Consequential late effects occur when an early effect is so severe that healing can not take place.
Examples of consequential late effects include:
- Skin - non healing ulceration following severe moist desquamation
- Oesophagus - healing of mucousitis can lead to formation of strictures when opposing surfaces stick together
- Head and neck - mucosa may become permanently ulcerated if a large dose is administered before repopulation can occur
Consequential late effects are fundamentally different to other late effects as they:
- Are a continuation of an early effect
- Are less dependent on the vascular and connective tissues seen with typical late effects
Types of Consequential Late Effects
Salivary Gland Dysfunction
Dysfunction of salivary glands is often seen during the delivery of radiation, yet unlike most other 'early effects' it persists following treatment completion, and may never fully recover. It is important to divide the three major glands into serous producing (parotid gland), mucous producing (sublingual gland) and mixed serous/mucous (submandibular), which explains the response of these glands to radiation.
A good review of this topic is provided by Redman in this article (PubMed Central, freely available).
Acute Response to Radiation
The merocrine serous cells of the salivary glands are particularly sensitive to an early death and dysfunction following low doses of ionising radiation (10 Gy over 1 week). The reason for this is not fully understood, but it is hypothesised that the increased concentration of metal ions in the secretory granules cause toxicity, either through increased free radical generation or toxic effects of these ions if the granule is damaged by radiation. If radiation continues, then further damage to the serous acini becomes irreversible and salivary production may be halted permanently.
The merocrine mucous producing cells of the submandibular and sublingual glands are less sensitive to ionising radiation but may still suffer permanent dysfunction.
Chronic Radiation Effects
Xerostomia usually persists after radiation is completed. It may show some resolution with time, depending on the administered dose. Histopathology shows loss of acini and replacement with fibrous tissue, with corresponding reduction in saliva production.
There is significant debate in the literature, due to different definitions of clinical endpoints (subjective measures of dry mouth, objective measures of flow rates from different glands, etc).
- The TD5/5 values are estimated to lie between 30 and 50 Gy
- The TD50/5 values are estimated to lie between 30 and 70 Gy
- In one study, the TD100/5 value was found to be 50 Gy.
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