Oncologic Emergencies

1. Oncologic Emergencies Haskell (Gill) Kirkpatrick M.D. 9/22/05

3. Malignant Spinal Cord Compression (MSCC) • Affects 5-10% cancer patients • Most commonly: breast, prostate, lung, lymphoma and multiple myeloma • 20% MSCC cases are initial presentation • Bone (axial skeleton) common site of metastasis • Vertebral and epidural venous plexus (Batson’s plexus) • Most common mechanisms • Hematogenous met to vertebral body extending into epidural space • Pathologic fracture of vertebral body (infiltrated with tumor) resulting in cord injury from bone fragmentation or instability • 65% cases affect thoracic spine • 20% cases lumbar spine (colon and prostate predilection) • Cervical and sacral involvement rare

6. Clinical Presentation of MSCC • Back pain: In certain cancer patients should be considered metastatic origin until proven otherwise • Periostium richly innervated • Vertebral body tender to palpation/percussion • Pain worse with recumbancy • Usually precedes neurologic symptoms (1-2 months) • Radicular pain most common with lumbosacral lesions • Thoracic radicular pain usually bilateral, band-like

7. Clinical Presentation of MSCC • Progression of motor findings: weakness, loss of gait, paralysis • Majority of compressions at thoracic level: paraparesis • Upper lumbar spine: conus medullaris syndrome • Distal lower extremity weakness, saddle paraesthesias and overflow leakage from bowel and bladder • Loss of bladder and bowel function generally a late finding • Majority of patients not ambulatory at time of diagnosis

8. Diagnosis of MSCC • Average time from onset symptoms to diagnosis: 3 months • MRI of whole spine is most sensitive test • Decision to use modality based on history of back pain • Suspicion for pain secondary to Degenerative disease • mostly affects lower cervical and lower lumbar spine • Waxes and wanes • Responds to NSAIDs and bed rest • Suspicion for pain secondary to MSCC • Thoracic spine • Progresses despite conservative treatments • Aggravated by supine position

10. Treatment of MSCC • Corticosteroids: Optimal dose? • “High dose” studied in only randomized trial (+/- XRT) • 96 mg IV bolus then 24 mg 4 X /day (tapered over 10 days) • Serious side effects (GI perforations and bleeding) • Most common regimen: • 10 mg bolus then 16 mg/day (divided over 4 doses) • Radiation therapy • Relieves pain in most patients • Pre-treatment neurologic fxn strong predictor of response • Underlying tumor type also predictor • Aggressive surgery • New data shows that all patients should be considered for decompressive radical resection

11. Patchell et al, ASCO 2003

12. Patchell et al, ASCO 2003

13. Patchell et al, ASCO 2003

16. Febrile Neutropenia • Should be considered an emergency • Early studies have shown high mortality when delay initiation of appropriate antibiotics • Before era of empiric antibiotics infection accounted for up to 75% of deaths associated w/ chemotherapy • Definitions: • Fever: single temp > 38.3°C (101.3°F) or 38.0°C (100.4°F) sustained greater than 1 hour • Neutropenia: usually ANC < 500 • Absolute neutrophil count (ANC)=total WBC X (%neutrophils + %bands)

17. Infection as Cause of Death in Cancer Patients Bodey GP et al, Ann Intern Med 1966;64:328

18. Organisms Causing Infection During Chemotherapy of Acute LeukemiaBodey GP et al, Ann Intern Med 1966;64:328

19. Infections

20. Febrile Neutropenia • Seeding of the bloodstream from endogenous flora in the GI tract most common cause • Commonly cultured bacterial pathogens • Gram neg (Pseudomonas, E Coli, Klebsiella etc..) • Gram pos (Coag-neg staph, staph aureus, streptococcus etc…) • Commonly cultured fungal pathogens • Candida species, Aspergillus • usually arise later as a secondary infection in patients with prolonged neutropenia and antibiotic use • Viral pathogens • HSV, VZV

21. Treatment of Febrile Neutropenia • Empiric Antibiotics • Appropriate coverage of known or suspected infection based on history/exam findings/radiographic studies • Monotherapy: • ceftazidime, imipenem, meropenem, or cefepime • Double coverage: • beta-lactam and an aminoglycoside • Awareness of institutional resistance patterns • Addition of empiric Vancomycin • Skin or catheter site infection, hypotensive, hx of MRSA colonization, mucositis, quinolone prophylaxis

22. Causes of Fever in Patients with Prolonged Neutropenia Who Are Receiving Broad-Spectrum Antibiotics Corey, L. et al. N Engl J Med 2002;346:222-224

23. Treatment of Febrile Neutropenia • Empiric anti-fungal coverage with persistent fever on broad-spectrum antibiotics and prolonged neutropenia • Amphotericin B (liposomal), caspofungin, voriconazole • Colony stimulating factors • Should not be used routinely • Appropriate for critically ill patients

24. General Principles for the Management of Fever in Patients with Neutropenia Pizzo, P. A. N Engl J Med 1993;328:1323-1332

29. Hyperleukocytosis • Neutrophil count (CML) > 250,000 may cause vasoocclusive complications • Leukemic blasts (AML) are nondeformable • Cause hyperviscosity at lower counts ( 70,000 +) • Leukostasis in microvasculature leads to clinical symptoms • Pulmonary: hypoxemia • CNS: headaches, vision changes/loss, focal deficits • Symptomatic hyperleukocytosis and AML associated with initial high mortality

30. Treatment of Hyperleukocytosis • Emergent leukophoresis can be used • Should be used as adjunct to chemotherapy • Temporizing measure • Initiate cytoreductive therapy ASAP • Blasts are rapidly accumulating • Can result in another oncologic emergency…

31. Tumor Lysis Syndrome • Rapid cell death in face of high tumor burden • Large amounts of intracellular metabolites released • Uric acid, potassium, phosphate.. • Most commonly associated with poorly differentiated lymphomas and leukemias • Burkitt’s • ALL (more commonly than AML) • Uric acid can deposit in kidney leading to ARF • Dialysis can support patient • Rasburicase or Elitek (urate oxidase): oxidizes uric acid to allantoin which is water soluble

33. Prevention of tumor lysis syndrome • Vigorous hydration • Allopurinol 300-900 mg/day • Ideally 2 days before cytotoxic therapy • Role of alkalinizing urine debatable • Increases the solubility of uric acid and decreases tendency for precipitation but… • Alkalinizing could promote calcium-phosphate deposition • Animal studies have shown that increased tubular flow rate is most important protective measure • Vigorous hydration with saline is likely as effective

35. SVCS: Primary Pathologic Diagnoses

36. Superior Vena Cava Syndrome • Invasion or external compression of SVC • Malignant tumors responsible for 80% cases • Infection and thrombosis account for most of the rest • Symptoms • Dyspnea • Facial swelling, arm edema, cyanosis • Signs • Venous distension on neck and chest wall • Facial edema

39. Superior Vena Cava Syndrome • 60% cases due to malignancy present without known diagnosis • CT preferred diagnostic tool • Importance of biospy • Short delay not compromise outcome most cases • Histology helps determine treatment and prognosis • Treatment responsive tumors: SCLC, germ cell tumors, NHL • Role for intraluminal stents?