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Late Effects



Radiation Therapy (RT) Related Toxicity


RT induced pulmonary damage may result from:

  • Mediastinal RT
  • Lung RT (single lung, bilateral lung or focal RT)
  • Total body irradiation (TBI)         


Damage may be:

  • Acute – Radiation pneumonitis
  • Chronic – Pulmonary fibrosis

RT also affects the growth of the bones, muscles and soft tissues of the thorax


Radiation Pneumonitis

This is a clinical syndrome with:

  • Cough
  • Dyspnea (shortness of breath)
  • Chest pain
  • Pleuritis
  • Low grade fever


RT pneumonitis usually occurs within 1-3 months after treatment

Pathophysiology:  Due to injury to alveolar cells, Type II pneumocytes and endothelial cells within days of treatment followed by a decrease in macrophages and an increase in fibroblasts within 6 months.

Imaging studies:

  • Chest X-ray – volume loss and linear densities
  • CT- Ragged infiltration


Pulmonary Fibrosis

Changes of pulmonary fibrosis start to occur within 2-4 months after RT and most changes present by 2 years.

Pathophysiology: Progressive fibrosis of the alveolar septa which collapse and are obliterated by connective tissue


 Risk factors for RT damage:

  • Total dose of RT
    • Large single doses of radiation cause the most damage
    • A single dose of 8.2 Gy is lethal in 5% of patients
    • A single dose of 11 Gy is lethal in 80% of patients
  • Fractionation schedule of RT
    • Fractionated RT is better tolerated (RT split into multiple small fractions)
    • Children with  Wilms tumor can tolerate 12 Gy bilateral lung RT if divided into daily doses of 1.5 Gy with a very low risk of pneumonitis
  • Volume of lung irradiated
    • Small volumes of lung can tolerate much higher doses of RT than total lung irradiation
  • Age of patient
    • Toxicity is more severe in young children because of the effect on lung growth and growth of the chest wall
  • Combined RT and chemotherapy
    • Use of chemotherapy which has pulmonary toxicity will exacerbate RT toxicity



Prevention of RT induced lung pulmonary damage

  • Minimize RT dose and field to lowest effective dose
  • Decrease fraction size (increased number of fractions)
  • Avoid RT if possible in young children
  • Avoid concomitant pulmonary toxic chemotherapy if possible
  • Prevent or avoid smoking or exposure to environmental toxins
  • Pharmacologic manipulation of radiation response:

1. Protectants:

Amifostine is a thiol –containing pro drug that acts as a free radical scavenger.

Side effects include nausea, vomiting and hypotension.

There is no evidence to show that it decreases the effectiveness of RT.

It has been shown to reduce the risk of pneumonitis in lung cancer patients but has not been evaluated in pediatric patients.

2. Mitigants:

Palifermin is a recombinant human keratinocyte growth factor.

In animals it has been shown to decrease severity and duration of pneumonitis and pulmonary fibrosis.

There is preliminary data showing positive results in adults.


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