Oncologic Emergencies

Table of Contents
1 Introduction
2 Spinal Cord Compression
3 Brain Metastases
4 Superior Vena Cava Syndrome
5 Febrile Neutropenia
6 Tumor Lysis Syndrome
7 Leukostasis
8 Hypercalcemia of Malignancy
9 Thrombosis of Malignancy


     Complications of cancer may be related to the primary malignancy or to its treatment and commonly arise from mechanical compression (e.g. superior vena cava syndrome), metabolic issues (e.g. tumor lysis syndrome), hematological factors (e.g. thrombosis), or infectious pathogens (e.g. febrile neutropenia). These complications may be the initial manifestation of an underlying malignancy or can occur during the course of treatment. The approach to the evaluation and management of an oncologic complication must be personalized and take into account the patient’s general condition, type and stage of cancer, available treatment options, and the patient’s and family’s personal values and preferences. This section will review the etiology, clinical presentation, diagnostic evaluation, and management of several common cancer complications and emergencies.

Spinal Cord Compression

    Spinal cord compression is a neurological emergency caused by neoplastic invasion of the epidural space resulting in bone destruction, vascular compromise, and mechanical compression of the spinal cord. Timely diagnostic evaluation and prompt initiation of treatment are essential to improving a patient’s chance of neurological recovery. Approximately 5% of patients with cancer develop spinal cord compression, most commonly from breast cancer, prostate cancer, lung cancer, non-Hodgkin’s lymphoma, renal cell carcinoma, or multiple myeloma. Patients often first develop localized back pain which may be worse at night and when lying supine. Symptoms can progress over days to weeks to include symmetric leg weakness, urinary retention, and/or sensory deficits below the affected spinal level. Careful neurological examination may reveal upper motor neuron signs including hypertonia, hyper-reflexia, and positive Babinski reflexes. Although most cases of spinal cord compression affect the thoracic (60%) or cervical (15%) spine, approximately 25% of patients have lumbar spine involvement and may develop features of cauda equina syndrome such as lower back pain, asymmetric flaccid leg weakness, saddle anesthesia, urinary retention, or decreased anal tone.

    Patients with neurological compromise from suspected spinal cord compression should undergo emergent magnetic resonance imaging (MRI) of the entire spine, as up to one-third of patients have multiple sites of metastatic disease. Dexamethasone 10mg IV should be immediately administered followed by 4mg every 6 hours to relieve back pain and reduce vasogenic edema within the spinal cord. Emergent neurosurgical decompression and stabilization is indicated for patients with significant neurological deficits or an unstable spine, which may be suggested by the presence of back pain with movement, lytic bone lesions, vertebral body collapse, or certain high-risk imaging findings. The Spinal Instability Neoplastic Score (SINS) has been developed to identify patients with unstable spines requiring emergency neurosurgical stabilization. Furthermore, a randomized controlled trial demonstrated that surgery followed by radiation therapy produces better neurological outcomes than radiation alone. External beam radiation therapy is therefore usually administered after neurosurgery but can be considered as the sole treatment of spinal cord compression in patients with a stable spine and minimal neurological deficits or highly-radiosensitive tumors (e.g. lymphoma, multiple myeloma, germ cell tumors). Emergent chemotherapy may also provide rapid relief of spinal cord compression in patients with hematological malignancies. As stated before, in all cases of spinal cord compression, timely diagnostic evaluation and initiation of treatment are essential to improving a patient’s chance of neurological recovery.

Table 1: The Spine Instability Neoplastic Score where a score between 0 and 6 indicates stability, a score between 7 and 12 indicates indefinite stability, and a score between 13 and 18 indicates instability. From Teixeira et al, Clinics 2013;68(2):213-218.

References and recommended reading:

Brain Metastases

    Approximately 10% to 30% of patients with cancer eventually develop brain metastases, most commonly due to the hematogenous spread of lung cancer, melanoma, renal cell carcinoma, breast cancer, or colorectal cancer. The clinical presentation of brain metastases is often insidious but may include seizures, focal neurological deficits (e.g. ataxia, vision defects, contralateral weakness), or symptoms of increased intracranial pressure (e.g. papilledema, headaches, vomiting). Patients with multifocal metastatic infiltration of the leptomeninges (i.e. leptomeningeal carcinomatosis) may present with cranial nerve palsies, altered mental status, or hydrocephalus from obstructed cerebrospinal fluid (CSF) outflow.

Image 1: CT of the head with IV contrast demonstrating a left brain solid tumor metastasis with surrounding vasogenic edema. Source: www.radiopaedia.org.

    Oncology patients with new neurological symptoms or behaviour changes should undergo MRI of the head with gadolinium due to its superior sensitivity in detecting brain metastases compared to CT with intravenous contrast. Lumbar puncture may reveal elevated CSF protein, mild lymphocytosis, and abnormal cytology in patients with leptomeningeal disease. However, this procedure should be avoided in those with large brain tumors or increased intracranial pressure due to the risk of cerebral herniation. A diagnostic biopsy of the brain lesion may be necessary in patients with ambiguous imaging findings or if there is no evidence of a primary malignancy on CT scans of the chest, abdomen, and pelvis.

    Symptomatic therapy with dexamethasone 10mg IV followed by 4mg every 6 hours is indicated to relieve cerebral vasogenic edema in patients with significant symptoms or mass effect on neuroimaging. Anti-epileptic drugs are not recommended as primary prevention but should be initiated after the first seizure in patients with brain tumors; non-CYP450 inducing medications (e.g. levetiracetam, topiramate, lamotrigine) are preferred to avoid pharmacological interactions with chemotherapy.

    Definitive treatment of brain metastases may involve surgery, radiation, and/or chemotherapy depending on the number of metastases as well as the patient’s underlying disease and performance status.

    Patients with a single large brain metastasis may achieve better neurological outcomes and prolonged survival with surgical resection. Whole brain radiation therapy or stereotactic radiosurgery (i.e. a high dose of precisely-targeted radiation to the tumor bed) is administered post-operatively to prevent recurrence. Patients with an isolated surgically inaccessible tumor or with a limited number of small tumors may be candidates for treatment with stereotactic radiosurgery alone. Those with multiple large brain metastases or a poor performance status may undergo palliative whole brain radiation therapy. However, the toxicities of whole brain radiation include alopecia, fatigue, and cognitive impairment which may negatively impact a patient’s quality of life. Systemic chemotherapy is rarely used to treat brain metastases due to chemoresistance and poor blood-brain barrier penetration, although it may be curative in cases of CNS lymphoma or metastatic germ cell tumors. There is also growing interest in the role of immunotherapy in melanoma and targeted tyrosine kinase inhibitors in EGFR- or ALK-positive non-small cell lung cancer (NSCLC) with brain metastases.

    Following treatment, patients should be closely monitored with repeat MRI of the brain every few months due to the 50% risk of recurrence of brain metastases within 1 year. The overall prognosis of patients with brain metastases is poor, with median survival ranging from 1 to 2 months if untreated and up to 3 to 6 months with radiation therapy.

References and recommended reading:

Superior Vena Cava Syndrome

    Superior vena cava (SVC) syndrome usually arises from external compression of the SVC by a malignant mass, particularly lung cancer (75% of cases) or non-Hodgkin’s lymphoma (10% of cases). Other less common neoplastic causes of SVC syndrome include thymoma, germ cell tumors, mesothelioma or other solid tumors with mediastinal metastases. Obstruction of the SVC leads to the formation of venous collaterals, increased venous pressure, and interstitial edema in the head and upper extremities. This results in face or arm swelling, subcutaneous venous distension, and facial plethora or cyanosis. Increased facial edema and plethora can be elicited by raising the arms above the head, a finding known as Pemberton’s sign. Severe cases of SVC syndrome can produce dyspnea or stridor from laryngeal edema, headache or altered mental status from cerebral edema, and syncope or hemodynamic instability from decreased venous return to the heart.

Image 2: MRI of the thorax demonstrating a right upper lobe lung cancer compressing the superior vena cava.

    Patients with suspected SVC syndrome should undergo diagnostic CT scan of the chest with intravenous contrast to confirm the presence of SVC obstruction and identify the underlying mass. Doppler ultrasonography should be performed to exclude deep vein thrombosis of the neck and arm veins secondary to venous stasis.

    Superior vena cava syndrome is considered an oncologic emergency; however, urgent pathologic diagnosis of the underlying malignancy is crucial to direct the appropriate treatment. Pathologic diagnosis may be safely achieved with peripheral lymph node biopsy, sputum cytology, CT-guided transthoracic needle biopsy, bronchoscopy with trans-bronchial biopsy, endobronchial ultrasound (EBUS), or surgical mediastinoscopy. Tumor markers such as ß-hcg and alpha-fetoprotein are useful in identifying patients with germ cell tumors.

    Superior vena cava syndrome is considered a medical emergency if there is life-threatening airway compromise or significant altered mental status from cerebral edema. Such patients should undergo emergency intravascular stent placement followed by anticoagulation, radiation therapy, and/or corticosteroids to relieve the SVC obstruction. However, most patients with gradual onset of disease and mild-to-moderate symptoms do not require emergent treatment. Symptomatic improvement can occur with supportive measures such as diuretics, dexamethasone, and raising the head of the bed. Chemotherapy alone typically relieves SVC obstruction within 1 to 2 weeks in chemosensitive malignancies such as small cell lung cancer, non-Hodgkin’s lymphoma, and germ cell tumors. Furthermore, radiation therapy produces symptomatic relief within several days for radiosensitive tumors including small cell lung cancer, lymphoma, germ cell tumor, and breast cancer. Patients with lymphoma may also demonstrate a rapid response to corticosteroids. Intravascular stent placement with anticoagulation may be considered for patients with radiation-resistant disease or for malignancies which respond less quickly to chemotherapy such as non-small cell lung cancer or mesothelioma. Finally, surgical jugular-femoral vein bypass grafting may be considered in patients with thymoma due to the poor response to chemoradiation. Regardless of the chosen modality, most patients with SVC syndrome experience symptomatic improvement with treatment of the underlying malignancy.

References and recommended reading:

Febrile Neutropenia

    Febrile neutropenia is a medical emergency with a 10% mortality rate. It is defined as the presence of fever in conjunction with an absolute neutrophil count (ANC) <500/microL or an expected ANC nadir <500/microL within 48 hours. Potentially life-threatening infection can arise from chemotherapy-induced immunosuppression and breakdowns in the skin or gastrointestinal mucosa resulting in seeding of the bloodstream with native flora. The majority of bloodstream infections are caused by gram positive cocci, although a pathogen is isolated in only 20-30% of cases. Consideration should also be given to gram negative bacilli (e.g. Pseudomonas, Enterobacteriaceae), fungi (e.g. candida, aspergillus, mucormycosis), and viruses (e.g. herpes simplex, herpes zoster, cytomegalovirus). Patients often present with subtle signs or symptoms of infection due to the impaired immune response of neutropenia.

    All patients should undergo a thorough history to seek out localizing symptoms of infection as well as a detailed physical examination with particular attention to infection-prone areas including intravenous catheter sites and the oropharynx, gingiva, lungs, abdomen, skin, genital, and perirectal areas (note that digital rectal examination is contraindicated). Initial laboratory investigations should include a complete blood count (CBC) with differential, serum electrolytes and creatinine, liver enzymes, chest x-ray, and blood cultures from all ports of any central venous catheters as well as a peripheral site. Further investigations should be tailored to localizing symptoms or signs of infection, including sputum cultures, viral nasopharyngeal swab, Legionella urinary antigen, bronchoscopy with broncho-alveolar lavage, serum galactomannan or beta-D-glucan, stool cultures and C. difficile testing, skin biopsy, lumbar puncture with CSF analysis, and CT imaging of the chest or abdomen if clinically indicated.

    Patients are at high risk of serious complications of febrile neutropenia if the anticipated duration of neutropenia is more than 7 days or if there is clinical instability, evidence of serious infection, or significant medical comorbidities. Patients at low risk of complications are typically outpatients undergoing chemotherapy for solid tumors with good performance status, no medical comorbidities, normal renal and hepatic function, and an anticipated duration of neutropenia less than 7 days. All patients experiencing febrile neutropenia should be admitted to hospital for intravenous antibiotics, granulocyte-colony stimulating factors (G-CSF), and monitoring. However, there are trials assessing the outcomes of giving oral antibiotic therapy and outpatient treatment after a brief period of observation in the emergency department for low risk patients. The Multinational Association for Supportive Care in Cancer (MASCC) has developed a Risk Index Calculator to guide the risk stratification and disposition of patients with febrile neutropenia.

    Management of febrile neutropenia requires initial resuscitation with intravenous fluids and the early administration of broad-spectrum antibiotics. Patients with evidence of sepsis or septic shock may require critical care support. International guidelines recommend initial antibiotic therapy with piperacillin-tazobactam, cefepime, or an anti-pseudomonal carbapenem (e.g. meropenem). Intravenous vancomycin should be added for extended gram-positive coverage in patients with hemodynamic instability, suspected catheter infection, skin or soft tissue infection, pneumonia, or known colonization with methicillin-resistant staphylococcus aureus (MRSA). Low risk patients may instead be treated with an oral empiric regimen of amoxicillin-clavulanic acid and an anti-pseudomonal fluoroquinolone (e.g. ciprofloxacin or levofloxacin). Patients with ongoing neutropenia who fail to defervesce after 4-7 days of antibiotics should undergo investigations for invasive fungal infection with serum galactomannan and beta-D-glucan testing along with CT of the sinuses and thorax, with consideration of empiric antifungal therapy with an echinocandin (e.g. caspofungin), voriconazole, or lipid formulation of amphotericin B. Antibiotics are typically continued until the patient is hemodynamically stable and afebrile for >48 hours with a rising ANC >500/microL. G-CSF are generally not recommended by clinical guidelines for the treatment of established febrile neutropenia due to their lack of mortality benefit. However, many oncologists advocate for their use in order to reduce the duration of neutropenia and length of hospitalization.

    Clinical guidelines do recommend the administration of G-CSF (e.g. filgastrim or pegfilgastrim) as primary prevention in patients with >20% risk of febrile neutropenia or as secondary prevention for patients with a history of febrile neutropenia due to the 50% risk of recurrence during subsequent chemotherapy cycles. G-CSF is not typically recommended for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) due to the lack of clinical benefit and potential long-term safety concerns regarding the effect of myeloid growth factors on these disorders. Selected patients at high risk of febrile neutropenia may also benefit from prophylactic oral levofloxacin and antifungal and pneumocystis jirovecii prophylaxis in accordance with local institutional policies. Appropriate antiviral prophylaxis should also be prescribed to selected patients with serology indicating previous exposure to herpes simplex, herpes zoster, or hepatitis B viruses. These preventive measures may reduce the risk of febrile neutropenia and serious infection in patients undergoing chemotherapy.

References and recommended reading:

Tumor Lysis Syndrome

    Patients undergoing cytotoxic chemotherapy for highly-proliferative or bulky malignancies are at risk for life-threatening metabolic abnormalities caused by tumor lysis syndrome (TLS). This occurs when lysed tumor cells release large quantities of lactate dehydrogenase (LDH), uric acid, potassium, and phosphate into the circulation. Oliguric acute kidney injury can arise from uric acid nephropathy. Renal dysfunction is further threatened by excess serum phosphate binding to calcium and resulting in hypocalcemia and calcium-phosphate deposition within the renal tubules. Other clinical manifestations of TLS include neuromuscular irritability (e.g. tetany, paresthesias), seizures, cardiac arrhythmias, hypotension, system inflammatory response syndrome (SIRS), multi-organ failure, and sudden death caused by profound electrolyte derangements and massive cytokine release.

    Tumor lysis syndrome most commonly affects patients with high-grade lymphomas (e.g. Burkitt lymphoma or diffuse large B cell lymphoma with LDH >2 times the upper limit of normal) or acute leukemias (e.g. acute lymphoblastic or myeloid leukemia with WBC >100,000/microL). Tumor lysis typically arises soon after the initiation of intensive chemotherapy, particularly in those with dehydration or pre-existing renal dysfunction. However, TLS can also develop in untreated patients from spontaneous necrosis of highly-proliferative neoplasms. Most patients with solid tumors, multiple myeloma, chronic myeloid leukemia (CML), indolent non-Hodgkin’s lymphoma, and Hodgkin’s lymphoma are at low risk for TLS, although there are increasing reports of TLS occurring in low risk malignancies treated with novel targeted therapies.

Image 3: Metabolism of uric acid with site of action of allopurinol and rasburicase. From Goldman et al., Blood 2001;97:2998-3003.

    Prevention of TLS involves frequent electrolyte and cardiac monitoring, aggressive intravenous hydration, and, in patients at intermediate-to-high risk, urate-lowering therapies such as allopurinol or rasburicase. Nephrotoxic agents such as non-steroidal anti-inflammatory drugs (NSAIDs) and intravenous contrast should be avoided in all patients. Intravenous fluids should be titrated to maintain a urine output >2mL/kg/hour to improve renal perfusion and minimize precipitation of uric acid and calcium-phosphate crystals. Intravenous furosemide may also be considered for patients with inadequate urine output or volume overload. Urinary alkalization with intravenous sodium bicarbonate may increase the urinary solubility of uric acid, but this practice is generally discouraged due to the lack of supportive evidence and risk of increased calcium-phosphate deposition from metabolic alkalosis. Additionally, patients with normal uric acid levels at intermediate risk of TLS should receive the xanthine oxidase inhibitor allopurinol to inhibit production of uric acid. Allopurinol is typically initiated 1 to 2 days before chemotherapy but is less effective in patients with pre-existing hyperuricemia or high risk of TLS. These patients should instead receive intravenous rasburicase, a recombinant urate oxidase enzyme that converts existing uric acid into the inactive metabolite allantoin. Rasburicase is highly effective at lowering uric acid levels and preventing urate nephropathy when given in daily doses of 0.2mg/kg until normal uric acid levels are achieved. Note that rasburicase is contraindicated in patients with G6PD deficiency due to the risk of methemoglobinemia and hemolytic anemia.

Table 2: Overview of the prevention of tumor lysis syndrome. From Cairo et al, 2010.

    Despite preventive measures, TLS occurs in up to 5% of patients and is defined as the presence of at least 2 of the following metabolic abnormalities 3 days before or 7 days following the initiation of chemotherapy: hyperuricemia (uric acid =476µmol/L), hyperkalemia (potassium =6mmol/L), hyperphosphatemia (phosphate =1.45mmol/L), or hypocalcemia (calcium =1.75mmol/L). Treatment of established TLS relies on the same principles as prevention, with frequent monitoring and administration of intravenous fluids, furosemide, and rasburicase until resolution of metabolic abnormalities is achieved. Hyperkalemia can be managed with insulin, salbutamol, diuretics, and stool resins. Exogenous calcium replacement should be avoided unless patients develop severe hyperkalemia or symptomatic hypocalcemia as it may worsen calcium-phosphate precipitation. Phosphate binders (e.g. sevelamer) may be helpful in conjunction with a diet low in potassium and phosphate. Renal replacement therapy with hemodialysis should be initiated for patients with severe renal failure, refractory electrolyte abnormalities, or persistent volume overload who do not respond to medical management.

References and recommended reading:


    Leukostasis is a medical emergency caused by extreme elevations in white blood cell (WBC) count greater than 50,000 to 100,000/microL. It most commonly occurs in acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL), but is also occasionally seen in chronic lymphocytic leukemia (CLL) or the blast crisis phase of chronic myeloid leukemia (CML). The excess number of blasts causes microvascular occlusion and tissue hypoxia, particularly in the lungs and central nervous system. Patients commonly develop dyspnea and hypoxemia from pulmonary infiltrates as well as neurological symptoms such as headache, visual disturbances, and altered mental status. Other life-threatening complications of leukostasis include end-organ ischemia, tumor lysis syndrome, disseminated intravascular coagulation (DIC), and intracranial hemorrhage.

    Leukostasis is a clinical diagnosis which requires immediate treatment given the 40% mortality rate within 1 week. Cytotoxic chemotherapy should be initiated immediately to reduce circulating blast cells and target the underlying malignancy. In the event of a delay to initiation of chemotherapy, cytoreduction may be accomplished with oral hydroxyurea which effectively reduces WBC count within 1 to 2 days. Alternatively, leukopharesis can be performed in several hour sessions via a central venous catheter to mechanically remove blast cells from the circulation. However, this procedure is prone to complications and has only a transient effect on leukocytosis. Supportive measures should be instituted for all patients including intravenous fluids, TLS prophylaxis, and correction of coagulopathy. Packed red blood cell (PRBC) transfusions and diuretics should be used cautiously as they may worsen serum hyperviscosity.

References and recommended reading:

Hypercalcemia of Malignancy

    Hypercalcemia occurs in 20-30% of patients with cancer and carries an extremely poor prognosis with a median survival of approximately 1 month. Over 80% of cases of malignant hypercalcemia are caused by excess bone resorption due to secretion of parathyroid hormone-related peptide (PTHrP) by squamous cell carcinomas, breast cancer, ovarian cancer, or renal cell carcinoma. Approximately 20% of cases are caused by bone destruction from solid tumor metastases or osteoclast-activating cytokines released by multiple myeloma. Hypercalcemia can also rarely arise from ectopic 1,25-(OH)2-Vitamin D production by lymphomas. Regardless of the etiology, hypercalcemia can lead to altered mental status, abdominal pain, nausea and vomiting, polyuria, profound volume depletion, and acute kidney injury.

    The diagnosis of hypercalcemia of malignancy should be confirmed with elevated serum total and ionized calcium in conjunction with a suppressed parathyroid hormone (PTH) level. Laboratory assays such as PTHrP, 1,25-(OH)2-Vitamin D, and serum and urine protein electrophoresis can help elucidate the mechanism of hypercalcemia. A bone scan or skeletal survey may reveal sites of bone involvement in solid tumors and multiple myeloma, respectively.

Image 4: Hypercalcemia can arise from lytic bone lesions as seen with this ‘moth-eaten’ appearance of the skull in a patient with multiple myeloma.

    Treatment of symptomatic or severe (>3.0-3.5mmol/L) hypercalcemia requires aggressive intravenous volume resuscitation (e.g. normal saline 200-500mL/hour IV) to restore renal perfusion and promote urinary calcium excretion. Intravenous bisphosphonates should also be administered to inhibit osteoclast activity. Either zoledronic acid 4mg IV over 15 minutes or pamidronate 60-90mg IV over 2 hours can be given with an expected onset of action within 1-3 days and a peak effect on calcium levels within 4-7 days. Bisphosphonates should be avoided or used cautiously in patients with severe or pre-existing renal impairment due to the risk of nephrotoxicity; the RANKL inhibitor denosumab may be considered in such cases instead. Patients with lymphoma and ectopic 1,25-(OH)2-Vitamin D production often respond well to corticosteroids. Finally, hemodialysis remains an effective option for patients with refractory severe hypercalcemia, profound renal impairment, or volume overload preventing the administration of intravenous fluids.

References and recommended reading:

Thrombosis of Malignancy

    Venous thromboembolism (VTE) affects 10-50% of patients with cancer and is the second most common cause of death in this population. The hypercoagulable state of malignancy is linked in part to increased tissue factor expression, vascular endothelial injury, and venous stasis induced by immobility. Malignancies at highest risk of VTE are primary brain tumors, hematological malignancies, and adenocarcinomas of the pancreas, stomach, lung, uterus, and ovary. Other risk factors for thrombosis in oncology patients include older age, poor performance status, advanced stage of malignancy, surgery, infection, hospitalization, cytotoxic chemotherapy, antiangiogenic agents (e.g. bevacizumab, thalidomide, lenalidomide), hormonal therapies (e.g. tamoxifen), erythropoietin, and central venous catheters.

Image 5: Causes of death in patients receiving chemotherapy. Adapted from Khorana et al., J Thromb Haemost 2007;5(3):632-4.

    Patients and clinicians should be vigilant for signs and symptoms of deep vein thrombosis (DVT) and pulmonary embolism (PE), which may include calf tenderness, lower extremity edema, dyspnea, tachypnea, hemoptysis, and pleuritic chest discomfort. Venous thromboembolism can also result in serious complications such as hypoxemia, chronic thromboembolic pulmonary hypertension, hemodynamic instability, or sudden cardiac arrest. Although uncommon, arterial thromboembolism can cause stroke or other end-organ infarction and may occur in cancer patients with thrombotic endocarditis or paradoxical embolism from DVT and a patent foramen ovale. Diagnosis of VTE is typically accomplished via CT pulmonary angiogram, ventilation-perfusion (VQ) scan, or Doppler ultrasonography of the lower extremities.

    Initial treatment of VTE focuses on acute resuscitative measures to address and protect the patient’s airway, breathing, and circulation and may require the administration of thrombolytics for patients with ongoing hemodynamic compromise secondary to pulmonary embolism. Once the patient has been clinically stabilized, the cornerstone of ongoing treatment for cancer patients with VTE is low molecular weight heparin (LMWH). The CLOT trial demonstrated the superiority of LMWH over the oral vitamin K antagonist warfarin in preventing recurrent VTE in patients with cancer. The duration of therapeutic anticoagulation is generally at least 6 months, and long-term anticoagulation may be considered for patients with ongoing active cancer or other risk factors due to the 10-20% annual risk of recurrence. Patients with renal dysfunction (i.e. creatinine clearance <30 mL/min) should only receive LMWH with close monitoring of anti-Xa activity; these patients may also be candidates for treatment with unfractionated heparin (UFH) followed by a vitamin K antagonist (e.g. warfarin) instead of LMWH. Furthermore, anticoagulation should be used with caution in patients with brain metastases from melanoma, choriocarcinoma, thyroid cancer, and renal cell carcinoma due to the increased risk of intracerebral hemorrhage. Inferior vena cava (IVC) filters may be considered for patients with established VTE for whom anticoagulation is contraindicated.

    Prevention of VTE with LMWH or UFH is recommended for most cancer patients undergoing surgery or hospitalization for an acute medical illness. In contrast, the role for thromboprophylaxis in outpatients with cancer remains uncertain.

    The SAVE-ONCO and PROTECHT trials demonstrated that LMWH reduces the incidence of VTE without increasing the risk of major bleeding when used as primary prevention amongst ambulatory outpatients with advanced cancer. However, clinical guidelines do not recommend thromboprophylaxis for most outpatients with cancer due to the relatively modest benefit seen in these clinical trials. Nevertheless, thromboprophylaxis is indicated for patients with multiple myeloma treated with thalidomide or lenalidomide, and can be considered on a case-by-case basis for other high-risk outpatients. The Khorana risk assessment score is recommended by the National Comprehensive Cancer Network (NCCN) to help risk stratify patients and guide decision-making around thromboprophylaxis in malignancy.

Table 3: A Khorana risk assessment score =3 can identify outpatients at high risk of venous thromboembolism. Adapted from Khorana AA, et al. Blood 2008;111:4902-4907.

References and recommended reading:

Written by Robert Puckrin. Reviewed by Dr. Rashida Haq.

This page was last modified: November 20, 2017.

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