The essentials of acute oncology

Metastatic spinal cord compression

Metastatic spinal cord compression (MSCC) occurs in 3–5% of patients with cancer.¹ MSCC is caused by epidural extension of vertebral metastases or following pathological compression fractures. MSCC is a medical emergency, because prompt investigation and early diagnosis facilitate the delivery of palliative therapies, which minimise symptoms and the risk of irreversible neurological disability.² MSCC is most common in breast, lung and prostate cancer, lymphoma or myeloma, but should be urgently investigated in any patient with cancer presenting with red flag symptoms (Table 1).

Definitive investigation is a whole-spine magnetic resonance imaging (MRI) scan within 24 h of presentation, because patients can present with multilevel disease. Initial management comprises dexamethasone (16 mg followed by 8 mg twice daily) with proton pump inhibitor (PPI) cover, analgesics and antiemetics. Steroids should be avoided before biopsy in patients in whom a new diagnosis of lymphoma is suspected. All patients should be discussed with the neurosurgical team for assessment of spinal stability. In patients with no known cancer diagnosis, full radiographic staging should be performed to identify a primary cancer and suitable biopsy site. Tumour markers, including serum paraprotein, prostate-specific antigen (PSA), alpha-fetoprotein (AFP), lactate dehydrogenase (LDH), human chorionic gonadotrophin (hCG) and cancer antigen 125 (CA125), can aid diagnosis.

The choice of therapy for MSCC is multifactorial, including the intrinsic radiosensitivity of the primary tumour, patient prognosis, the severity of MSCC, and spinal stability. In general, patients with good performance status and single-level disease should be offered neurosurgical decompression. Patients with poor performance status and multilevel disease are usually better candidates for palliative radiotherapy. Pretreatment neurological function is the strongest predictive factor for neurological outcome.⁵ Median overall survival has been estimated at 6 months and is better in ambulant versus non-ambulant patients.⁶

Vasogenic oedema and raised intracranial pressure

Vasogenic oedema and raised intracranial pressure (ICP) can complicate primary brain tumours and secondary brain metastases. Vasogenic oedema is caused by disruption of the blood–brain barrier following tumour secretion of a variety of angiogenic factors, such as vascular endothelial growth factor (VEGF).⁷ Raised ICP occurs following tumour mass effect or obstructive hydrocephalus and manifests as severe vasogenic oedema. Although presentation varies depending on the site of the lesion, common symptoms include headache, vomiting, changes in vision and seizures. Physical examination can reveal a decreased Glasgow Coma Score (GCS), VIth nerve palsy, papilledema, and the triad of bradycardia, hypertension and bradypnea known as Cushing's reflex. Patients should undergo urgent neuroimaging with computed tomography (CT) and/or MRI. Signs of imminent neurological compromise include midline shift, cerebral oedema, hydrocephalus and acute haemorrhage.³ A GCS score <12 warrants urgent intensive treatment unit (ITU) assessment. Initial management includes high-dose dexamethasone (16 mg followed by 8 mg twice daily) with PPI cover, analgesics and antiemetics. Prophylactic anticonvulsants are not recommended for routine use.⁸ In refractory cases, hypertonic saline and mannitol might be required.

Superior vena cava obstruction

Malignant superior vena cava obstruction (SVCO) is caused by direct tumour invasion, external compression or tumour thrombus.⁹ Increased venous pressure results in head, neck and upper limb oedema, cyanosis and swelling of subcutaneous vessels.¹⁰ The most common cause is bronchogenic malignancy, followed by lymphoma, thymic and germ cell malignancies.¹¹ Investigation is with contrast-enhanced CT, which can assess the primary tumour, the site of occlusion or stenosis and the extent of tumour thrombus. In patients who are unstable and present with life-threatening complications, such as airway obstruction, stridor, hypotension or decreased GCS, urgent endovenous recanalisation with SVC stent placement should be organised.¹² In patients who are stable, accurate histological diagnosis is needed to direct anti-cancer therapy, because patients with small cell lung cancer, lymphoma or germ cell tumours might be more suitable for chemotherapy than for endovascular stenting. Prognosis varies significantly depending on the underlying tumour.¹¹ If tumour thrombus is present, anticoagulation should be considered.

Hypercalcaemia of malignancy

Malignant hypercalcaemia occurs in 20–30% of patients with advanced cancer,¹³ following tumour secretion of parathyroid hormone-related peptide (PTHrP) and vitamin D, or cytokine release for osteolytic metastases.¹⁴ Both mechanisms result in increased osteoblastic bone resorption and increased tubular calcium resorption.¹⁵ Symptoms include depression, musculoskeletal pain and abdominal pain.¹⁶ Investigation with serum total calcium, PTH, PTHrP, phosphate, vitamin D, serum creatinine and estimated glomerular filtration rate (eGFR) will enable a correct diagnosis in most cases. Grading is based upon local laboratory guidelines. In severe hypercalcaemia, patients are usually volume deplete, and intravenous fluid therapy forms the mainstay of initial management, promoting calciuresis.¹⁷ Following 24 h of parenteral fluid therapy, intravenous bisphosphonates are used first line to reduce bone resorption, and calcium levels fall steadily over a period of 1–5 days (Table 1). In refractory cases, repeat bisphosphonates, calcitonin, glucocorticoids or denosumab (off label) can be trialled.¹⁷

Chemotherapy

Cytotoxic chemotherapy causes cancer cell death by interfering with the cell cycle and inhibiting cell division. However, chemotherapy also causes cytotoxicity in rapidly proliferating non-cancerous epithelial cells and acute emergency toxicity can present with nausea and vomiting, diarrhoea, pneumonitis or myelosuppression (Table 2).3,4,18 The common toxicities of specific chemotherapeutic agents in solid tumours are presented in Table 3.

Radiotherapy

There have been significant advances in linear accelerator technology with the development of image-guided intensity-modulated and stereotactic radiotherapy. Despite this, radiation toxicity can occur and is dependent on the site of treatment. Acute presentations typically include gastrointestinal toxicity and pneumonitis (Table 2). Radiotherapy can rarely cause acute oedema of the brain and spinal cord, and patients presenting with new neurological symptoms should have repeat brain or spinal imaging with CT or MRI. Treatment involves dexamethasone 4–8 mg twice daily.³ Increasing the dexamethasone dose above 16 mg/day has not been shown to provide additional benefit.²⁰

Targeted therapy

Targeted therapies interact with specific molecules involved with cell proliferation and growth. Toxicity is variable depending on the mechanism of action, and an overview is provided in Table 4.19 The most common oral targeted therapies are tyrosine kinase inhibitors (TKIs), which typically cause rash, diarrhoea, fatigue, nausea, sore mouth and paronychia as side effects. Multiple targeted drugs have recently been identified with an elevated risk of pneumonitis and this should be carefully investigated for in any patient presenting with breathlessness or a dry cough.

Steroid therapy

Patients with cancer are often prescribed glucocorticoids, especially as supportive care. The risk of adrenal insufficiency should be considered in any unwell patient with cancer. Clinicians should enquire whether patients carry a Steroid Emergency Card.²¹ Top-up glucocorticoid therapy should be prescribed during ‘sick days', such as when presenting to the emergency department with acute illness.

Immunotherapy

The acute toxicity of immunotherapy is discussed in another article within this edition.

Neutropenic sepsis

Febrile neutropenia or neutropenic sepsis is a medical emergency and represents a potentially life-threatening complication of systemic anti-cancer therapy. Neutropenic sepsis can be diagnosed in a patient presenting with a temperature over 38.0°C and an absolute neutrophil count (ANC) of <1.0×10⁹/L. However, fever might not always be present and can be masked by concomitant steroid therapy. Therefore, neutropenic sepsis should be suspected in any unwell patients within 60 days of receiving systemic anti-cancer therapy.

Initial evaluation should involve a detailed cancer history, including chemotherapy regimen and any prophylactic antibiotic administration. Physical examination should assess circulatory and respiratory function, and patients with should receive prompt resuscitation. Intravenous broad-spectrum antibiotics should be given within 1 h of blood cultures being taken.²² Their administration should not wait for the full blood count results. Empirical antibiotic treatment should be based on local guidelines, epidemiological patterns of causative pathogens and antimicrobial resistance.²³ Invasive aspergillosis should be considered in patients with prolonged, profound neutropenia; Pneumocystis jirovecii pneumonia should be considered in patients treated with corticosteroids; and invasive candidiasis should be considered in those with mucositis. C reactive protein (CRP) levels lack specificity, and an elevated CRP in isolation should not be the sole trigger to prompt initiation of antimicrobial therapy. The use of procalcitonin is currently exploratory.²⁴

Advice about the use of granulocyte colony-stimulating factor (G-CSF) should be sought from the acute oncology team; however, G-CSF is indicated if the patient is septic, has an ANC <0.5×10⁹/L or is at elevated risk of complications.²² G-CSF can be stopped once the ANC is above 1×10⁹/L. Assessment of risk of medical complications using the Multinational Association of Supportive Care in Cancer (MASCC) should be performed. Select low-risk patients can be managed as outpatients following a period of observation after initial empiric therapy.²² Mortality varies depending on the MASCC score: under 5% if the MASCC score is ≥21, but potentially up to 40% if the MASCC score is <15.^23,25 Prognostic factors include the degree and duration of neutropenia, older age, poor performance status, obesity and metastatic bone marrow infiltration.²⁵