Late effects of the lung have been studied extensively in humans and animal models.
Arrangement of the Lung
The functional subunits of the lung are groups of alveoli serviced by a single respiratory bronchiole. There are, therefore, numerous FSUs within the lung tissue which explains its significant volume effect.
Endpoints for normal lung effects
There are two endpoints normally quoted for lung effects:
- Radiation pneumonitis, a subacute effect
- Lung fibrosis, a late effect
Radiation pneumonitis
Radiation pneumonitis is a potentially fatal condition caused by inflammation of lung in response to radiation.
Clinical symptoms
There are is a broad spectrum of severity and corresponding symptoms. Mild cases may be asymptomatic or have a dry cough. Moderate cases may complain of a productive cough (possibly with haemoptysis), fevers or mild breathlessness. Severe cases present with severe dyspnoea requiring admission for respiratory support.
Imaging features
Chest X-ray may show increased opacity in the radiation portal, although changes may involve other areas of the lung (see The Abscopal Effect). CT scans shows ground glass opacity in the affected area.
Pathological features
Microscopically, the alveoli are filled with an inflammatory infiltrate. Unlike other causes of pneumonitis, there is evidence of radiation effect, with bizarre type II pneumocytes and fibroblasts.
Clinical course
Most cases respond without treatment, and more severe cases will usually respond to corticosteriods. Symptoms do not generally last beyond 6 months. Occasionally, pneumonitis may be progressive and fatal. Patients will nearly always develop radiation fibrosis in the affected area.
Radiation fibrosis of the lung
Radiation fibrosis of the lung occurs months to years after radiation exposure, is a common sequelae of radiation pneumonitis but may occur without without it.
Clinical Features
The symptoms caused by fibrosis of the lung are related to the amount of lung involved. Small areas are asymptomatic, only seen on routine imaging. Larger areas may cause dyspnoea and a dry cough.
Imaging Features
On plain x-ray, the affected lung may appear normal or may show increased markings. Dense fibrosis and scarring may cause retraction of the lung and neighbouring organs. CT shows similar features.
Pathological Features
Histopathology shows obliteration of alveoli and replacement with fibrous tissue. The remaining vessels are abnormal with hyalinisation.
Clinical course
Fibrosis is usually permanent, but rarely involves the lung outside of the treatment area. The severity is highly dependent on the amount of lung involved.
Scoring systems
RTOG / EORTC
| Grade 0 | Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 |
|---|---|---|---|---|---|
| No effect | Asymptomatic or mild symtpoms Silent x-ray findings |
Moderate symptomatic pneumonitis fibrosis, low fever, patchy consolidation |
Severe symptoms; Confluent x-ray findings |
Severe insufficiency Requiring O2 Assisted ventilation |
Death |
LENT/SOMA
Pending
Radiobiological Tolerance of Lung
Effect of Total Dose and Volume
The lung is a sensitive organ with a pronounced volume effect due to the parallel arrangement of its function subunits. The latest data on lung toxicity, released in the QUANTEC papers in 2010, has the following dose / response guidelines:
| Dose to Lung (Conventional Fractionation) |
Risk of Symptomatic Pneumonitis |
|---|---|
| V20 < 30% | < 20% |
| Mean 7 Gy | < 5% |
| Mean 13 Gy | 10% |
| Mean 20 Gy | 20% |
| Mean 24 Gy | 30% |
| Mean 27 Gy | 40% |
Effect of Fractionation
The lung has a low alpha/beta ratio, in the order of 3 Gy. This means that large fraction sizes are likely to cause significantly more damage; with a single dose of 10 Gy to both lungs the rate of pneumonitis approaches 50 - 60%.
Summary of Lung Tolerance
The lung responds to radiation in a subacute (radiation pneumonitis) and late fashion (radiation fibrosis). The lung is sensitive but small volumes can be treated to high dose with minimal risk of long term morbidity. Radiation pneumonitis is the dose limiting endpoint; lung fibrosis tends to occur in irradiated areas but varies considerably in severity (mostly dependent on the volume of lung irradiated).
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