Radiation-induced pulmonary fibrosis is the late manifestation of radiation-induced lung disease (RILD) and is relatively common following radiotherapy for chest wall or intrathoracic malignancies.
This article does not deal with changes seen in the the acute phase. Please refer to the article on radiation-induced lung disease (RILD) for a general discussion and radiation pneumonitis for specific discussion of acute changes.
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For discussion of epidemiology of radiation induced lung disease please refer to the parent article: radiation induced lung disease (RILD).
The late phase typically occurs between 6 and 12 months following completion of radiotherapy course and can continue to progress for up to 2 years 1.
Ionising irradiation promotes damage to lung epithelium releasing inflammatory mediators that attract inflammatory cells, which in turn secret profibrotic cytokines and chemokines thereby amplifying the inflammatory response. These profibrotic mediators stimulates fibroblasts to produce extracellular matrix proteins (e.g. collagen) resulting in the excess deposition of these material 6.
Although changes in the lung are usually confined to the irradiated field, changes in the remainder of the lung may also on occasion be seen 1.
Volume loss, mediastinal shift and bronchiectasis may all be seen. In some instances a straight edge conforming to the irradiation portal may be evident. Review of previous imaging will usually show progression from radiation pneumonitis (hazy opacities) progressively becoming more reticular or linear with gradual loss of volume 5.
CT not only is able to better delineated parenchymal changes including volume loss and bronchiectasis, but often demonstrates the change restricted to the irradiated field, rather than respecting anatomical boundaries (e.g. pleural fissures). It should be noted however that with stereotactic radiation therapy (SRT) the shape of the irradiated field will not have straight edges or conform to the traditional conventional radiotherapy portals. As such it may be less obviously artificial in shape 2.
Changes include 1,3,5:
- volume loss
- linear scarring
- chronic consolidation often with air-bronchograms
- traction bronchiectasis
- mediastinal shift
- pleural thickening
- ipsilateral pleural effusion
Cavitation is usually not a feature, and suggests superimposed infection 1.
Although MRI may have a role helping to distinguish malignancy from fibrosis, care must be taken in interpreting results as, granulation tissue, oedema and areas of necrosis can all mimic tumour nodule, especially when fibrosis is also present 4.
FDG-PET is useful in differentiating radiation fibrosis from recurrent or radiation-induced malignancy, as the former will not be metabolically active 1.
Treatment and prognosis
When fibrosis has become established, no treatment is available, other than follow-up to assess for tumour recurrence.
If a clear demarcation conforming to the irradiation port is seen then there is often little difficulty in making the diagnosis, especially when a history of chest radiotherapy is known.
A knowledge of the time course of the changes with respect to radiotherapy, total dose administered, administration of chemotherapy, and shape of the portal used can all have a significant impact on the differential, and thus should be sought if they have not been provided by the referring clinician.
- pulmonary fibrosis
- other causes of bronchiectasis
- tuberculosis (especially in cases where the lung apices have been irradiated)
- recurrent or radiation induced malignancy:
- may be difficult to distinguish from scarring / late phase consolidation
- follow-up will show malignancy to increase in size
- involvement of chest wall or bone, or lymph node increase may be present 3
- often lack air-bronchograms and has convex outer border 1,3
- FDG-PET is useful as it will demonstrate increased metabolic activity in malignancies 1
- 1. Choi YW, Munden RF, Erasmus JJ et-al. Effects of radiation therapy on the lung: radiologic appearances and differential diagnosis. Radiographics. 24 (4): 985-97. doi:10.1148/rg.244035160 [pubmed citation]
- 2. Aoki T, Nagata Y, Negoro Y et-al. Evaluation of lung injury after three-dimensional conformal stereotactic radiation therapy for solitary lung tumors: CT appearance. Radiology. 2004;230 (1): 101-8. doi:10.1148/radiol.2301021226 [pubmed citation]
- 3. Glazer HS, Levitt RG, Lee JK et-al. Differentiation of radiation fibrosis from recurrent pulmonary neoplasm by magnetic resonance imaging. AJR Am J Roentgenol. 1984;143 (4): 729-30. AJR Am J Roentgenol (citation) [pubmed citation]
- 4. Charles HC, Baker ME, Hathorn JW et-al. Differentiation of radiation fibrosis from recurrent neoplasia: a role for 31P MR spectroscopy? AJR Am J Roentgenol. 1990;154 (1): 67-8. AJR Am J Roentgenol (citation) [pubmed citation]
- 5. Chest radiology. edited by Jannette Collins, Eric J. Stern. Philadelphia : Wolters Kluwer Health/Lippincott Williams & Wilkins, c2008. ISBN:0781763142 (find it at amazon.com)
- 6. Advances in Cancer Research. Academic Press. (2013) ISBN:0124072038. Read it at Google Books - Find it at Amazon