SFGH 2.10 AM Report Pearls: Radiation-Induced Lung Injury and TLS

Radiation-Induced Lung Injury

— Populations at risk are those who have undergone thoracic or neck irradiation. Interestingly, animal and human studies suggest a role for genetic susceptibility to irradiation injury. Polymorphisms in MTHFR and ATM genes have been associated with an increased risk of radiation pneumonitis. There is increased risk with the dose and volume of the lung exposed to radiation.

— In addition, some chemotherapy agents are sensitizers to radiotherapy and are associated with a higher risk of developing radiation-induced lung injury. Specifically, concurrent and induction versus sequential chemotherapy increases the risk. Identified agents include: doxorubicin, taxanes, cyclophosphamide, vincristine, mitomycin, bleomycin, gemcitabine, and bevacizumab.

— Radiation-induced lung injury consists of both radiation pneumonitis as well as fibrosis. Less commonly, areas of the lung outside of the radiation port can be involved and appear to be c/w a hypersensitivity reaction.

— Diagnosis is based on the correlation of signs/symptoms with the timing of radiation and the pattern of radiographic changes.

— Symptoms = dyspnea, non-productive cough, (pleuritic) chest pain, fever (rare), and fatigue. The symptoms are typically subacute and develop 4-12 weeks following irradiation. The time course for radiation fibrosis is chronic and symptoms typically develop 6-12 months after radiation.

— Imaging: CXR may show nonspecific opacities and can show volume loss. CT shows patchy alveolar ground glass opacities or scattered consolidations.

— Optimal treatment is not known. For symptomatic patients, typical treatment is steroids (prednisone dosed at at least 60mg/day) for 14 days followed by a long taper over 3-12 weeks. If patients are asymptomatic, a conservative approach with serial monitoring of symptoms, CXR, and PFTs is typically pursued. If fibrosis is present, patients are unlikely to benefit from glucocorticoid treatment.

Pearls on Tumor Lysis Syndrome (TLS)

In adults, TLS is most commonly associated with the following malignancies:

  1. Aggressive non-Hodgkin lymphomas (e.g., Burkitt lymphoma) (28%)
  2. Leukemia – the most common are AML (27%) and ALL (19%) as compared to CLL (10%) and CML (9%)
  3. Solid tumors only accounted for 1% of all cases

Note: the percentages are taken from a trial of 387 adults in which the efficacy and safety of rasburicase was being evaluated.

Pathophysiology:

TLS is caused by massive lysis of cells that release potassium, phosphate, and nucleic acids (breakdown of nucleic acid à uric acid). The uric acid and phosphorus precipitates and deposits in the renal tubules, which ultimately leads to AKI.

Definition:

Diagnosis is based on both lab values and clinical presentation.  Clinically, TLS is associated with cardiac arrhythmias and seizures. The laboratory values typically associated with TLS are the following:

Uric acid > 8 mg/dL

Potassium > 6 mEq/L

Phosphorus > 4.5 mg/dL

Calcium < 7 mg/dL

Creatinine > 1.5x ULN

Key Elements of Treatment:

  1. Supportive care – continuous cardiac monitoring and measurement of electrolytes, creatinine, and uric acid every  4-6 hours.
  2. Rasburicase (initial dose = 0.2 mg/kg) with repeated doses as needed
  3. IVF +/- loop diuretic
  4. Early renal consultation for possible RRT
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