Family physicians must be able to recognize any oncologic emergencies that patients present with in their offices, on hospital wards, or in emergency departments (Box 1).1 This article reviews the presentation and management of 3 common oncologic emergencies: malignant spinal cord compression (SCC), superior vena cava obstruction (SVCO), and febrile neutropenia.
Common oncologic emergencies
Spinal cord compression
Superior vena cava obstruction
Febrile neutropenia
Pericardial effusion
Tumour lysis syndrome
Hyperviscosity syndrome
Hypercalcemia
Syndrome of inappropriate antidiuretic hormone secretion
Immunotherapy-related complications
Data from Higdon et al.1
Malignant SCC
Spinal cord compression occurs when malignant cells within the vertebrae or epidural space compress the thecal sac, leading to venous congestion within the epidural vasculature and vasogenic edema. Spinal cord infarction and irreversible neurologic damage can occur if the compression is not alleviated promptly (Figure 1).2,3 Spinal cord compression is most commonly seen with prostate, breast, and lung cancers,4 although non-Hodgkin lymphoma, renal cell carcinoma, and multiple myeloma are also causative. All levels of the spine can be affected, but the most frequent site of cord compression is the thoracic spine.5 Any complaint of worsening back pain in a patient with a history of malignancy should prompt providers to include SCC in their differential diagnosis.
Acute spinal cord compression owing to metastatic involvement of vertebral body
Signs and symptoms of SCC (Box 2)2 are similar to those seen with cauda equina syndrome. However, in contrast with cauda equina syndrome, the level of sensory disturbance in SCC corresponds to the vertebrae involved, and the central nature of SCC causes hyperreflexia as opposed to hyporeflexia.
Signs and symptoms of SCC
Signs
Weakness
Sensory level
Hyperreflexia and clonus (variable)
Loss of anal sphincter tone
Symptoms
Back pain (exacerbated by Valsalva maneuvers)
Numbness below the spinal level involved
Paresthesia
Weakness
Urinary retention (often reported as incontinence owing to overflow)
Bowel incontinence (often reported as diarrhea owing to loss of sphincter control)
SCC—spinal cord compression.
Data from Ropper and Ropper.2
Contrast-enhanced magnetic resonance imaging is the most sensitive imaging modality for the diagnosis of SCC (Figure 1).2,6,7 If magnetic resonance imaging is unavailable or contraindicated, contrast-enhanced computed tomography can be used.
Initial management of SCC includes immediate administration of dexamethasone. An intravenous bolus of 10 mg followed by 4 mg of dexamethasone every 6 hours will diminish pain, perilesional edema, and associated disability.8 Urgent consultation with neurosurgery and radiation oncology should be sought. The best clinical outcomes are achieved with direct decompressive surgery followed by postoperative radiotherapy; however, not all patients are surgical candidates (Box 3).9-11
Factors favouring surgical decompression for SCC
Undiagnosed malignancy requiring tissue for pathology or unknown primary cause where the cancer diagnosis is in doubt
Pathological vertebral fracture with unstable spine
Relatively radioresistant tumour
Previous radiotherapy at the level of SCC
Disease localized to a single vertebral level
Good prognostic factors (age <65 y, life expectancy >6 mo, systemic treatment options)
SCC—spinal cord compression.
Data from Walji et al.9
Radiation therapy is the mainstay of treatment for SCC as only 10% to 15% of patients qualify for surgical decompression.12 External beam treatments are typically 20 Gy, administered in 5 fractions, although a single fraction of 8 Gy can be offered.13 Stereotactic body radiation therapy is reserved for postoperative treatment or for radioresistant or recurrent spinal metastases given the time required for treatment planning.14-17 Chemotherapy has little role in the treatment of SCC given its delayed onset of action. Physicians should also ensure patients receive pain control, management related to bowel and bladder function, and referral to rehabilitation services.18 Venous thromboembolic prophylaxis should not be overlooked given elevated risk in these patients.19 Treatment within 48 hours of neurologic deficits will help prevent loss of limb function and loss of bladder and bowel function and improve quality of life.20,21 The most important factors in predicting ambulatory status posttreatment are pretreatment ambulatory status and time from development of motor deficits to radiotherapy or surgery.22-24
Malignant SVCO
Superior vena cava obstruction occurs when there is extrinsic compression of the SVC or direct invasion by a tumour, impairing venous return to the heart. Lung cancers and non-Hodgkin lymphoma account for most cases of malignant SVCO.25 Thrombus formation caused by indwelling venous devices can also put oncology patients at increased risk of SVCO.26
The most common presenting symptoms of malignant SVCO are secondary to venous congestion and include face or neck swelling (87%), cough (70%), upper extremity swelling (64%), dyspnea at rest (64%), and dilated neck and chest veins (38%) (Figure 2).27,28 Collateral vessels develop with slowly growing tumours, causing a gradual onset of symptoms; while in an acute obstruction, symptoms present abruptly.28 In severe SVCO, laryngeal edema with associated stridor and confusion secondary to raised intracranial pressure can occur. Symptoms typically worsen when the patient is supine, as flow through the residual SVC lumen may be further compromised.
Clinical findings and pathogenesis of SVCO
Investigation should begin with a chest x-ray scan. Typical x-ray scan findings include superior mediastinal widening or a mass located in a position to cause SVCO, often with an associated pleural effusion (Figure 3).29 Contrast-enhanced computed tomography can identify the precise location and extent of obstruction and detect the presence of a thrombus.30 For some patients SVCO will be the initial presentation of malignancy, so a biopsy should be obtained.
Chest x-ray scan depicting SVCO in a patient with small cell lung cancer: Broadened mediastinum is visible (dotted arrow) and pleural effusion (solid arrow).
Treatment options depend on symptom severity and tumour histologic findings. General measures include head elevation and use of glucocorticoids. Despite minimal evidence, steroids are given to help prevent edema in patients receiving urgent radiotherapy.31 Insertion of an endovascular stent is the most effective and immediate means of resolving symptoms in acute SVCO.32 Anticoagulation treatment and thrombus removal should be considered for SVCO secondary to thrombus formation.33,34 If symptoms are mild to moderate, radiotherapy can be first-line treatment. Chemotherapy can be considered for chemosensitive malignancies such as lymphoma or small cell lung cancer.31
Febrile neutropenia
Febrile neutropenia occurs when myelosuppression from chemotherapy, and occasionally targeted therapies, results in decreased neutrophil production that causes impaired immune response to bacterial infections.35 Any patient with a fever receiving these treatments should be assessed thoroughly and providers should have a low threshold for initiating antibiotic therapy.
Febrile neutropenia is defined as a single oral temperature of 38.3°C or higher or a sustained temperature of 38°C or higher for at least 1 hour, and absolute neutrophil count (ANC) of 1.0 × 109/L or less; severe neutropenia is defined as ANC of 0.5 × 109/L or less.36 Elderly or profoundly immunosuppressed patients may not be able to mount a fever and may be afebrile despite the presence of infection. In these patients, clinicians must be aware of alternative presentations for sepsis such as hypothermia, hypotension, or clinical deterioration.35 Myelosuppression typically occurs 1 week after chemotherapy treatment.37
Patients receiving chemotherapy or select targeted therapies who present with fever require a complete history, physical examination, and investigations to establish ANC and determine possible infectious sources (Box 4).38 Blood cultures should always be drawn and central venous access devices should be carefully assessed, as these are common portals for infection. The presence of mucositis identifies a breakdown of mucosal barriers, allowing for a translocation of enteric bacteria with potentially worse outcomes.37 Rectal examinations should not be performed owing to increased risk of bacteremia. Chest x-ray scans may not show lung infiltrates in neutropenic patients due to their decreased ability to mount an inflammatory response.39 Only 20% to 30% of patients with febrile neutropenia will have an identifiable infectious cause.40
Recommended workup for febrile neutropenia
Complete blood cell count with differential leukocyte count
Creatinine level
Blood urea nitrogen level
Electrolytes
Hepatic transaminase enzymes
Total bilirubin
Blood cultures from central venous catheter, if present, and from peripheral vein site
Culture specimens from any suspected site of infection (eg, urine, throat, skin)
Consider viral culture
Chest x-ray scan if respiratory signs or symptoms
Data from Freifeld et al.38
Empiric broad-spectrum antibiotic therapy should be initiated once cultures are drawn, ideally within 1 hour of triage.36 The Multinational Association for Supportive Care in Cancer risk index is a validated online tool that can be used to determine who must be admitted to hospital and who can safely be treated as outpatients (Box 5).36,41,42 Clinicians should have a low threshold for admission, and any patients who look systemically unwell or have unstable vital signs should be treated as inpatients. Patients with no measurable neutrophils are not candidates for outpatient therapy.
Criteria for low-risk outpatient treatment for febrile neutropenia
Outpatient with controlled malignancy
MASCC risk index score ≥21
No clinical evidence of any specific infection
No signs or symptoms of systemic infection other than fever (eg, no hypotension, rigours, respiratory insufficiency)
No clinically significant comorbid illness
ANC >0.1 × 109/L, recovery of neutrophils expected within 7 to 10 d
Peak temperature <39°C, no neurologic or mental status changes, respiratory rate <24 breaths per minute
No hepatic or renal insufficiency
No nausea, vomiting, diarrhea, or severe mucositis
No antibiotics in past 7 d
No known allergies to penicillin or quinolones
ANC—absolute neutrophil count, MASCC—Multinational Association for Supportive Care in Cancer.
Data from Crepso et al.36
Suggested antibiotic treatments for low- and high-risk patients are presented in Box 6.35,36,38 Low-risk outpatient treatment should be prescribed for at least 7 days. Patients should be reassessed if fever persists beyond 48 to 72 hours, if there is any clinical deterioration, or if there are positive blood culture results or microbiological tests not susceptible to the chosen antibiotic regimen.36 Clinicians should consider patterns of antibiotic resistance in their setting when choosing therapies.
Antibiotic treatments for febrile neutropenia in low- and high-risk patients
Low risk
750 mg of ciprofloxacin taken orally every 12 h, and 875 mg of amoxicillin and 125 mg of clavulanic acid taken orally twice daily
If patient is allergic to β-lactams, consider oral ciprofloxacin and oral clindamycin
High risk
Intravenous infusion of 4 g of piperacillin and 0.5 g of tazobactam every 6 h
If patient is allergic to penicillin, prescribe fluoroquinolone and clindamycin
Consider addition of vancomycin if patient is clinically unstable, is known to have MRSA, or has central venous catheter or skin infections
Consider addition of antifungals or antivirals if there is clinical evidence of infection or if patient has persistent fever after 4 to 7 d of antibacterial regimen with no identified source of infection
MRSA—methicillin-resistant Staphylococcus aureus.
Data from Taplitz et al,35 Crepso et al,36 and Freifeld et al.38
Patients admitted with febrile neutropenia can be stepped down from intravenous infusion to oral regimens if they remain afebrile, have evidence of ongoing neutrophil recovery, and have negative blood culture results.42 Granulocyte colony–stimulating factors such as filgrastim promote neutrophil production in the bone marrow, and they are used prophylactically in patients receiving curative chemotherapy with a high risk of neutropenia but are not typically recommended in the treatment of febrile neutropenia.38
Conclusion
This article summarizes important clinical aspects of SCC, SVCO, and febrile neutropenia. As SVCO and SCC can be the first presentation of cancer, family physicians must be able to recognize their presentations in primary care. A greater understanding of oncologic emergencies will assist family physicians in the care of patients with cancer, where timely intervention can preserve quality of life and reduce mortality.
Footnotes
Competing interests
None declared
- Copyright © 2023 the College of Family Physicians of Canada