Oncologic Emergencies

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Oncologic Emergencies

• Haskell (Gill) Kirkpatrick M.D.
• 9/22/05

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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 (Batsons
  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

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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

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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

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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

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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

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Patchell et al, ASCO 2003
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Patchell et al, ASCO 2003
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Patchell et al, ASCO 2003
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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 gt 38.3C (101.3F) or 38.0C
  (100.4F) sustained greater than 1 hour
• Neutropenia usually ANC lt 500
• Absolute neutrophil count (ANC)total WBC X
  (neutrophils bands)

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Infection as Cause of Death in Cancer
Patients Bodey GP et al, Ann Intern Med
196664328

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Organisms Causing Infection During Chemotherapy
of Acute Leukemia Bodey GP et al, Ann Intern Med
196664328
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Infections
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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

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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

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Causes of Fever in Patients with Prolonged
Neutropenia Who Are Receiving Broad-Spectrum
Antibiotics
Corey, L. et al. N Engl J Med 2002346222-224
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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

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General Principles for the Management of Fever in
Patients with Neutropenia
Pizzo, P. A. N Engl J Med 19933281323-1332
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Hyperleukocytosis

• Neutrophil count (CML) gt 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

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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

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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
• Burkitts
• 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

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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

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SVCS Primary Pathologic Diagnoses
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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

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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?

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