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Oncologic Emergencies

Alex DeWeerd

Leukostasis

Definition:

  • Hyperleukocytosis is a WBC count >100,000/microL most commonly in a patient with leukemia. Leukostasis is hyperleukocytosis + clinical symptoms of decreased tissue perfusion in end organs (CNS, lungs, heart, kidneys, etc)

Pathophysiology:

  • Leukostasis is thought to be due to increased blood viscosity caused by a large population of leukemic blasts that are less deformable than mature leukocytes. As blasts increase in the blood, plugs of these more rigid cells form in the microcirculation and impede flow. The blast-endothelial cell interactions lead to endothelial cell damage, cytokine release, and subsequent hemorrhage and local hypoxemia within tissues most notably the CNS and lungs.

Presentation

  • Primarily occurs with AML and ALL. This is not common with CLL or CML, which present with high leukocyte counts in the absence of a significant increased portion of peripheral blasts
  • Respiratory: dyspnea, hypoxia (note CXR can show diffuse interstitial or alveolar infiltrates or may be normal)
  • PaO2 by ABG often falsely low from WBC consuming O2 in vitro. Trust SpO2.
  • CNS: headache, AMS, vision changes, dizziness, tinnitus, gait instability, neuro deficit

Evaluation

  • CBC w/ diff and peripheral blood smear
  • Imaging: CT head to evaluate neuro deficit and to check for ICH
  • Chest X-Ray vs. CT chest to evaluate dyspnea and air space abnormalities

Management

  • Call Hematology
  • Emergent cytoreduction
    • Leukapheresis: page Nephrology and place dialysis catheter.
    • Hydroxyurea and chemotherapy per hematology fellow
  • Transfer/admit to ICU

Tumor Lysis Syndrome (TLS)

Background

  • Lysis of malignant cells either spontaneously or in response to chemotherapy causing release of K, Phos, nucleic acids, and cytokines
  • Consequences:
    • Hyperkalemia: most urgent and immediately life threatening
    • Hyperphosphatemia: binds Ca and leads to CaPhos crystal deposition à AKI, HypoCa
    • Hyperuricemia (from breakdown of DNA) à precipitation in renal tubules à AKI
    • Hypocalcemia: can cause mental status changes, neuromuscular irritability/spasms
    • Hypotension, AKI from cytokine release
  • TLS labs
    • Uric acid ≥ 8, Ca2+ ≤ 7, K+ ≥ 6, or PO43- ≥ 4.5 OR
    • >25% change from baseline in these values

Evaluation

  • Risk Stratification:
    • Highest risk after starting chemotherapy, but can occur spontaneously
    • Highest risk if rapidly progressive, chemo-sensitive, myelo or lymphoproliferative disease; bulky disease, extensive organ/marrow infiltration
  • Tumor characteristics which confer a higher risk of developing TLS
    • High (>5% risk): ALL (WBC> 100K or LDH 2x ULN), AML (WBC> 100K), Burkitt’s (III/IV or LDH≥2xULN, DLBCL with bulky disease, intermediate risk + AKI/CKD
    • Intermediate: ALL (WBC<100K, LDH <2x ULN), AML (WBC 25-100K), Burkitt’s LDH<2x ULN), DLBCL (non-bulky, LDH>ULN), CLL (if tx with fludarabine, rituximab, lenalidomide, or venetoclax +LN 5-10 cm or ALC≥25K), plasma cell leukemia, rare chemo-sensitive solid tumors (small cell)
    • Low: all others

Management

  • Prevention:
    • High risk: q6-8h TLS labs, IVF (±loop diuretic if volume overload), allopurinol, ± rasburicase
    • Intermediate – q8h TLS labs, IVF, allopurinol
    • Low – daily TLS labs, IVF
  • IVF: goal to maintain UOP 80-100 mL/hr
  • Allopurinol: 300 mg PO BID for CrCl > 20 mL/min, UpToDate renal dosing if lower
  • Rasburicase ($$$): contraindicated in G6PD (send G6PD if not urgent and AA, Asian or Jewish descent)
    • Given if uric acid > 8 mg/dL. Get fellow approval before ordering
  • Treatment: (Can use as night/cross cover handoff)
    • K+ > 5.5: STAT EKG, lokelma 10g TID, 10 U insulin+ 1 amp D50
      • If EKG changes, then calcium gluconate and D5W at 100 mL/hr with repeat BG in 1 hr
    • Uric acid > 8 with 25% change from baseline: page hematology fellow to discuss rasburicase
    • PO4 > 4.5 with 25% change from baseline: start/↑ phos binder (sevelamer)
    • IV calcium: do not administer unless symptomatic AND hyperphosphatemia is corrected
      • With high phos, IV calcium can lead to calcium deposition and renal failure
    • Hemodialysis: may be necessary if poor renal function and/or anuria. Consider Nephrology consultation early if worsening Cr, refractory symptoms, or refractory electrolyte abnormalities.

Superior Vena Cava (SVC) Syndrome

Background

  • Commonly associated malignancies: lung cancer (NSCLC or SCLC), Non-Hodgkin or Hodgkin lymphoma, mediastinal germ cell tumors, thymic malignancies
  • Partial or complete obstruction of the SVC impedes blood return from the upper extremities, head, neck, and brain resulting in upstream congestion
  • Can be secondary to a mass in the mediastinum or thrombosis (e.g. foreign body, central venous catheter)

Presentation

  • Facial or neck swelling without generalized edema
  • Sense of head fullness, exacerbated by leaning forward or lying down
  • Pulmonary: dyspnea, stridor, hoarseness, cough (due to edema narrowing the nasal passages and larynx or mechanical airway obstruction)
  • Physical exam
    • Facial/neck edema particularly of the eye lids in the morning, distended neck and chest veins
    • Can also sometimes see upper extremity swelling, papilledema, plethora
    • Look for associated lymph node enlargement anywhere particularly including supraclavicular, cervical, and axillary region

Evaluation

  • CXR: may show mass, perihilar or mediastinal disease, mediastinal widening, or pleural effusion
  • Contrasted CT scan ± CT Venography: phased to get a view of clot contribution to obstruction to guide decision regarding anticoagulation or stenting
    • Radiology attending can coordinate with techs (requires verbal direct request)
  • MRI/MRV may provide additional information (often not possible due to pt too sick)
  • Non-malignant causes on the differential: post-radiation fibrosis, fibrosing mediastinitis (can be seen from prior infections such as histoplasma, TB, nocardiosis, aspergillus, blastomycosis), central AV fistula

Management

  • Assess airway and prepare for intubation if needed
  • Keep head of bed elevated
  • Thrombosis:
    • Removal of lines/catheters associated with thrombus
    • Consideration of anticoagulation
  • Tumor compression: the type of tumor guides treatment (tissue biopsy is key)
  • Stat/urgent consultations:
    • Interventional radiology: possible stenting/dilatation (Fastest modality, if available)
    • Radiation oncology: radiation therapy (Takes days to weeks to work)
    • Medical oncology: help with diagnosis and chemotherapy (Fast if highly chemo-responsive cancer
    • Interventional pulmonology: help with tissue dx

Spinal Cord Compression

Background

  • Malignancies where cord compression is most commonn
    • Multiple myeloma, lymphoma (both Hodgkin and NHL); lung, breast, and prostate cancer
  • Tumor mass, compression, and often displaced bone -> occupies the epidural space and impinges the thecal sac or nerve roots of the spinal cord or any spinal nerves including the cauda equina. This can lead to edema of the spinal cord white and gray matter, which eventually leads to infarction of the cord. This vasogenic edema is where glucocorticoids can play a role.

Presentation

  • Back pain (most often initial symptom, typically worse at night), motor, or sensory deficits
  • Cauda equina syndrome: bowel or bladder incontinence, ataxia

Evaluation

  • Neurologic exam with sensation testing seeking level below an identified dermatome
  • Back pain that exacerbated by movement -> mechanically unstable spine until proven otherwise (requires surgical evaluation and potential stabilization)
  • Lab testing: If no known malignancy check CBC, CMP, SPEP, and (in males) PSA
  • Bladder U/S if suspicion or retention with or without overflow incontinence
  • If suspected, order whole spine MRI w and w/o contrast. If pt unable to have MRI, CT myelography may be considered.

Management

  • Immediate high dose steroids: give dexamethasone to minimize mineralocorticoid effects. Most common dosing is 10mg IV x1 followed by 4mg PO or IV q6h
  • Consider stat/urgent consultation with:
    • Spine Team (Neurosurgery or Orthopedic surgery holds pager): consult early, ask for an operative plan from them ASAP. Affects other possible interventions.
    • Radiation oncology: one of the rare cases where overnight radiation would be considered. Requires that patient is able to lie flat for a CT simulation (rad onc orders this), and rad onc cannot proceed until Spine surgery makes a definitive call about whether or not to operate first
    • Medical oncology: help with diagnosis and chemotherapy
  • Ensure regular neuro-vascular checks and close monitoring

Brain Metastases

Background

  • Common malignancies: Lung (NSCLC), breast, kidney, colorectal carcinomas, and melanomas
  • Significantly more common than primary brain tumors
  • 80% of brain metastasis occur in the cerebrum at grey/white matter junction via hematogenous spread (smaller blood vessel diameter at the junction essentially traps tumor cells)

Presentation

  • Highly variable: so consider brain mets any cancer pt with neurologic or behavioral changes
  • Headache: worse in the mornings, with bending over or with Valsalva
  • Nausea/vomiting
  • Cognitive dysfunction: changes in memory, mood or personality
  • Neuro: focal neurologic deficits, seizures, stroke (particularly melanoma, choriocarcinoma, thyroid, and renal carcinomas)
  • Signs of elevated ICP: papilledema, vision changes, drowsiness, presyncope Evaluation
  • STAT CT if concerned for stroke or elevated ICP
  • MRI with contrast: most sensitive, can differentiate between metastases vs. other lesions
    • Suggestive features: multiple lesions, location, circumscribed margins, vasogenic edema, contrast enhancement
  • If pt has no known primary tumor: consider CT C/A/P ± PET to identify primary
  • Biopsy with histopathology and IHC: if diagnosis in doubt or if only a single lesion is present

Management

  • If severe HA, N/V, focal neuro deficits: systemic glucocorticoids
    • Dexamethasone 10mg IV x1 followed by 4mg IV q6h (or PO if tolerated)
  • Stat/urgent consults:
    • Neurosurgery: diagnostic/therapeutic intervention. Note they will need a tissue diagnosis ASAP if not known; except in cases of emergency; affects operative plan.
    • Radiation oncology: will also need tissue diagnosis, and will have to coordinate with neurosurgery about timing of surgery versus radiation. Patient must be able to lie flat; they will need a CT simulation if radiation is to be offered.
    • Medical oncology: help with diagnosis and chemotherapy. Evolving systemic therapies can be effective for controlling metastatic disease to the brain, particularly with melanoma and NSCLC subtypes (ALK, EGFR)
  • Ensure regular neuro-vascular checks and close monitoring
  • Do not perform LP without input from neurology