The references included in this review were identified by searches of PubMed, Current Contents, and citation searches on Web of Science with the search terms “IMRT”, “radiation injury”, “skin”, “salivary gland”, “lung”, “breast”, “cervix”, “prostate”, “bladder”, “rectum”, “inflammation”, “fibrosis”, “angiotensin”, “TGF-beta”, “interleukin”, “KGF”, “mechanism”, “carcinogenesis”, “hyperbaric oxygen treatment”, and “wound healing”. Reference lists in selected papers and the authors' personal
ReviewEffects of radiation on normal tissue: consequences and mechanisms
Section snippets
General principles of normal tissue injury
The pathological processes of radiation injury begin immediately after radiation exposure, but the clinical and histological features may not become apparent for weeks, months, or even years after treatment. In the lung, for example, changes detected 6 weeks after irradiation are mild even after a high dose but by 6 months there is widespread fibrosis (figure 2). Radiation injury is commonly classified as acute, consequential, or late effects, according to the time before appearance of
Treatment-related factors
The risk, severity, and nature of early, consequential, and late reactions in a patient depend on several factors. Radiation-related treatment factors include the total dose, the dose per fraction, and schedule of treatment (ie, one versus two or three treatments per day). The current practice of fractionating radiotherapy treatments arose from observations that late effects were less severe and better local tumour control rates could be achieved with multiple, small radiation fractions than
Patient-related factors
Patient-related factors include trauma or surgery in an irradiated site and co-morbidities, particularly those involving impaired vascularity, such as diabetes and hypertension.32, 33 Age may be a factor, but age by itself must not be considered a reason for avoiding the use of a curative regimen.
Some groups of patients may have a genetic susceptibility to the development of radiation injury. For example, patients with genetic abnormalities such as ataxia telangiectasia develop severe radiation
The role of the tumour
In addition to the contribution of radiation itself, the presence of the tumour may predispose the surrounding normal tissue to injury. Tumours change their surroundings in several ways. They physically distort normal tissue architecture39, 40 resulting in defects that can add to damage produced by therapy.41 Tumours also release proteolytic enzymes that facilitate invasion and metastasis.42 Tumour vessels leak fibrinogen, which is converted to fibrin, resulting in collagen deposition and
Common clinical manifestations of radiation injury
Radiation injury varies from organ to organ, thus a comprehensive discussion is beyond the scope of this review, but is covered in other papers.5, 26, 47, 48, 49 For each area discussed here—the thorax (lung and breast tumours), head and neck, and pelvis (prostate and cervical tumours)—we describe symptoms, the histopathology underlying the symptoms, medical management of the symptoms, and future prospects for preventing or treating radiation toxicity.
Assessing normal tissue responses
When a new cancer therapy is evaluated, the toxic effects on normal tissues must be assessed and compared with standard therapy. A new scoring system has recently become available: common terminology criteria for adverse events v3·0 (CTCAE, http://ctep.cancer.gov/reporting/ctc.html). It was developed from two earlier scoring systems, the common toxicity criteria (CTC), developed by the National Cancer Institute (NCI) for evaluating acute toxicity of new chemotherapeutic agents and acute effects
Prospects for the future
Progress in cancer research is being made in many biological and technological areas. As cancer therapy improves and more patients survive longer, we need to direct research towards elucidating the processes that lead to complications of therapy. The NCI has identified long-term survival from cancer as one of the new areas of public health emphasis, particularly “studying adverse long-term or late effects of cancer and its treatment” (http://plan.cancer.gov/public/survivor.htm#studying).
It is
Search strategy and selection criteria
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