Oncological emergencies

Oncological emergencies

• Divided into:
  • Local tumor effects
    • Malignant airway obstruction, bone metastases, pathological #, malignant spinal cord compression, malignant pericardial effusion and SVC syndrome
  • Biochemical derangement
    • Hypercalcaemia, hyponatraemia, adrenal insufficiency, tumor lysis syndrome
  • Haematological derangement
    • Febrile neutropaenia, hyperviscosity syndrome, thromboembolism
  • Therapy-related
    • Nausea and vomiting
    • Extravasation of chemotherapeutic agents

Malignant airway obstruction

• Usually insidious process but can be acute in the setting of infection, haemorrhage or loss of protective muscle tone
• Local radiotherapy can cause acute tissue breakdown and obstruction
• Can be divided into upper airway (down to vocal cords) and central airway
• Can divide into endoluminal, extraluminal or mixed
• Required plain X-ray, CT and endoscopic visualisation
• Direct laryngoscopy discouraged as may convert partial obstruction to complete one through bleeding and oedema
• Supplemental O2, patient positioning to achieve most patent airway possible
• Airway instrumentation may be required acutely
• Definitive prolonged relief may be obtained via neodymium-yttrium-aluminium-garnet laser photoradiation +- self-expanding stent +- external radiation therapies (take longer though)

Bone metastases and pathological fracture

• Mostly axial skeleton (calvarium included) and proximal aspects of limbs
• Mostly metastases from solid bone tumors (e.g. breast, lung, prostate) that localise to red marrow (high blood flow)
• Can get osteolytic (moth-eaten) appearance, poorly demarcated osteoblastic lesions and/or periosteal reactions
• Plain X-ray shows only 50% of metastatic bone lesions
• CT with contrast can show 3-D bone integrity and soft tissue extension
• MRI can delineate soft tissue and marrow involvement
• Total body bone scan can screen for additional metastases (sensitive but not specific for cancer)
• Treatment
  • Analgesia, fracture management (often open surgical repair required)
  • 80% of painful bone metastases can be helped with palliative radiotherapy but can take several weeks after a 5-day course to see benefit

Malignant spinal cord compression

• 20% of cancer patients will develop neoplastic involvement of vertebral column
• 3-6% of cancer patients will develop spinal cord compression
• Mostly vertebral body metastases from solid organ tumors (thoracic mostly)
• 90% of patients with malignant spinal spinal cord compression will have back pain
  • Unrelenting, progressive, worse when supine and thoracic area (therefore worse at night)
• 80% of patients with malignant spinal cord compression have history of cancer
• Motor symptoms in 60-85%
• Sensory symptoms in 40-80%
• Autonomic/bladder/bowel in 40-60% and a late finding
• Weakness is most apparent proximally and may progress to complete paralysis
• Sensory changes may initially be band of paraesthesia around trunk and then distal anaesthesia
• Urinary retention (with overflow incontinence), fecal incontinence and impotence are late manifestations
• MRI is imaging modality of choice for cord compression and to identify additional vertebral lesions
• Entire spine should be imaged due to high likelihood of multiple level involvement (although cervical spine rarely involved and can leave out if no symptoms localising to there)
• CT +- myelography is used if MRI contraindicated or inaccessible
• Plain X-ray may identify an abnormality in 80% of patients with painful vertebral metastases but is less useful is suspected cord compression as radiographic findings do not always correlate with level of spinal cord compression and causes other than vertebral body metastases will not produce visible changes
• If initial CT is performed, ensure entire spine is imaged as lower limb symptomatology can arise from cord compression at any level above this

• Rx
  • Opioid analgesics
  • Dexamethasone 10mg IV bolus then 4mg q5h if any delay to imaging
  • Further treatment may include ongoing corticosteroids, radiotherapy, surgery or combination depending on premorbid state and degree of motor impairment
  • Radiotherapy has beneficial response in 70% of cases with functional outcome directly correlated to preceding function (90% of those that can walk before radiotherapy can walk afterwards and 50% of those with motor function but not ambulatory prior to radiotherapy regain the ability to walk but few patients with paraplegia regain motor function in lower limbs)
  • Considered a radiotherapy emergency
  • Consult oncology, radiotherapy and spinal surgery early in course of suspected spinal cord compression as complex management required

• Surgery may be indicated if:
  • Good general condition able to undergo surgery
  • Appropriate prognostic life expectancy
  • Rapidly progressive symptoms
  • Clinical worsening during radiotherapy
  • Unstable vertebral column

Malignant pericardial effusion and tamponade

• Seen in 35% of cancer patients (although effusions often small and remain undiagnosed)
• Symptomatic effusions usually secondary to lung or breast cancer and less commonly melanoma, leukaemia, lymphoma or as a complication of radiotherapy/chemotherapy
• Only require treatment if symptomatic with USS-guided pericardiocentesis +- pericardial window
• Intrapericardial chemotherapy and treatment of primary cancer can reduce fluid production
• Typically indicates advanced disease and most patients die within 1 year of diagnosis

SVC syndrome

• Most commonly external compression by malignant mass (lung cancer in 70% and lymphoma in 10%) but intravascular thrombosis due to indwelling catheter or pacing wire accounts for 30%
• Rarely constitutes an emergency as material deterioration is rare within 1-2 weeks of diagnosis (only exception being raised ICP)
• Clinical manifestations correlate with JVP of 20-40mmHg
• Most common symptoms are facial swelling, dyspnoea, cough and arm swelling
• Less commonly hoarseness, syncope, headache and dizziness
• In extreme cases, raised ICP may manifest as visual changes, dizziness, confusion, seizures or obtundation
• May see violaceous hue or plethora of face with distended neck and chest wall veins

• Ix
  • CXR
  • CT with contrast
  • If no known intrathoracic cancer, need tissue diagnosis prior to chemotherapy and highly desirable prior to radiotherapy
• Initial management
  • Head elevation
  • Supplemental O2 to reduce WOB
  • Corticosteroids and loop diuretics often used but no evidence of clinical role (steroids would be expected to help in lymphoma though)
• Radiation therapy effective in 75% of patients, reflecting incidence of radiosensitive tumor types

• Intravascular stents produce a more rapid improvement and are preferred if severe symptoms and for tumor types that do not respond well to chemo/radiotherapy (e.g. mesothelioma, fibrosing mediastinitis or intravascular thrombosis
• Chemotherapy effective in 80% of lymphoma patients, 80% of SCLC and 40% of non-SCLC (no evidence of additive benefit of radiotherapy in these cases)
• Can treat intravascular thrombosis with catheter-directed fibrinolytics and removal of indwelling catheter + post-fibrinolytic anticoagulation
• Recurrence seen in 20% of lung cancer patients treated with chemo-radiotherapy and 10% following intravascular stenting

Hypercalcaemia

• Seen in 5-30% of patients with advanced cancer
• Breast cancer, lung cancer and multiple myeloma mostly
• Three key mechanisms:
  • PTHrP (solid organ tumors) (80%)
  • Osteoclastic bone destruction (bone mets from lung/breast Ca and MM)
  • Vitamin D analogue synthesis (lymphomas – usually Hodgkin’s)
• Classically lethargy, confusion, anorexia and nausea
• Can be difficult to differentiate from tumor burden disease
• Constipation is common
• Osmotic diuresis secondary to hypercalcaemia also seen
• Rate of rise of calcium is the strongest predictor of symptoms vs. actual level

Hypercalcaemia

• Asymptomatic and Ca <3.5mmol/L – No treatment
• Symptomatic
  • IV N/S at rate adjusted to cardiovascular reserve
    • 1-2L bolus then 200-250mL/hr
    • Results in modest decrease over 24-48 hours but rarely normalises level
    • Frusemide only added if renal or heart failure to prevent volume overload
    • Has no additive effect to saline in actually reducing calcium level
  • Bisphosphonates
    • Only after adequate hydration to prevent calcium deposition in kidneys
    • Produce sustained decrease in calcium levels 12-48 hours after administration lasting 2-4 weeks
    • Slow IV infusion to prevent bisphosphonate-calcium complexes from precipitating in kidneys and to prevent local phlebitis seen iwht pamidronate
  • Calcitonin 4U/kg SC or IV q12h lowers plasma Ca within 2-4 hours but can cause tachyphylaxis within 3 adys
  • Steroids may be helpful in steroid-sensitive tumors such as lymphomas/MM

Hyponatraemia

• SAIDH associated with bronchogenic cancer, other cancers or secondary to chemotherapy, opioids, carbamazepine and SSRI’s
• Results in hyponatraemia, reduced serum osmolality and less than maximally dilute urine with euvolaemia, absence of diuretic therapy and normal renal, adrenal and thyroid function
• Must be suspected if normovolaemic hyponatraemia in cancer patient
• Anorexia, nausea, malaise followed by headache, confusion, obtundation, seizures and coma
• Water restriction is key
• If Na >125 – Usually asymptomatic. Water restrict to 500mL/day
• Na 110-125 – Usually mild-moderate symptoms. Frusemide 0.5-1mg/kg PO with IV N/saline to maintain euvolaemia with net free water clearance
• Na <110 or severe symptoms – 3% hypertonic saline 150mL bolus for seizures/coma then 25-100mL/hr targeting Na rise of 0.5-1mmol/L/hr and maximum 10mmol/24 hours

Adrenal insufficiency

• Usually Addisonian crisis secondary to long-term steroid use
• Rarely adrenal tissue replacement by malignant tissue
• Clues include mild hypoglycaemia, hyponatraemia, hyperkalaemia and hypotension refractory to volume replacement and vasopressors
• Need rapid IV rehydration, hydrocortisone 100-150mg IV then infusion 100-200mg over 6 hours
• Obtain serum cortisol prior to therapy if possible to help future management

Tumor lysis syndrome

• Metabolic crisis due to massive cytolysis and release of intracellular contents
• K, Phos, Calcium, nucleic acids (metabolise to uric acid) and intracellular proteins
• Mostly with treatment of haematologic cancers due to rapid cell turnover and growth rates, bulky tumor mass and high sensitivity to antineoplastic agents
• Uncommon with solid tumors or without prior chemotherapy
• Clinical effects: AKI, seizure, dysrhythmias, arrest
• Lab effects: Hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia)
• Renal failure
  • Strongest predictor of morbidity and is usually due to uric acid precipitation in renal tubules
  • Phosphorous may also chelate calcium and precipitate in tubules
  • Hypovolaemia may also contribute
• Cancer cells can contain 4x usual phosphate vs. normal cells with resultant release and hypocalcaemia

Tumor lysis syndrome

• Prophylactic allopurinol and maintaining adequate hydation are keys to prevention
  • Allopurinol prevents further uric acid synthesis but does not reduce current uric acid levels. Benefit seen at 48-72 hours
• Admit to ICU due to abrupt biochemical changes leading to instability
• Aggressive IV fluid administration to increase urinary excretion of solutes is the cornerstone of care and will counteract precipitation in tubules
• Treat hyperkalaemia as usual but avoid calcium use unless cardiovascular instability (ventricular dysrhythmias or wide QRS) or neuromuscular irritability (seizures) as can cause metastatic precipitation of calcium phosphate
• Hyperphosphataemia can be treated with phosphate binders or insulin dextrose therapy
• Haemodialysis fixes everything

Febrile neutropaenia

• Defined as absolute count <1.0×10^9/L, severe <0.5 and profound <0.1
• Fever is defined as temp >=38.3 on one occasion or >38.0 persisting >1 hour
• Nadir of neutrophils usually seen 5-10 days after last chemotherapy dose and recovery seen within another 5 days
• 50-70% of febrile neutropaenics have infectious aetiology
• Risk of infection depends upon duration and severity of neutropaenia + indwelling catheters/comorbidities
• Fever is the most common finding heralding infection and localising symptoms/signs are usually absent or muted
  • To the point of no pyuria in UTI and no radiographic changes in LRTI
• Need full examination with special attention to:
  • Oral cavity, perianal area and IV catheter sites MUST be examined
  • DRE is relatively contraindicated until after antibiotic delivery
  • Clotted catheters represent high risk of infection due to bacterial colonisation and central venous catheters carry risk of endocarditis

Febrile neutropaenia

• Take BC from peripheral stab + each central line lumen if present
  • Time to positive culture helps to elucidate if central line is infected or not (if >120min difference = significant)
• Full septic screen obviously
• Low-risk febrile neutropaenia
  • Appear well, no abdo pain, no physical signs of infection, normal CXR and neutropaenia expected to resolve within 7 days
  • Possible outpatient therapy but MUST consult with oncologist
• High-risk febrile neutropaenia
  • Not meeting all of above criteria

Febrile neutropaenia

• Treatment
  • Empiric antibiotics DEFINITELY recommended if neutrophil count <0.5
  • Little convincing evidence for empirical Ab if count >1.0
  • If between 0.5 and 1.0, other risk factors for bacterial infection must be balanced against risks of therapy
  • Gram-positive bacteria make up 60% of confirmed infections
  • Bacteraemia most commonly from:
    • Aerobic gram-positive (60-70%): S. aureus, Staph. Epidermidis (not a contaminant), Viridans Streptococci, Enterococcus faecalis/faecium or
    • Aerobic gram-negative: E. coli, Klebsiella, Pseudomonas
    • Consider viral/fungal (catheter) and parasitic
  • IV PipTaz 4.5g IV then q6h
  • IV Gent + PipTaz (metro south)
  • Add Vancomycin if: Haemodynamic instability, radiographic pneumonia, catheter-related infection, skin or soft tissue infection, known colonisation with resistant gram-positive organism or severe mucositis when fluoroquinolone prophylaxis was recently used
  • IV Meropenem +- Vanc as above if known ESBL

Febrile neutropaenia

• Median duration of fever
  • Low-risk patients: 2 days
  • High-risk patients: 5-7 days
  • Therefore, continue antibiotic therapy for 2-4 days before assessing clinical response and making therapeutic adjustments (unless deterioration or culture results return)
  • Continue empiric antibiotics until documented infection clinically resolved and/or absolute neutrophil count >0.5

Febrile neutropaenia

• Who gets their lines removed?
  • Tunnel infection
  • Persistent refractory bacteraemia
  • Atypical mycobacterial infection
  • Candidaemia

Hyperviscosity syndrome

• Most commonly Waldenstrom’s macroglobulinaemia and IgA-producing myeloma or polcythaemia (Hct > 0.60), leukaemia with WCC >100
• Dehydration exacerbates the condition
• Presentation is often vague with fatigue, abdo pain, headache, blurred vision or ALOC
• Cutaneous or mucosal bleeding is common
• Intravascular thrombosis may occur
• Hyperleukocytosis often causes dyspnoea and fever
• Fundoscopy
  • Retinal venous engorgement look like linked sausages, along with exudates, haemorrhages and papilloedema

Hyperviscosity syndrome

• Labs
  • Rouleaux formation (red cells stacked like coins)
  • Serum clotting
  • Can measure serum viscosity but will not identify it if due to polycythaemia or leukocytosis
• Treatment
  • iV fluids, early haematologist and emergency plasmapheresis or leukopheresis
  • If in a coma, emergency phlebotomy of 2U with replacement crystalloid can be performed

Hyperleukocytosis

• WCC >100 x10^9/L (some texts say >50)
• Risk factors
  • Age <1, male, M4/5 leukaemia, Philadelphia chromosome
• Complications
  • Leukostasis
  • Tumour lysis syndrome
  • DIC
  • Intracranial haemorrhage if Plt <20
• Leukocytoreduction with chemo +- leukapheresis is key to management

Hyperleukocytosis

• Leukostasis
  • Aka Symptomatic hyperleukocytosis
  • Medical emergency mostly seen with AML or CML with blast crisis
  • Characterised by extremely high blast count and decreased tissue perfusion
  • Pathological diagnosis with white cell plugs in microvasculature
  • Clinically diagnosed when hyperleukocytosis presents with respiratory or neurological distress
  • Mortality 40% at 1 week if untreated
  • Presents with microvasculature obstruction (lungs – dyspnoea/resp failure) and CNS (headache, ALOC, seizure, stroke, ICH)
  • 80% present with fever and should be treated with empirical Abs
  • More common in AML than ALL as myeloblasts are larger and more adhesive

Hyperleukocytosis

• Management in ED
  • Aggressive fluid resus
  • Prophylaxis of tumour lysis syndrome
  • Avoid anything that will increase viscosity e.g. PRBC, diuretics
  • Platelets do not increase viscosity and should be given if Plt <20 to reduce risk of ICH
  • Cytoreduction
    • Induction chemo or leukopheresis
    • Only chemo has ben proven to improve survival though
  • Hydroxyurea cytoreduction if asymptomatic hyperleukocytosis and cannot have chemo
  • Hydroxyurea with leukopheresis if symptomatic hyperleukocytosis and cannot have chemo
  • Can emergently do 2 unit phlebotomy with fluid resus if in coma
  • Leukopheresis is contraindicated in acute promyelocytic leukaemia as worsens coagulopathy specifically seen with this subtype

Thromboembolism

• Second leading cause of death in cancer patients
• Symptomatic DVT in 15% of all patients with cancer and up to 50% of advanced malignancies
• Chemo or hormonal therapy for breast cancer increases risk substantially
• LMWH for at least 6 months for cancer patients with VTE is recommended (Tintinalli) as more efficacious than warfarin (? NOAC’s)

Chemotherapy-induced vomiting

• Anticipatory – Conditioned reflex prior to administration
• Acute vomiting – First 24 hours with maximal intensity at 5-6 hours
• Delayed – Maximal intensity at 48-72 hours and can last up to 7 days
• Consider corticosteroids, benzodiazepines and olanzapine as well as usual agents

Extravasation of chemotherapeutics

• Significant tissue damage primarily vesicants including anthracycline, taxane, platin salt and vinca alkaloids
• Pain, erythema and swelling
• Stop infusion, aspirate line and remove catheter
• Elevate and immobilise limb
• Consult with oncologist immediately and early referral to plastics for anthracycline and vinca alkaloids
• Anthracyclines (doxorubicin, daunorubicin)
  • Dry cooling, dexrazoxane IV infusion and dimethyl sulfoxide to area
• Vinca alkaloids
  • Dry warming and hyaluronidase SC around area
• Cisplatin, mitomycin
  • Dry cooling, dimethyl sulfoxide over area
• Paclitaxel
  • Hyaluronidase SC around area

Last Updated on March 8, 2023 by Andrew Crofton