8.2 Oncologic Emergencies

1. Oncologic Emergencies

1. Febrile Neutropenia

• Definitions:
  • Fever: A single oral temperature ≥ 38.3°C (101.0°F) OR a sustained temperature ≥ 38.0°C (100.4°F) over ≥ 1 hour.
  • Neutropenia: Absolute Neutrophil Count (ANC) < 500 cells/mcL, or an ANC expected to fall < 500 cells/mcL over the subsequent 48 hours ($\text{ANC} = \text{WBC} \times [\%\text{Neutrophils} + \%\text{Bands}] / 100$).
• Risk Stratification: Calculate the MASCC (Multinational Association for Supportive Care in Cancer) Risk Index Score:
  • Score ≥ 21 indicates low risk (candidates for outpatient oral therapy with Ciprofloxacin + Amoxicillin-Clavulanate if clinically stable and reliable).
  • Score < 21 indicates high risk (mandates inpatient admission and IV broad-spectrum antibiotics).
• EMERGENCY MANAGEMENT PROTOCOL (Door-to-Antibiotic Time ≤ 60 Minutes):
  1. Obtain 2 sets of blood cultures immediately (1 set from a peripheral vein and 1 set from every lumen of any central venous catheter).
  2. Promptly initiate empiric broad-spectrum IV antipseudomonal monotherapy within 1 hour:
     • First-line Monotherapy Agents: Cefepime (2 g IV q8h), Piperacillin-Tazobactam (4.5 g IV q6h), or Meropenem (1 g IV q8h).
     • Specific Indications to Add IV Vancomycin: Hemodynamic instability / septic shock, suspected catheter-related infection, clinical evidence of pneumonia, severe skin/soft-tissue infection, or known MRSA colonization. (Do not start vancomycin routinely for uninformative fever alone).

2. Tumor Lysis Syndrome (TLS)

• Pathophysiology: Massive, rapid destruction of malignant cells following chemotherapy (or spontaneously in Burkitt lymphoma, ALL, AML), releasing intracellular ions and nucleic acids into the circulation.
• Cairo-Bishop Diagnostic Criteria (Laboratory TLS): ≥ 2 of the following electrolyte abnormalities within 3 days before or up to 7 days after starting cytotoxic therapy:
  1. Hyperuricemia: Serum Uric Acid ≥ 8.0 mg/dL (or 25% increase from baseline).
  2. Hyperkalemia: Serum Potassium ≥ 6.0 mEq/L (or 25% increase) → risk of fatal cardiac arrest and arrhythmias.
  3. Hyperphosphatemia: Serum Phosphorus ≥ 4.5 mg/dL (or 25% increase) → binds calcium to form calcium phosphate crystals, precipitating in renal tubules.
  4. Hypocalcemia: Corrected Serum Calcium ≤ 7.0 mg/dL or ionized Ca < 1.12 mmol/L (or 25% decrease) → tetany, seizures, QT prolongation.
• Clinical TLS: Laboratory TLS plus at least 1 clinical complication: Acute kidney injury (creatinine ≥ 1.5x baseline), cardiac arrhythmia, seizure, or sudden death.
• Prevention & Management:
  • Aggressive IV Hydration: Isotonic crystalloid at 2–3 $\text{L/m}^2\text{/day}$ (target urine output > 100 mL/hr). Do NOT alkalinize urine with sodium bicarbonate (alkaluria worsens calcium phosphate precipitation in renal parenchyma).
  • Allopurinol (300 mg daily PO/IV): Competitive xanthine oxidase inhibitor; prevents new uric acid synthesis (does not degrade existing uric acid); indicated for low/intermediate risk TLS.
  • Rasburicase (0.2 mg/kg IV or fixed 3–6 mg single dose): Recombinant urate oxidase enzyme; rapidly catabolizes existing insoluble uric acid into soluble Allantoin, decreasing uric acid levels within 4 hours. Indicated for high-risk TLS or established severe hyperuricemia.
  • CRITICAL CONTRAINDICATION FOR RASBURICASE: Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency. Rasburicase catabolism of uric acid generates hydrogen peroxide ($H_2O_2$). In G6PD-deficient erythrocytes (lacking NADPH), hydrogen peroxide triggers catastrophic severe hemolytic anemia and methemoglobinemia.

3. Malignant Spinal Cord Compression (MSCC)

• Etiology: Epidural metastatic disease from solid tumors (prostate, breast, lung, renal cell carcinoma) or multiple myeloma.
• Clinical Presentation: Progressive back pain (present in > 95% of cases) that worsens when recumbent / supine (due to distention of epidural venous plexus) and with Valsalva maneuvers (coughing, straining). Followed by motor weakness, sensory deficit with a clear dermatomal level, and late autonomic dysfunction (urinary retention, overflow incontinence, loss of anal sphincter tone).
• EMERGENCY MANAGEMENT PROTOCOL:
  1. Immediate IV Dexamethasone: Administer a 10 to 16 mg IV bolus immediately, followed by 4 to 16 mg daily divided q6h. Do not delay steroid administration for imaging; early corticosteroids reduce vasogenic spinal cord edema and prevent permanent paralysis.
  2. Urgent Whole-Spine MRI: Perform sagittal T1/T2 with axial MRI of the entire spine within 12–24 hours (multiple non-contiguous epidural metastases occur in > 30% of patients).
  3. Multidisciplinary Triage: Urgent neurosurgery and radiation oncology consultation. Direct surgical decompressive resection followed by postoperative radiation therapy is superior to radiation alone for patients with spinal instability, bony compression, radioresistant tumors, or progressive neurologic deficits with life expectancy > 3 months (Patchell trial).

4. Hypercalcemia of Malignancy

• Mechanisms:
  1. Humoral Hypercalcemia of Malignancy (~80%): Tumor secretion of Parathyroid Hormone-related Protein (PTHrP); associated with squamous cell carcinomas (lung, head/neck, esophagus), renal, and bladder cancer. Labs: Elevated PTHrP, suppressed intact PTH, normal 1,25-dihydroxyvitamin D.
  2. Osteolytic Bone Metastases (~20%): Extensive bone metastases with local osteoclast activation (breast cancer, multiple myeloma). Labs: Normal PTHrP, suppressed PTH.
  3. 1,25-Dihydroxyvitamin D (Calcitriol) Overproduction (<1%): Extrarenal 1-alpha-hydroxylase expression in lymphomas. Labs: Elevated 1,25-(OH)2-D, suppressed PTH.
• Phased Management Protocol:
  • Phase 1 (Immediate Volume Expansion): Aggressive IV 0.9% Normal Saline (200–300 mL/hr, 2–4 L in first 24–48 hours) to restore intravascular volume, enhance GFR, and promote urinary calcium excretion. (Add loop diuretics like furosemide only after euvolemia is restored and only if fluid overload occurs).
  • Phase 2 (Rapid Acute Reduction): Subcutaneous/IM Calcitonin (4 to 8 units/kg q12h); rapidly inhibits osteoclast resorption and enhances renal excretion within 2–4 hours. Tachyphylaxis develops within 48 hours due to calcitonin receptor downregulation.
  • Phase 3 (Sustained Osteoclast Inhibition): IV Zoledronic Acid (4 mg over 15 min) or IV Pamidronate (60–90 mg over 2–4 hours); onset of action in 48–72 hours, nadir at 4–7 days. Dose reduce for baseline renal insufficiency.
  • Refractory Disease or Severe Renal Failure (CrCl < 30 mL/min): Subcutaneous Denosumab (120 mg) (monoclonal antibody targeting RANKL) effectively suppresses osteoclasts without renal clearance.

5. Superior Vena Cava (SVC) Syndrome

• Etiology: Extrinsic compression or intravascular thrombosis of the SVC, caused by intrathoracic malignancies (~75%: small cell lung cancer, NSCLC, mediastinal lymphoma) or indwelling central venous catheters/pacemaker leads.
• Clinical Presentation: Dyspnea, facial fullness, facial and neck edema, periorbital swelling, distended collateral veins over the upper chest wall, and conjunctival injection. Pemberton Sign: Elevation of both arms above the head for 1 minute induces severe facial plethora, cyanosis, and inspiratory stridor due to thoracic inlet narrowing.
• Diagnostic Evaluation: Contrast-enhanced CT of the chest with IV contrast defines the level of obstruction, tumor extent, and presence of intraluminal thrombus.
• Management: Elevate head of bed, supplemental oxygen. Urgent Endovascular SVC Stenting provides rapid and complete symptomatic relief within 24–48 hours. Followed by definitive histology-directed systemic chemotherapy (for SCLC or lymphoma) or palliative radiotherapy (for NSCLC).