Oncologic Emergencies

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Oncologic Emergencies

• Greg V. Manson
• Sept 5, 2008 and Sept 18, 2008

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Oncologic Emergencies

• 4 Major types
• Metabolic emergencies (hypercalcemia,
  hyponatremia, hypoglycemia, adrenal failure,
  lactic acidosis)
• Hematologic emergencies (hyperleukocytosis, DIC,
  thrombosis )
• Infectious / Inflammatory emergencies (typhlitis,
  pancreatitis, chemo infiltration, hemorrhagic
  cystitis )
• Mechanical emergencies (cerebral
  herniation/status epilepticus, cardiac tamponade,
  SVC syndrome?)

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911 VS 30512
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Case 1

• 77 y/o AAM w/ PMHx of CAD s/p CABG, DM, gout,
  bipolar I disorder, 5 year history of CLL comes
  to UCC fast track w/ severe fatigue, nausea, mild
  abdominal discomfort. Pt admitted to VA on ward
  3B. He was seen by heme/onc and started on oral
  hydroxyurea after diagnosis of acute blastic
  transformation. Youre signed-out to follow up
  on PM renal function panel.

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Case 1

• potassium 5.3 mEq/L
• calcium 8.1 mg/dL
• phosphate 5.5 mg/dL
• lactate dehydrogenase (LDH) 28,900 U/L
• and uric acid 14.3 mg/dL
• creatinine was normal, at 1.1 mg/dL

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TUMOR LYSIS SYNDROME
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Tumor Lysis Syndrome

• TLS Metabolic derangements caused by the massive
  and abrupt release of cellular components into
  the blood after the rapid lysis of malignant
  cells. (?phos , ?K , ?uric acid , ?Ca)
• Uric acid crystals and/or CaPO4 in renal tubules
  impaired renal function, ARF, even death
• ?phos leads to ?Ca tetany, seizures,
  arrhythmia
• ?K life-threatening arrhythmia

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Tumor Lysis Syndrome WHO GETS IT?

• High tumor cell proliferation rate, large tumor
  burden, tumor chemosensitivity
• ALL, AML, NHL, Burkitts Lymphoma (heme
  malignancies) Small cell gtgtgt Hodgkins disease,
  Multiple Myeloma, Solid Tumors ( breast, GI,
  prostate etc.)
• Signs and Symptoms are non-specific Can occur
  before chemo, but usually within 12 to 72hrs
  after starting chemo

Nausea Vomiting Diarrhea Anorexia Syncope
Lethargy Edema Fluid overload Cramps Sudden death
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Tumor Lysis Syndrome WHO GETS IT?

• Usually develops after chemotherapy (paclitaxel,
  fludarabine, etoposide, thalidomide, bortezomib,
  and hydroxyurea )
• Can occur after radiation therapy,
  corticosteroids, chemoembolization, intrathecal
  chemotherapy, rarely from spontaneous necrosis
• LDH is considered by some a measure of tumor load
  and a marker of TLS risk

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Tumor Lysis Syndrome Prevention Management

• The best management is prevention.
• FLUIDS and HYDRATION
• Aggressive hydration and diuresis
• Improve intravascular volume, renal blood flow,
  GFR (decrease solute in distal nephron/renal
  microcirculation)
• /- diuretics (contraindicated in hypovolemia and
  obstructed uropathy)

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Tumor Lysis Syndrome Prevention Management

• ALKALINIZATION OF URINE
• -Uric acid gt 10xs more soluble in pH of 7.0
  compared to pH of 5.0
• -Xanthine/hypoxanthine is also significantly
  more soluble in basic urine
• - Historically used, but not based on evidence
  based practice. NOT RECOMMENDED
• -Complications of alkalinization outweighs
  benefits (calcium phosphate precipitation,
  metabolic alkalosis)

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Tumor Lysis Syndrome Prevention Management

• ALLOPURINOL
• -Competitive inhibitor of xanthine oxidase which
  decreases conversion of purine metabolites to
  uric acid. Used prophylactically for TLS
• -Prophylactic option for patients with a medium
  risk of TLS
• -Limitations
• ----1)ineffective in reducing uric acid levels
  before chemoTx
• ----2) Xanthine and hypoxanthine
  precipitate?obstructive uropathy
• ----3)reduces clearance of some chemoTx
  (azothiopurine 6-mercaptopurine)

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Tumor Lysis Syndrome Prevention Management

• RASBURICASE (recombinant urate oxidase)
• -promotes catabolism of uric acid
• Uric acid ? allantoin (10x more soluble than
  uric acid)
• -100 adult pt (w/ aggressive NHL) got 3 to 7
  days of rasburicase beginning day 1 of chemo
• 1)Uric acid levels decreased w/i 4 hrs of
  rasburicase
• 2)Normalized uric acid levels maintained
  throughout chemo
• 3)No increase in creatinine observed
• 4)No patient required dialysis
• -One European and one US study showed that
  rasburicase prophylaxis resulted in net savings
  in health care costs (9,978 for 7 day stay VS.
  51,990 for 21 day stay w/ HD)

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Case 2

• 55 y/o w/ Hx of AML s/p stem cell transplant
  several months prior. Comes to ICC for scheduled
  and routine RBC transfusion. He is also
  receiving outpatient chemo therapy via PICC. Pt
  complains of fatigue and constipation. ICC
  nurses note temp of 36.1 C, BP 82/58,
  orthostasis. He is given 1L IVF and has routine
  labs drawn as he is transferred to Tower 6. He
  is admitted under the diagnosis of hypotension.
  

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Case 2

• Upon admission to floor he denies any other
  complaints, and is compliant w/ meds.
  Additionally he has been taking tylenol for 1 day
  hx of headache and 2 weeks of bisacodyl
  suppositories
• His admission vitals 99.5, 109/76, 88, 20, 97
  on room air but is actively rigoring when you
  arrive
• WBC 0.2 , ANC0.06

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NEUTROPENIC FEVER
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Neutropenic Fever

• Neutropenia
• ANC lt 500 or lt1000 w/ a predicted nadir of lt500
  cells
• ANC (WBC) x ( of neutrophils of bands)
• Nadir usually occurs 5 to 10 days after last
  chemo dose and usually recovers w/i 5 days of
  nadir (certain leukemia/lymphoma regimens cause
  longer lasting and more profound neutropenia)
• Fever
• - Single temp of 38.3oC (101.3oF)
• - Sustained Temp of 38.0oC (100.4oF) for more
  than 1 hour

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Neutropenic Fever

• Before era of empiric antibiotics, infections
  accounted for 75 deaths related to chemotherapy
• Fever is commonly the only symptom. Common
  infections present atypically (asymptomatic UTIs,
  PNA w/o infiltrates, meningitis w/o nuchal
  rigidity, bacteremia w/ only fatigue)
• Avoid digital rectal exams/manipulations
• Careful oral exam and exam of catheter sites if
  any
• Pan Cx

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Neutropenic Fever

• BACTERIA
• Until 1980s, GNR (P.aeruginosa) were the most
  commonly identified pathogens
• 1995-2000, Gram organisms 62-76 of all
  bloodstream infections
• Trend toward Gram due to introduction of
  long-term indwelling lines (Hickmans,Mediports)
• FUNGAL
• - Risk increases w/ duration and severity of
  neutropenia, prolonged antibiotic use, and number
  of chemotherapy cycles
• -Candida (lines), aspergillus (immunocompromised,
  skin,sinus, PNA) gtgtgthisto, blasto, coccidio,
  TB(prolonged steroids, other high risk patients)

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(Neutropenic Fever) TREATMENT

• Numerous regimens studied monotherapy
  demonstrated equivalent to two drug regimens
  (i.e. piperacillin/tazobactam , cefepime,
  meropenem)
• In critically ill, add on aminoglycoside (better
  G - coverage)
• Addition of Gram () as initial empiric coverage
  in patients w/o port/catheter/line or mucositis
  has no proven clinical benefit (?VRE)
• Vancomycin or Linezolid

-Skin or catheter infection -Hx of MRSA
colonization -recent quinolone proph
-Clinical deterioration -Hypotension -Mucositis
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(Neutropenic Fever) TREATMENT

• Fungal coverage (candida or aspergillus ssp. )
• Routinely added after 5-7 days of persistent
  neutropenic fever w/o clear source
• Post mortem of fatalities after prolonged febrile
  neutropenia (1966-1975) 69 w/ evidence of
  systemic fungal disease
• Tx with liposomal amphotericin B (most common),
  voriconazole(? failed noninferiority trial?),
  caspofungin (passed noninferiority trial, less
  nephrotoxic aspergillus failure?)
• No fluconazole ? efficacy

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(Neutropenic Fever) TREATMENT

• Colony Stimulating Factors (CSF)
• NOT routinely used for neutropenic fever unless
  the patient had previous bout of neutropenic
  fever with prior chemo cycle.
• Not shown to decrease mortality
• Beneficial effects are quite modest
• Used in neutropenic septic shock/severe sepsis
  (hypotension, organ dysfunction, PNA)
• Used in patients whose bone marrow recovery is
  expected to be especially prolonged.

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Case 3

• 64 y/o WM w/o significant past medical history
  comes to ED w/ complaints of progressive LBP. He
  notes pain initially started approx 6-8 weeks ago
  w/o inciting event. He is normally very active
  and enjoys jogging/biking currently still
  working as bartender. He went to Chagrin
  Highlands Urgent Care two weeks ago and got
  routine lumbosacral films which were essentially
  normal. He was discharged home w/ course of high
  dose NSAIDS. He comes to UH ED w/ complaints of
  persistent and progressive band like lower back
  pain. He notes new unsteadiness when he walks
  for the last two days, which prompted him to come
  to medical attention.

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Case 3

• In ED vitals and labs were within normal limits
• MRI of spine showed metastatic disease diffusely
  noted w/ thecal sac impingement at level of L2-L3
• PSA sent from ED 68

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SPINALCORD COMPRESSION
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Spinal Cord Compression

• Neoplastic epidural spinal cord compression
• Neoplastic invasion of space between vertebrae
  and spinal cord (epidural invasion)
• Defined as ANY thecal sac indentation
  radiographically (spinal cord or cauda equina)

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LOCATION

• Thoracic spine 60
• Lumbosacral spine 30
• Cervical spine 10

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Spinal Cord Compression

• Cord compression is a common complication in
  oncology patients (5-10 of all cancer patients
  prostate, lung, breast) which is a cause of pain
  and irreversible loss of neurologic function.
• NOT immediately life threatening unless it
  involves C3 or above
• Back pain is the precursor to spinal cord injury
  in almost all (96)patients w/ spinal mets. Pain
  similar to disc disease except ? pain supine,
  ?upright

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Spinal Cord Compression

• Besides back pain
• Radicular pain
• Motor weakness
• Gait disturbance
• Bowel bladder dysfunction

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Spinal Cord Compression

• Diagnosis
• Back pain known malignancy SCC until proven
  otherwise
• Plain films NOT enough
• Exam has poor accuracy with localizing level
• MRI without contrast is the best test for SCC
  when suspected
• Can resort to CT (myelography) if pt cannot
  tolerate MRI, is not candidate for MRI, or not
  available.

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Spinal Cord Compression

• TREATMENT
• Steroids
• Radiation Therapy
• Surgery

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Spinal Cord CompressionTreatment

• Corticosteroids
• Provides pain relief and anti-inflammation
• Dexamethasone Loading dose of 10mg to 16mg
  followed by 4mg q 4hrs.
• Higher doses (100mg) may be associated w/
  slightly better outcome in exchange for higher
  incidence of adverse effects. Reserved for
  paraplegia/paraparesis generally. (low vs high
  dose studies equivocal)
• Taper once definitive treatment is underway

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Spinal Cord CompressionTreatment

• Radiation Therapy
• This alone can be used for patients who are
  ambulatory and for pretreatment before paresis
  occurs.
• Doses is variable and determined by the quantity
  of previous XRT, type of tumor, and the field of
  treatment
• For extensive disease limited survival
  meaningful palliation (short courses)
• Chemotherapy can be used but most tumor types not
  particularly chemosensitive (unless NHL,
  Hodgkins, germ cell, breast).

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Spinal Cord CompressionTreatment

• Surgery---evolving science
• THEN Previous studies Laminectomy w/ or w/o RT
  vs RT alone NO difference in outcome
• Decompressive resection reserved for unstable
  spine, life threatening compression, unknown
  etiology, tumors that are not reliably
  radiosensitive or chemosensitive.
• NOW Newer studies show surgical intervention
  XRT show BETTER functional status than XRT
  alone (anterior approach, improvements in
  instrumentation)

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Spinal Cord CompressionTreatment

• Other Management issues
• Quickly involve Rad/onc and NeuroSx / Ortho
• Analgesia opioids, steroids
• Bed rest controversial- but generally
  unnecessary
• Anticoagulation DVT prophylaxis
• Bowel regimen autonomic dysfunction, opioids,
  limited mobility all contribute to constipation
• Spinal bracing only in patients with refractory
  pain

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Spinal Cord CompressionPrognosis

• Best predictor is pre-treatment
  functional/neurologic status
• Rapid onset and quick progression poor Px
• 75 of patients treated correctly while still
  ambulatory, will remain ambulatory
• Only 10 of patients presenting with paraplegia
  will regain ambulatory status

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References

• Guidelines for the Management of Pediatric and
  Adult Tumor LYsis Syndrome An Evidence Based
  Review. Bernard et al. Journal of Clinical
  Oncology. Vol 26. June 1 2008
• Harrisons Principles of Internal Medicine.
  Kasper, Dennis MD, et al. 16th ed. 577-582.
  2006.
• Oncologic Emergencies Diagnosis and Treatment.
  Halfdanarsan et al. Mayo Clinic Procedings. June
  2006 81(6). 835-848
• Fever in the neutropenic adult patient with
  cancer. Robbins,Gregory. Up to Date Online.
  May 31, 2008
• Oncologic Emergencies for the Internist.
  Krimsky, William, et al. Cleveland Clinic Journal
  of Medicine. Vol 69. 3. March 2002
• Treatment and Prognosis of Epidural Spinal Cord
  Compression, Including Cauda Equina Syndrome.
  Schiff, David et al. Up to Date Online. May 31,
  2008.
• Tumor Lysis Syndrome. eMedicine. Koyamangalath
  Krishnan

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Learning Objectives

• Identification of 3 major oncologic emergencies
• Management of tumor lysis syndrome
• Management of neutropenic fever
• Management of spinal cord compression