Oncologic Emergencies Alex Raufi PGY2 Updated: 5/2015

Objectives Identify key oncologic emergencies Review initial management Know when to consult

Identifying Oncologic Emergencies Tumor Lysis Syndrome Hyperleukocytosis and Leukostasis Disseminated Intravascular Coagulation (DIC) Spinal Cord Compression Brain Metastases causing increased ICP *Superior Vena Cava (SVC) Syndrome NOT a true emergency! NOTE: SVC syndrome NOT true emergency and is the only one of these scenarios that does NOT require an urgent heme-onc consult

Case 1 A 30 y/o male p/w 4 wk hx of rapidly enlarging cervical LAD & fevers x1 wk Vitals: 39C, BP 95/60, HR 110, RR 24 PE sig. for cervical and axillary LAD as well as splenomegaly 137 | 103 | 6 / ------------------------------ 112 6.6 | 27 | 3.8 \ \ 6.6 / 55,000 --------- 90 / 20.1 \ LDH 12,000 mg/dL Phosphorus 9.9 mg/dL Urate 18.6 mg/dL

Case 1 Next step in management? Combination chemotherapy Corticosteroid therapy Hemodialysis, IV NS, rasburicase Radiation therapy To answer this question one must first recognize that the patient is presenting with Tumor Lysis Syndrome.

Tumor Lysis Syndrome Etiology: rapid cell turnover Pathophysiology: Most commonly ALL & Burkitt Lymphoma Spontaneous or treatment induced Pathophysiology: Tumor cell death ↑ PO42- ↓ Ca2+ ↑ K+ ↑ Urate ↑ Lactate ↑ LDH

Tumor Lysis Syndrome Initial management: Frequent electrolyte monitoring Initial IVF rate: ~3L/m2/day Rasburicase (superior to Allopurinol) Sodium bicarbonate Urine target pH of 7.0 prevents urate deposition in renal tubules Dialysis for: Severe oliguria Persistent hyperkalemia Hyperphosphatemia-induced symptomatic hypocalcemia Rasburicase will require heme-onc fellow approval by pharmacy

Case 1 Next step in management? Combination chemotherapy Corticosteroid therapy Hemodialysis, IV NS, rasburicase Radiation therapy To answer this question one must first recognize that the patient is presenting with Tumor Lysis Syndrome.

Case 1 Next step in management? Combination chemotherapy Corticosteroid therapy Hemodialysis, IV NS, rasburicase Radiation therapy Treatment for TLS, as we will discuss shortly, includes Hemodialysis, IV NS, rasburicase, hence answer C is correct.

Hyperleukocytosis & Leukostasis Etiology: Commonly AML (large blasts) Presentation: Neuro: confusion, somnolence, CVA Pulm: dyspnea, respiratory alkalosis Cards: angina, rarely MI Dx: WBC >100,000 + signs/sx from tissue hypoxia Lower level of suspicion for hyperleukocytosis/stasis if WBC<100,000 as it is very rare

Hyperleukocytosis & Leukostasis Initial management: Cytoreduction via Chemotherapy = 1st line If symptomatic but must delay chemo: Leukapheresis + Hydroxyurea If NO symptoms but must delay chemo: Hydroxyurea 20-40% of these patients die within 1st week of presentation! Of note Chemotherapy is only treatment proven to improve survival

Disseminated Intravascular Coagulation (DIC) Etiology: Leukemia (acute promyelocytic leukemia [APL]) Gram negative sepsis Chemo: L- Asparaginase Pathophysiology: Excess thrombin generation Consumption of clotting factors & platelets Accelerated fribinolysis Presentation: Thrombosis and bleeding

Disseminated Intravascular Coagulation (DIC) Diagnosis + schistocytes (30% of cases) ↓ platelets ↓ or decreasing fibrinogen ↑ D-dimer (fibrin split products) ↑PT/PTT Initial management: Treat underlying cause APL: All-trans retinoic acid (ATRA) If serious bleeding: FFP Cryoprecipitate – less volume than FFP Platelets Consulting heme-onc depends on severity and cause

Case 2 64 y/o male p/w 3 mo hx of progressive back pain and 2 wk hx of lower extremity weakness. Vitals: 37C, BP 110/71, HR 111, RR 18 PE sig. for tenderness at T10-T11 vertebral bodies, lower extremity muscle strength 3+ bilaterally, & increased reflexes in both lower extremities

Case 2 Labs: Hg 6.5 g/dL, WBC 8500/uL, Ca 12 mg/dL, Total protein 13 g/dL MRI shows vertebral body mass with extension into epidural space (T12) with compression of spinal cord

Case 2 Next step in management? Biopsy of epidural mass Corticosteroids followed by radiation therapy Lenalidomide Radiation therapy

Spinal Cord Compression Etiology: Breast Lung Prostate MM Lymphoma Presentation: Sudden weakness, heaviness Incontinence of bowel Urinary retention Dx: MRI

Spinal Cord Compression Initial management: Dexamethasone 20mg IV then maintenance Radiation therapy Surgical decompression Rad/Onc or Neurosurgery should be consulted before heme-onc

Case 2 Next step in management? Biopsy of epidural mass Corticosteroids followed by radiation therapy Lenalidomide Radiation therapy Clearly this is cord compression but what one must keep in mind is that radiation therapy alone would not address the swelling associated with spinal cord compression. Steroids also have the added benefit of directly treating the hypercalcaemia in this case of MM (bx results not shown) with invasion into the cord

Brain Metastases causing increased Intracranial Pressure (ICP) Etiology: Melanoma, Breast, Lung Presentation: Persistent HA, nausea/vomiting, AMS Dx: CT/MRI Initial Treatment Dexamethasone 8-10mg IV q6 hrs Mannitol Whole brain radiation Rad/Onc or Neurosurgery should be consulted before heme-onc

Superior Vena Cava Syndrome Etiology: Lung (65% of cases) Diffuse Large B Cell Lymphoma Hodgkin Disease Presentation Dyspnea Facial edema, cyanosis, plethora Cough Upper extremity edema

Superior Vena Cava Syndrome Initial management: CXR Treatment directed towards underlying d/o Bx is required NOT an oncologic emergency

Summary Tumor Lysis Syndrome Hyperleukocytosis and Leukostasis Fluids, electrolyte monitoring, rasburicase, dialysis Hyperleukocytosis and Leukostasis 1st Chemo, 2nd hydroxyurea + Leukapheresis if sx Disseminated Intravascular Coagulation (DIC) Treat underlying cause, FFP/cryo/plts for severe bleeding Spinal Cord Compression Brain Metastases causing increased ICP Both require steroids and radiation Superior Vena Cava (SVC) Syndrome NOT a true emergency! Biopsy to determine therapy

Bibliography http://www.clevelandclinicmeded.com/me dicalpubs/diseasemanagement/hematology -oncology/oncologic- emergencies/Default.htm MKSAP16 http://www.uptodate.com/