Relative to Role as Provider of Care in Oncologic Emergencies

Relative to Role as Provider of Care in Oncologic Emergencies. Nursing Management I

 

Cancer is considered a chronic disease. However, a number of acute conditions associated with cancer and its treatment can occur. These conditions, or complications, often require immediate medical intervention and are thus considered oncologic emergencies. Early diagnosis of such conditions is essential to avoid life-threatening situations.

 

 

Syndrome of Inappropriate Antidiuretic Hormone

  OVERVIEW

 

In healthy people, antidiuretic hormone (ADH) is secreted by the posterior pituitary gland only when more fluid (water) is needed in the body, such as when plasma volume is decreased (see Chapter 11). In people with certain health problems, ADH is secreted inappropriately or wheot needed by the body.

Cancer is the most common cause of the syndrome of in­appropriate antidiuretic hormone (SIADH). The type of can­cer most commonly associated with SIADH is carcinoma of the lung (especially small cell lung cancer), but SIADH may occur in other types of cancer, especially when tumors are present in the brain. Some tumors actually make and secrete ADH, whereas others stimulate the brain to synthesize and se­crete ADH. In addition, certain drugs commonly used in clients with cancer can cause the problem (most notably mor­phine sulfate and cyclophosphamide).

In SIADH, excessive amounts of water are reabsorbed by the kidney and put into systemic circulation. The increased water causes hyponatremia (decreased serum sodium levels) and some degree of fluid retention. Mild symptoms occur and include weakness, muscle cramps, loss of appetite, and fatigue. Serum sodium levels range from 115 to 120 mEq/L (normal range is 135 to 145 mEq/L). More serious signs and symptoms are related to water intoxication, including weight gain, nervous system changes (especially personality changes), confusion, and extreme muscle weakness. As the sodium level approaches 110 mEq/L, seizures, coma and, eventually, death may follow unless the condition is rapidly treated.

 

The syndrome of inappropriate antidiuretic hormone secretion (SIADH) is a clinical syndrome in which enhanced secretion or action of antidiuretic hormone (ADH) due to various disease processes and medications causes persistent hyponatremia and inappropriately elevated urine osmolality.

Normally, ADH, or arginine vasopressin, is secreted from the posterior lobe of the pituitary gland in response to a decrease in plasma volume or an increase in serum osmolality. In SIADH, secretion of ADH is not caused by a hemodynamic disturbance and is mediated through nonosmotic receptors, resulting in water retention and dilutional hyponatremia. The  incidence of hyponatremia in hospitalized patients is 2.5%, and SIADH is the most common cause of hyponatremia in this population.

As early as 1957, Schwartz described SIADH in 2 patients with bronchogenic carcinoma.

Pathophysiology

ADH is a nonapeptide hormone that is synthesized in the hypothalamus and transported down the pituitary stalk to the posterior pituitary, where it is stored.

 

 

Increased osmotic pressure caused by increased plasma osmolality is a major stimulus for ADH release, which is mediated through the osmoreceptors in the hypothalamus.

 

 

 

 

Volume depletion is another major stimulus for ADH release, which is mediated through baroreceptors at various sites, including the left atrium, pulmonary veins, carotid sinus, and aortic arch. The antidiuretic  action of ADH occurs when the active hormone binds to the V2 receptors on the cells lining the collecting tubules in the kidney, stimulating cyclic adenosine monophosphate and leading to the insertion of aquaporin-2 channels into the apical membrane of the collecting tubule cells. This in turn facilitates transport of solutefree water through the tubular cells, causing water reabsorption in the renal medulla.

In SIADH, ADH is inappropriately secreted, resulting in unregulated water reabsorption and a measured dilutional hyponatremia.

 

 

ETIOLOGY

SIADH usually results from either increased secretion of ADH by the posterior pituitary or ectopic secretion of ADH from another site (Table).

 

 

 

Causes of excess release of ADH from the pituitary gland include central nervous system disturbances6–8 and certain drugs.

Pulmonary conditions, such as pneumonia, tuberculosis, acute respiratory failure, asthma, and atelectasis, have also been associated with increased production of ADH.  SIADH is one of the most frequent causes of hyponatremia in hospitalized patients with AIDS, in whom SIADH can be related to adrenal insufficiency or pneumonia. Finally, postoperative states in patients who undergo major abdominal and thoracic surgical procedures as well as chronic pain syndromes can result in increased secretion of ADH; in these scenarios, ADH release is believed to be mediated by pain afferents.

Ectopic secretion of ADH has been associated with small cell lung cancer, bronchogenic carcinoma, duodenal tumors, pancreatic tumors, thymus tumors, olfactory neuroblastoma, sarcoma, malignant histiocytosis, mesothelioma, and other occult tumors.

Other mechanisms implicated in SIADH include increased sensitivity to ADH in the kidney; reset osmostat, in which ADH release is normally regulated around a lower osmolality set-point, leading to mild asymptomatic hyponatremia (124–134 mEq/L) that fluctuates around the reset level of serum sodium; failure to suppress ADH completely at low osmolality (incomplete pituitary stalk section); and exogenous administration.

Medications that can increase sensitivity to ADH and result in SIADH include chlorpropamide, tolbutamide, carbamazepine, mizoribine, nonsteroidal anti-inflammatory drugs, and cyclophosphamide.

Approximately 30% of patients who underwent transsphenoidal pituitary surgery developed hyponatremia due to inappropriate secretion of ADH from the injured pituitary stalk. Miscellaneous causes of SIADH include cachexia, malnutrition, and administration of desmopressin.

Clinical Features

The signs and symptoms of SIADH depend on both the degree of hyponatremia and the rate at which hyponatremia develops. Patients whose sodium concentration has decreased slowly over a long period of time may be completely asymptomatic. In these patients, there can be nonspecific symptoms such as anorexia, nausea, vomiting, irritability, headaches, and abdominal cramps. Conversely, patients who have undergone rapid declines in sodium concentration tend to have more symptoms.

 

 

A serum sodium concentration less than 120 mEq/L or serum osmolality less than 240 mOsm/kg is considered serious, irrespective of the rate of decline. With this degree of hyponatremia, patients can experience cerebral edema, which may manifest as headache, nausea, restlessness, irritability, muscle cramps, generalized weakness, hyporeflexia, confusion, coma, or seizures and can cause permanent brain damage, brainstem herniation, or death.

 

EVALUA TION AND DIAGNOSIS

As SIADH has a varied etiology, a careful history is important and should include comorbidities, current medications, and patients’ symptoms. There are no significant findings in the physical examination of a patient with SIADH, although signs of dehydration or edema would make the diagnosis unlikely. Patients with moderate to severe hyponatremia need to be thoroughly assessed to rule out potential complications.

The key points in diagnosing SIADH are the serum sodium concentration, tonicity of plasma and urine, urine sodium concentration, and clinical volume status.

Findings of hyponatremia (serum sodium concentration < 135 mEq/L), hypotonicity (plasma osmolality < 280 mOsm/kg), inappropriately concentrated urine (> 100 mOsm/kg), and an elevated urine sodium concentration (> 20 mEq/L) are consistent with SIADH; however, a low urine sodium concentration (< 20 mEq/L) does not exclude the diagnosis.4,5,13,17 Patients with SIADH are clinically euvolemic (subclinical plasma volume expansion without clinically significant edema).

Hypouricemia occasionally may be associated with SIADH as a result of increased excretion of nitrogen waste and plasma dilution.

Because SIADH is a diagnosis of exclusion, it is necessary to rule out thyroid, adrenal, cardiac, liver, and kidney dysfunction through laboratory testing (thyroid-stimulating hormone level, cortisol stimulation test, braiatriuretic peptide level, liver function tests, serum blood urea nitrogen level, and serum creatinine level).4,13 Assay of serum ADH level is not mandatory.

Common causes of SIADH can be screened for by chest radiograph and computed tomography head scan, if clinically indicated.

Supplemental diagnostic findings that are only of theoretical interest and are not required for the diagnosis of SIADH include an abnormal water load test result (this test is not recommended as it can precipitate severe hyponatremia) and inappropriately increased ADH levels relative to plasma osmolality.

 

 

SIADH AND CEREBRAL SALT WASTING SYNDROME

 

Cerebral salt wasting syndrome (CSWS) is a rare syndrome that has been described in patients with cerebral tumors and subarachnoid hemorrhage and in patients who have undergone transsphenoidal pituitary surgery.

 CSWS mimics SIADH (ie, hyponatremia,  increased urine osmolarity, urine sodium > 20 mEq/L, and urine osmolality > serum osmolality), but in fact represents appropriate water resorption in the face of a salt wasting and a secondarily hypovolemic state. These patients may also have hypouricemia due to increased urinary uric acid excretion. The etiology of CSWS is unclear. Fluid restriction may help differentiate SIADH from CSWS, as restriction will correct the hypouricemia and increased fractional excretion of urate in patients with SIADH, whereas in patients with CSWS both will persist after fluid restriction. The treatment of CSWS differs from that of SIADH. Infusion of isotonic saline to correct the volume depletion is usually effective in reversing the hyponatremia in CSWS since euvolemia will suppress ADH secretion. Some patients may benefit from fludrocortisone therapy

 

TREATMENT

Treatment of SIADH depends on the symptoms, serum sodium concentration, rapidity of onset of hyponatremia, and primary etiology. Although treating the underlying etiology is essential to the resolution of SIADH, doing so is often difficult due to noncompliance.

Fluid restriction is the first-line treatment in mild asymptomatic hyponatremia (serum sodium concentration > 125 mEq/L), which generally improves with correction of the underlying cause and restriction of free fluid intake to between 800 and 1000 mL/day. If there is no response, fluid intake can be restricted to 500 to 600 mL/day, but compliance is very difficult. To enhance compliance, patients must be educated that a regular diet contains 700 to 1000 mL of water even before accounting for free water intake.

In mild symptomatic hyponatremia, a loop diuretic (not thiazides) can be added to fluid restriction. Loop diuretics interfere with the action of ADH in the collecting tubule by inhibiting free water reabsorption, eventually achieving a negative water balance. Careful attention must be given when using loop diuretics to prevent depletion of other electrolytes.

If saline is used to treat hyponatremia in SIADH, the osmolality of the infused saline generally must exceed the osmolality of the patient’s urine. Therefore, infusion of isotonic saline (osmolality of 308 mOsm/L) is not recommended in patients with SIADH whose urine osmolality exceeds 308 mOsm/L because it may actually worsen their hyponatremia. In such cases, the kidney excretes the solute from normal saline in concentrated urine, while the unexcreted volume is retained as free water, resulting in a net fluid gain and exacerbation of the hyponatremia. However, one study demonstrated that isotonic saline improved the serum sodium level in water-restricted SIADH patients as long as the sodium and potassium concentration of the urine did not exceed the sodium concentration of the infused isotonic saline (ie, 154 mEq/ L).25.

Symptomatic patients with severe hyponatremia (serum sodium concentration < 125 mEq/L) may require hypertonic saline in addition to fluid restriction.

Hypertonic saline can be infused via a pump with careful monitoring, and urine osmolality can be followed to guide therapy. As a rule of thumb, hypertonic saline can be switched to isotonic saline when the urine osmolality is less than 300 mOsm/L. Caution must be taken in correcting hyponatremia, as aggressive and overly rapid correction may induce central pontine myelinosis, a demyelinating condition that affects the pontine and extrapontine neurons, leading to quadriplegia, pseudobulbar palsy, seizures, coma, or even death. Patients at high risk for central pontine myelinosis include those with hypokalemia or burns, patients on thiazide diuretics, alcoholics, and the elderly. To avoid this serious consequence, the serum sodium level should be raised at a rate no faster than 1 to 2 mEq per hour, and the rate should not exceed 8 to 12 mEq per day. Once the serum sodium rises above 125 mEq/L, the risk of seizure and death is reduced and the daily correction should be slowed to 5 to 6 mEq per day.

Patients with chronic SIADH (ie, those with reset osmostat syndrome or cancer) may benefit from a highsodium diet combined with loop diuretics. In most instances where SIADH is induced by medications, resectable tumors, or lung pathologies, serum sodium normalizes after removal of the offending agent. In patients with severe SIADH due to unresectable tumors or in chronic states of any kind, demeclocycline 600 to 1200 mg daily in divided doses can be used. This agent improves SIADH by interfering with the kidney’s  response to ADH at the collecting tubule. Although expensive, it is well tolerated. Other agents that can be used in long-term management include urea and diuretics. Lithium should be avoided because it potentiates the central nervous system side effects of hyponatremia.

Recently, the vasopressin receptor antagonist conivaptan was approved for the treatment of dilutional hyponatremia (SIADH). Conivaptan causes loss of body water without loss of electrolytes. It is given intravenously.

Several other vasopressin receptor antagonists are being evaluated in clinical trials.

Chronic, asymptomatic, mild to moderate hyponatremia where the cause is known but not easily or quickly reversed may be managed without fluid restriction or medications. Patients with stable, chronic sodium levels above 125 mEq/L who are asymptomatic may not derive much benefit from treatment considering the expense of demeclocycline and the discomfort of severe water restriction.

 

 COLLABORATIVE MANAGEMENT

SIADH is managed by treating the condition and the cause. Treatment regimens for SIADH usually include fluid restriction (sometimes total fluid intake is reduced to 1 L/day), increased sodium intake, and drug therapy. A commonly used drug for this condition is demeclocycline, a form of tetracy-cline antibiotic, which is taken orally. The mechanism of ac­tion appears to be antagonistic to ADH. Serum sodium levels must be monitored closely, because hypernatremia can develop suddenly as a result of this treatment.

A second method for managing SIADH is to reduce or eliminate the underlying cause. The immediate institution of appropriate cancer therapy, usually either radiation or chemotherapy, can cause such tumor regression that ADH synthesis and release processes return to normal.

 

Hypercalcemia

 OVERVIEW

Hypercalcemia (increased serum calcium level), a late mani­festation of extensive malignancy, occurs most often in clients with bone metastasis. Cancer in bone causes the bone to release calcium into the bloodstream. In clients with cancer in other parts of the body—especially the lung, head and neck, kidney, or lymph nodes—the tumor secretes parathyroid hormone (parathormone), causing bone to release calcium. Decreased physical mobility also contributes to or worsens hypercalcemia. Early signs and symptoms of hypercalcemia include fatigue, loss of appetite, nausea, vomiting, constipation, and polyuria (increased urine output). More serious signs and symptoms include severe muscle weakness, diminished deep tendon reflexes, paralytic ileus, dehydration, and electrocar-diographic (ECG) changes. The severity of signs and symptoms depends on how high the serum calcium level is and how quickly it developed.

 

 COLLABORATIVE MANAGEMENT

Hypercalcemia as a consequence of cancer develops very slowly for many clients, which allows the body time to adapt to this electrolyte change. As a result, symptoms of hypercal­cemia may not be evident until the serum calcium level is greatly elevated. Because adaptation does occur, hypercal­cemia associated with cancer is treated only when clinical manifestations are present.

Conservative management, such as oral hydration alone, may be enough to reduce the serum calcium to an acceptable level. Normal saline is the fluid of choice when parenteral hy­dration is needed.

Many drugs lower serum calcium levels. Some agents, such oral glucocorticoids, calcitonin, diphosphonate, gallium ni­trate, and mithramycin, lower levels quite dramatically. These agents do not cure hypercalcemia but instead reduce serum calcium levels temporarily. When cancer-induced hypercal­cemia is life threatening or accompanied by renal impairment, dialysis can temporarily reduce serum calcium levels.

 

Spinal Cord Compression

 OVERVIEW

Spinal cord compression and damage occur when a tumor di­rectly enters the spinal cord or when the vertebral column col­lapses from tumor entry. Tumors may begin in the spinal cord but more commonly spread from other areas of the body, such as the lung, prostate, breast, and colon. Spinal cord compres­sion causes back pain, usually before neurologic deficits oc­cur. Neurologic deficits are related to the spinal level of com­pression and include numbness; tingling; loss of urethral, vaginal, and rectal sensation; and muscle weakness. If paral­ysis occurs, it is usually permanent.

 

Figure 1 Spinal Cord Compression

Lateral view of the spine showing a metastasis in the verte­bral column with extension into the spinal canal, resulting in severe cord compression.

 

 

Malignant spinal cord compression is one of the complications of malignan­cy that can seriously affect patients’ quality of life and disrupt the lives of families striving to care for them.

 How often does it occur?

Which cancer patients are at high risk for spinal cord compression?

What causes cord compression?

What findings indicate impending cord compression?

How is spinal cord compression best diagnosed?

What is the functional prognosis?

What factors impact survival?

Which patients will benefit from steroid or radiation therapy or from surgery?

Which treatment approach should be taken first?

In this article, I will review the data that can help answer these questions.

 

 

 Epidemiology

In the last 5 years of life, 2.54% of patients dying with cancer will have at least one episode of spinal cord compression . Of the half million patients who die of cancer each year, 12,700 of them will be at risk for pain, paraplegia or paralysis, incon­tinence, and possible institutionalization because of spinal cord injury. Prostate, breast, and lung cancer each account for 15%–20% of cases of cord compression; non-Hodgkin’s lymphoma, myeloma, and renal cell carcinoma account for 5%–10% each; and colorectal cancer, primary cancer of un­known origin, and sarcoma account for most of the remaining cases . In 20% of cancer patients, spinal cord compression is the initial manifesta­tion of malignancy; 30% of these patients are found to have lung cancer. The cumulative incidence of cord compression in patients who are 40–60 years old is 7.37% for patients with breast cancer, 15.38% for patients with myeloma, and 16.98% for patients with prostate cancer

The location of the metastases is proportional to the volume or mass of bone in each region: 60% of metastases occur in the thoracic spine, 30% in the lumbosacral spine, and 10% in the cervical spine. Breast and lung cancer typi­cally cause thoracic lesions, whereas colon and pelvic carcinomas commonly affect the lumbosacral spine. In 10%–38% of patients, the spinal cord is compressed at multiple sites. New occurrences of cord compression arise in a different site in approximately 10% of patients a median of 4.5 months (range, 1–25 months) after the initial occurrence

 

 Pathophysiology

Spinal cord compression due to malignancy (Figure 1) is defined as a “compression of the thecal sac by tumor in the epidural space, either at the level of the spinal cord or cauda equina”

Most cancers cause spinal cord compres­sion by direct extension from a metastasis in the vertebral body. In 75% of cases, soft tissue epidural metastases are found; in the remaining 25%, frank bone collapse may occur, with bone fragments sometimes adding to the compression. Patients with lymphoma or retroperitoneal tumors may suffer cord compression from tu­mors that grow through the intervertebral fora­men and compress the cord without involving the vertebra. Cord injury arises from ischemia and vasogenic cord edema, which occurs at the level of compression through blockage of venous outflow or central perforating vessels in the cord.

Prostaglandin E2 (PGE2) and, in response to hypoxia, vascular endothelial growth factor (VEGF) increase vascular permeability and vasogenic edema. Neurologic dysfunction in the ischemic cord arises from demyelination, mediated by lipid peroxidation and both enzymatic and nonenzymatic lipid hydrolysis. The spinal cord may also infarct from ischemia due to blockage of venous flow, occlusion of small ar­teries, or occlusion of the major spinal arteries.

Once the cord infarcts, the neurologic damage is permanent.

 

Presentation

Back pain is the most common symptom, occur­ring in 83%–95% of patients hours to months be­fore the compression is diagnosed, but it is not an independent predictive factor. Pain is usu­ally described as sharp, shooting, deep, or burning. It is precipitated by coughing, bending, sneezing, or, in 20% of patients, simply lying flat. Pain can be local, radicular only, or radicular and local. The pain is caused by the expanding tumor in the bone, bone collapse, and/or nerve damage. The location of the pain does not always correspond to the site of compression.

For example, compression at C7 can cause pain referred to the midscapular region, and compression at T12 can present only with pain referred to the sacroiliac joint or hip. In a prospective study of patients with spinal cord com­pression, the site of the pain and the sensory levels did not predict the site of the compression: 54% of patients with T1–T6 compression had lumbosacral pain, and a like percentage of patients with lumbo­sacral compression had thoracic pain. In only 16% of patients did the sensory level correlate with the level of compression seen on magnetic resonance imaging (MRI).

Following pain in frequency are radiculopathy, weakness, sensory changes (paresthesias, loss of sensation), sphincter incontinence, and auto­nomic dysfunction (hesitancy, urinary retention).

It is difficult to determine the prevalence of ra­diculopathy, weakness, sensory changes, or incon­tinence in patients with spinal cord compression because the majority of descriptive studies were retrospective studies published in the mid-1990s, when MRI was just beginning to be used for diagnosis and patients were presenting with fairly advanced disease. Those studies indicated that weakness was present in 60%–85% of patients at the time of diagnosis and was often the reason patients sought medical attention. Two thirds of these patients were nonambulatory at diagnosis, and more patients were paraparetic than were paralyzed. Over half the patients presented with sensory changes, which either started in the toes and rose in a stocking-like pattern to the level of the lesion  or started one to five levels below the level of the actual cord compression. Autonomic dysfunction occurred late and was never the “sole presenting symptom”. About half of the patients needed catheters at diagnosis.

 

DELAYS IN DIAGNOSIS

Three prospective studies offered insights into causes of the delays in diagnosis. Levack et al identified patients by daily prospective review of emergency MRI scans, radiotherapy referral lists, and referral from clinicians at three Scottish on­cology centers. The authors identified 319 pa­tients who had altogether 324 episodes of meta­static spinal cord compression. Of these patients, 261 (82%) were interviewed at a median of 3 days after diagnosis of metastatic cord compression, and 248 (78%) gave a detailed personal history.

These patients presented with significant pain and long-standing functional abnormalities. Weak­ness, lasting a median of 20 days, was reported by 84% of the patients, and only 18% of these patients were ambulatory. Altered sensations were experi­enced by 68% of the patients for a median of 12 days. Difficulty passing urine at least once was re­ported by 56% of the patients, and 25% had urinary retention, but only 5% reported fecal incontinence. Most patients had opioid-related constipation.

Patient, clinician, and institutional factors con­tributed to the delay in diagnosis. Patients usually presented after the symptom had been present for some time or after they developed significant weakness. These patients were cared for by gener­al practitioners, who were unable to expedite the needed diagnostic studies at the referral centers. The referral hospitals were limited by the lack of a guideline for evaluation of patients with acute back pain and cancer, having only guidelines for patients with back pain who did not have cancer.

In the second study, Husband  identified 301 consecutive patients over a 3-year period and also found that the longest delays in diagnosis occurred in patients presenting to general prac­titioners or district general hospitals; delays were much shorter among patients who were first seen at a regional cancer center. Of patients with signs and symptoms of cord compression, only 30% of those seen by general practitioners and 21% of those seen at a district general hospital were referred for therapy without delay, compared with 67% at regional cancer centers. Significant increases in the number of days to treatment were observed from the onset of back pain, spinal cord compression , or weakness, but not from loss of ambulation. Patients without a known diagnosis of cancer also experienced significant delays in treatment, compared with patients with known cancers.

In the third study, Mitera and Loblaw noted that when patients thought their new symptoms were related to their previous cancer, the median delay to treatment was significantly less than when patients felt their symptoms had other etiologies (5.5 days vs 17 days). Both Hus­band and Mitera and Loblaw urged educational interventions to reduce delay

 

CAUDA EQUINA SYNDROME

Patients with cauda equina syndrome (Figure 2) present differently from those with spinal cord compression.

Patients experience diminished sensation over the buttocks, posterior-superior thighs, and perineal region in a saddle distribution. Between 60% and 80% of these patients have de­creased anal sphincter tone. Urinary retention and overflow incontinence are important predictors, with a sensitivity of 90% and a specificity of 95%. If the diagnosis is uncertain, a urinary post-void residual evaluation should be performed; ab­sence of a post-void residual evaluation essentially rules out cauda equina syndrome, with a negative predictive value of 99.99% .

 

Figure 2 Cauda Equina Syndrome

 

Tumor growth impinges on the thecal sac, resulting in the compression of the nerves of the cauda equina. Patients with cauda equina syndrome may present with bladder disturbances, sphincter dysfunction, or diminished sensation in the buttocks, thighs, and perineum.

 

Diagnosis

As with any patient who has cancer, the goals of care, the condition of the patient, and the po­tential for therapeutic success define the urgency and extent of diagnostic studies. Because parapa resis and paraplegia are such devastating compli­cations, and because therapy is usually well toler­ated, urgent diagnosis of spinal cord compression should be seriously considered, even in patients with limited overall prognoses.

MRI is the gold standard for diagnosing epi­dural disease and spinal cord compression and for treatment planning. MRI sensitivity is 93%, its specificity is 97%, and its overall accuracy is 95% in revealing spinal cord compression. Treatment planning utilizing MRI altered radia­tion therapy field borders in 45% of patients with suspected spinal cord compression.

 

 

 

Fig: MRI of the spine (saggital section) showing pathological fracture dislocation of Thoracic vertebra T5 posteriorly and compressing on the spinal cord

 

 

Fig: MRI of the spine (transverse section) showing tumour (thyroid carcinoma metastasis – white arrow) invading and destroying the T5 vertebral body with compression of the spinal cord

 

 

 

 

 

 

 

 

 

 

 

 

(a) Sagittal MRI of the thoracic spine showing the spinal cord compression (white arrow). (b) Axial MRI of the mid-thoracic level demonstrating the amount of cord displacement by the extramedullary mass (white arrow). (c) Axial CT of the mid-thoracic spine region. Note the overgrowth of the marrow in response to anemia as a compensatory mechanism (white arrow). (d) Pathology slide of the bone marrow in the lamina of the thoracic spine showing fibroadipose tissue, extramedullary hematopoiesis with erythroid hyperplasia. The inset shows the deposits of foamy histiocytes

 

Plain x-ray films do not have adequate sensitivity and have a false-negative rate of 10%–17%. Vertebral metastases are visible on x-ray films only when 50% of the bone is lost. In addition, 25% of patients with spinal cord compression have no bone destruction, and so bone films and bone scans are not helpful if they are normal.

The routine MRI is done with T1-weighted sagittal images because the vertebral metastases can be easily seen as a reduction in signal from the tumor, compared with the bright appearance of normal marrow containing fat. The radiologist can visualize the cord, cerebrospinal fluid, and ex­tradural masses. An MRI scan of the entire spine is necessary because simultaneous occult disease is not unusual in patients with spinal cord com­pression.

 For example, disease was seen at two different spinal levels in 15% of a heteroge­neous group of cancer patients and in 41% of patients with prostate cancer.

The T1-weighted sagittal images alone may not be sensitive enough, however, to detect epidural metastases that could be treated before compres­sion develops. Kim et al found that a com­plete MRI study (T1-weighted and T2-weighted sagittal images and T1- and/or T2-weighted axial images) was superior to T1-weighted sagittal im­ages alone in detecting epidural disease. The sen­sitivity of T1-weighted sagittal images alone for vertebral metastases was 87% and for cord com­pression was 70%, but for epidural metastases it was only 46%. The specificity for cord compression was 97% and for epidural disease was 89%. Axial images were better able to reveal epidural disease without compression. The recommended practice, therefore, is to obtain T1-weighted sagittal images with T1- or T2-weighted axial images in the areas of interest. Since MRI rarely detects asymp­tomatic cervical disease, it is sufficient to scan only the thoracic and lumbosacral spine in patients who present without cervical pain .

 

Prognosis

Pre-treatment ambulatory status is the most important predictor of ambulation post treatment and of improved survival. Overall, 75%–100% of ambulatory patients remain ambulatory , and 50% of those who survive a year after treatment are still ambulatory . About 14%–35% of paraparetic and 15% of paralyzed patients regain “useful” function after radiation therapy . About 80% of patients who re­quire a catheter before treatment still need one after therapy.

The duration of motor deficit development before the onset of radiation therapy is also an important prognostic factor; slower development predicts a better outcome. Of those patients whose motor deficit was present for   more than 14 days, 86% were ambulatory after therapy. Only 55% of those who had symptoms for 8–14 days and only 35% of those with weakness for 1–7 days before therapy became ambulatory. Patients with motor deficits for the shortest time between onset and treatment showed the least improvement and most deterioration following therapy.

Median survival after spinal cord compression depends on the number of metastases, the type of tumor, and the patient’s functional status. Female patients, patients with radiosensitive tumors with a single metastasis, and patients with myeloma or cancer of the breast or prostate have the longest survival. Patients with multiple metastases, visceral or brain metastases, and lung or gastrointestinal cancers have the shortest sur­vival.

A database search of the Ontario Cancer Reg­istry, which captures over 97% of cancer cases in Ontario, did not provide data on functional out­comes but did provide data on survival from di­agnosis. Median survival was 3 months from diagnosis in treated patients and 1 month in un­treated patients.

Cancer patients who had spinal cord compression in the last year of life spent twice as many days in the hospital than those who did not have cord compression.

A similar relationship between tumor type and survival was seen in patients who needed rehabili­tation after radiation therapy. A prospective study of 60 patients admitted to an inpatient re­habilitation facility at a tertiary care cancer center measured survival from the date of MRI diagno­sis of spinal cord compression and examined a number of variables that might predict survival. In this population, only tumor type was a statis­tically significant predictor of survival. Patients with lung and gastrointestinal malignancies had a median survival of 2.1 months and 0.6 months, re respectively, those with breast cancer had a median survival of 3.1 months, and those with genitouri­nary cancers had a median survival of 4.6 months. Overall median survival was 4.1 months.

In addition to tumor type, retrospective and prospective observational studies have demon­strated the importance of functional status to survival. The studies have shown that the median survival for patients who could walk after comple­tion of therapy was 7.9–9.0 months but was only 1–2 months for nonambulatory patients

A series of 107 patients operated on for spinal metastases without spinal cord compression further supports the relationship of overall survival to postoperative performance status . In this series, 37 patients had lung cancer and 30 had breast cancer. Even in the absence of preoperative cord compression and neurologic abnormalities, the patients’ prognoses were related to Karnofsky performance status.

With such limited prognoses, the implications for referral of patients with spinal cord compression to hospice programs are clear. Patients with spinal cord compression from lung cancer, pa­tients who are nonambulatory after therapy, and patients who need admittance to a rehabilitation facility all meet hospice criteria of a life expectancy of less than 6 months if the disease takes its usual course. Family resources—personal, emotional, and financial—may be too limited to allow for home hospice care for these patients. However, the availability of home hospice care should be explored if the patient and family are agreeable. For patients who do not elect hospice care, the oncology or primary care team should strongly consider working with the patient and family to identify goals of care. Because they have such a limited life span, helping those patients work on legacies, closure of personal relationships, selec­tion of health proxies, and preferences regarding resuscitation are of prime importance.

 

Prevention

To prevent spinal cord compression, patients and clinicians must have a high index of suspicion. Delays in diagnosis have serious consequences, including loss of mobility, loss of bladder function, and decreased survival. Although it does not predict for clinical spinal cord compression, the recent onset of back pain, in the absence of other symptoms or a specific cause, such as injury, in a patient with known cancer probably warrants an MRI scan if morbidity from spinal cord compression is to be avoided. No validated predictive models exist that would allow the clinician to omit performing an MRI in this population.

Kienstra et al prospectively evaluated 170 cancer patients with recently developed back pain, radicular pain, or both to determine which tests could predict the presence of spinal epidu­ral metastases. All patients with back pain had a standard neurologic examination and plain x-ray films of the entire spine, as well as an MRI scan. A multivariate analysis of risk factors was derived from the medical history, neurologic examination, and plain films. None of the risk models identified a population of patients in whom an MRI scan could be omitted.

Bayley et al attempted to determine the factors that could predict clinically occult spinal cord compression in 68 patients with prostate cancer and known bone metastases, including 65 with known vertebral metastases. None of these patients had a history of spinal cord disease or neurologic symptoms, and all had normal findings oeurologic examination. Of the 68 patients, 64 (94%) were receiving continuous hormonal therapy for metastatic disease; however, 61 of these 64 patients had hormone-refractory disease, as demonstrated by increasing prostate-specific antigen levels or an increasing number of bone metastases on bone scans. All 68 patients underwent a screening MRI scan. The scan was considered positive if it demonstrated impinge­ment of the subarachnoid space by metastatic tu­mor involving the vertebrae, distortion or collapse of a vertebra with impingement of the subarach­noid space by bone fragments, or frank spinal cord compression or involvement of the cauda equine by either process.

Clinically occult disease was found on MRI in 32% of these patients; 17% had subarachnoid disease, and 15% had spinal cord or cauda com­pression. Multivariate analysis showed that hav­ing more than 20 metastases on a bone scan and the length of time on hormone therapy were inde­pendent predictors and were significantly associ­ated with disease in the subarachnoid space or with spinal cord compression (P = 0.04). Moreover, in patients with more than 20 metas­tases, the risk of occult disease increased from 32% to 44% as the duration of hormone therapy increased from 0 to 23 months. In patients with fewer than 20 metastases, the risk increased from 11% to 17%. The existence of back pain at pre­sentation of metastatic disease was not predic­tive of later development of spinal cord disease. Clinical evidence of spinal cord compression with demonstrated dysfunction developed in 4 of the 46 patients who had vertebral metastases but a negative initial screening MRI scan.

Talcott et al  also sought to develop a pre­dictive model for spinal cord compression. They retrospectively analyzed 342 episodes of suspected spinal cord compression in 258 patients by re­viewing all charts from February 1, 1985 through September 30, 1988. The diagnosis of spinal cord compression was made by computed tomography, not MRI, and included both thecal sac compres­sion and spinal cord displacement. Using regression analysis, they identified six independent predictive factors: inability to walk, heightened deep tendon reflexes, vertebral compression fractures, age under 60 years, known bone metastases, and duration of bone metastases of greater than 1 year. Patients with none of these risk factors had a 4% incidence of spinal cord compression, those with one risk fac­tor had a 10% incidence, those with any two or three factors had a 21%–23% incidence, those with four factors had a 52% incidence, and those with five factors had an 87% incidence of spinal cord compression. Unfortunately, the two most predic­tive combinations of two or three risk factors would have identified patients who already had significant neurologic impairment.

These combinations were:

(1)                  inability to walk, weakness, and bowel or blad­der dysfunction (all three required),

(2)                  and (2) objective weakness, heightened reflexes, and spinal point tenderness (two of three required).

There is a suggestion that local irradiation of a single metastasis and strontium-89 treatment can decrease the incidence of spinal cord compression in patients with hormone-refractory prostate cancer . A retrospective chart review of 415 patients with prostate cancer who had baseline bone scans at diagnosis identified 172 who had undergone medical or surgical castration for bone metastases. Hormone-refractory prostate cancer with bone pain developed in 147 patients and was treated with lo­cal radiation therapy (10 patients), strontium-89 46), olpadronate (66), both strontium-89 and ol­padronate (9), and none of these (16). Of the 147 patients, 24 developed spinal cord compression, including 2 (4.3%) who were given strontium-89, 14 (21.2%) who had been treated with olpadronate alone, and 8 (50%) who had received no therapy; none of the patients who received local irradiation developed spinal cord compression.

In summary, to prevent cord compression, spi­nal epidural disease must be diagnosed as early as possible. To minimize morbidity from spinal cord compression, epidural disease must be recognized before there are functional consequences. The prevalence of back pain in people without cancer makes an early diagnosis of spinal epidural disease problematic. Patients with cancer, their families, their primary care physicians, and emergency room physicians may easily mistake the pain of cord compression for that of benign spine disease and may assess and treat the pain using algorithms that do not apply to cancer patients. The oncology team may therefore need to carefully follow pa­tients at high risk for spine disease, such as patients with lung, prostate, kidney, or breast cancer and those with myeloma or lymphoma, and educate them about this potential complication. Patients need to know that back pain may be an early harbinger of malignant disease, whether or not any motor, sensory, or autonomic symptoms or findings are present. Promptly reporting the new onset of back pain will enable the patient’s primary or emer­gency care physician or the oncology team to or­der a timely MRI scan. To date, however, there are no published educational interventions that have been shown to be effective. A screening MRI scan may be considered for the subset of high-risk prostate cancer patients (ie, those with more than 20 bone metastases and those who have been on hormone therapy for several years) who have a 44% incidence of spinal epidural disease and for other high-risk patients (eg, patients with lung, prostate, kidney, or breast cancer; those with myeloma or lymphoma with longstanding known bone metas­tases; or those who have a vertebral fracture evident on a plain x-ray film)

 

COLLABORATIVE MANAGEMENT

Nurses caring for clients with spinal cord compression must recognize the condition early. The nurse assesses the client for neurologic changes consistent with spinal cord compression. The nurse also teaches clients and families to recognize the symptoms of early spinal cord compression and to seek med­ical assistance as soon as symptoms are apparent.

Treatment is largely palliative. High-dose radiation is usu­ally administered to reduce the size of the tumor in the area and relieve compression. Radiation may be given in conjunc­tion with chemotherapy to treat the total disease. Surgery is occasionally performed to remove the tumor from the area and rearrange the bony tissue so less pressure is placed on the spinal cord. External back or neck braces may be prescribed to reduce the weight borne by the spinal column and to reduce pressure on the spinal cord or spinal nerves.

 

 

 

   Case Sade

Mr. K, 68 years old, comes to the oncology clinic for his scheduled appointment. He seems uncomfortable and walks much slower than usual. When asked about the presence of pain, Mr. K states: “The low back pain that I have had on and off for years is acting up again.” He rates his pain as 3 to 4 during the day but 7 to 8 at night, when he is in bed. Mr. K took several doses of oxycodone, but it only took the edge off his pain. Mr. K’s wife says symptoms are trouble getting up from the chair last night, leg weakness and complaints that his legs are cold and his feet are numb, he denies constipation and urinary retention. On assessment he has an unsteady gait, and he is unable to stand without holding on to a stationary object.

He has bilateral leg weakness and some loss of pinprick sensation and cannot feel the vibration of the tuning fork in either leg. Muscle strength and sensory function are normal in the upper extremities. There is some percussion tenderness over his lumbar spine. His mental status is normal, with memory and cognition intact. Emergency MRI shows the vertebrae at L5 to be compressed by a tumor mass.

 

 

 

Sepsis and Disseminated Intravascular Coagulation

 OVERVIEW

Sepsis, or septicemia, is a condition in which microorganisms enter the bloodstream.

 

 

Necrotizing soft tissue infection of the lower abdominal wall causing sepsis. 
Ongoing operative debridement was required for infectious source control.

 

Septic shock is a life-threatening result of sepsis and a common cause of death in clients with cancer. Clients with cancer are at increased risk for infection and sep­sis because their white blood cell counts are often low and their immune function is usually impaired..

Disseminated intravascular coagulation (DIC) is a condition that indicates a problem with the blood-clotting process. DIC is triggered by many severe illnesses, including cancer. In clients with cancer, DIC is caused by sepsis (usually a gram-negative infection), by the release of thrombin or thromboplastin (clot-ting factors) from cancer cells, or by blood transfusions. DIC is most often associated with leukemia and with adenocarcinomas of the lung, pancreas, stomach, and prostate.

Extensive, abnormal clot formation occurs throughout the small blood vessels of clients with DIC. This widespread clot­ting consumes all circulating clotting factors and platelets. This process is followed by extensive bleeding. Bleeding from many sites is the most common problem and ranges from minimal to fatal hemorrhage. The blockage of blood vessels from clots decreases blood flow to major body organs and results in pain, stroke-like signs and symptoms, dyspnea, tachycardia, oliguria (decreased urine output), and bowel necrosis (tissue death).

 

Disseminated intravascular coagulation

 

 

 

 COLLABORATIVE MANAGEMENT

 

DIC is a life-threatening problem and has a mortality rate greater than 70% even when appropriate therapies are insti­tuted. Therefore the best treatment plan for sepsis and DIC is prevention. The nurse identifies those clients at greatest risk for the development of sepsis and DIC. Strict adherence to aseptic technique is practiced during invasive procedures and during the manipulation of nonintact skin and mucous mem­branes in immunocomprornised clients. The nurse teaches clients and family members the early clinical manifestations of infection and sepsis and when to seek medical assistance. When sepsis is present and DIC is likely, treatment focuses on reducing the infection and halting the DIC process. Ap­propriate IV antibiotic therapy is initiated. During the early phase of DIC, anticoagulants (especially heparin) are admin­istered to limit unnecessary clotting and prevent the rapid consumption of circulating clotting factors. Cryoprecipitated clotting factors are administered when DIC has progressed to the later phase and hemorrhage is the primary problem.

 

Metastatic brain tumors

Introduction

The terms metastatic brain tumor, metastasis to the brain, or secondary brain tumor are different names for the same type of brain tumor. A metastatic brain tumor begins as a cancer elsewhere in the body and spreads to the brain. Sometimes this process results in a single tumor. Approximately 10–20% of all brain metastases are single tumors. Sometimes metastasis causes multiple tumors.

Metastatic brain tumors and their symptoms are in part treatable. Longer survival, improved quality of life and stabilization of neurocognitive function for patients with brain metastasis is the goal of treatment, and improvements have been witnessed thanks to treatment advances in the last decade Lung, breast, melanoma (skin cancer), colon and kidney cancers commonly spread to the brain. Breast cancer and kidney cancer often cause single tumors in the brain. Lung, melanoma and colon cancers tend to cause multiple tumors.

A metastatic brain tumor is usually found when a cancer  patient begins to experience neurological symptoms and a brain scan (CT or MRI) is ordered.

Fewer than 10% of all brain metastases are found before the primary cancer is diagnosed. This may  happen when a person has an MRI scan for another medical reason, and the brain tumor is “incidentally” found. Occasionally, the person may have neurological symptoms, undergoes a brain scan and has no history of cancer when the brain tumor is detected.

Increasingly, cancer patients offered new therapies (i.e., clinical trials) are required to undergo brain imaging, part of what is termed radiologic staging, that may incidentally discover brain metastases.

If the site of the primary cancer is not found, this is called an “unknown” primary site.

Frequently, the primary site may have been too tiny to be seen or to cause symptoms. In that situation, the metastatic brain tumor is found first and subsequently the primary site is discovered. Markers found in the blood, the appearance of the tumor on scan, and a tissue sample (if surgery is done) help to focus the search for the primary disease site and to guide treatment.

The metastatic brain tumor usually contains the same type of cancer cells found at the primary site.

For example, small-cell lung cancer metastatic to the brain forms small-cell cancer in the brain. Squamous-cell head and neck cancer forms squamous-cell cancer in the brain.

 

Incidence

As more effective cancer diagnostics and treatments are developed, and as larger numbers of cancer patients live longer, an increasing number of cancer patients are diagnosed with metastatic brain tumors.

 

Metastatic brain Tumors

 

• Metastatic brain tumors are the most common brain tumor in adults.

• The exact incidence of metastatic brain tumors is not known but is estimated between 100,000 and 170,000 people per year. These numbers are based on data reported by individual hospitals, estimates from a few individual city-based statistics and observations from autopsy results. The American Brain Tumor Association is funding research into the incidence and prevalence of these tumors.

Research indicates that approximately 10–20% of metastatic brain tumors arise as a single tumor and 80+% as multiple tumors within the brain.

• About 85% of metastatic lesions are located in the cerebrum (the top, largest component of the brain) and 15% are located in the cerebellum (the bottom, back part of the brain).

The incidence begins to increase in those ages 45–64 years and is highest in people over 65 years of age.

• Although melanoma spreads to the brain more commonly in males than in females, gender does not seem to play a role in the overall incidence of brain metastases.

Central nervous system (CNS) metastasis is not common in children, accounting for only 6% of CNS tumors in children.

Researchers have also found that women with breast cancer appear to be at higher risk of developing a meningioma, a benign type of primary brain tumor, than those who have not had breast cancer.

 

 

 

Cause

Metastatic brain tumors begin when cancer located in another organ of the body spreads to the brain. Cancer cells, visible under a microscope and detectable by a technique called flow cytometry, separate from the primary tumor and enter the circulatory (blood) system.

The immune system attempts to destroy these migrating bloodborne cancer cells.

However, if the number of cancer cells becomes very high, the immune system may become overwhelmed or tolerant of these cells. Scientists believe circulating tumor cells use the bloodstream or lymph system for access to other organs, initially migrate and enter the lungs, then move on to other organs and in particular, the brain.

Some scientists believe cancer cells may break away from the primary cancer site while that cancer is still in its earliest stages. Research shows that these traveling cells (circulating tumor cells) exit the blood or lymphatics and enter another part of the body. In a new organ, the tumor may lie dormant or rapidly enlarge causing new symptoms referable to the new site of metastasis.

The growth of metastatic tumors is often independent of the primary site of cancer from which the tumors originally originated.

In some situations, the process of tumor spread and growth in the metastatic organ occurs rapidly. Since blood from the lungs flows directly to the brain, lung cancer is capable of quickly spreading to the brain. Sometimes, this happens so fast that the brain metastases are found before the primary lung cancer is found.

Scientists also know that primary cancers tend to send cells to particular organs. For example, colon cancer tends to metastasize to the liver and the lung. Breast cancer tends to metastasize to bones, the lungs and the brain. It is believed these organ preferences may be caused by small attractant molecules that direct and guide tumor cells to the metastatic site. In other instances cancer cells may be able to adhere, or stick, only to select organs based upon adherent molecules expressed in a particular organ.

 

Symptoms

The symptoms of a metastatic brain tumor are the same as those of a primary brain tumor, and are related to the location of the tumor within the brain. Each part of the brain controls specific body functions. Symptoms appear when areas of the brain cao longer function properly.

Headache and seizures are the two most common symptoms.

• The causes of headaches include the metastatic tumor itself that causes distortion of surrounding brain, swelling (also called edema) from fluid leakage through tumor blood vessels and compression of the brain due to the growing tumor. Headaches may also be related to bleeding, which can require surgery.

While swelling around the tumor is more common, bleeding from ruptured blood vessels in the tumor occurs in a small percentage of patients. Headaches may also be caused by cystic (water filled cavities) changes in the tumor or by interruption of spinal fluid circulation in brain resulting in a condition called hydrocephalus.

·             A seizure is a brief episode of abnormal electrical activity in the brain caused by a brain tumor, surgery, or hemorrhage that disrupts brain electrical activity.

During normal electrical activity, the nerve cells in the brain communicate with each other through carefully controlled electric signals. During a seizure, abnormal electrical activity occurs, that may stay in a small area or spread to other areas of brain. The result is a partial (or focal) or generalized seizure.

Disturbance in the way one thinks and processes thoughts (cognition) is another common symptom of a metastatic brain tumor. Cognitive challenges might include difficulty with memory (especially short term memory) or personality and behavior changes. Motor problems, such as weakness on one side of the body or an unbalanced walk, can be related to a tumor located in the part of the brain that controls these functions. Metastatic tumors in the spine may cause back pain, weakness or changes in sensation in an arm or leg, or loss of bladder/bowel control. Both cognitive and motor problems may also be caused by edema, or swelling, around the tumor.

 

Diagnosis

A brain scan may be part of the initial screening process when the primary cancer is diagnosed, or a scan may be ordered if a person living with cancer  begins to have symptoms of a brain or spinal cord tumor.

 

 

 

Metastatic tumors are diagnosed using a combination of neurological examination and imaging (also called scanning) techniques. A physician may use more than one type of scan to make a diagnosis. MRI or CT is the most commonly available – the use of contrast dye makes the tumor(s) easier to see. Magnetic resonance spectrometry (MRS) is used to measure chemical content in the brain.

PET (position emission tomography) scans collect detailed information about the way the tumor uses glucose (sugar), and can help differentiate between healthy tissue, cancer cells, dead disease tissue, and swelling. Full body PET scans can be helpful in identifying the primary cancer site when brain metastases are found first. Your physician will determine the type of imaging most appropriate for you.

The images will help your physician learn:

• Size and number of tumors

• Exact location of the tumor(s) within the brain or spine Impact oearby structures Although scans provide the physician with a “probable” diagnosis, examination of a sample of tumor tissue under a microscope confirms the exact pathologic diagnosis.

The tissue sample may be obtained during surgery to remove the tumor, or during a biopsy. A biopsy is a surgical procedure to remove a small amount of tumor for diagnosis.

If a metastatic tumor is diagnosed before the primary cancer site is found, tests to locate the primary site will follow. These tests may include blood tests, a chest X-ray or CT, an abdominal or pelvic CT, a body PET scan, or other tests as needed. The pathology report of tissue collected during surgery can also help the doctor determine possible sites of the primary cancer if testing fails to do so.

If you already have a history of cancer, your doctor will determine the tests that might be helpful.

 

 

An MRI image (left) shows a metastatic brain tumor from lung cancer in the deep right parietal lobe (arrow). A photograph taken during surgery (center) shows the use of a minimally invasive port, only half an inch in diameter, to gain access so that the neurosurgeon can remove the tumor with minimal injury to the overlying normal brain. An MRI image following surgery (right) shows complete removal of the tumor (arrow) and the hardly visible surgical tract (below arrow).

 

 

 

 

Fig. Illustration and MRI of multiple metastatic brain tumorsthat have spread from the melanoma skin cancer on the face.

 

 

 

 

Treatment

 

 

Once your scan shows a suspected brain tumor, your next step will likely be a consultation with a neurosurgeon or radiation oncologist. The neurosurgeon will look at your scans to determine if the tumor(s) can be surgically removed, or if other treatment options would be more reasonable for you.

The three main categories of treatments include surgery, radiation and chemotherapy. More than one type of treatment might be suggested.

When planning your treatment, your doctor will take several factors into consideration.

• Your history of cancer

• The status of that cancer

• Your overall health

• Number and size of metastatic tumors

• Location of the metastatic tumor(s) within the brain or spine

Early treatment of your brain tumor will focus on controlling symptoms, such as swelling of the brain and/or seizures.

• Steroids (most commonly dexamethasone or decadron) are drugs used to reduce the swelling that can occur around a brain tumor. Reducing the swelling in the brain can reduce the raised brain pressure, and thus temporarily reduce the symptoms of a metastatic brain tumor.

• Antiepileptic (anti-seizure) drugs such as levetiracetam or phenytoin are commonly used to control seizures.

Research shows that the number of metastases is not the sole predictor of how well you might do following treatment. Your neurological function (how you are affected by your brain metastases) and the status of the primary cancer site (i.e. the presence/absence of metastases in other parts of the body) appear to have more influence over survival than the number of brain metastases.

Treatment decisions will take into account not only long term survival possibilities, but your quality of life during and after treatment, as well as cognition concerns.

 

SINGLE OR LIMITED BRAIN METASTASES

 

If you have a limited number of metastatic brain tumors (generally one to three tumors, or a small number of tumors that are close to each other) and if the primary cancer is treatable and under control, your treatment plan may include surgery to confirm the diagnosis and remove the tumor, followed by a form of radiation therapy.

That radiation may be whole-brain radiation therapy, whole-brain radiation plus stereotactic radiosurgery or stereotactic radiosurgery alone.

If you have a limited number of metastatic brain tumors and your primary cancer is not well controlled, your treatment plan will likely be whole-brain radiation and possibly chemotherapy.

 

MULTIPLE BRAIN METASTASES

 

If you have multiple brain metastases – four or more rain tumors – and have a known history of cancer, whole-brain radiation therapy may be suggested. If there is a question about the scan results or the diagnosis, a biopsy or surgery to remove the brain tumors may be done. This will allow your physicians to confirm that the brain tumors are related to your cancer. If the tumors prove to be metastatic from your primary cancer, your treatment plan will likely be whole-brain radiation.

If you do not have a history of cancer, your physicians will order tests to try to determine the primary site. If no other cancer site is found, surgery to obtain a tissue sample may be performed. Surgery would likely be followed by whole-brain radiation.

 

In general, the primary treatment for multiple metastatic brain tumors (or multiple tumors that are not close to each other) is whole-brain radiation. The goal of this therapy is to treat the tumors seen on scan plus those that are too small to be visible. As a result, whole-brain radiation may be both preventive and therapeutic.

There is increasing interest in the role of chemotherapy for metastatic brain tumors though at present results of chemotherapy are inferior to radiation therapy with or without surgery. A neuro-oncologist or a medical oncologist specializing in the treatment of brain tumors can help determine of this additional therapy would be of help to you.

 

SPINAL METASTASES

 

Metastases to the spine are most often caused by lymphoma, breast, lung or prostate cancers. These metastatic tumors usually involve the bones of the spine – the vertebrae – and then spread and encroach upon the spinal cord. Radiation therapy alone, or surgery plus radiation, may be used to treat metastatic tumors to the spine.

 

MENINGEAL METASTASES

Spread of cancer cells to the meninges, the covering of the brain and spine, and the cerebrospinal fluid (CSF) within which the brain and spine float, is called leptomeningeal metastases (also called carcinomatous meningitis, neoplastic meningitis, leukemic meningitis or lymphomatous meningitis). This type of metastases occurs most commonly with lymphoma, leukemia, melanoma, and breast or lung cancers, and may be treated with radiation therapy or radiation therapy and a regional form of chemotherapy wherein chemotherapy is administered into the water or CSF compartment of the brain (so called intra-CSF chemotherapy).

Intra-CSF chemotherapy is administered into the CSF, which is found between the layers of the brain covering, the so called meninges.

Intra-CSF chemotherapy may be given by means of a spinal tap or lumbar puncture (intrathecal chemotherapy) or by using a reservoir and catheter (for example an Ommaya device) that is surgically implanted (intraventricular chemotherapy).

The purpose of these devices is to place the chemotherapy drug into the spinal fluid allowing it to “bathe” the cancer cells.

Your doctor will decide which treatment plan is best for you based your primary cancer, the amount of cancer cells present in the spinal fluid, your neurological symptoms and your general medical health.

 

SURGERY

 

One of the first treatments considered for metastatic brain tumors is tumor removal, or resection. A neurosurgeon – a surgeon specially trained to operate on the brain and spine – will determine if your tumors can be surgically removed by evaluating your health and disease status.

• Factors supporting surgery include a single tumor larger than 3 cm (the size of a small pearl), location outside of speech or motor related areas of the brain, and limited and/or somewhat stable disease in other parts of the body. Symptomatic tumors are more likely to be surgically removed.

• Reasons surgery may not be suggested include a tumor that might better respond to radiation, multiple tumors – especially if they are far apart from each other – and tumors in brain locations where specific function resides, for example, language areas.

If surgery is not possible or the primary cancer has not been found, a biopsy may still be done to confirm the tumor type. Once the diagnosis is confirmed, radiation and or chemotherapy (depending on the type of cancer) may be part of the treatment plan.

 

 

RADIATION

Radiation therapy can be used to treat single or multiple brain metastases. It may be used therapeutically (to treat a metastatic brain tumor), prophylactically (to help prevent brain metastases in people newly diagnosed with small-cell lung cancer or acute lymphoblastic leukemia), or most commonly as palliative (non-curative) treatment (to help relieve symptoms caused by the metastatic brain tumor).

Some types of cancer are more responsive to radiation than others. Small-cell lung tumor and germ-cell tumors are highly sensitive to radiation, other types of lung cancer and breast cancers are moderately sensitive, and melanoma and renal-cell carcinoma are less sensitive.

Different types of radiation can be used for metastatic brain tumors.

 

Whole-Brain Radiation

 

Whole-brain radiation is a common form of radiation for metastatic brain tumors, especially when multiple tumors are present, and has been used for several decades. It is delivered in 10 or more reduced doses called “fractions.” By dividing the doses in smaller amounts, the normal brain is somewhat protected from the toxic effects of radiation. An important and common concern about whole-brain radiation is its possible impact on cognition and thinking. Research focused in this area is ongoing, and studies indicate that the presence of the brain tumor may cause thinking changes before treatments even begin. However, researchers continue to explore new ways of delivering radiation, as well as the impact of whole-brain radiation therapy on  cognition.

 

Radiosurgery

 

Recent advances have made stereotactic radiosurgery, also known as LINAC radiosurgery, Gamma Knife or CyberKnife (different machines using a similar method), an effective treatment option for some patients with brain metastases. Radiosurgery focuses high doses of radiation beams more closely to the tumor than conventional external beam radiation in an attempt to avoid and protect normal surrounding brain tissue. This approach is most commonly used in situations where the tumor is  small and in eloquent regions of the brain, for example, speech and motor localized areas.

Small tumors are generally considered to be 3 cm or less in diameter and limited iumber. Radiosurgery can also be used to treat tumors that are not accessible with surgery, such as those deep within the brain. It may also be used for recurrences if whole-brain radiation was previously given, or as a local “boost” following whole-brain radiation.

There are many different pieces of equipment used to deliver radiosurgery; each has a brand name created by their manufacturer.

 

Brachytherapy

 

Interstitial radiation, or brachytherapy, is the use of radioactive materials surgically implanted into the tumor to provide local radiation. This technique is rarely utilized today for brain metastases.

 

Radioenhancers

 

Radioenhancers or so called radiation sensitizers are compounds which make the tumor more sensitive to the effects of radiation, are under investigation.

Sometimes, the addition of chemotherapy prior to, or during, radiation treatment can also have this effect.

 

CHEMOTHERAPY

 

Historically, chemotherapy has not often been used to treat metastatic brain tumors due to the blood-brain barrier and drug resistance. However, new research indicates that it may be an effective treatment modality for some patients.

The decision to use chemotherapy depends on the status of systemic disease, primary site, tumor size and number in the brain, available drugs, and previous history of chemotherapy treatment, if any.

• Recent studies show that some tumors may be sensitive to drug therapy. Small-cell lung cancer, breast cancer, germ cell tumors and lymphoma are among these tumors. Some new targeted agents for metastatic breast cancer (lapatinib in combination with capecitabine) and melanoma (ipilimumab) may prove useful for brain metastases from these particular cancers.

• Intra-CSF chemotherapy (drugs placed within the brain/spine water compartment) may be used for leptomeningeal metastases – cancer cells that metastasize to the covering layers of the brain and spinal cord.

Chemotherapy may be combined with other therapies such as radiation. Some tumors that are sensitive to chemotherapy in other parts of the body may become resistant to the chemotherapy once in the brain. The cause for this resistance is unknown. A different drug may be considered if you received chemotherapy for your primary cancer, or a different type of therapy may be considered.

 

 

Fig. Pre- and Post-operative images of patient with metastatic brain tumor

 

 

 

 

INTEGRATIVE HEALTH CARE

 

 

Integrative health care brings the physical, mental, emotional and spiritual components of health into the treatment plan, and beyond. Integrative therapies support the health and healing of the whole person. Treatment and supportive areas may include diet, exercise, stress reduction, lifestyle enhancements, massage, acupuncture, herbs, mind-body therapies and spiritual growth, among others. Many major cancer centers now offer some components of integrative health care. Talk with your healthcare team if you would like to learn more about these complementary approaches.