Lec 4 Heme/Onc
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What are the 4 types of cancer-related complications?
- 1. metabolic or hormonal
- 2. structural
- 3. chemotherapy-related
- 4. hematologic
Give examples of metabolic or hormonal cancer-related complications.
- 1. tumor lysis syndrome (TLS)
- 2. hypercalcemia of malignancy
- 3. SIADH
- 4. paraneoplastic syndrome
Give examples of structural cancer-related complications.
- 1. superior vena cava syndrome
- 2. pleural or pericardial effusion
- 3. spinal cord compression
Give examples of chemotherapy-related cancer-related complication.
- 1. extravasation
- 2. diarrhea/constipation
Give examples of hematologic cancer-related complications.
- 1. febrile neutropenia
- 2. hyperviscosity syndrome
- 3. thromboembolic risk associated with cancer
What is tumor lysis syndrome (TLS)?
- metabolic cancer-related complication resulting from abrupt release of cellular components into the blood
- may result in acute renal failure
What is the pathophysiology of TLS?
- release of nucleic acids --> HYPERuricemia -->uric acid crystals precipitate in renal tubules --> acute obstructive nephropathy
What are the tumor-related risk factors of TLS?
- 1. type of malignancy - more common w/ acute hematologic malignancies
- 2. high tumor burden
- 3. chemotherapy - sensitive disease
What are the patient-related risk factors of TLS?
- 1. pre-existing renal dysfunction
- 2. elavated uric acid, WBC, LDH
- 3. dehydration
What is the Cairo-Bishop Classification?
2 or more laboratory changes up to 7 days after chemotherapy
What are the laboratory changes associated with TLS?
- uric acid: > 8.0 mg/dL or > 25% increase from baseline
- potassium: > 6 mEq/L or > 25% increase from baseline
- phosphorus: > 6.5 mg/dL (children), > 4.5 mg/dL (adults) or > 25% increase from baseline
- calcium: < 7 mg/dL or 25% decrease from baseline
What is the clinical presentation of TLS?
- not making urine
- may not have swelling
- feeling more "gouty"
- non-specific complaints = just don't feel right
- renal failure
- arrhythmias (heart racing)
- EKG will probably show an abnormality
What are the goals of therapy for TLS?
- prompt management and treatment of TLS while maintaining renal & cardiopulmonary support
- recognition of high reisk patients and prevention (prophylaxis to prevent TLS & prevent those at high risk)
- avoid acute renal failure complications (stay hydrated)
What is the treatment outline for TLS?
- 1. potentially aggressive emergency care
- 2. fluids and hydration
- 3. management of hyperuricemia
- 4. management of electrolytes
- 5. monitoring and follow-up
What is the hydration schedule for a patient with TLS receving chemotherapy?
- Maintain UOP 80-100 ml/m2/hour
- Hydrate 24-48 hours prior to chemo (esp if high risk) and continue 48-72 hours after chemo ==> in order to maintain a good urine output
How is hyperuricemia managed in patients with TLS?
- allopurinol (renally adjust)
- does NOT work on already produced uric acid!
- prophylaxis with allopurinol before starting chemo to make sure pt doesn't develop hyperuricemia
Which drug is a recombiant modified urate oxidase that can be used for management of hyperuricemia secondary to leukemia, lymphoma or solid tumor malignancies?
How is rasburicase administered/dosed?
- single course of treatment
- not given prophylactically
- works on uric acid already produced
What are the black box warnings for rasburicase?
What are the adverse effects of allopurinol use?
diarrhea, nausea, increased LFTs, toxicity (if not renally adjusted)
What is the important monitoring issue associated with rasburicase?
- need to collect blood for uric acid analysis in pre-chilled heparinized tubes
- immerse in ice water
- analyze samples within 4 hours
- crystals will form if not done properly
- can't use if pt has a G6PD deficiency
What patient monitoring must occur in patients with TLS?
- renal function (ins/outs) --> SCr lags behind ~2 days before accurate reflection
What is the incidence of hypercalcemia of malignancy?
- ~25% of cancer patients
- most common cancers: lung, breast, hematologic, etc.
How is corrected calcium calculated?
observed calcium + 0.8 (4 - albumin)
What kind of prognostic sign is hypercalcemia of malignancy?
What is the pathophysiology of hypercalemia of malignancy?
- increased osteoclastic bone resorption (cytokines & tumor-released products)
- enhanced renal tubular and intestinal reabsorption
- medication causes (Ca supplements --> Tums, thiazides, lithium)
What is the clinical presentation of hyepralcemia of malignancy?
- "stones, bones, abdominal groans, psychic moans"
- Renal: kidney stones, polyuria, polydipsia, dehydration, decreased urine output
- GI: constipation, N/V, anorexia, loss of appetite
- Neurologic: fatigue, lethargy, depession, loss of deep tendon reflexes, seizures, etc.
- Cardiovascular: EKG changes, arrhythmias that may lead to cardia arrest
What is the therapy for hypercalcemia of malignancy?
- discontinue exogenous sources of calcium
- ultimate management is therapy for cancer
- hydration (normal saline 200-500 ml/hr)
- diuresis (to enhance renal excretion of calcium AFTER establishing rehydration
- inhibiting accelerated bone resorption --> bisphosponate therapy
- alternatives (if Ca elevated after 2nd dose of bisphosphonate) --> glucocorticoids, calcitonin, mithramycin, gallium nitrate, dialysis
Describe how superior vena cava syndrome occurs.
- tumor is pressing against SVC and may be affecting BP
- tumor is invading the vessel walls and pressing against SVC
- possible thrombosis of the vessel
- over time, if the tumor remains stable and isn't growing the SVC can make collateral veins and bypass it
What are the causes of SVC syndrome?
- 1. malignancy: lunch cancers most common
- 2. non-oncologic: TB, aneurism
What are the signs and symptoms of SVC syndrome?
- facial/neck swelling
- upper extremity swelling
- dysphagia, stridor (high pitched wheezing sound d/t blockage of larynx)
- sensation of fullness in head
- distended neck and chest veins
- facial, neck, arm edema
- facial plethora (flushed)
How is SVC syndrome classified?
- based on symptoms
- 0 = asymptomatic
- 5 = death
- 1-4 = how bad symptoms are and what the patient is experiencing
How is diagnosis of SVC syndrome made?
- imaging studies
How is SVC syndrome managed?
- 1. treat underlying cause - chemo/radiation therapy (cancer or infection as cause)
- 2. endovascular revascularization
- 3. supportive measures (elevate head of bed for easier breathing; oxygen)
- 4. corticosteroids or diuretics (can use if other options aren't working; do it if it doesn't hurt the patient)
- 5. anticoagulation for thrombosis-related obstruction
What are the most common cancers associated with malignant pleural and pericardial effusions?
- pleural: lung, breast, lymphoma
- pericardial: lung, breast, leukemia/lymphoma, GI, sarcomas, melanoma
What is the pathophysiology of malignant pleural and pericardial effusions?
- impaired balance between normal fluid production and elimination
- accumulation of fluid around heart or lungs
- capillary leak, obstruction of lymphatic drainage to allow fluid to get across
- increase in hydrostatic pressure or decrease in oncotic pressure
What is the clinical presentation of malignant pleural and pericardial effusions?
- dyspnea, cough, chest pain
- PE: decreased breath sounds, dullness to percussion, decreased fremitus, pericardial rub
What is the treatment for malignant pleural and pericardial effusions?
- thoracentesis or chest tube drainage
How does a thoracentesis or chest tube drainage work?
- diagnostic tap: take a little bit of fluid off to send for culture to make sure not infectious
- therapeutic: drain off as much as possible
What is pleurodesis/sclerotherapy?
- instillation of agent/medication into the pleural space
- makes the inside linings of lung irritated so they don't adhere to one another
What agents/medications can be used in pleurodesis/sclerotherapy?
- talc (baby powder)
How common is malignant pleural and pericardial effusions?
100,000 cases annually
How common is SVC syndrome?
~15,000 in US each year
How often does spinal cord compression occur and when does it occur?
~ 5% of cancer population withhin the last 2 years of life
What is spinal cord compression?
a tumor pressing on the spinal cord
What is the clinical presentation of spinal cord compression?
- pain: mainly back pain
- motor findings: weakness, hyperreflexia below level of compression (+ Babinski sign, diminished lower extremity deep tendon reflexes)
- sensory findings: parasthesias (ascending numbess most common = feet moving up)
- autonomic dysfunction: urinary retention
What are the therapy options for spinal cord compression?
- high-dose dexamethasone
- surgery and radiation
- supportive care
What are the goals of therapy of spinal cord compression?
- pain management
- preserving or even improving neurologic function
- maintaining or improving QOL
How often dose chemo-related extravasation occur?
Define chemotherapy-related extravasation.
the accidental leakage of chemotherapy from the vein into the surrounding tissue (damage can involve nerves & tendons)
What agents can cuase extravasation?
- irritants: cisplatin, oxaliplatin, irinotecan, topotecan, paclitaxel, others
- vesicants: anthracyclines, vinca alkaloids, paclitaxel, mitomycin
What are the patient-related risk factors of extravasation?
- collapsed vein
- dehydrated patient, therefor didn't get a good vein in the first place
- small veins
- older patient
- thin skin (possibly)
- impaired circulation
- obese patient
What are the procedure-related risk factors of extravasation?
- bad insertion site
- new nurse furst time putting in a line
- inexperienced staff that hasn't dealt with chemo very much
- bolus more likely to extravasate
- pt thrashing around may present a problem
How can extravasation be prevented?
- patient and staff education (pt should alert staff if burning, warmth, etc.)
- check patency of lines, appropriate veins and equipment
- avoid easily "dislodged" lines (make sure line is in good)
- flush the line before and after administration
- use thin cannulas with high gauges
- monitor closely
- recognition of patient symptoms (pain, swelling, redness, burning, stinging) --> later symptoms (erythema & edema)
How can extravasation be managed?
- stop infusion - leave needle/cannula/catheter in place
- aspirate as much drug as possible (use another access site)
- apply antidote (if applicable)
- withdraw IV access
- elevate area to minimize swelling
- mark affected area and photograph
- plastic surgery may be necessary
What are the possible antidotes/specific management for extravasation?
- "localize and neutralize"
- "disperse and dilute"
What does "localize and neutralize" mean?
- application of cold pack to affected area
- cold causes vasoconstriction to localize the extravasation
- (DMSO, dexrazoxane, sodium thiosulfate)
What does "disperse and dilute" mean?
- application of warm compress to affected area
- warm causes decreased local drug concentrations
- (oxaliplatin, hyaluronidase, possibly surgery depending on the degree of extravasation)
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