Facilitator Version
Facilitator Version
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:
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 à increased AKI and cardiac dysrhythmias.
Wow, you have done an awesome job so far, but that Creatine has gone from 2.1 à 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.
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 non-small 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 à bone resorption (aka humoral hypercalcemia of malignancy)
3. Lymphomas – increased production of calcitriol à 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 / Symptoms / Treatment<12 / Minimal (i.e. constipation) / Monitor, low Ca diet, avoid thiazides
12-14 (chronic) / Minimal / Monitor, low Ca diet, avoid thiazides
12-14 (acute) / WITH neuro changes / IVF, calcitonin, bisphosphonate
14-18 / Regardless / IVF, calcitonin, bisphosphonate
>18 / Regardless / 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.