Mednotes

L2 Cancer Oncological emergencies and late effects

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tagscancer, lecture, oncological-emergencies, treatment-toxicity
aliasesOncological Emergencies and Late Complications

13 min read

Overview

This lecture covers the recognition and principles of management of six oncological emergencies — spinal cord compression, superior vena cava obstruction, neutropenic fever/sepsis, tumour lysis syndrome, malignant hypercalcaemia, and venous thromboembolism — each illustrated with a clinical case. It then turns to awareness of the chronic and late toxicities of cancer treatment: a broad catalogue of sequelae, immunotherapy immune-related adverse events, EGFR-inhibitor toxicity, and the sequelae of breast cancer therapy. The unifying thread is that many of these problems are precipitated by, or are the long-term price of, the treatment itself.

Spinal cord compression

  • Presenting complaint: back pain.
  • Common cancers: Breast cancer, non-small cell lung cancer, multiple myeloma, prostate cancer — generally with known bone involvement.
  • Time-critical: “If they walk in, they will walk out.” Treatment must begin within hours, not days, to maximise the chance of neurological recovery.

Symptoms:

  • Pain is radicular, exacerbated by coughing/straining, not relieved by bed rest, and frequently precedes neurological signs.
  • Suspect in any cancer patient with severe back pain in a root distribution; patients with known bone metastases should self-refer without delay.
  • Late symptoms: leg weakness (plus arms if the lesion is cervical), sensory loss, urinary retention, dribbling, or incontinence of urine/faeces.

Investigation and management:

  • Plain x-rays are normal in 1 in 5.
  • MRI whole spine is the gold standard; it is not uncommon to find more than one critical lesion. (CT myelogram is an alternative.)
  • Speed is essential: fewer than 10% of patients with established paraplegia from metastatic disease walk again.
  • Dexamethasone 16 mg / 24 h should be given immediately.
  • Best outcomes come from surgical decompression/stabilisation of the spine followed by radiotherapy. Surgery is neither feasible nor appropriate in many (frailty, extensive bone destruction, extensive disease elsewhere).
  • Chemotherapy is rarely indicated, only in chemosensitive disease e.g. BRAF-mutant melanoma, EGFR-mutant NSCLC, high-grade lymphoma.
  • Case MRI features: bone oedema, cord oedema, and a collapsed vertebral body compressing the cord.

Superior vena cava obstruction (SVCO)

Causes/associations: NSCLC (50%), SCLC (15-20%), non-Hodgkin’s lymphoma, germ cell tumours and thymomas (thymic epithelial tumours), and central venous (CV) access devices. Long-term venous access devices (venous access port, PICC catheter) can themselves cause it.

Symptoms:

  • Facial oedema and plethora (worse on raising the arms above the head).
  • Chemosis (eyes).
  • Fixed engorgement of the external and internal jugular veins.
  • Collateral veins over the anterior and lateral chest wall.
  • Arm oedema.
  • Stridor.
  • Cerebral oedema (papilloedema / agitation / delirium).

Acute management:

  • Sit the patient up.
  • Establish IV access.
  • 100% O2 if appropriate.
  • Dexamethasone 8 mg bd PO/IV — to reduce peri-tumoural oedema; some malignancies are steroid-responsive, e.g. lymphoma.
  • CXR and CT scan remain essential; involve the oncology team early.

Therapeutic options: endovascular stenting, thrombolysis, chemotherapy (chemosensitive disease e.g. BRAF-mutant melanoma, EGFR-mutant NSCLC, high-grade lymphoma), radiotherapy, and anticoagulation for tumour thrombus.

Neutropenic fever / sepsis

Definition (all together):

  • Fever ≥38.3°C, or ≥38.0°C sustained over a one-hour period, AND
  • Neutrophil count <0.5 × 10⁹/L, or <1.0 × 10⁹/L predicted to fall to <0.5 × 10⁹/L, AND
  • Chemotherapy in the last 6 weeks.

Management: take cultures then give empiric broad-spectrum antibiotics. Goal is door-to-antibiotics ≤30 minutes.

Illustrative case (Toni, 45, metastatic triple-negative breast cancer on doxorubicin-cyclophosphamide; diarrhoea and febrile on day 10; T 39.2°C, BP 95/68, P 120):

  • FBC showed a pancytopenic picture with WBC 1.2 and neutrophils 0.7 × 10⁹/L (neutropenic).
  • Blood culture grew Gram-positive cocci in the anaerobic bottle; second set and breast swab unremarkable (skin flora).
  • Faecal PCR and Clostridioides difficile toxin PCR were not detected.
  • CXR: right chest port tip at the cavoatrial junction, right mid-to-lower zone consolidation.
  • Serial counts fell to a neutropenic nadir around 27-Dec and recovered by 10-Jan.

Tumour lysis syndrome (TLS)

Definition: a potentially fatal metabolic condition occurring with a large tumour cell burden. Large volumes of tumour cells are rapidly destroyed and intracellular contents (potassium, uric acid, phosphorus, nucleic acids) are released into the extracellular space and circulation.

Resulting derangements: ↑K (hyperkalaemia), ↑PO4 (hyperphosphataemia), ↑urate (hyperuricaemia), ↓Mg (hypomagnesaemia), ↓Ca (hypocalcaemia), metabolic acidosis, and renal impairment.

  • Timing: usually within 24-48 hours after initiation of treatment (including steroids).
  • Death can result from AKI or cardiac arrest due to arrhythmias from hyperkalaemia.

Cairo-Bishop laboratory definition (value, and change vs baseline):

  • Uric acid ≥476 µmol/L, 25% increase.
  • K⁺ ≥6 mmol/L, 25% increase.
  • PO4³⁻ ≥1.45 mmol/L (adults), 25% increase.
  • Ca²⁺ ≤1.75 mmol/L, 25% decrease.

High-risk patients:

  • Disease-based: acute leukaemia, high-grade lymphoma, small cell carcinoma, germ cell tumour.
  • Comorbidity-based: renal impairment, dehydration, elevated LDH, hyperuricaemia.

Prevention (the best strategy):

  • Allopurinol (inhibits uric acid synthesis) 24-48 hours before commencing treatment.
  • Establish hydration and diuresis (dilutes excess electrolytes and increases excretion), aiming for 100 ml/hr for >6 hours pre-chemotherapy, with diuretics to maintain output.

Uric acid metabolism (targets for therapy): nucleic acids → purines → hypoxanthine → (xanthine oxidoreductase, XOR) → xanthine → (XOR) → uric acid, which is then either converted to allantoin (water-soluble) via urate oxidase (uricase)/rasburicase or renally excreted. Allopurinol and febuxostat inhibit XOR; sulfinpyrazone and probenecid promote renal excretion of uric acid.

Monitoring: each unit has a protocol; check electrolytes regularly during and after chemotherapy; daily weight; ECG if potassium/calcium change. Calcium supplementation is not usually necessary unless there is neuromuscular irritability. Consider alkalinising the urine (acetazolamide or sodium bicarbonate), which reduces uric acid precipitation by converting it to the more soluble urate salt — evidence is controversial and policies vary.

Acute management:

  • Hyperkalaemia (>6 mmol/L): ABG and correct acidosis if present (hyperkalaemia is harder to correct otherwise); ECG. If no hyperkalaemia-related changes → increase hydration, consider calcium resonium. If changes present → IV calcium gluconate. If K >6.5 (or rapidly rising) → glucose/insulin infusion plus salbutamol nebulisers.
  • Acidosis (pH <7.3): IV sodium bicarbonate, ICU.
  • Hypomagnesaemia: IV replacement.
  • Hypocalcaemia: it is due to hyperphosphataemia; do not replace in asymptomatic patients (risk of calcium phosphate precipitation). If hyperphosphataemia is present, correct it first, then give IV replacement.
  • Hyperuricaemia: rasburicase (recombinant urate oxidase) — risk of severe hypersensitivity reaction.
  • Renal replacement therapy (dialysis) may be necessary for hyperkalaemia or hyperuricaemia.

Malignant hypercalcaemia

  • Clinical picture: “stones, bones, moans, abdominal groans and psychiatric overtones.”
  • Most common cause: humoral hypercalcaemia from secretion of parathyroid hormone-related peptide (PTHrp). Can occur with any malignancy and is a poor prognostic sign.
  • Acute management: hydration and bisphosphonates.

Other points from the slide:

  • ECG: QRS decrease / PR increased.
  • Thiazide diuretics and colecalciferol (vitamin D) are flagged (highlighted) [slide does not elaborate — both raise calcium].
  • Frusemide if becoming fluid overloaded.
  • Bisphosphonates take 4-10 days to work.
  • Pain relief and laxatives.

Venous thromboembolism (VTE)

Overarching goal: prevent clot propagation and life-threatening dyspnoea.

Deep vein thrombosis (DVT):

  • Case: 86-year-old, started tamoxifen 2 weeks ago, new right leg swelling (right calf 39 cm vs left 35 cm; right ankle 24 cm vs left 21 cm), swollen since last night, slightly warmer, no pain, obs stable — i.e. unilateral leg swelling.
  • USS: right popliteal vein thrombus, 2 cm above the knee crease, with augmentation on Doppler.

Pulmonary embolism (PE):

  • Presentation: often an incidental finding; dyspnoea; pleuritic chest pain.
  • Investigations: FBC, U&E, LFTs, coags (± D-dimer), hs-troponin I, and CT pulmonary angiogram (CTPA).
  • CXR sign: Hampton’s hump (pulmonary infarction).

Treatment options:

  • Low molecular weight heparin (enoxaparin) 1.5 mg/kg SC od OR 1.0 mg/kg SC bd.
  • Coumarin derivative — warfarin (vitamin K antagonist).
  • DOAC/NOAC — rivaroxaban, dabigatran.
  • Caval filter (IVC filter traps the clot).
  • Thrombolysis considered if there is right heart strain.

Disseminated intravascular coagulation (DIC):

  • Beware the patient with clots AND bleeding — consider DIC.
  • Mechanism: a consumptive coagulopathy leading to microangiopathic haemolytic anaemia.
  • Case: 49-year-old with NSCLC adenocarcinoma, PE at diagnosis, on rivaroxaban, presenting with PV bleeding (thickened endometrium on USS, Mirena coil, short benefit). Labs supported DIC/MAHA: Hb 72 (low), platelets 35 (low), haptoglobin <0.08 (low), D-dimer >20000, INR 1.5, fibrinogen 1.2 (low), with nucleated RBCs and metamyelocytes present.

Late complications and chronic toxicities

A broad catalogue of sequelae was listed:

  • Cognitive (“chemo brain” through to the frail elderly); chemotherapy-induced amenorrhoea; chemotherapy-induced peripheral neuropathy; weight gain; arthralgias and myalgias.
  • Cardiovascular risk factors post-platinum: lipids, hypertension, weight management, general activity.
  • Fertility; family and genetics; vaginal/vulval stenosis or dryness; erectile dysfunction; stoma management.
  • Painful neuropathy after breast or lung cancer surgery; orchiectomy pain; cosmesis; financial toxicity (loss of income); vasomotor symptoms of menopause; pouchitis; amputation; osteonecrosis of the jaw; cardiomyopathy.
  • Secondary malignancies: mantle radiotherapy → increased risk of breast and thyroid cancer; cyclophosphamide → bladder cancer; tamoxifen → uterine cancer; olaparib → MDS; cyclophosphamide/ifosfamide/anthracyclines → MDS.

Endocrinopathies (with replacement therapy):

  1. Thyroid → thyroxine.
  2. Pituitary ACTH deficiency → hydrocortisone.
  3. Exocrine pancreatic dysfunction → Creon.
  4. Endocrine pancreatic dysfunction → insulin.
  5. Gonadal → testosterone.

Also: salivary glands — a Sjögren’s-like syndrome (dry mouth, dry eyes); neurological sequelae with chronic disability; chronic “-itis” of renal/liver/fibrosis.

irAEs by organ system:

  • Eye: uveitis, conjunctivitis, scleritis/episcleritis, blepharitis, retinitis.
  • Endocrine: hyper- or hypothyroidism, hypophysitis, adrenal insufficiency, diabetes.
  • Respiratory: pneumonitis, pleuritis, sarcoid-like granulomatosis.
  • Liver: hepatitis.
  • Cardiovascular: myocarditis, pericarditis, vasculitis.
  • Renal: nephritis.
  • Gastrointestinal: colitis, ileitis, pancreatitis, gastritis.
  • Skin: rash, pruritus, psoriasis, vitiligo, DRESS, Stevens-Johnson.
  • Neurologic: neuropathy, Guillain-Barré, myelopathy, meningitis, encephalitis, myasthenia.
  • Blood: haemolytic anaemia, thrombocytopenia, neutropenia, haemophilia.
  • Musculoskeletal: arthritis, dermatomyositis.

EGFR inhibitor toxicity

Agents: cetuximab/panitumumab, or erlotinib/gefitinib/osimertinib. Toxicities: seborrheic skin type, acneiform rash, macular rash, onycholysis, onychoschizia and onychorrhexis, paronychia, diarrhoea. MET/ALK inhibitors cause oedema.

Breast cancer therapy (chemo-induced amenorrhoea / endocrine therapy and oestrogen withdrawal)

  1. Pelvic symptoms: atrophic vaginitis (sterile pyuria), dyspareunia. Rx: Ovestin, lubricants and moisturisers.
  2. Arthralgias and myalgias + chemotherapy-induced peripheral neuropathy: exercise 30 minutes, 5 days a week; celecoxib or ibuprofen SR.
  3. Vasomotor symptoms (hot flashes/flushes/diaphoresis): venlafaxine/SSRIs (careful with tamoxifen and CYP2D6), gabapentin, oxybutynin, clonidine, NK1/3 inhibitors (Veozah); OTC options (black cohosh, gel/crystal pads, sheets in the fridge, ice packs, pedestal fan).
  4. Bone health: vitamin D level and prophylaxis; bone mineral density every 2-3 years; adjuvant zoledronic acid or for osteoporosis.

Transcript flag (Slide 37): the 6-per-page handout appendix (deck pages 35-40) reproduces earlier slides as thumbnails; the lab/culture/microbiology thumbnails for slides 14-17 were too small to read at that resolution. This is not a content gap — those slides are captured in full above.

Self-test

  1. List the cancers commonly responsible for spinal cord compression.
  2. Explain the meaning of “if they walk in, they will walk out” and why spinal cord compression is time-critical.
  3. Describe the immediate drug treatment and the definitive management of spinal cord compression.
  4. List the presenting symptoms of superior vena cava obstruction.
  5. Which malignancies most commonly cause SVCO, with the percentages given?
  6. Describe the acute management steps of SVCO and list the therapeutic options.
  7. Define neutropenic fever, including all three criteria.
  8. What is the door-to-antibiotics goal in neutropenic sepsis, and what must be done before antibiotics?
  9. Define tumour lysis syndrome and list the metabolic derangements it produces.
  10. State the Cairo-Bishop laboratory thresholds for TLS.
  11. Explain how allopurinol and rasburicase each lower uric acid, and why they act at different points.
  12. List the disease-based and comorbidity-based risk factors for TLS and the best prevention strategy.
  13. A patient with high-grade lymphoma develops K⁺ 6.7 mmol/L with ECG changes 24 hours after starting chemotherapy. Describe how you would manage the hyperkalaemia.
  14. Why should hypocalcaemia not be corrected in an asymptomatic TLS patient who has hyperphosphataemia?
  15. State the most common mechanism of malignant hypercalcaemia and its acute management.
  16. Distinguish the presentation of DVT from that of PE, and list the investigations for suspected PE.
  17. List the anticoagulant treatment options for VTE.
  18. A patient has simultaneous clotting and bleeding with low platelets, low fibrinogen and a D-dimer >20000. Name the condition and explain its mechanism.
  19. Name four late toxicities that are secondary malignancies, each with its causative treatment.
  20. Describe the endocrine immune-related adverse events of immunotherapy and their replacement therapies.
  21. List the skin and nail toxicities of EGFR inhibitors.
  22. Describe the management of vasomotor symptoms in breast cancer endocrine therapy and the caution regarding tamoxifen.
  23. Integrative: give two oncological emergencies precipitated by starting cancer treatment, and the mechanism in each.

Answers

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