Radiation therapy (RT) is a frequently used modality for cancer treatment. Acute and/or chronic skin changes may occur and carry risk of influencing quality of life during and after completion of RT. Radiation reactions may lead to delays in treatment, diminished cosmesis, and functional deficits. Lifestyle factors, treatment modalities, topical agents, and, in some cases, wound dressings may be utilized to help prevent or ameliorate radiation-induced skin reactions. While rigorous evidence supporting specific interventions may be lacking or contradictory, this article summarizes the current knowledge of the etiology, manifestations, and interventions available for prevention and management of radiation dermatitis. Further well-designed studies are needed to confirm the efficacy of current recommendations and facilitate development of novel strategies for optimal care of patients with radiation dermatitis.
Radiation therapy (RT) remains an essential component of cancer treatment, with nearly 50% of cancer patients receiving RT at some point during the course of their illness. Of those receiving RT, as many as 95% may experience some form of radiation dermatitis, or radiation-induced skin injury. Radiation dermatitis can manifest as acute erythema and desquamation, or as chronic effects including skin atrophy, telangiectasias, and fibrosis. These skin changes result from a combination of RT features and intrinsic patient risk factors. While a reduced total dose of radiation and use of an advanced mode of radiation delivery may help to mitigate the severity of radiation effects on the skin, radiation dermatitis remains one of the most common side effects of RT. This condition can affect a patient’s quality of life both during and after treatment. If severe, it carries the risk of limiting the dose of radiation or interrupting the treatment schedule, which could negatively impact treatment efficacy. Consequently, managing radiation-induced skin injury during and after treatment is an important aspect of cancer care. Despite technological advances in radiation delivery and growing interest in managing skin reactions, there is no gold standard in the management of radiation dermatitis. This article highlights the typical skin reactions associated with RT, as well as current evidence-based approaches to management and intervention.
Pathophysiology and Clinical Presentation
The high energy x-rays used in modern RT produce both direct and indirect ionization events that not only result in injury to cancer cells, but also pose a risk of injury to normal tissues (Figure 1). Most patients undergoing RT receive small, daily doses of radiation; the clinical goal is to achieve tumor killing after repeated exposure while minimizing harm to healthy surrounding tissue. Inevitably, however, a small fraction of rapidly proliferating cells in the basal layer of the skin are injured or destroyed, precipitating a decrease in the population of differentiated epidermal keratinocytes; this can result in desquamation—ie, the peeling and shedding of the epidermis—depending on the total dose of radiation delivered. Impairment of the skin barrier function carries the risks of wound formation, loss of immune function, and infection. Further, radiation can also damage the microvascular system, increasing the risk of tissue hypoxia and fibrosis, and activating an inflammatory cascade, leading to acute and chronic skin changes.[4-6]
The acute phase of radiation dermatitis is often defined as the changes seen within 90 days following RT. The development of acute radiation dermatitis follows a predictable course (Table 1). While multiple systems exist for the grading of skin effects from RT, the ones most commonly referenced are the Radiation Therapy Oncology Group grading scale and the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03 (Table 2).[7,8] Transient, mild erythema can occur within hours of RT, likely due to capillary dilation shortly after patient exposure to radiation. However, the more conventional, sustained hyperpigmentation or erythema associated with RT typically does not occur until 2 to 4 weeks into treatment. Hair follicles and sebaceous glands can be affected early in the course of RT, leading to dry skin and hair loss. As erythema develops, a sunburn-like reaction can ensue, with associated edema, pruritus, tenderness, and a burning sensation. Dry desquamation, which manifests as pruritus and flaking of the skin, may occur 3 to 6 weeks into the RT regimen, at cumulative doses above 20 Gy. With increasing radiation doses above 30 to 40 Gy, patients may develop moist desquamation—a condition that is characterized by tender, red skin associated with serous exudate, hemorrhagic crusting, and the potential for development of bullae. Due to breakdown of the skin barrier, this stage is generally painful. It is characterized by increased susceptibility to contact injury, particularly in flexural areas prone to frictional stress; by infection; and by ulcer formation. In cases of extreme desquamation, clinicians may need to withhold RT for a period of time, to allow for sufficient re-epithelialization before the patient resumes treatment.
Figures 2 and 3 provide examples of different stages of dermatitis and illustrate how varying degrees of dermatitis can occur within the same radiation field. The acute skin reaction typically peaks at 1 to 2 weeks after completion of RT. As the epidermal keratinocytes repopulate and the immune response cascade reverses, the symptoms of acute dermatitis resolve in most patients. The time to resolution of any desquamation, erythema, and edema typically is 2 to 4 weeks following the end of treatment. It is not uncommon for residual postinflammatory hyperpigmentation to persist, but this typically wanes over subsequent months posttreatment.
Chronic radiation dermatitis is typically defined as changes that occur more than 90 days following a course of RT (Figure 4). Chronic skin changes may result from aberrant or dysregulated alterations in proinflammatory and profibrotic cytokines.[4-6,11] These changes may include hypopigmented and/or hyperpigmented skin that persists or develops after resolution of the acute phase of dermatitis. There may be sustained loss of certain skin structures such as sebaceous glands, hair follicles, and nails, as well as textural changes to the skin.[12,13] Thinning or atrophy of the epidermis and dermis may be observed, although some patients may develop induration and thickening of the dermis. Telangiectasia may occur as a result of blood vessel dilation, while damage to blood vessels may also result in tissue hypoxia, predisposing the patient to development of skin ulceration and/or chronic wounds. Radiation-induced fibrosis is a potentially serious sequela of RT that may cause poor cosmesis, lymphedema, skin retraction, persistent hyperpigmentation, and joint immobility.[15-17] In summary, depending on the severity and location of chronic skin changes after RT, there is potential for decreased quality of life due to pain, recurrent wounds, decreased range of motion, and cosmetic dissatisfaction.
Both the likelihood of developing radiation dermatitis and the severity of symptoms are dependent on a variety of factors. These include:
• The proximity of the radiation target to the skin.
• The energy of the radiation used.
• The radiation dose and fractionation schedule of treatment.
• The size of the skin surface area exposed to radiation.
• The presence or absence of radiosensitizing concurrent chemotherapy.
Thus, significant radiation dermatitis is most often seen in patients receiving treatment for sarcoma and cancers of the skin, breast, head and neck, vulva, and anus, since the target area of treatment is often close to the skin, with limited ability to spare the skin from higher doses of radiation exposure (Table 3).[18-21] Certain patient-specific factors can also increase the risk and severity of radiation dermatitis; these include malnutrition, smoking, excessive skin folds, elevated body mass index, underlying vascular or connective tissue disease, and genetic factors such as inherited DNA repair deficiencies (eg, as seen in Fanconi anemia and ataxia-telangiectasia syndromes).
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