Oncological emergencies

Cancer and its treatment may lead to a range of potentially life-threatening conditions that require urgent action to correct them. Most oncological emergencies can be classified as metabolic, haematological, structural, or treatment-related¹ .

This article discusses the following:

• Hypercalcaemia.

• Neutropenia.

• Tumour lysis syndrome.

• Leukostasis.

• Hyperviscosity syndrome.

• Raised intracranial pressure.

• Spinal cord compression.

• Cauda equina syndrome.

• Superior vena cava obstruction.

• Syndrome of inappropriate ADH secretion.

Other oncological emergencies include hypoglycaemia, pericardial effusion and cardiac tamponade, seizures, hyperviscosity syndrome (this is usually associated with Waldenström's macroglobulinaemia) and airway obstruction² .

Adverse effects of chemotherapy may also require urgent intervention - eg, extravasation and anaphylactic reactions³ .

Hypercalcaemia^{3 4}

See also the separate Hypercalcaemia article.

Hypercalcaemia occurs in 10-30% of patients with malignancy and is most commonly associated with breast cancer, lung cancer, non-Hodgkin's lymphoma and multiple myeloma, although it may be seen with any malignancy⁵ .

What is hypercalcaemia?

Hypercalcaemia is the most common, serious metabolic disorder associated with malignancy, affecting up to one third of cancer patients at some point in their disease course. Malignancies most commonly associated include lung cancer, breast cancer, renal cancer, multiple myeloma and adult T-cell lymphoma. Hypercalcaemia symptoms may mimic the features of terminal malignancy. Hypercalcaemia is a poor prognostic indicator in malignant disease and may indicate uncontrolled tumour progression and metastasis. The 30-day mortality rate of cancer patients admitted to hospital with hypercalcaemia is almost 50%.

The symptoms of hypercalcaemia are nonspecific; delayed recognition can worsen morbidity and mortality. Presenting features of hypercalcaemia include nausea and vomiting, anorexia, thirst and polydipsia, polyuria, lethargy, bone pain, abdominal pain, constipation, confusion and weakness. Renal tract stones may occur. There is no absolute level of calcium at which patients become symptomatic; the rate of increase is usually more significant than the magnitude of elevation.

Investigation

Ionised calcium is the most reliable laboratory test. If total calcium is used, it is important to calculate the corrected calcium level to allow for hypoalbuminaemia. Other investigations should include alkaline phosphatase, renal function and electrolytes, X-rays (may show lytic or sclerotic lesions of the bone) and a bone scan (to identify any metastases).

Management

There may be a palliative benefit from improving the symptoms of hypercalcaemia, even in patients with advanced malignancies. Urgent intervention is required to treat symptomatic hypercalcaemia. Management includes intensive rehydration and intravenous bisphosphonates.

Neutropenic fever⁶

See also the separate Neutropenic Patients and Neutropenic Regimes article.

Febrile neutropenia is most often seen as an effect of cytotoxic therapy. The neutrophil count usually reaches its lowest level 5 to 10 days after the last dose of chemotherapy. Febrile neutropenia is defined as an oral temperature ≥38.5°C or two consecutive readings of ≥38.0°C for two hours and an absolute neutrophil count ≤0.5 x 10⁹/L.

Up to 80% of patients receiving chemotherapy for haematological malignancies will develop neutropenic fever at least once during the course of therapy. Patients with solid tumors are reported to develop neutropenic fever at a rate of 10-50% during the course of chemotherapy. The likelihood of fever increases with the duration and the severity of neutropenia as well as the rate of decline of the absolute neutrophil count⁵ .

There is a significant mortality from febrile neutropenia, of between 5% in people with solid tumours to 11% in those with haematological malignancies. Signs and symptoms of neutropenic fever can be minimal, especially in those also on corticosteroids. Infection is responsible for at least half of the cases of neutropenic fever.

• Gram-positive cocci are now responsible for the majority of culture-positive cases of neutropenic fever, including Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, Enterococcus faecalis and Enterococcus faecium. Corynebacterium is the most likely Gram-positive bacillus.

• Gram-negative bacilli include Escherichia coli, Klebsiella spp. and Pseudomonas aeruginosa.

• Candida is the most common fungal infection but aspergillosis and other systemic mycoses can cause more serious infections.

• Often no causative organism is found (in which case the prognosis is better than in those with proven bacteraemia) and the patient improves as the neutrophil count increases.

The vulnerability to infection substantially rises at a neutrophil count less than 1 x 10⁹/L but the risk continues to increase as the neutrophil count falls.

Management

• The patient should have an infection screen, including blood cultures, urine cultures, swabs of any indwelling catheters, intravenous cannulae and central lines, CXR, sputum cultures, cultures from any open wounds and stool cultures.

• Empirical antibiotic therapy should be started immediately based on local guidelines, with modification based on the results of microbiological investigations.

• The addition of antifungal coverage should be considered in high-risk patients who remain febrile after 3-7 days of broad-spectrum antibiotics with no identified causative organism.

• The National Institute for Health and Care Excellence (NICE) does not recommend the use of granulocyte-colony stimulating factor (G-CSF) for the routine prevention of neutropenic sepsis⁷ .

Tumour lysis syndrome⁸

Tumour lysis syndrome is a severe metabolic disturbance caused by the abrupt release of large quantities of cellular components into the blood following the rapid lysis of malignant cells.

Tumour lysis syndrome is a rare metabolic crisis with an estimated mortality of 29-79%. With early and aggressive intervention, the mortality rate can be reduced significantly. Tumour lysis syndrome occurs due to the liberation of intracellular components into the circulation. The incidence increases with malignancies that have rapid cell turnover (eg, haematological malignancies)⁵ .

Tumour lysis syndrome is characterised by hyperuricaemia, hyperkalaemia, hyperphosphataemia and hypocalcaemia. Tumour lysis syndrome occurs most often in patients with haematological malignancies - eg, acute lymphoblastic leukaemia (ALL) or Burkitt's lymphoma. Treatment-provoked tumour lysis syndrome can occur following chemotherapy, radiotherapy, surgery or ablation procedures.

Typically, onset of tumour lysis syndrome is within 1-5 days of starting chemotherapy (but can be delayed by days or weeks in patients with a solid tumour). The metabolic disturbances can cause seizures, acute kidney injury and cardiac arrhythmias. Although such clinical tumour lysis syndrome is rare (affecting 3-6% of patients with high-grade tumours), the mortality is as high as 15% and a third of patients require dialysis. Patients particularly at risk have treatment-sensitive tumours, renal impairment or volume depletion. High pre-treatment urate, lactate and lactate dehydrogenase (LDH) are also risk factors.

Investigation

Full metabolic and biochemical profile to detect the above abnormalities. Monitoring of serum lactate, urate and LDH may predict the imminent onset of the syndrome.

Tumour lysis syndrome management

The key to the management of tumour lysis syndrome is prevention, with a risk assessment for all patients with any haematological malignancy prior to receiving chemotherapy:

• Low-risk patients: vigilant monitoring of electrolyte levels and fluid status.

• Intermediate-risk patients: seven days of allopurinol along with increased hydration. Urinary alkalinisation is no longer recommended.

• High-risk patients: prophylaxis, usually with a fixed single dose of 3 mg rasburicase (recombinant urate oxidase), along with increased hydration. Allopurinol is unnecessary and may reduce the effectiveness of rasburicase.

Clinical signs of tumour lysis syndrome require a multidisciplinary approach with involvement of haematologists, nephrologists and intensive care physicians, with transfer to an intensive care/high dependency facility. Tumour lysis syndrome treatment includes:

• Intravenous hydration (without potassium).

• Daily rasburicase infusion.

• Intravenous calcium gluconate for symptomatic hypocalcaemia .

• Cardiac monitoring

• Dialysis (not peritoneal) may be needed in severe cases.

• Alkalinisation of the urine is not recommended.

Leukostasis³

Leukostasis is associated with a very high white cell count, respiratory failure, intracranial haemorrhage (but it can affect any organ system) and early death. Without prompt treatment the mortality rate can be up to 40%. Leukostasis occurs in 5-13% of patients with acute myeloid leukaemia (AML) and 10-30% of adult patients with ALL. The risk is greater for younger patients, and infants are most often affected. A white cell count greater than 50,000/m³ indicates a particularly poor prognosis.

There is usually a high fever and examination may show papilloedema, retinal vein bulging, retinal haemorrhage and focal neurological deficits. Myocardial infarction, limb ischaemia, renal vein thrombosis and disseminated intravascular coagulation may occur. Thrombocytopenia is usually present.

Management

• Rapid cytoreduction is the initial treatment, ideally with induction chemotherapy, which can dramatically reduce the white cell count within 24 hours.

• There is a very high risk of tumour lysis syndrome and so close monitoring of electrolytes and prophylaxis with allopurinol or rasburicase are required.

• Leukophoresis is usually started when the blast count is greater than 100,000/m³ or in the presence of symptoms.

• Cytoreduction can also be achieved by hydroxyurea but is usually reserved for patients with asymptomatic hyperleukocytosis who are unable to receive immediate induction chemotherapy.

Hyperviscosity syndrome⁵

Hyperviscosity syndrome is a rare but potentially catastrophic consequence of a significant excess in serum proteins (eg, Waldenström’s macroglobulinaemia or multiple myeloma) or cellular components (eg, white blood cells in acute leukaemias or polycythaemias).

Hyperviscosity syndrome results in relative hypoperfusion, and resultant clinical manifestations represent end-organ dysfunction. The classic triad of hyperviscosity syndrome is mucosal or skin bleeding, visual changes, and focal neurological deficits. The diagnosis should be considered in any patient with a markedly elevated white blood cell count (above 100 x 104) or haemoglobin (approaching 200 g/L) associated with symptoms of hypoperfusion.

Blood transfusion can significantly worsen hyperviscosity syndrome and should be avoided if possible. The mainstays of therapy are decreasing serum viscosity through IV fluid resuscitation, plasmapheresis, or leukopheresis. Phlebotomy (eg, for polycythaemia) or even urgent chemotherapy (eg, acute leukaemia) may also be indicated.

Raised intracranial pressure

See also the separate Raised Intracranial Pressure article.

Cranial metastases affect around a quarter of patients who die from cancer⁹ . Lung, breast and melanoma are the tumours that most commonly metastasise to the brain. The clinical picture varies with site of metastases and the rate of rise of intracranial pressure. Small metastases may bleed and cause acute symptoms. Common symptoms and signs of cranial metastases include:

• Headache.

• Nausea and vomiting.

• Behavioural changes.

• Seizures.

• Focal neurological deficit.

• Falling level of consciousness.

• Papilloedema.

• Unilateral ptosis or third and sixth cranial nerve palsies.

• Bradycardia (late sign).

Investigation

CT or MRI scanning should be conducted urgently to delineate the lesion, if the result is likely to affect the patient's management.

Management

• If the patient has lost consciousness and requires ventilation, then higher than average respiratory rate should be used to aim for low normal pCO₂ (30-35 mm Hg), which helps reduce intracranial pressure.

• Mannitol may be given as a diuretic along with dexamethasone to reduce symptoms and the likelihood of cerebral herniation.

• Further management may involve cranial irradiation, surgery ± radiation or 'gamma knife' radiosurgery, depending on the site, type and number of metastases.

• High-dose dexamethasone alone may be appropriate in the palliative situation. The usual starting dose is 8 mg morning and mid-day, reducing after three days as the symptoms improve or stopping completely after seven days if there has been no improvement.

Spinal cord compression¹⁰

This condition must be diagnosed and treated quickly to prevent permanent neurological disability. It may occur because of extradural spread from a vertebral body metastasis, direct metastases or from a vertebral crush fracture. Cancers that most often metastasise to bone and cause spinal cord compression are cancers of the breast, kidney, thyroid, prostate and lung.

• If spinal metastases are thought to be the cause of the pain, seek urgent (within 24 hours) specialist advice from a metastatic spinal cord compression co-ordinator if available, or alternatively a palliative care consultant or oncologist.

• If there are associated neurological features suggestive of spinal cord compression, seek immediate specialist advice.

• Unless contra-indicated (including a significant suspicion of lymphoma), offer all people with metastatic spinal cord compression a loading dose of 16 mg of dexamethasone as soon as possible after assessment.

Metastatic extradural spinal cord compression is treated with radiotherapy, corticosteroids, and surgery, but there is uncertainty regarding their comparative effects¹¹ .

See the separate Spinal Cord Injury Compression article.

Cauda equina syndrome

See the separate Cauda Equina Syndrome article.

Superior vena cava obstruction

This may be due to compression of the superior vena cava, caused by primary or secondary tumours. Lung cancer (~85% of cases), lymphoma and metastatic tumours are the most common causes.

Management

Therapy is directed at the underlying cause. This is normally chemotherapy for lymphoma/small cell lung cancer, with early response and resolution of superior vena cava obstruction within weeks being the usual outcome. Radiotherapy is usually used for non-chemosensitive tumours or patients who do not respond to chemotherapy. See the separate Superior Vena Cava Obstruction article.

Syndrome of inappropriate ADH secretion

See also the separate Hyponatraemia article.

Tumour cells may secrete ADH, particularly in the case of small cell lung cancer. The syndrome of inappropriate ADH secretion affects 1-2% of cancer patients. The condition should be considered whenever a patient with malignancy presents with hyponatraemia. It is often asymptomatic but may cause:

• Depression and lethargy.

• Irritability and other behavioural changes.

• Muscle cramps.

• Seizures.

• Depressed consciousness leading to coma.

• Neurological signs (such as impaired deep tendon reflexes and pseudobulbar palsy).

Management

Successful treatment of the underlying malignancy will improve the condition. Fluid restriction is recommended¹² .