Oncologic Emergencies

Greg V. Manson
Sept 5, 2008 and Sept 18, 2008

Oncologic Emergencies
4 Major types

Metabolic emergencies (hypercalcemia,

hyponatremia, hypoglycemia, adrenal failure, lactic acidosis)

Hematologic emergencies
(hyperleukocytosis, DIC, thrombosis )

Infectious / Inflammatory emergencies

(typhlitis, pancreatitis, chemo infiltration, hemorrhagic cystitis )

Mechanical emergencies (cerebral

herniation/status epilepticus, cardiac tamponade, SVC syndrome?)

911 VS 30512

Case 1:
77 y/o AAM w/ PMHx of CAD s/p CABG, DM, gout, bipolar I disorder, 5 year history of CLL comes to UCC fast track w/ severe fatigue, nausea, mild abdominal discomfort. Pt admitted to VA on ward 3B. He was seen by heme/onc and started on oral hydroxyurea after diagnosis of acute blastic transformation. Youre signed-out to follow up on PM renal function panel.

Case #1
potassium 5.3 mEq/L calcium 8.1 mg/dL phosphate 5.5 mg/dL lactate dehydrogenase (LDH) 28,900 U/L and uric acid 14.3 mg/dL creatinine was normal, at 1.1 mg/dL

TUMOR LYSIS SYNDROME

Tumor Lysis Syndrome

TLS: Metabolic derangements caused by the massive and abrupt release of cellular components into the blood after the rapid lysis of malignant cells. (phos , K , uric acid , Ca) Uric acid crystals and/or CaPO4 in renal tubules = impaired renal function, ARF, even death phos leads to Ca : tetany, seizures, arrhythmia K = life-threatening arrhythmia

Tumor Lysis Syndrome: WHO GETS IT?

High tumor cell proliferation rate, large tumor burden, tumor chemosensitivity ALL, AML, NHL, Burkitts Lymphoma (heme malignancies) Small cell >>> Hodgkins disease, Multiple Myeloma, Solid Tumors ( breast, GI, prostate etc.) Signs and Symptoms are non-specific: Can occur before chemo, but usually within 12 to 72hrs after starting chemo
Nausea Vomiting Diarrhea Anorexia Syncope Lethargy Edema Fluid overload Cramps Sudden death

Tumor Lysis Syndrome: WHO GETS IT?

Usually develops after chemotherapy

(paclitaxel, fludarabine, etoposide, thalidomide, bortezomib, and hydroxyurea )

Can occur after radiation therapy, corticosteroids, chemoembolization, intrathecal chemotherapy, rarely from spontaneous necrosis LDH is considered by some a measure of tumor load and a marker of TLS risk

Tumor Lysis Syndrome Prevention & Management

The best management is prevention. FLUIDS and HYDRATION:
Aggressive hydration and diuresis Improve intravascular volume, renal blood flow, GFR (decrease [solute] in distal nephron/renal microcirculation) +/- diuretics (contraindicated in hypovolemia and obstructed uropathy)

Tumor Lysis Syndrome Prevention & Management

ALKALINIZATION OF URINE: -Uric acid > 10xs more soluble in pH of 7.0 compared to pH of 5.0 -Xanthine/hypoxanthine is also significantly more soluble in basic urine - Historically used, but not based on evidence based practice. NOT RECOMMENDED -Complications of alkalinization outweighs benefits (calcium phosphate precipitation, metabolic alkalosis)

Tumor Lysis Syndrome Prevention & Management

ALLOPURINOL: -Competitive inhibitor of xanthine oxidase which decreases conversion of purine metabolites to uric acid. Used prophylactically for TLS -Prophylactic option for patients with a medium risk of TLS -Limitations: ----1)ineffective in reducing uric acid levels before chemoTx ----2) Xanthine and hypoxanthine precipitateobstructive uropathy ----3)reduces clearance of some chemoTx (azothiopurine & 6-mercaptopurine)

Tumor Lysis Syndrome Prevention & Management

RASBURICASE (recombinant urate oxidase) :
-promotes catabolism of uric acid: Uric acid allantoin (10x more soluble than uric acid) -100 adult pt (w/ aggressive NHL) got 3 to 7 days of rasburicase beginning day 1 of chemo: 1)Uric acid levels decreased w/i 4 hrs of rasburicase 2)Normalized uric acid levels maintained throughout chemo 3)No increase in creatinine observed 4)No patient required dialysis -One European and one US study showed that rasburicase prophylaxis resulted in net savings in health
care costs ($9,978 for 7 day stay VS. $51,990 for 21 day stay w/ HD)

Case #2:
55 y/o w/ Hx of AML s/p stem cell transplant several months prior. Comes to ICC for scheduled and routine RBC transfusion. He is also receiving outpatient chemo therapy via PICC. Pt complains of fatigue and constipation. ICC nurses note temp of 36.1 C, BP= 82/58, + orthostasis. He is given 1L IVF and has routine labs drawn as he is transferred to Tower 6. He is admitted under the diagnosis of hypotension.

Case #2:
Upon admission to floor he denies any other complaints, and is compliant w/ meds. Additionally he has been taking tylenol for 1 day hx of headache and 2 weeks of bisacodyl suppositories His admission vitals : 99.5, 109/76, 88, 20, 97% on room air but is actively rigoring when you arrive WBC = 0.2 , ANC=0.06

NEUTROPENIC FEVER

Neutropenic Fever
Neutropenia:
ANC < 500 or <1000 w/ a predicted nadir of <500 cells ANC = (WBC) x (% of neutrophils + % of bands) Nadir usually occurs 5 to 10 days after last chemo dose and usually recovers w/i 5 days of nadir (certain
leukemia/lymphoma regimens cause longer lasting and more profound neutropenia)

Fever:
- Single temp of 38.3oC (101.3oF) - Sustained Temp of 38.0oC (100.4oF) for more than 1 hour

Neutropenic Fever
Before era of empiric antibiotics, infections accounted for 75% deaths related to chemotherapy Fever is commonly the only symptom. Common infections present atypically
(asymptomatic UTIs, PNA w/o infiltrates, meningitis w/o nuchal rigidity, bacteremia w/ only fatigue)

Avoid digital rectal exams/manipulations Careful oral exam and exam of catheter sites if any Pan Cx

Neutropenic Fever
BACTERIA: Until 1980s, GNR (P.aeruginosa) were the most commonly identified pathogens 1995-2000, Gram + organisms = 62-76% of all bloodstream infections Trend toward Gram + due to introduction of long-term indwelling lines (Hickmans,Mediports) FUNGAL: - Risk increases w/ duration and severity of neutropenia, prolonged antibiotic use, and number of chemotherapy cycles -Candida (lines), aspergillus (immunocompromised, skin,sinus, PNA) >>>histo, blasto, coccidio, TB(prolonged steroids, other high risk patients)

(Neutropenic Fever)

TREATMENT

Numerous regimens studied: monotherapy demonstrated equivalent to two drug regimens (i.e.: piperacillin/tazobactam , cefepime,
meropenem)

In critically ill, add on aminoglycoside (better G coverage)

Addition of Gram (+) as initial empiric coverage in patients w/o port/catheter/line or mucositis has no proven clinical benefit (VRE) Vancomycin or Linezolid :
-Clinical deterioration -Hypotension -Mucositis -Skin or catheter infection -Hx of MRSA colonization -recent quinolone proph

(Neutropenic Fever)

TREATMENT

Fungal coverage (candida or aspergillus ssp. ):

Routinely added after 5-7 days of persistent neutropenic fever w/o clear source Post mortem of fatalities after prolonged febrile neutropenia (1966-1975) = 69% w/ evidence of systemic fungal disease Tx with liposomal amphotericin B (most common), voriconazole(? failed noninferiority trial?), caspofungin (passed noninferiority trial, less nephrotoxic
aspergillus failure?)

No fluconazole = efficacy

(Neutropenic Fever)

TREATMENT

Colony Stimulating Factors (CSF):

NOT routinely used for neutropenic fever unless the patient had previous bout of neutropenic fever with prior chemo cycle. Not shown to decrease mortality Beneficial effects are quite modest Used in neutropenic septic shock/severe sepsis (hypotension, organ dysfunction, PNA) Used in patients whose bone marrow recovery is expected to be especially prolonged.

Case #3:
64 y/o WM w/o significant past medical history comes to ED w/ complaints of progressive LBP. He notes pain initially started approx 6-8 weeks ago w/o inciting event. He is normally very active and enjoys jogging/biking ; currently still working as bartender. He went to Chagrin Highlands Urgent Care two weeks ago and got routine lumbosacral films which were essentially normal. He was discharged home w/ course of high dose NSAIDS. He comes to UH ED w/ complaints of persistent and progressive band like lower back pain. He notes new unsteadiness when he walks for the last two days, which prompted him to come to medical attention.

Case #3:
In ED: vitals and labs were within normal limits MRI of spine showed metastatic disease diffusely noted w/ thecal sac impingement at level of L2-L3 PSA sent from ED = 68

SPINAL CORD COMPRESSION

Spinal Cord Compression

Neoplastic epidural spinal cord compression Neoplastic invasion of space between vertebrae and spinal cord (epidural invasion) Defined as ANY thecal sac indentation radiographically (spinal cord or cauda equina)

LOCATION:
Thoracic spine: 60% Lumbosacral spine: 30% Cervical spine: 10%

Spinal Cord Compression

Cord compression is a common complication in oncology patients (5-10% of all cancer patients: prostate, lung, breast) which is a cause of pain and irreversible loss of neurologic function. NOT immediately life threatening unless it involves C3 or above Back pain is the precursor to spinal cord injury in almost all (96%)patients w/ spinal mets. Pain similar to disc disease: except pain supine, upright

Spinal Cord Compression

Besides back pain:
Radicular pain Motor weakness Gait disturbance Bowel bladder dysfunction

Spinal Cord Compression

Diagnosis
Back pain + known malignancy = SCC until proven otherwise Plain films NOT enough Exam has poor accuracy with localizing level MRI without contrast is the best test for SCC when suspected Can resort to CT (myelography) if pt cannot tolerate MRI, is not candidate for MRI, or not available.

Spinal Cord Compression

TREATMENT
Steroids Radiation Therapy Surgery

Spinal Cord Compression:

Treatment

Corticosteroids
Provides pain relief and anti-inflammation Dexamethasone: Loading dose of 10mg to 16mg; followed by 4mg q 4hrs. Higher doses (100mg) may be associated w/ slightly better outcome in exchange for higher incidence of adverse effects. Reserved for paraplegia/paraparesis generally. (low vs high dose studies = equivocal) Taper once definitive treatment is underway

Spinal Cord Compression:

Treatment

Radiation Therapy
This alone can be used for patients who are ambulatory and for pretreatment before paresis occurs. Doses is variable and determined by the quantity of previous XRT, type of tumor, and the field of treatment For extensive disease; limited survival = meaningful palliation (short courses) Chemotherapy can be used but most tumor types not particularly chemosensitive (unless NHL, Hodgkins, germ cell, breast).

Spinal Cord Compression:

Treatment

Surgery---evolving science
THEN:
Previous studies: Laminectomy w/ or w/o RT vs RT alone = NO difference in outcome Decompressive resection reserved for unstable spine, life threatening compression, unknown etiology, tumors that are not reliably radiosensitive or chemosensitive.

NOW: Newer studies show surgical intervention + XRT show BETTER functional status than XRT alone (anterior approach, improvements in instrumentation)

Spinal Cord Compression:

Treatment

Other Management issues

Quickly involve Rad/onc and NeuroSx / Ortho Analgesia: opioids, steroids Bed rest: controversial- but generally unnecessary Anticoagulation: DVT prophylaxis Bowel regimen: autonomic dysfunction, opioids, limited mobility all contribute to constipation Spinal bracing: only in patients with refractory pain

Spinal Cord Compression:

Prognosis

Best predictor is pre-treatment functional/neurologic status

Rapid onset and quick progression = poor Px 75% of patients treated correctly while still ambulatory, will remain ambulatory Only 10% of patients presenting with paraplegia will regain ambulatory status

References:
Guidelines for the Management of Pediatric and Adult Tumor LYsis Syndrome: An Evidence Based Review. Bernard et al. Journal of Clinical Oncology. Vol 26. June 1 2008 Harrisons Principles of Internal Medicine. Kasper, Dennis MD, et al. 16th ed. 577582. 2006. Oncologic Emergencies: Diagnosis and Treatment. Halfdanarsan et al. Mayo Clinic Procedings. June 2006: 81(6). 835-848 Fever in the neutropenic adult patient with cancer. Robbins,Gregory. Up to Date Online. May 31, 2008 Oncologic Emergencies for the Internist. Krimsky, William, et al. Cleveland Clinic Journal of Medicine. Vol 69. 3. March 2002 Treatment and Prognosis of Epidural Spinal Cord Compression, Including Cauda Equina Syndrome. Schiff, David et al. Up to Date Online. May 31, 2008. Tumor Lysis Syndrome. eMedicine. Koyamangalath Krishnan

Learning Objectives
Identification of 3 major oncologic emergencies Management of tumor lysis syndrome Management of neutropenic fever Management of spinal cord compression