Oncologic Emergencies

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Oncologic Emergencies

• Cristina I. Truica MD
• Medical Director, Multi-Disciplinary Center for
  Breast Health

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Oncologic Emergencies

• Superior Vena Cava Syndrome
• Spinal Cord Compression
• Metabolic Emergencies
• Urologic Emergencies

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SVC Syndrome

• Obstruction of blood flow through SVC
  (head, neck, arms, upper thorax)
• Middle mediastinum lymph nodes, trachea, aorta,
  R mainstem bronchus, pulm artery, sternum
• Compression/invasion/thrombosis primary or
  metastatic tumor or central venous access device

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Symptoms/Signs

• Life threatening cerebral edema (intracranial
  pressure) or laryngeal edema ( airway compromise)
• Dyspnea- most comon symptom- 60
• Sensation of fullness in the head or facial
  swelling- 50, headaches, visual disturbance,
  dizziness ,rarely progressing to laryngeal edema,
  Sz, coma
• Cough 24, Arm swelling

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Signs

• Venous distension in the neck/chest wall
• Facial edema
• Plethora
• Sx aggravated by bending down or stooping

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Etiology

• 78-86 Malignant disease
• 65 Lung cancer
• Small cell lung cancer 38 (most common
  histologic subtype)
• NSCLC in 26
• Lymphoma 8 DLCL or lymphoblastic
• 20- noncancerous dg
• mediastinal fibrosis from histoplasmosis,sarcoidos
  is, benign tumors
• thrombosis (CVC or pacemaker related)

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Diagnostic Procedures

• CXR mass, superior mediastinal widening (60),
  pleural effusion (25)
• CT scan
• MRI
• sputum cytology dg in 50 of pt
• Bronchoscopy/Mediastinoscopy (complic 5)
• thoracenthesis
• biopsy of supraclavicular node

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Treatment

• BIOPSY ! Treat depending on pathology
• SCLC RR to chemo 93, XRT 94, relief of SVC in
  7-10 days
• NHL CR in 81
• Nonmalignant causes surgery for SVC if sudden
  onset, progression or persistence after 6-12
  months of observation

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Spinal Cord CompressionMalignant Epidural Spinal
Cord Compression

• Compressive indentation, displacement,
  
  
  or encasement of the spinal
  cords thecal sac by metastatic or locally
  advanced cancer
• posterior extension of VV body mass,
• or anterior or anterolateral extension of mass
  from dorsal elements or from vv foramen
• 20,000 patients/ year in US

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Spinal Metastases
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Spinal Cord Compression

• Multiple myeloma -most common primary bone tumor
  and 10-15 of malign epid SDz
• 3-7.4 of pt with lung, prostate, breast, kidney
  cancer
• non-spinal osteogenic sarcoma, melanoma
• breast cancer 25 of cases of MESCC diagnosed in
  cancer hospitals
• 10-40 present with MESCC as initial sx

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MESCC

• Thoracic mets twice as common as lumbar
• Extension of tumor from the vertebral body in
  85-90
• Intramedullary lesions0.8-3.8 of all cases
  (melanoma)
• Lung cancer 26 with squamous histology 9 with
  AK, 14 with SCLC

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Symptoms

• Pain 95 of adults, increased by cough, Valsalva,
  lying supine
• Pain may be radicular in nature
• Weakness, sensory loss, changes in bowel and
  bladder function
• Urinary retention, laxity of anal sphincter

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Spinal Cord Compression

• History, physical, neurologic eval
• Plain spine Xrays normal films do not exclude dg
• Bone scan information on entire skeleton in one
  exam
• MRI se 93 , sp 97 ( intramedullary lz)
• MRI multiple sites in 40-50 of cases

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Can outcome be predicted?

• Pretreatm neurologic dysfct- strongest predictor
  of treatment outcome
• Almost all pt who are ambulatory remain
  ambulatory
• Fewer than 10 of paraplegic pt will walk again
• Surgery /Radiation

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Treatment

• Steroids decadron 10-100 mg initial dose and 4mg
  every 6 hours
• No advantage of higher doses vs lower doses
• After 2 days on a stable dose of IV can switch to
  oral 4-8 mg every 6 hours
• Taper steroids every 4 days

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Metabolic Emergencies

• Hypercalcemia
• Tumor Lysis syndrome
• Hyperuricemia
• Hypoglycemia
• Adrenal Failure

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Hypercalcemia

• Most common life-threatening metabolic disorder
  in pt with cancer
• Highest incidence in myeloma and breast cancer,
  NSCLC
• Diff dg primary hyperparathyroidism

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Hypercalcemia-Symptoms

• Severity of sx not exclusively related to degree
  of elevation in serum calcium.
• Other factors age, PS, hepatic, renal dysfct
• Fatigue, lethargy, irritability, constipation,
  nausea, polyuria to severe hyper Ca CNS/cardiac
  depression
• short QT, prolonged PR, T wave changes

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Pathophysiology

• PTH-related protein (higher MW,retains homology
  to PTH) binds the PTH receptor
• Activation of bone resporbtion
• Increased tubular reabsorbtion of calcium
• P renal wasting, hypophosphatemia
• Prostaglandins E
• Cytokines- TGFalpha (inducer of bone resorbtion),
  TNF

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Effects of Elevated Bone Turnover on Trabecular
Thickness and Architecture
Severe Bone Loss
Bone Loss
Normal

• Decreases in thickness and connections lead to
  reduced strength and increased susceptibility to
  fracture

Adapted with permission from Mosekilde L. Calcif
Tissue Int. 199353(suppl 1)S121-S126.
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Estrogens and Androgens Help Maintain Normal
Bone Remodeling
Bone formation
Estrogen Androgen
Osteoblast
()
M-CSF RANKL
Estrogen Androgen
Osteoclast
(-)
Bone resorption
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Treatment

• Treatment of the underlying cancer
• Increase urinary excretion
• Saline infusion 300-400cc/hr for 3-4 hrs
  furosemide restricted to balancing fluid intake
  and urinary output
• Fluids alone not very effective

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Hypercalcemia Treatment

• Bisphosphonates chemical analogues of
  pyrophosphate resistant to hydrolysis by
  pyrophosphatase
• Adsorb to the surface of hydroxyapathite and
  inhibit Ca release from the bone by interfereing
  with activity of osteoclasts
• Low oral bioavailability

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P-C-P core structure promotes binding to bone
matrix
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Bisphosphonates

• Nitrogen containing BIsP (more potent)
• Pamidronate 60-90mg over 2 hrs, onset of action
  24-48 hrs
• Zoledronate (Zometa) 4mg over 5 min
• Alendronate
• Risendronate, Ibandronate
• Non-nitrogen Clodronate, etidronate

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Mechanism of Bisphosphonate Inhibition of Cancer
Treatment Induced Bone Loss (CTIBL)
Matureosteoclasts
Bone Loss
Aminobisphosphonates
Inhibit Farnesyldiphosphate synthase in
Osteoclast-cholesterol biosynth- Osteoclast
inactivation
Bisphosphonates
Bone
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Hypercalcemia treatment

• Galium Nitrate inhibitor of bone resorbtion (in
  pt who do not respond to two P infusions given
  48-72 hrs apart )
• Calcitonin 8U/kg sc/im every 6 hrs for 2- 3 days
• Corticosteroids inhibit osteoclast-mediated bone
  resorbtion and decrease gastrointestinal Ca
  resorbtion

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Tumor Lysis Syndrome Cell Death

• Hyperuricemia, lactic acidosis
• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia (a result of hyper P)
• With large tumor burden, exquisitely sensitive to
  cytotoxic treatment
• High grade lymphoma, leukemias

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Tumor Lysis Syndrome

• Identify pt at risk
• Hydration started 24-48 hr before chemo
• Allopurinol inhits xanthine oxidase converts
  hypoxanthine and xanthine to UA
• Monitor electrolytes
• Rasburiucase recombinant urate oxidase breaks
  down preexisting uric acid into water solluble
  allantoin

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Neutropenic Fever

• Neutropenia absolute decrease in nuetrophils
• clinically significant if ANC
• serious if
• idiosyncratic neutropenia sulfa, pen,
  anticonvulsants, antipsychotics, phenothiazines,
  acetaminophen, aspirin

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Neutropenia

• Infectionsgram negative and viral
• Autoimmune disorders polymyositis, SLE, Feltys
  sdr
• Spenomegaly
• chronic idiopathic neutropenia, cyclic
  neutropenia
• nutritional def folic ac, vit B12
• Lymphoma, ALL, MM, MDS

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Urologic Emergencies

• Urinary Tract infection Urinary
  sepsis/periuretral abscess
• Cystitis chemical cystitis
• Bladder hemorrhage
• Urinary Obstruction

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Cystitis

• Suprapubic discomfort, frequency, dysuria,
  urgency, urge incontinence, hematuria
• Sx relief pyridium, antispasmodics (ditropan),
  pro-banthine, levsin, urispas

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Cystitis

• Sx frequency, urgency, dysuria, nocturia 24
• microhematuria 7-53 gross hematuria 0.6-15
• oxazaphosphorines
• cyclophosphamide phosphoramide mustard acrolein
• ifosfamide iphosphoramide mustard acrolein

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Cystitis

• Mesna sodium 2 mercaptoethane sulfonate
  (sulfhydryl compound)
• does not penetrate the cells
• sulfhydryl terminal acrolein group
• IV , half life is 35 min
• side effects diarrhea, headaches