Oncologic Emergencies

1
Oncologic Emergencies

• Jimmy J. Hwang, MDLombardi Cancer Center
• Georgetown University Medical Center

2
Oncologic Emergencies

• Patient with Cancer, but not all symptoms (and
  etiologies) necessarily pertain to cancer
• New Symptoms Related to the Cancer
• Headache
• Mental Status Changes
• Pain
• Weakness
• Complication of Therapy
• Neutropenia
• Diarrhea
• Vomiting

3
Oncologic Emergencies

• Neutropenic Fever
• Spinal Cord Compression
• Brain Metastases
• Metabolic/Electrolyte Changes
• Tumor Lysis Syndrome
• Hypercalcemia
• SVC Syndrome
• Chemotherapy Complications

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Neutropenic Fever Definitions

• Whose definitions are they, anyways?
• Neutropenia
• Calculating the Absolute Neutrophil Count
  (ANC) Absolute WBC x (Neutrophil Band)
• ANC lt500
• Trends in Neutropenia
• Fever?
• T38.3 or 38.5C, OR
• Serial values gt38.0C

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Neutropenic Fever Etiology

• Sources
• Enteric Bacteria
• Skin Flora
• Community Acquired Agents
• Iatrogenic/Instrumentation
• Agents
• Gram Negative Rods
• Gram Positive Cocci
• Fungi
• Other

6
Neutropenic Fever Evaluation

• Physical Examination!
• Blood cultures BEFORE starting antibiotics
• Urine culture
• Chest X-Ray

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Neutropenic Fever Selecting Therapy

• One Antibiotic?
• 3rd or 4th gen. cephalosporin/carbapenam/imipenem
  
• Two Antibiotics?
• Aminoglycoside (or fluoroquinolone)
  antipseudomonal penicillin or cephalosproin

8
Neutropenic Fever Duration of Therapy

• Duration
• Approx. 7 days if quick defervesence
• Approx. 14 days if persistent fevers (ie 72 hours
  after initiating antibiotics)
• Growth Factors
• Use if patients are hypotensive/septic/severe
  cellulitis or sinusitis/abscess/prolonged
  neutropenia expected (ASCO 2000 guidelines)
• Only decreases duration of neutropenia by 1-2 days

9
Neutropenic Fever Adjusting Therapy

• Depends on cultures
• If persistent fever for more than 3-4 days,
  consider antifungal
• Vancomycin? No, if not clinically suspected
  source. There is a negative study(Cometta, Clin
  Inf Dis 2003)
• No clear role for antiviral, except
• Symptomatic
• Leukemia with positive titers

10
Neutropenic Fever Oral Antibiotics?

• Only if low risk
• No symptoms
• Normal studies/evaluation
• No comorbidities
• Cancer with good response
• Quick recovery anticipated
• Amoxicillin/ClavulanateCiprofloxacin

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Spinal Cord Compression Presentation

• Back/Neck Pain
• Radicular pain
• Worse with Valsalva/Straight leg raise
• Neurologic Findings depend on location
• Weakness (more with lamina involvement?)
• Constipation/Incontinence
• Paresthesias

12
Spinal Cord Compression Etiology

• Thoracic (70)gtLumbosacralgtCervical
• Primary Tumor
• Lung Cancer
• Breast Cancer
• Prostate Cancer
• Renal Cell Carcinoma
• Nasopharyngeal Carcinoma
• Multiple Myeloma

13
Spinal Cord Compresion Evaluation

• Physical Examination!
• MRI The new gold standard
• Approx 95 sensitivity/44-93 specificity
• Myelogram The old gold standard
• Plain X-Ray
• Bone scan may help find other locations of disease

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Spinal Cord CompressionTreatment

• Corticosteroids does dose matter?
• Dexamethasone 10 or 100 mg IV bolus, then
• Dexamethasone 4-24 mg IV q 6 hr,
• If stable for 48 hrs, may change to PO
• Clearly results in increased ambulation rates
  (Sorensen, Eur J Cancer 1994, but only 57 pts
  treated)
• Neurosurgical/-Orthopedic Evaluation
• Radiation Oncology Evaluation
• Depends on patient condition, life expectancy (ie
  cancer condition)

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Spinal Cord Compression Treatment

• If no improvement in 12-48 hr, improvement
  becomes less likely to occur
• Perhaps 40 recover motor function if compromised
  initially (Rades, JCO 2007)
• Recovery depends on condition at presentation
  (Sorenson, Cancer 1990)
• If ambulatory, 79 remain ambulatory
• If paraplegic, 21 become ambulatory
• If paralyzed, 6 become ambulatory

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Spinal Cord Compression Surgery?

• No history of cancer, or very well controlled
  disease (ie needs a diagnosis)
• Failure of radiation (at site of disease)
• Unstable spine
• Bony compression of cord

17
Spinal Cord Compression Radiation?

• Radiosensitive tumor (SCLC, lymphoma)
• Short life expectancy
• Paraplegic (especially if gt48hr)
• Medically not a surgical candidate
• Dose around 3000 cGy (2000-4500 cGy), often over
  about 2 weeks

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Spinal Cord Compression Treatment

• Patchell, Lancet 2005
• 101 pt paraplegic lt48 hr, one area of
  involvement
• Randomized to surgery-gt 30 Gy XRT OR XRT
• Surgery resulted in longer duration of retaining
  the ability to walk (126 d v. 35 d), time
  continent (129 d v. 12 d) and more patients
  becoming able to walk (9/16 v. 3/16)
• No difference in median survival (129 d v 100 d)

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Brain Metastases Presentation

• Headache
• Mental Status Changes
• Lethargy/Confusion
• Depression
• Neurologic Findings
• Seizure 10-30

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Brain Metastases Etiology

• Lung Cancer
• Breast Cancer
• Melanoma
• Renal Cell Carcinoma
• Colorectal Cancer

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Brain Metastases Evaluation

• CT scan v. MRI
• Neurosurgical Evaluation
• If one tumor
• If only two or three?
• Radiation Oncology Evaluation
• Radiosurgery
• Whole Brain Radiation

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Brain Metastases Treatment

• Corticosteroids Does Dose Matter? (in Animals)
• Dexamethasone 10 mg IV bolus, then
• Dexamethasone 4 mg IV/PO q 6 hrs (lower may be OK
  if no herniation)
• May double every 48 hours if no improvement
• Antiepileptics?

23
Brain Metastases Treatment

• Radiation
• Whole Brain Radiation
• Radiosurgery
• Gamma Knife
• CyberKnife
• Surgery
• 1 to 3 lesions, in one hemisphere
• Radiation-resistant
• Herniation

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Brain Metastases and TreatmentAnticoagulation?

• Limited Data, but it appears safe
• Main concerns tumor types especially prone to
  bleeding renal cell, melanoma, and those who
  have prior bleed
• Olin, Arch Int Med 1987, v. 147, p. 2177
• 48 pts with cancer, DVT/PE received IVC filter or
  anticoagulation
• No significant difference in outcomes
• 1 GI bleed, 1 asymptomatic CNS bleed with
  anticoagulation group 1 PE in IVC filter group

25
Tumor Lysis Syndrome

• Etiology Death of Fast Growing Cells, especially
  with high burden disease (more in males, young?)
• Mostly Hematologic Malignancies,
• Occasionally with solid tumors, reports in
• breast cancer,
• SCLC
• seminoma

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Tumor Lysis Syndrome

• Results in biochemical abnormalities
• Hyperkalemia
• Hyperuricemia
• May result in
• Renal Failure
• Cardiac Arrhythmia
• Metastatic calcification/Nephrocalcinosis

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Tumor Lysis Syndrome Treatment

• Maintain IV Hydration
• Allopurinol 300 mg, or Rasburicase
• Alkalinization of Urine? (pHgt7)
• Dialysis?
• Calcitriol? (If phosphate is normal)

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Hypercalcemia Presentation

• Gastrointestinal
• N/V/Constipation/Abdominal Pain
• Renal/Dehydration
• Neurologic
• Bone pain
• Cardiac shortened QT
• Correction of Calcium?
• Ca 0.8 x (4.0-actual albumin)

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Hypercalcemia Etiology

• Humoral hypercalcemia of malignancy
• PTH rp (N-terminal is similar to PTH)
• Squamous Cell Ca Lung/HeadNeck
• Bone involvment
• Myeloma
• Metastatic Disease, esp. Prostate/Breast Ca.
• Tumor secretion of 1,25 (OH) vitamin D from tumor
  (most often lymphoma)

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Hypercalcemia Treatment

• Hydration, Hydration, Hydration
• NSS 200-500 cc/hr as needed (often up to 4L)
• Bisphosphonates
• Pamidronate 90 mg IV over 2-4 hr
• Zolendronate 4 mg IV over 15 minutes
• Steroids? Mostly for lymphoma
• Calcitonin? 4u/kg, beware tachyphylaxis
• Phosphate?
• Treat underlying cause!
• Radiation, chemotherapy

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Bone Metastases

• Etiology May be any, but especially prostate,
  breast cancer, and to a lesser extent myeloma,
  lung or gastroesophageal cancer
• Location of Metastasis is Key
• Evaluation of Weight Bearing
• Orthopedic Evaluation?
• Pain Management
• NSAID and steroids are often helpful

32
Superior Vena Cava (SVC) Syndrome Presentation

• Facial/Arm Edema
• Dyspnea/Stridor
• Cough
• Chest pain
• Pleural effusion
• Occasionally syncope/dizzy/hoarse
• Differential Diagnosis Cardiac Tamponade

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SVC Syndrome Etiology

• Malignancy
• Lung Cancer
• Thymoma
• Lymphoma
• Germ Cell Tumor
• Metastatic Malignancy (most often Breast Cancer)
• Non-malignant
• Syphilis
• TB/Granuloma (sarcoidosis)
• Histoplasma (fibrosing mediastinitis)
• Thrombosis
• Goiter

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SVC Syndrome Evaluation

• Chest X-Ray
• CT scan of Chest
• Venogram
• Biopsy!!!
• Before treatment including steroids, if youre
  not sure

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SVC Syndrome Treatment

• Depends on underlying disease
• Chemotherapy
• Corticosteroids dexamethasone 6-10 mg po/IV q 6
  hrs
• Radiation often relieves symptoms in malignancy
  in 3-7 days
• Surgery bypass? Stent
• Anticoagulation, especially if no response to
  radiation after several weeks

36
Diarrhea Etiology

• Infection
• Disease Process
• Obstruction
• Blood?
• Radiation
• Enteritis occurs during third week, or later
• Chemotherapy
• Secretory
• Inflammatory

37
Diarrhea Evaluation

• Quantity
• Quality/Composition
• Other symptoms (dizzy, nausea, fever, bleeding)
• Concurrent Medications
• Diet

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Diarrhea Grading Toxicity (NCI)

• 1 Increase of lt4 stools/day
• 2 Increase of 4-6 stools/day, OR Nocturnal
  stools
• 3 Increase of 7 stools/day, OR incontinence, OR
  need for IVF
• 4 Physiologic consequences/ hemodynamic collapse
  requiring ICU

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Diarrhea Treatment

• Hydration
• Dietary changes
• Small meals
• Bland food
• Avoid Alchohol, Lactose
• Rule out infection
• Concurrent antibiotics, especially if neutropenic
• Loperamide
• With Irinotecan, recommend use 2 mg po q2hr until
  diarrhea free for 12 hours
• Octreotide

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Nausea/Vomiting Etiology

• Risk factors Gender, age, alcohol use
• ? Hyperemesis gravidarium, motion sickness
• Acute
• Chemotherapy Trigger Zone in area postrema
• Dopamine, serotonin, histamine, substance P,
  endorphins, acetylcholine, GABA may all activate
• Cell damage in the intestines, activating vagus,
  splanchnic nerves
• Delayed
• Substance P seems to be a key mediator
• Anticipatory
• Radiation Induced

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Nausea/Vomiting Grading Risk

• Combination Chemotherapy risks are additive
• High Risk (gt90 chance of emesis)
• Cisplatin (gt50 mg/m2), cyclophosphamide (gt1500
  mg/m2), dacarbazine
• Moderate Risk
• Low Risk (10-30)
• Taxoids, fluoropyrimidies, gemcitabine,
  etoposide, mitoxantrone
• Minimal Risk (lt10)
• Vinca alkaloids, bleomycin

Kris, JCO 2006, v. 24, p. 2932
42
Nausea/Vomiting Treatment

• Acute
• 5-HT3 Receptor Antagonists
• Ondansetron/granisteron/dolasetron/palonosetron/tr
  opisetron
• Dopamine Receptor Antagonists
• Prochloroperazine/triethylperazine, haloperidol
• Other Metoclopramide, dronabinol
• Delayed
• Corticosteroids, especially dexamethasone
• NK1 Receptor antagonists (aprepitant)
• Anticipatory Benzodiazepines, perhaps SSRI
• Radiation Induced 5HT3 Receptor antagonists

Kris, JCO 2006, Vol. 24, p. 2932
43
Nausea/Vomiting Prophylaxis

• High Risk
• Aprepitant/Dexamethasone/5HT3 antagonist
• On Days 2, 3 Aprepitant/Dexamethasone
• Moderate Risk
• Dexamethasone/5HT3 antagonist
• On Days 2,3 Aprepitant OR Dexamethasone OR 5HT3
  antagonist
• Low Risk
• Dexamethasone

Kris, JCO 2006, v. 24, p. 2932
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Complications of Chemotherapy

• Doxorubicin Cardiac toxicity (cumulative)
• Cisplatin
• Ototoxicity/Tinnitus
• Neuropathy
• Bleomycin Pulmonary toxicity
• 5-FU/Capecitabine Hand foot syndrome
• Mitomycin, Gemcitabine TTP

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Thrombotic Thrombocytopenic Purpura (TTP)

• Aka Hemolytic Uremic Syndrome (HUS)
• Five cardinal features, but rarely have all five,
  three is usually good enough to make diagnosis
• Microangiopathic hemolytic anemia
• Thrombocytopenia
• Mental status changes
• Renal Failure/insufficiency
• Fever

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TTP Peripheral Smear
Zupancic, Lancet Oncology 2007, p634
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TTP/HUS

• Differential Diagnosis
• DIC/Sepsis
• Chemotherapy induced myelosuppression
• Hepatic insufficiency
• Etiology
• ADAMTS 13 deficiency and large vWF multimers
• Infectious Shiga toxin
• Drugs chemotherapy, ticlid/plavix, other
• Cancer
• Idiopathic

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TTP/HUS Treatment

• Plasmapheresis/plasma exchange/plasma infusion
• Steroids
• Immunoadsorption (protein A column), rarely used
• Chemotherapy induced Discontinuing chemotherapy
  alone may be sufficient

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Other Oncologic Complications

• Paraneoplastic syndromes
• Complications from therapy
• Neuropathy
• Dehydration/Renal Insufficiency
• Complications from disease
• Pain control

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Oncology/Hematology

• Cancer is bad
• The balance between hope and reality
• Goals matter Patients, Families, Ours
• Call me if I can help
• Pager 202 405 2282
• Office 202 444 1287
• Email jh96_at_gunet.georgetown.edu