Download Module # 5 - Oncological Emergencies

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Module # 5 - Oncological Emergencies
Objectives:
1. Be able to recognize oncological emergencies
2. Understand appropriate initial workup for oncological emergencies
3. Understand acute management of oncological emergencies
References:
Uptodate articles on “Tumor Lysis Syundrome: Prevention and Treatment”, “Treatment and prognosis
of neoplastic spinal cord compression”, “Clinical features and diagnosis of neoplastic spinal cord
compression”, “Tumor lysis syndrome: Definition, pathogenesis, clinical manifestations”,
“Hypercalcemia of malignancy”
Zuckerman, et. Al. “How I treat hematological emergencies in adults with acute leukemia.” Blood.
September 6 2012.
CASE 1: Tumor Lysis Syndrome
In a bleary-eyed daze 8 hours into a grueling OCD shift, your pager flashes those ominous 5 digits that
you know come from the heme/onc floor. With significant trepidation you return the page. The nurse
casually informs you that the AM labs for a patient reveal a serum phosphorous of 5.6. Not being super
educated in normal lab values you brush it off and tell the nurse you’ll look the patient up.
What should you be worried about?
Tumor lysis syndrome.
What other history do you want about this patient?
Type of cancer/tumor burden: TLS most commonly occurs with high grade lymphomas (especially the
Burkitt subtype), and ALL. Can also occur with other tumor types with a high proliferative rate, large
tumor burden, or high sensitivity to cytotoxicity.
Timing of treatment/response to treatment: Expect TLS 3 days prior to initiation of chemo or 7 days
after. A rapid decline in WBC should raise increased concern.
Coexisting conditions: Particularly pre-existing hyperuricemia, nephropathy, exposure to nephrotoxins,
dehydration, simply because these can exacerbate the worst stuff about TLS.
Patient is a 22 year old female without any significant past medical history who presented to the ER with
fever and fatigue. Found to have a WBC of 540. Quickly diagnosed with AML and started on Cytarabine2
days ago.
Patient’s labs are as follows:
142
7.
9
102
23
36
2.1
62
8.3
272
98
Uric acid 12
LDH 1900
Phos 5.6
Ca 4.6
What labs are you REALLY interested in?
Technical lab classification of TLS requires 2 or more of the following:
Uric acid >/= 8 or 25% increase
K >/= 6 or 25% increase
Phosphorous >/= 4.5 or 25% increase
Calcium </=7 or 25% decrease, or ionized Ca <1.12
Also, note that the elevated creatinine indicates some early renal damage.
Elevated LDH can indicate increased likelihood of developing TLS.
The patient also rapidly dropped their WBC count, meaning a large number of cells have been lysed with
their contents spilling into the patient’s blood.
Ok, so you should probably actually go see this patient. What sorts of symptoms are you going to ask
about?
Symptoms related to the electrolyte abnormalities described above, namely nausea, vomiting, anorexia,
lethargy, hematuria, cardiac dysrhythmias, seizures, muscle cramps, tetany, syncope, heart failure
symptoms. You could try asking about sudden death. I don’t think it will go well. Of course chemo itself
can cause many of these symptoms, so the context of lab values is critical.
When you walk in the room, patient is shaking like a leaf. She says she feels “ok” but that she vomited
up the meager meal she’d forced down. Denies any muscle cramping or tetany. On physical exam, vital
signs are stable, and other than the fact that she looks SICK, you find nothing notable.
The blasé nurse you spoke to earlier is suddenly very excited and wants to transfer the patient to the
MICU. What do you think? Who do you call at this point?
Those labs are scary. Call the MICU. Call renal, too.
MICU resident is pretty moody. They tell you vital signs are stable. You know better and put up a fight.
What consequences of TLS are you so worried about?
Main cause of death is ARF or cardiac dysrhythmias.
While MICU meanders over, you note that the patient has been on prophylactic allopurinol and IVF. At
this point, what else can you do to treat this patient? How does it work?
Rasburicase at 0.2mg/kg. Unlike allopurinol which only prevents the formation of uric acid, rasburicase
will actually catalyze the oxidation of uric acid making it much more water soluble and excretable.
Probably should treat that hyperkalemia, too. Kayexelate, obviously, and glucose plus insulin, beta
agonists as temporizing measures. Calcium gluconate to prevent cardiac dysrythmias.
You gonna replace that Ca?
NO! Or rather, only at the lowest doses to relieve symptoms, which this patient is not complaining of. Ca
x Phos is >60 causes increased precipitation of CaPhos  increased AKI and cardiac dysrhythmias.
Wow, you have done an awesome job so far, but that Creatine has gone from 2.1  4.6. She has
stopped making urine. What now?
Sure hope you got that renal fellow involved early, because you’re heading to dialysis. Indications for HD
include severe oliguria/anuria, persistent hyperkalemia, or hyperphosphatemia-induced symptomatic
hypocalcemia.
So, put it all together. Tell me about the pathophysiology of TLS.
Spontaneous
cell turnover
Chemo
Cancer cell death
↑P
↑K
Precipitation
w/ Ca
Precipitation
in heart
Arrhythmia
↓Ca
↑Nucleic acid
↑Uric acid
Precipitation in
renal tubules
ARF
CASE 2: SVC Syndrome
On a routine call day at the VA, you are asked to admit a patient with, per the ER doctor, “a really bad
case of allergies.” With a resigned sigh, you go evaluate the patient. She is a 45 year old female without
significant past medical history who reports a 3 week period of increasing shortness of breath, nasal
stuffiness, cough, head fullness, and facial swelling. Symptoms typically worsen whens he bends
forward. Patient reports prior to this she has been reasonably healthy but has smoked a pack of
cigarettes a day for 30 years. On physical exam, vital signs are stable. Neck veins on the right seem
distended. Patient’s face is plethoric. You ask for her driver’s license because maybe her face just looks
like that all the time. Here’s what you see:
Differential?
Well, allergies, but also think about superior vena cava syndrome secondary to malignancy pressing on
the vessel, neoplastic invastion, or thrombosis. Also(less likely here) pericardial tamponade, heart
failrure, aortic aneurysm, vasculitis, TB, histoplasmosis, fungal infections.
What studies do you want now?
Technically, very obvious SVC syndrome can be diagnosed on physical exam alone. CT scan can confirm
the diagnosis and give accurate information on the location of the obstruction and may guide attempts
at biopsy by mediastinoscopy, bronchoscopy, or percuatenous FNA.
CT shows a spiculated mass in the right upper chest invading the mediastinum. Mediastinal
lymphadenopathy causing compression of the SVC and right main pulmonary artery. Now that you’ve
got this back, the patient’s boy friend shows up and informs you that she’s a very brilliant computer
engineer. What you thought was jus t a chronically “slow” mental state turns out to be a very acute
change. Do you need any further diagnostic tests? How are you going to treat this patient?
The fact that the patient has some mental changes is concerning for cerebral edema, in which case
emergency treatment with steroids is indicated. Other concerning symptoms include decreased cardiac
output or upper airway edema. The patient will need treatment with radiation or chemotherapy as soon
as possible, however SVC syndrome is rarely fatal despite our perception of it as an “oncological
emergency”, therefore, patient should first undergo some sort of biopsy before radiation/chemo. This is
thanks to the magic of collateral vessels that can typically compensate for the obstruction. Radiation
before biopsy can preclude proper diagnosis in 50% of cases.
Biopsy results show Non-small cell lung cancer. What are the tumors that are the most likely causes of
SVC syndrome?
60% malignancy, most commonly (in order) non-small cell lung cancer, small cell lung cancer, lymphoma,
germ cell tumors. Other causes include intravascular devices and fibrosing mediastinitis.
Biopsy is consistent with non-small cell lung cancer. Patient is shipped off to UNM for radiation and you
are left with a hopelessly dissatisfying sense of irresolution.
CASE 3: Hypercalcemia of malignancy
You are admitting a 65 year old man with past medical history significant for unresectable stage IV nonsmall cell lung cancer who was sent to the ER from clinic after routine lab work revealed a calcium of
12.4 and an albumin of 1.8. He only complains about some constipation and about a bajillion aching
joints. On physical exam, he seems a little drowsy, but is alert and oriented x3. Decreased breath sounds
in the right lung.
What other questions/symptoms are you going to ask about?
Symptoms of hypercalcemia: “Stones, bones, groans, psychic moans.” N/V, changes in mental status,
constipation, abdominal/flank pain, lethargy, depression, weakness, headache, polyuria.
When etiology is not known, also ask about other medications patient may be taking, any history of
malignancy, risk factors for HIV/AIDs.
What other workup is indicated?
Measure the albumin for corrected calcium level or ionized calcium level.
Corrected total calcium (mg/dL) = (measured total calcium mg/dL) + 0.8 (for every decrement in the
serum albumin of 1 g/dL below the reference value)
EKG: QT interval shortening is common, and, in some cases, the PR interval is prolonged. At very high
levels, the QRS interval may lengthen, T waves may flatten or invert, and a variable degree of heart block
may develop.
Circulating PTH
The rest of the chemistry panel
What cancers typically cause hypercalcemia of malignancy? By what mechanism (briefly) do they
typically do so?
There are 3 major mechanisms.
1. Breast and multiple myeloma – osteolytic metastases –> local release of bone destroying
cytokines
2. Squamous cell cancers (lung, head and neck), renal, bladder – Production of PTHrP  bone
resorption (aka humoral hypercalcemia of malignancy)
3. Lymphomas – increased production of calcitriol  increased intestinal absorption of calcium
Albumin is 1.8. Do you need to treat the hypocalcemia RIGHT NOW?
Oh my, yes. Like with all electrolyte abnormalities, the decision of whether or not to treat is dependent on
degree of lab value abnormality, acuity, and symptoms. Mainstay is normal saline, calcitonin, and
bisphosphonate. Note that calcitonin will only work for a couple days, and bisphosphonates will not reach
maximum affect for 2-4 days.
Calcium level
<12
Symptoms
Minimal (i.e. constipation)
12-14 (chronic)
Minimal
12-14 (acute)
14-18
>18
WITH neuro changes
Regardless
Regardless
Treatment
Monitor, low Ca diet, avoid
thiazides
Monitor, low Ca diet, avoid
thiazides
IVF, calcitonin, bisphosphonate
IVF, calcitonin, bisphosphonate
Hemodialysis
Of course, treating the acute hypercalcemia is appropriate, but unfortunately the hypercalcemia will
progress as the patient’s tumor burden progresses. He can be on chronic bisphosphonates for bone
protection.
Case 4: Malignant spinal cord compression
The VA ER wants you to admit a patient for intractable back pain. Great.
67 year old male with past medical history of chronic back pain from a helicopter crash 30 years ago
presents with progressive worsening of the pain over past 2 weeks. Pain is constant, 10/10, worse with
laying flat, seems to radiate into his legs when he has a bowel movement. He feels he could walk if the
pain were controlled. Denies any recent trauma or strain, has not taken anything to improve the pain.
Patient has no other significant past medical history, but he’s one of those mountain men that lives in a
shack somewhere in the Pecos and hasn’t seen a doctor in 30 years.
What else do you want to know?
Alarm symptoms: New weakness, numbness, parasthesias, bowel/bladder dysfunction (usually urinary
retention). If these are positive, start asking the cancer questions. In this patient, symptoms/risk factors for
prostate cancer, lung cancer, multiple myeloma, lymphoma would be at the top of the list.
Now that you mention it, the patient notes about a decade of difficulty urinating. His father died when he
was 60 of “some kind of cancer.”
What physical exam maneuvers will you test/what findings are you looking for?
Full neuro exam, of course.
Weakness is present in 60-85% of patients with ESCC at the time of diagnosis. Increased pain with
Valsalva is telling. Weakness is typically symmetrical, but not always. Weakness is followed by loss of
gait function and paralysis.
Sensory findings are less common, usually ascending and about 1-5 levels below the compression. If the
lesion is a cauda equina lesion, you can have saddle sensory loss, but this may not occur in lesions
above the cauda equina. Gotta check that rectal tone and the prostate.
Percussion of the spinal cord should reproduce pain.
Maneuvers are typically not positive in spinal cord compression include Lhermitte sign (electric like pain
down the spine with neck flexion) and nuchal rigidity. These should have you investigating other causes.
Patient has 5/5 strength bilateral upper extremities, 3/5 strength bilateral lower extremities, although your
exam is limited by his severe pain. He seems to have poor rectal tone, although it’s hard to tell because
you’ve done, like one test of rectal tone in your medical career. You think you feel a fairly abnormal,
nodular prostate. What diagnostic tests do you want now?
MRI of the entire thecal sac. This will tell you if there is actual spinal cord compression. Plain films provide
false negatives in 20% of cases of ESCC. If an MRI is contraindicated for some reason, you can use CT
myelography. Routine blood work to evaluate for other malignancies, i.e. CBC, blood smear, metabolic
profile including calcium and LFTs. In this patient a PSA is not a bad idea.
MRI demonstrates a large epidural lesion compressing the spinal cord resulting in deformation. Also
shows a 8 cm x 6 cm region in the prostate with low signal intensity and extracapsular extension. CBC,
metabolic panel, and LFTs are unremarkable, but PSA is 78 (nl 1-4).
While you wait for more qualified people to wake up from their cozy beds, what do you do
immediately?
Steroids! High dose glucocorticoids have generally been used (e.g 96mg IV followed by 24 mg po qid for
3 days, then tapered over 10 days). Efficacy over normal doses steroids has been questioned. General
recommendation is to use high dose for patients with neuro deficits (like this poor fella) and moderate
doses (eg bolus of 10mg IV followed by 16mg daily po in divided doses).
Also, consider calling neurology and oncology.
Give the poor guy some pain meds and an aggressive bowel regimen given tendency for poor bowel
function associated with opiates and ESCC.
Uh oh. What should you put in under “activity orders”?
Ad lib. No need to confine the patient to bed. Patients will avoid maneuvars that trigger pain and no risk
that movement will worsen neurological status.
What are the experts going to do when they get into the hospital/what factors go into their
decision?
Definitive therapy is getting that tumor out of the spinal cord by whatever means is most appropriate,
depending on the case. Those experts will want to know whether or not the tumor is sensitive to radiation
or chemo, the functional status of the patient, and the degree of ESCC. In this otherwise healthy patient
with a fairly high grade ESCC, he will likely undergo surgical decompression followed by radiation
therapy.
As you explain the diagnosis to the patient, he looks up at you with those tear-filled eyes of a man who
never cries and asks, “does this mean I’ll never walk again, doc? Am I going to die?” What do you
answer? What factors determine a patient’s prognosis in this situation?
There is a scoring system for prognostication in malignant ESCC outcomes post-radiotherapy that factors
in type of tumor, interval from tumor diagnosis to ESCC diagnosis, visceral mets at the time of radiation,
motor function before radiation, and time of developing motor deficits before radiation. This guy has a
score of 34, corresponding to a six month survival of 42% and post radiation ambulatory rate of 70%.
MKSAP Questions 105, 128.
Post Module Evaluation
Please place completed evaluation in an interdepartmental mail envelope and address to Dr.
Wendy Gerstein, Department of Medicine, VAMC (111).
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(1= not effective at all, 5 = extremely effective)
3) Were there any obvious errors, confusing data, or omissions? Please list/comment below:
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4) Was the attending involved in the teaching of this module? Yes/no (please circle).
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