1. Oncologic Emergencies Douglas Eyolfson, MD, FRCP(C) Department of Emergency Medicine University of Manitoba

2. Objectives Categories of complications due to cancer Review selected oncologic emergencies in detail Diagnostic considerations of oncologic emergencies Treatment of selected oncologic emergencies

3. Cancer: Challenges Patients uncertain of diagnosis/treatments (Incorrect) assumption of futility Increasing number of treatable cancers Increasing survival times Increasing treatment options Complications as initial presentation of malignancy

4. Complications: Categories Local tumour compression Biochemical/metabolic derangement Myelosuppression Thromboembolic disease

5. Local Tumour Compression Acute spinal cord compression Superior vena cava syndrome Malignant pericardial effusion Upper airway obstruction

6. Biochemical/Metabolic Derangement Hypercalcemia Tumour lysis syndrome Hyperviscosity syndrome SIADH Adrenocortical insufficiency

7. Myelosuppression Granulocytopenia & sepsis Immunosuppresssion & opportunistic infections Thrombocytopenia & hemorrhage

8. Thromboembolic Disease Deep venous thrombosis Pulmonary embolus SVC syndrome

9. Acute Spinal Cord Compression Neoplastic epidural spinal cord compression (ESCC) Includes cauda equina syndrome Defn: Any radiologic evidence of thecal sac compression Severe back pain  permanent loss of neurologic function Diagnosis often delayed

10. ESCC Typically metastases to vertebrae (85-90%) Any 1 0 cancer site »Lung »Breast »Lymphoma Varying locations »Thoracic: 60% »Lumbosacral: 30% »Cervical: 10% 20% are initial presentation of malignancy

11. ESCC: Clinical Features Pain »83-95% first symptom »Often precedes neurologic findings by 7 weeks Motor findings »Present in 60-85% at time of diagnosis »Typically (not 100%) symmetrical Sensory findings »Sensory typically 1-5 levels below compression Bladder & bowel dysfunction »Late finding

12. ESCC: Diagnosis Any patient with cancer »Back pain »Neurologic findings »Bowel/bladder symptoms Any patient with unexplained back pain or neurologic findings Any patient with unexplained bowel/bladder symptoms

13. ESCC: Diagnosis l MRI »Gold standard »Spinal cord, bone soft tissues »Contraindicated with indwelling metal »Requires lying still (sometimes patient unable) l Myelography »Previous prefered modality »Equivalent sensitivity to MRI »Consider if contraindications to MRI

14. ESCC: Diagnosis CT »More availability »Low sensitivity, high specificity X-ray »Limited utility »High predictive value if vertebral collapse or pedicle erosion corresponding to radiculopathy »Insufficient sensitivity Bone scan »No information about thecal sac

15. ESCC: Treatment Start when diagnosis suspected Glucocorticoids (Dexamethasone) High dose »Paraparesis or paraplegia »96mg bolus, ½ dose q every 3 days Low dose »Minimal or no neurologic findings »10 mg bolus, 16 mg daily in divided doses »Taper when definitive treatment underway

16. ESCC: Treatment l Spine unstable »Changes in pain/findings with position, subluxation/translation, bilateral facet destruction »Surgical stabilization + resection l Spine stable »Radiotherapy

17. Superior Vena Cava Syndrome Invasion or compression of SVC »Right lung (lung CA 60-85%) »Lymph nodes (NHL 10%) »Other mediastinal structures Thrombus within SVC

18. SVC Syndrome: Clinical Features Typically slow progression Edema to head and neck »Striking, little clinical consequence Laryngeal compression »Dyspnea, stridor Increase ICP »Headache, N&V, coma

19. SVC Syndrome: Diagnosis CT »Most useful »Collateral vessels found: Sens. 96%, Spec. 92% Venography »Most useful if clot is sole etiology MRI venography »Contrast dye allergy Early tissue diagnosis essential

20. SVC Syndrome: Treatment Rarely immediately life-threatening »Slow progression Supportive care Steroids »Lymphoma/thymoma (glucocorticoid-responsive) Diuretics Anticoagulants »Thrombus

21. SVC Syndrome: Definitive Treatment Highly-dependant on type »Early tissue diagnosis essential Radiation Chemotherapy Endovascular Stent

22. Hypercalcemia 20-30% of cancer patients »Breast »Lung »Multiple myeloma Malignancy often clinically evident when hypercalcemia found Associated with poor prognosis

23. Hypercalcemia: Pathophysiology l Humoral hypercalcemia (80%) »PTHrP »Squamous cell carcinoma (lung, head, neck) »Renal »Bladder »Breast »Ovarian l Osteolysis »Bone metastases (breast) »Multiple myeloma

24. Hypercalcemia: Clinical Features Lethargy, weakness »Neuromuscular dysfunction N&V, anorexia, constipation Confusion  Coma Dehydration EKG changes »Shortened QT interval

25. Hypercalcemia: Treatment Measure PTH and PTHrP »PTHrP may direct further treatment Fluid resuscitation »Ensure adequate renal function »Dialysis may be indicated Diuretics »Furosemide 80mg IV Steroids not helpful acutely »May be part of later chemotherapy

26. Tumour Lysis Syndrome (TLS) Massive Tumour cell lysis Release large amounts of intracellular substances »K+»K+ »PO 4 - »Nucleic acids  uric acid »Hypocalcemia Arrhythmias Renal failure

27. TLS: Setting Usually post-chemotherapy (3-7 days) Hematologic malignancies »NHL, ALL, Burkitt’s lymphoma Solid tumours (rare) »Breast, small cell lung, neuroblastoma, Spontaneous TLS (rare) »NHL, acute leukemias

28. TLS: Clinical Presentation Typically 3-7 days post-chemotherapy Associated with metabolic abnormalities N&V, diarrhea, anorexia Hematuria, oligo/anuria Cramps, tetany, seizures CHF, arrhythmias, syncope Sudden death

29. TLS: Prevention Aggressive IV hydration »200 mg/kg/day »Monitor renal function/output Allopurinol/Rasburicase »Prevent formation/promote breakdown of uric acid Urinary alkalinization not useful

30. TLS: Treatment 3-5% develop TLS despite preventative measures Aggressive IV fluids »Resuscitation »Hyperphosphatemia Hyperkalemia »Ca 2+, ventolin, insulin/glucose, Na-polystyrene Diuretics Treat hypocalcemia only if symptomatic Rasburicase »Hyperuricemia »0.2mg/kg

31. TLS: Dialysis Rarely needed since rasburicase Severe oliguira or anuria Persistant hyperkalemia Hyperphosphatemia-induced sypmptomatic hypocalcemia Prognosis excellent if instituted early

32. Hyperviscosity Syndrome Waldenstrom’s macroglobulinemia »Increased serum proteins Multiple myeloma/CML »Increase cell concentrations Increase viscosity > 3 X normal »Sludging »Reduced microcirculatory perfusion

33. Hyperviscosity Syndrome: Presentation Weakness, lethargy, fatigue Stupour, coma CHF Hematology »Rouleau formation on smear Biochemistry »Laboratory difficulties (serum stasis in analyzers)

34. Hyperviscosity Syndrome: Treatment IV fluid resuscitation Immediate hematology referral Phlebotomy with RBC replacement »Temporizing measure Plasmapheresis

35. Immunosuppression in Cancer Cachexia & malnutrition Granulocytopenia Impaired antibody production »CLL, multiple myeloma Impaired cellular immunity »Lymphoma Steroid use Chemotherapy

36. Sepsis in Cancer: Presentation l Often nonspecific »Impaired febrile response »Impaired localization of infections »Neutropenia/impaired WBC shift l Weakness, lethargy l Altered LOC l Hemodynamic instability

37. Sepsis in Cancer: Diagnosis High index of suspicion »Cancer/chemotherapy »Fever »Hemodynamic compromise (beware tachycardia) Early full septic workup »Blood/urine culture »Chest X-ray »+ LP (don’t delay antibiotics) »VBG, lactate, etc. Cardioresp/hemodynamic monitoring »Include foley

38. Sepsis in Cancer: Treatment Early broad-spectrum antibiotics »Pip/Tazo »Ceftazidime Aggressive IV fluids »Pressors if required Frequent reassessment »I & O »Frequent labs

39. Conclusions Presentations of cancer and complications increasing Complications may be first presentation of cancer Complications often life-threatening Survivability increasing Vigilance and aggressive treatments required