Oncologic Emergencies & Symptom Management

Oncologic Emergencies & Symptom Management

1. ONCOLOGIC EMERGENCIES Terry Gruchow MHS PA-C Internal Hospital Medicine Moffitt Cancer Center Tampa, Florida March 10, 2018

2. Oncologic Emergencies I have no financial relationships, commercial interests or conflicts to disclose

3. EMERGENCIES Crisis Unforeseen combination of circumstances Condition requiring immediate action

4. ONCOLOGIC EMERGENCIES HYPERCALCEMIA TUMOR LYSIS SYNDROMES SIADH HYPERVISCOSITY STATES ELEVATED INTRACRANIAL PRESSURE/CEREBRAL EDEMA SPINAL CORD COMPRESSION SUPERIOR VENA CAVA SYNDROME URGENCIES NEUTROPENIC FEVER Miscellaneous

5. Hypercalcemia of Malignancy Humoral H ypercalcemia ( PTHrP ) - B one resorbing activity . I nteracts with renal PTH receptor -Stimulate renal calcium resorption Squamous Cell Carcinoma Renal C ell Carcinoma Ovarian and Breast Cancer 1,25 (OH)2 Vit . D Production – Increased osteoclastic bone resorption . Intestinal absorption of calcium - Myeloma - Lymphoma

6. Hypercalcemia of Malignancy Local O steolytic H ypercalcemia Breast cancer Multiple myeloma Lymphoma/leukemia Lung cancer Prostate cance r

7. Clinical Manifestations of Hypercalcemia Total Calcium > 12 mg/ dL Rapidity of increase MOANS, STONES and GROANS Altered mental status, renal calculi, constipation/cramps, n/v, seizures RENAL: Dehydration, polyuria/ dipsia CV: bradycardia , arrhythmia (Shortened QT) Muscle weakness, lethargy, psychosis

8. Treatment of Hypercalcemia MILD Hypercalcemia Avoid inactivity and ambulate Avoid dehydration Severe Hypercalcemia Rehydrate Increase renal calcium excretion Decrease Bone Resorption

9. Treatment of Hypercalcemia Rehydration : IVF NS at rate necessary to achieve diuresis of 100 cc/ hr or as limited by CV status R enal C alcium Excretion : L oop diuretics (furosemide). Heart Failure, Renal Insufficiency Decrease Bone Resorption : B isphosphonates ( zoledronate / pamidronate / etidronate , etc ) Monitoring Check electrolytes q 8 to 12 hours 12-lead EKG and telemetry – Shortened QT interval Calcitonin Antagonizes effects of PTH. Results seen in 12 – 48 hrs. Short term Effects.

10. Tumor Lysis Syndrome Syndrome of Metabolic D isorders – S equelae to spontaneous or treatment-induced cell death. The resulting electrolytes and metabolites overcome the kidney’s ability to maintain homeostasis. TLS has historically been associated with: poorly differentiated highly proliferative treatment-sensitive high tumor burden myelolymphoproliferative disorders (acute leukemias /lymphomas) Rare in pts with epithelial malignancies

11. Tumor Lysis Syndrome Etiology: Massive release of K, PO4, Uric Acid and other breakdown products of dying tumor cells, 12 – 72 hrs post cytotoxic and/or radiation Clinical Presentation: Nausea/vomiting, diarrhea, muscle cramps, paresthesia , seizures, tetany , syncope, fluid overload, chest pain and palpitations. Labs: CBC, CMP , Mag, PO4, Uric Acid, LDH

12. Tumor Lysis Syndrome DX: Renal failure, Hyperuricemia , Hyperphosphatemia , Hypocalcemia and Hyperkalemia H yperuricemia : Most common metabolic abnormality - uremia , acute renal failure and an elevated anion gap metabolic acidosis. Signs and symptoms: nausea/vomiting , mental status changes, flank pain ( urate nephrolithiasis ), chest pain (uremic pericarditis ), seizures, edema, oliguria/anuria, and non cardiogenic pulmonary edema

13. Tumor Lysis Syndrome: Hyperphosphatemia Manifestations: Symptomatic hypocalcemia. ARF, Arrhythmias Hypocalcemia M anifestations: M uscle cramps, P aresthesias , T etany , Mental status changes, Seizures, Hypotension and QT prolongation. Trousseau’s and Chvostek’s - dramatic when present but of unknown sensitivity and specificity. Hyperkalemia Presentation : Muscle weakness, Ekg Changes

14. Tumor Lysis Syndrome Laboratory TLS: 2 or more of  Uric acid Potassium Phosphate Calcium Clinical TLS: Lab TLS plus  renal failure, arrhythmias , seizures , sudden death

15. Treatment of Tumor Lysis Syndrome “Prevention is better than cure” Allopurinol prophylaxis with isotonic saline prior to antitumor treatment Treat individual electrolyte abnormalities Treat Renal failure or cardiac arrhythmias

16. Tumor Lysis Syndrome Treatment Hyperuricemia : Hydration/Diuresis – NS IVF and Diuretics (Lasix or Mannitol ) Decrease Uric Acid Production – Allopurinol Increase U ric Acid Destruction – Rasburicase Use of Allopurinol vs Rasburicase - Based on WBC, LDH, Uric Acid and Tumor Type and Extent

17. Tumor Lysis Syndrome Treatment Hyperkalemia Mild (<6) : Avoid p.o. and IV potassium. D/C offending medications Moderate (6 – 7): Same as Mild. EKG monitoring, Na polystyrene sulfonate , NS IVF Severe (>7): Symptomatic and EKG changes. Moderate Txt plus Calcium gluconate , Insulin/D50. Possible hemodialysis

18. Tumor Lysis Syndrome Treatment Hyperphosphatemia /Hypocalcemia Symptomatic hypocalcemia: IV calcium. Otherwise, treat hyperphosphatemia with phosphate binders, then address calcium

19. SIADH Normovolemic Hyponatremia Broncogenic Carcinoma: ADH production Presentation: Nausea, Myalgia, Mental Status Changes, Headaches, Fatigue Labs: Dec. Serum Na (<135), Inc. Urine Na (>40), Dec. Serum Na Osmolality (<280), Inc. Urine Na Osmolality (>100) Txt: Fluid Restriction, Diuretic Therapy, Demeclocycline . Avoid Central Pontine Myelinolysis

20. HYPERVISCOSITY SYNDROMES Due to elevated levels of compounds with high molecular weights, such as proteins. Seen in polycythemias, leukemia, monoclonal gammopathies ( IgM ) in Waldenstrom’s macroglobulinemia , or IgA or IgG in multiple myeloma, sickle cell anemia and sepsis.

21. HYPERVISCOSITY SYNDROMES Symptoms/Signs: Bleeding, headache, SOB, altered MS, visual disturbances, CHF, Raynaud’s phenomenom Labs: Serum and Plasma Viscosity W ide globulin gap – significant paraprotein . Rarely occurs unless plasma viscosity is 4 or greater (NL: 1.4 – 1.9) TX: Urgent plasmapheresis (Myeloma) Leukapheresis (Leukemic) Phlebotomy ( Polycythemic Crisis)

22. Pathophysiology Of Hyperviscosity syndromes Decreased Flow In the CNS vasculature Decreased Platelet function Expanded Plasma volume Thrombosis Symptoms 5 “ D ’ s ” Deafness Diplopia Dizziness Decreased vision Dull headache Symptoms Epistaxis Symptoms Shortness of breath Congestive Heart Failure Symptoms Visual Inpairment Physical Exam Nystagmus Papilledema Ataxia Physical Exam Mucosal hemorrhages Fundus hemorrhages And exudates Physical Exam S3, rales, elevated jugular venous pressure Lower extremity Edema e.t.c. Physical Exam “ sausaqge-linked ” retinal veins Central retinal vein thrombosis

23. Herniation Syndromes Mechanisms of increased intracranial pressure (ICP) in cancer patients Vasogenic Edema : Brain metastases from melanoma and lung cancer. Cerebral hemorrhage : M elanoma, choriocarcinoma , renal cell carcinoma and papillary thyroid cancer. CSF Obstruction : Large mass lesions or tumor burdens, e.g. leukostasis with acute leukemias or leptomeningeal carcinomatosis . CSF obstruction due to large infectious burdens of Cryptococcus, Aspergillus , Candida, Listeria and Herpes Simplex Virus. Cancer-induced hypercoagulopathy : Sinus venous thrombosis. At the other end of the spectrum, cancer patients on anticoagulation for venous thromboembolism, thrombocytopenic after chemotherapy or inherently prone to spontaneous bleeding e.g. promyelocytic leukemia, may have elevated acute ICP because of coagulopathies.

24. Herniation Syndromes Central Decreased consciousness Headache/Focal neurological deficits Cheyne Stoke respirations/fixed pupil Uncal Rapid loss of consciousness Ipsilateral hemiparesis /Lateral pupil dilation Temporal lobe mass Tonsillar Occipital headache Hiccups/emesis/respiratory compromise Posterior fossa mass

25. Increased Intracranial Pressure Symptoms: Headache most common SX (increased in the morning after lying supine all night) and is relieved with emesis. Depressed level of consciousness, lethargy and coma. Signs: Ocular findings: Papilledema, when early, causes lack of venous pulsations of the optic disc, while later, the margin of the optic disc becomes blurred. Koscher -Cushing triad: hypopnea, hypertension and bradycardia Abnormal Posturing Depressed Level of Consciousness

26. Increased Intracranial Pressure Diagnosis: Gold standard: Measurement of the intracranial pressure (ICP) – NL: <15 mm Hg, > 20 mm Hg - pathologic . Role of CT scans; L ess accurate than direct measurement. In a prospective study of 753 patients whose initial CT scans were negative for midline shifts or mass lesions, a 10-15% chance of developing elevated ICP during their hospitalization was found. MRI with gadolinium: Modality of choice as better able to distinguish between infectious, neoplastic and ischemic etiologies of increased ICP which would affect treatment strategies.

27. Increased Intracranial Pressure: Management IV dexamethasone 10 - 100 mg load, then 4 - 24 mg qd (if from tumor induced vasogenic edema) Head elevation (facilitate gravity assisted cerebral venous drainage) Isotonic fluids to maintain euvolemic iso /hyper-osmolality (goal to keep the cerebral perfusion pressure (CPP) 60-75 mmHg. CPP is mean arterial pressure (MAP) – ICP* Intubation/hyperventilation (keep pCO2 25-30: stimulates cerebral vasoconstriction)

28. Increased Intracranial Pressure: Management IV Mannitol in unstable patients to promote osmotic diuresis (dose of 20-25% @ 0.75-1.0 g/kg IV initially, then 0.25-0.5g/kg every 3-6 h is recommended by most experts. This is to be discontinued if the serum osmolality exceeds 300) Neuro-surgical decompression (herniation) Supportive Care

29. Spinal Cord Compression Infection Hematoma Herniated disc Vertebral fractures Myelopathy Metastasis ( prostate, thyroid, breast, lung , RCC, NHL,,MM). Thoracic (70%), LS (20%), Cervical (10%). P T B arnum L oves K ids Leptomeningial disease

30. Spinal Cord Compression Symptoms  Back pain, not relieved by lying down  Weakness/sensory paresthesia  Thoracic: Weak/paresthesia is ascending Gait disorder Sphincter late  Lumbar: Sphincter early

31. Spinal Cord Compression Suspect the diagnosis Aggressive evaluation with MRI (CT myelogram ). Entire Spine Neurosurgery: Tissue dx, Resection of Tumor, Vertebral Fracture, Vertebral Stabilization. Initial Consult XRT consultation IV Dexamethasone Pain control

32. Cardiac Tamponade/Pericardial Injury Secondary to metastasis: Thoracic Radiation injury Infection Uremia Hypothyroidism

33. Cardiac Tamponade Beck’s Triad Hypotension  Decline in cardiac output Muffled Heart Sounds Distended Neck Veins Dyspnea  Most common Cough, chest pain, generalized weakness T achycardia, peripheral edema, Kussmaul’s sign, pulsus paradoxus (abnormally large decrease in systolic blood pressure (>10 mmHg) on inspiration)

34. Cardiac Tamponade Workup  EKG: Sinus tachycardia : Low voltage : Electrical alternans  ECHO: Right atrial collapse  CXR  Pericardial Bx

35. Cardiac Tamponade Management  Asymptomatic with mild effusion: No emergent treatment Symptomatic: Drain fluid. Pericardiocentesis or Surgical pericardiectomy

36. Superior Vena Cava Syndrome Thoracic Malignancy 85 to 95% of cases, CVC DX: SOB, facial/neck/UE swelling, chest pain, headaches. Bending forward or lying flat worse PE: thoracic vein distention, edema of face, tachypnea Workup: CXR, CT, Histologic dx to determine therapy TX: Treat Underlying disease, stenting, surgery, thrombolytics

37. GU Obstruction Causes: prostate CA, Bladder CA, Retroperitoneal tumors like sarcoma and metastasis Dx: CT scan, ultrasound, MRI in some cases elevated creatinine, anuria Treatment: Relative obstruction – TURP/TURBT, stents percutaneous nephrostomy tubes Treat infections, fluid imbalances, etc.

38. Leukostasis Acute Leukemias  High blast counts Presentations: Resp. distress, confusion, CNS bleed Clinical dx  Heart failure, infection, Imaging: CXR  nonspecific diffuse infiltrate Txt: Leukapheresis . Hydrea as adjunct.

39. Pulmonary Complications Airway Obstruction Stents, intubation, laser therapy, brachytherapy Massive Hemoptysis – 400-600cc/24 hr Resection, laser therapy, embolization Toxic Lung Injury Supportative care, must exclude other acute causes

40. Oncologic Urgencies Bony Metastasis Common Tumors – Prostate, Thyroid, Breast, Lung, Kidney “ P.T. B arnum L oves K ids.” Treatment Bisphosphonates and Chemotherapy Surgery for femoral neck/shaft lesion or pathologic fx and consider with other significant lesions in the weight bearing skeleton like the spine. XRT including radiopharmaceuticals 89 SR

41. Oncologic Urgencies Neutropenic Fever ANC< 500, Fever: single 101 One hr 100.4 Panculture , Empiric ABX Avoid Sepsis Syndrome Typhlitis /Enteritis DVT/PE Extravasation of vesicants. Stop infusion and plastic surgery consult.

42. Oncologic Emergencies Thank you for your attendance and attention