hyperintense on T1-weighted images and hypointense on T2-weighted images due to either melanin or blood products. A brain biopsy may be necessary if the primary tumor remains elusive. Patients with signs of severe increased intracranial pressure may benefit from surgical decompression.

TREATMENT

Treatment with corticosteroids such as dexamethasone is important in reducing intracranial pressure and edema. Commonly, a dose of 10 mg of dexamethasone, either orally or intravenously, followed by 4 mg every 6 hours, is given. As previously discussed, it is controversial as to whether anticonvulsants are necessary in patients who have not experienced seizures. However, individuals who have had a seizure warrant anticonvulsant therapy.

The decision to pursue surgical resection is dependent on several variables, such as the number of brain metastases, the location, the size, the likelihood of response to treatment, and the patient’s overall health status. The most important factor when considering surgery is the tumor burden located outside the brain. Improved survival and quality of life have been shown in patients with single lesions when they have been treated with whole brain radiotherapy and surgery. Factors that portend a better response to surgical and radiotherapy include presentation at a younger age, absence of extracranial disease, and later than early development of brain metastasis.

Radiation therapy has been shown to decrease the mortality from neurologic dysfunction. The most common regimen is given over a period of 2 weeks using 30 Gy in 10 fractions. Radiation therapy improves neurologic symptoms in 50% to 93% of patients. A Cochrane review of several studies suggests that the combination of radiotherapy and epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with non–small cell lung cancer improved overall survival. Complications from radiotherapy include brain necrosis, brain atrophy, cognitive deterioration, leukoencephalopathy, and neuroendocrine dysfunction. Stereotactic radiation via the gamma knife, linear particle accelerators, or charged particles can also be used. This has been found to decrease toxicity to healthy tissue and minimize side effects. Stereotactic radiation is often used in tumors that are surgically inaccessible; complications from stereotactic radiation include seizures, headaches, nausea, hemorrhage, and radiation necrosis. For the most part, chemotherapy is not used for brain metastasis due to challenges in delivering the agents across the blood-brain barrier.

PROGNOSIS

Favorable prognostic factors include age less than 60, two or less brain metastases, good baseline function, and successful surgical resection. Individuals with single brain metastasis who receive brain radiation plus surgery have a median survival of 10 to 16 months. Patients who have metastasis to infratentorial regions of the brain carry a worse prognosis than those with supratentorial metastasis.

COMPREHENSION QUESTIONS

53.1 A 56-year-old man presents to the emergency department (ED) with confusion and motor deficits. CT imaging shows multiple lesions to the brain. A metastatic tumor is suspected. Which of the following is the most common primary tumor causing the brain metastases in this patient?

A. Breast

B. Melanoma

C. Renal

D. Lung

E. Thyroid

53.2 A 50-year-old man is noted to have some symptoms suggestive of a brain tumor. Which of the following is the most common symptom of brain tumors?

A. Seizures

B. Headaches

C. Papilledema

D. Personality changes

E. Ataxia

53.3 A 45-year-old man with a history of smoking presents after experiencing a generalized tonic-clonic seizure. He has been experiencing dull left-sided headaches over the past 2 months. His examination reveals hyperreflexia on the right with mild weakness of the right iliopsoas and finger extensor muscles. The MRI of the brain shows a large 7- × 10-cm lesion over the left frontal region with associated midline shift. A chest x-ray shows a left lower lobe mass. What is the next step?

A. Consult neurosurgery for immediate brain biopsy and debulking.

B. Start dexamethasone at a dose of 10 mg followed by 4 mg every 6 hours. Concomitantly begin an anticonvulsant medication.

C. Start dexamethasone at a dose of 100 mg followed by 4 mg every 6 hours and hold off on starting anticonvulsant medication.

D. Consult the oncology service to assist you in deciding on chemotherapy.

E. Start whole brain radiation therapy.

ANSWERS

53.1 D. This is a 56-year-old man with multiple metastases to the brain. We are not given any other risk factors or information. Lung cancer is the most common tumor metastasizing to the brain, accounting for approximately 50% of all cases.

53.2 B. Headache is the most commonly found symptom associated with brain tumors and is found in approximately half of cases. About a third of affected individuals will have cognitive loss such as memory loss, language disorder, or seizures. Nausea and vomiting and papilledema are late findings only in about 10% to 12% of cases.

53.3 B. Patients with brain metastasis that present with seizures should be started on anticonvulsant therapy in addition to dexamethasone. In this particular case, there is associated midline shift that warrants immediate management.

    CLINICAL PEARLS    

▶ Metastatic tumors account for the majority of brain tumors in adults. ▶ Enhancing brain lesions on MRI located at the gray-white junction are likely to be metastatic brain tumors. ▶ The most common malignancy to metastasize to the brain is lung, followed by breast cancer. ▶ Patients who present with new-onset headaches, personality changes, and mood disorders should be evaluated for an intracranial structural lesion, such as central nervous system (CNS) metastases.

REFERENCES

Jiang T, Min W, Li Y, Yue Z, Wu C, Zhou C. Radiotherapy plus EGFR TKIs in non-small cell lung cancer patients with brain metastases: an update meta-analysis. Cancer Med. 2016;5(6):1055-1065. 

Nathoo N, Toms SA, Barnett GH. Metastases to the brain: current management. Expert Rev Neurother. 2004;4(4):633-640. 

Sawaya R, Ligon BL, Bindal RK. Management of metastatic brain tumors. Ann Surg Oncol. 1994; 1(2):169-178.

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