Radiation-Induced Skin Injuries (RSI) Review PDF

Radiation therapy has been adapted to effectively treat a variety of malignant tumours, with an estimate of 50% of all diagnosed cancer cases being able to receive radiation as part of their treatment regimens (Australian Institute of Health and Welfare, 2017). It remains a cornerstone of treatment,...

Radiation therapy has been adapted to effectively treat a variety of malignant tumours, with an estimate of 50% of all diagnosed cancer cases being able to receive radiation as part of their treatment regimens (Australian Institute of Health and Welfare, 2017). It remains a cornerstone of treatment, offering hope to many. Despite its impact on the successful treatments of many cancers, radiation therapy comes with the unfortunate consequence of radiation-induced skin injuries (RSI) with up to 90% of radiation therapy patients develop moderate to severe RSI (Yang et al., 2020), with 67% of those cases developing complications due to wound development (Simman et al., 2023). This review explores the pathophysiology of RSI, preventative interventions, treatment options and query long term treatments for chronic ulcers. Owing to its complexities, treating healthcare providers must have a comprehensive understanding of the pathophysiology of RSI to create management strategies that will prevent the formation of wounds and encourage the healing process. **[Literature Search:]** A literature review of works published between 2018 and 2024 was conducted over several different databases including Medline, PubMed, EBOSC and ResearchGate. After removal of duplicates, the articles were reviewed and systematically culled. Inclusion criteria focussed on systematic reviews, meta-analyses and one case study. Search terms included but not restricted to "Radiation induced skin Injuries", "Radiation Dermatitis management", "wound healing" and "radiotherapy". Exclusion criteria included articles that focussed their study on RSI from non-therapeutic sources were not included in this review, as well as non-human studies, perspective trials and non-English papers. 12 articles were found to meet appropriate criteria. **[Discussion:]** **What is Radiation-induced skin injuries (RSI):** RSI occurs when the skin and underlining tissues are exposed to high doses of radiation, irreversibly damaging the microvascular and small blood vessels endothelial blood cells in the skin tissue (Simman et al., 2023). It is known by a variety of terms, including radiodermatitis, x-ray dermatitis, radiation skin injury or radiation dermatitis. They can develop within the first few days to a week after radiation treatment and usually confined to the area of treatment. The damaged skin forms wound that can take a prolonged period to heal and are more susceptible to infections. Acute radiation dermatitis occurs within 90 days of exposure to ionising radiation, with the time of onset varying from days to weeks after the initial exposure (Jakub Pazdrowski et al., 2024). Its severity can also vary from mild erythema to moist desquamation. The first symptoms begin to develop around 10 to 14 days after they receive a dose between 6-20 Gy. The patient may describe discomfort as their skin tension increases, accompanied by an itching or burning sensation and even pain (Simman et al., 2023), eventually leading to dry scaling skin classified as desquamation. Doses higher than 30 Gy can damage the epidermis to the point that it inhibits its ability to repair itself, leading to blister formation -- more commonly known as moist desquamation, impairing the skin barrier function and increasing the risk of infection, especially bacterial (Deng Guangmei et al., 2024). The table below describes early post-radiation reactions as per the National Cancer Institute. **NCI**: National Cancer Institute -Common Terminology Criteria. Grade 0 1 2 3 4 5 ------- --- ----------------------------------------- ---------------------------------------------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------- --------------------------------------------------------------------------------------------------------- --- Parched desquamation and faint erythema Patchy moist desquamation limited to skin folds and creases, moderate to brisk erythema, and mild oedema Moisture desquamation in places other than the creases and wrinkles of the skin, bleeding brought on by a small cut or trauma Full-thickness dermal ulceration or necrosis, as well as spontaneous haemorrhaging at the affected area *(National Cancer Institute, 2017)* Chronic RSI (cRSI), or delayed onset radiation ulcers, can present months to years after the initial exposure to radiation therapy (Goel et al., 2022). Unlike acute radiation induced skin injuries, chronic radiation skin injuries complications are progressive and complicated, caused by an imbalance of proinflammatory and profibrotic cytokines. It can manifest itself in a variety of ways including changes in skin appearce, the development of wounds, ulcerations, necrosis, fibrosis and secondary cancers. Patient may describe subjective symptoms such as tingling or numbness. Other symptoms include vascular changes, dermis atrophy and fragility, pigmentation changes and cicatrical alopecia (hair loss related to scar tissue) (Jakub Pazdrowski et al., 2024). Radiation induced fibrosis is characterized by thickening of the skin, lymphedema and reduced range of movement. According to Jakub Pazdrowski et al. (2024) radiation therapy increases the risk of non-melanoma skin cancers. In order to rule out subsequent cancer, the diagnosis of these wounds entails a physical examination, biopsy, and histological analysis. Given the large dose that patients with soft tissue sarcomas and breast or head and neck cancer get through their skin and their expected extended survival, a increase in the prevalence of chronic radiation dermatitis is anticipated (Spałek, 2016). The most crucial strategy for preventing chronic radiation dermatitis is to employ appropriate radiation therapy techniques to shield healthy skin from needless radiation exposure. The majority of the time, chronic radiation dermatitis is an irreversible, progressive illness that can significantly lower a patient\'s quality of life. Table 2 Clinical Diagnosis of cRSI Clinical Manifestations of Chronic Radiation induced Skin injuries -------------------------------------------------------------------- ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- Skin Atrophy Wrinkly skin is the most prevalent sign of skin atrophy. Stronger reactions could be accompanied by scaling, shine, or thinning of the skin. Commonly presents at grade II or III lesions. Telangiectasia occurs when tiny capillaries enlarge, resulting in the formation of spider veins and red lines or patterns on the skin. Typical sign in lesions of grade II or III. may endure or vanish at some point. Radiation induced Fibrosis a syndrome where subcutaneous tissue loses its ability to stabilize connective tissue after radiation therapy, resulting in a stiffer and more sclerosis in the exposed area Dyspigmentation Could emerge soon after radiation and then diminish, or it could last for months, years, or even longer. Following radiation therapy, there are two conditions: hyperpigmentation and hypopigmentation. This might be irreversible. Reduction of Loss of Skin Appendages Radiation can induce hair loss, decrease sweat secretions, harm the skin, and reduce or destroy all hair follicles, sebaceous glands, and sweat glands. Radiation induced Ulcers. Ulcers are a late lesion that can appear anywhere on the body, but they usually do so in the radiation-exposed areas. If left untreated, they can enlarge and spread. (Hoang Thanh Tuan, 2023) **Pathophysiology of Radiation Damage Skin Injuries.** Radiation-induced skin injuries, known by several different terms, including radiation dermatitis, cutaneous radiation injuries or radiodermatitis, occur due to the exposure of skin to ionizing radiation and is a common side effect of radiation therapy for cancer treatments. On a molecular level, the structural damage begin immediately begins up exposure, with the basal keratinocytes, hair follicle stem cells and melanocytes being highly sensitive to radiotherapy (Wang & Tepper, 2021). The radiation causes the cellular fluid to become ionized, generating free radicals that cause oxidative stress and irreversibly break DNA strands. This damage triggers an inflammatory response, characterized by the pro-inflammatory cytokines and increased vascular permeability, resulting in oedema and erythema (Goel et al., 2022). In the acute stage, patients may report symptoms such as increased inflammation at the radiation site. Over time, this process leads to acute effects such as erythema, desquamation and ulceration, as well as chronic effects such as fibrosis and atrophy (Goel et al., 2022). Because of the nature of radiation therapy, the healing process gets interrupted before it can the injury could begin it final stages of healing (Christ et al., 2021). The severity of these injures depend on several factors such as radiation dose, exposure duration and individual factors that may cause the patient to become more susceptible to injury then others. Clinicians must have a thorough understanding of the pathophysiology of repetitive strain injuries (RSI) in order to prevent and diagnose skin injuries early and implement early therapies. Early intervention and the implementation of personalized treatment regimens, practitioners can improve patient outcomes and satisfaction. Furthermore, it facilitates the evaluation of risk factors, the management of severe reactions, and the provision of patient education regarding side effects and skin care during radiation therapy, all of which lead to increased patient satisfaction and compliance. **Risk Factors** **Numerous risk factors might aggravate RSI and have an impact on it. Poor diet hinders the skin\'s natural capacity to repair and rejuvenate, and skin disorders such as psoriasis or eczema make people more vulnerable. Areas with overlapping skin folds, such as the groin or under the breasts, are more vulnerable to severe reactions, and using certain skin treatments right before radiation treatment can exacerbate skin reactions (Wei et al., 2018). The danger is further increased by obesity, as it results in more skin folds and pressure points, as well as by extended or repeated radiation treatments. Moreover, due to concurrent treatments, Jaschke et al. (2017) states that the constant exposure increases skin sensitivity and radiation susceptibility. The risk is further increased by elements like smoking, being a woman, being older, and coming from specific ethnic origins** **(Xie et al., 2021).** **Level of Injury** The degree and depth of tissue damage triggered by radiation-induced skin injuries can be used to categorize them into multiple stages. Erythema, which is characterized by inflammation at the site of injury due to capillary dilatation, is a common presentation for mild injuries. Dry desquamation, a condition in which the skin becomes flaky, dry, and may peel off, can occur with moderate injuries. If the damage gets worse, wet desquamation may occur, which can cause blisters and open lesions to form when the skin becomes damaged and starts to peel off. Serious wounds such as ulceration and necrosis, which cause damage to the skin\'s deeper layers and underlying tissues, leaving open wounds that are vulnerable to infection and may need significant medical care. Over time, chronic consequences including fibrosis and atrophy might occur, resulting in irreversible alterations to the suppleness and texture of the skin. Cancer Institute NSW (2023) suggests the use of the Common Terminology Criteria for Adverse Events (CTCAE) for use of a grading scale to determine the level of injury that may develop during radiation therapy. **Grade** **Description** ----------- --------------------------------------------------------------------------------------------------------------------------------------------------------------- **1** Faint erythema or dry desquamation **2** Moderate to brisk erythema, patchy moist desquamation; mostly confined to skin folds and creases: moderate oedema **3** Moist desquamation in areas other than skin folds and creases, bleeding induced by minor trauma or abrasion **4** Life-threatening consequences; skin necrosis or ulceration of full thickness dermis ulceration; spontaneous bleeding from involved site; skin graft indicated **5** Death Table 3 CTCAE Grading for Radiation Dermatitis -- Used by NSW Health and Cancer Institute NSW to grade level of injury - (National Cancer Institute, 2017) **Preventative Measures** Preventing RSI involves several strategies aimed at minimizing skin damage during radiation therapy. Patient education on proper skin care and early signs of dermatitis is essential for timely intervention and management. Skin care regimens are crucial, including the use of mild, low pH soaps and moisturizers to keep the skin hydrated and intact (Yang et al., 2020). There is a strong emphasis in research on the importance of patient education, promoting personal hygiene and ensuring that any developing wound are treated aseptically, promoting patient comfort, reducing skin trauma and reducing the symptom burden of radiation dermatitis (Yang et al., 2020 & Jakub Pazdrowski et al., 2024). Yang et al (2020) suggests patients commence high fat diets, increasing protein uptake to support muscle mass and lowering inflammation with increased healthy fat intake, whilst Goel et al (2022) simply suggests an uptake of Vitamin A,C and F. It's generally recommended by most sources that patients practice hygiene regimes using soap-free washes with warm water (Yang et al, 2020., Goel et al, 2022 & Jakub Pazdrowski et al., 2024). Theres little evidence to suggest that using skin care treatments prior to radiation reduces skin toxicity (Soriano et al., 2019). Patients should be encouraged minimizing irritation or trauma to their skin by wear non-irritant, loose-fitting clothing, avoid shaving, use appropriate sun protection and avoid wearing jewellery (Cancer Institute NSW, 2023). Although betamethasone and mometasone furoate are clinically suggested to lower the prevalence of RSI (Behroozian et al., 2023), they may also have unfavourable side effects such as wet desquamation, skin thinning, which could raise the risk of bacterial infections (Deng Guangmei et al., 2024). Barrier films and dressings, such as hydrocolloid or silicone-based products, provide a protective layer over the skin, reducing friction and exposure to radiation (Behroozian et al., 2023). Additionally, advanced radiation techniques like intensity-modulated radiation therapy (IMRT) and proton therapy can precisely target tumours while sparing surrounding healthy tissue, thereby reducing the risk of dermatitis. +-----------------------------------+-----------------------------------+ | Management of Acute Radiation | | | Injuries | | +===================================+===================================+ | Topical Corticosteroids | Proven to effective in reducing | | | eczema development, reduces the | | | prevalence of wet desquamation | | | and lower the severity of | | | developed RSI. Delays the | | | occurrence of grade 3 RSI. | | | | | | (Deng Guangmei et al., 2024) | +-----------------------------------+-----------------------------------+ | Barrier Protection | Using barrier films or dressings, | | | such as hydrocolloid or | | (silicon-based dressings) | silicone-based products, can | | | protect the skin from further | | | irritation and reduce friction. | | | These dressings also help | | | maintain a moist wound | | | environment, which is conducive | | | to healing. Suggest products may | | | include | | | | | | - Silicon atrumen | | | | | | - Silicon mepitel | | | | | | - Mepilex lite | | | | | | - Hydrosorb | | | | | | (Behroozian et al., 2023 and Yang | | | et al., 2020) | +-----------------------------------+-----------------------------------+ | Silver based dressings & | Silver based dressings have been | | Ointments. | shown to reduce the overall wound | | | depth and severity of RSI. This | | | is dues to their antimicrobial | | | properties, reducing risk of | | | infection, reducing inflammation | | | as well as maintaining a moist | | | environment. Yang el al. (2020) | | | suggests the following types: | | | | | | - Silver Sulfadiazine: a | | | topical antibacterial agent | | | that is primarly used as a | | | topical cream for burns. | | | | | | - Silver nylon dressings: a | | | non-adhesive nanocrystalline | | | material that helps control | | | skin toxicity, mitigating | | | side effects such as itching, | | | pain and burning sensation. | | | | | | - Acticoat 3/7 | | | | | | - Allevyn Ag | | | | | | - Silver-containing foam | | | dressings with Safetac: a | | | silver containing foam that | | | is transparent and gently | | | adheres to the wound site. It | | | provides a moist healing | | | environment without | | | interfering with radiation | | | dosage. | | | | | | - Mepilex AG | +-----------------------------------+-----------------------------------+ | Advanced Radiation Techniques | Utilizing advanced radiation | | | techniques like | | | intensity-modulated radiation | | | therapy (IMRT) and proton therapy | | | can help minimize skin damage by | | | precisely targeting the tumour | | | while sparing surrounding healthy | | | tissue | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | Chronic Radiation Injury | | | Management | | +===================================+===================================+ | Non-Surgical Management | The care of chronic ulceration | | | and wound induced by radiation | | | therapy should follow the same | | | standards as other chronic wound | | | care regimes. There does appear | | | to be a pattern in which | | | non-surgical wound regime appear | | | to be more effective than others. | | | | | | - Topical anti-septics | | | | | | - Silver-Sulfadiazine | | | | | | - Povidone | | | | | | - Non-adhesive dressings | | | | | | - Silver derivatives | | | dressings | | | | | | - Mepilex Ag | | | | | | - Aquacell Ag | | | | | | - Acticoat 3/7 | | | | | | - Hydrocolloid dressing | | | | | | - Duoderm | | | | | | - Comfeel | | | | | | Soriana et al, (2019) suggests | | | the use of marcrophage-activating | | | drugs such as | | | tretrachlorodecaoxide or using | | | autolytic agents such as | | | flamminol to facilitate | | | debridement of tissue that has | | | turned nectrotic. | | | | | | For areas of fibrosis, topical | | | agents like silicone gels or | | | sheets can help soften and | | | flatten scar tissue. Products | | | containing urea or lactic acid | | | can be particularly effective in | | | managing dry, thickened skin. | | | | | | (Soriano et al. 2019) | | | | | | (Hoang Thanh Tuan, 2023) | | | | | | (Jakub Pazdrowski et al., 2024) | +-----------------------------------+-----------------------------------+ | Physical Therapy: | Physical therapy and massage can | | | improve mobility and reduce | | | stiffness in areas affected by | | | fibrosis. Techniques such as | | | manual lymphatic drainage can | | | help manage lymphedema, a common | | | complication of chronic radiation | | | injury. | +-----------------------------------+-----------------------------------+ | Laser Therapy | Fractional laser therapy with | | | low-intensity helium-neon laser | | | can be used to treat | | | radiation-induced fibrosis and | | | improve skin texture and | | | elasticity. This treatment | | | promotes collagen remodelling and | | | can reduce the appearance of | | | scars. | +-----------------------------------+-----------------------------------+ | Hyperbaric Oxygen Therapy (HBOT): | Refers to the application of 100% | | | oxygen into at pressures above | | | atmospheric pressure. This is | | | effective due to the induced | | | hypoxia from radiation causing | | | wound healing delay. Oxygen | | | therapy effectively increases | | | oxygen supply to afflicted | | | tissue, reduce inflammatory | | | exudate on the wound and | | | accelerate the drying and healing | | | of the wound. | | | | | | In NSW, this treatment is only | | | available in Sydney and on the | | | Central coast which may make it | | | unfeasible for rural patients to | | | access. | | | | | | (Simman et al., 2023) | | | | | | (Yang et al., 2020) | +-----------------------------------+-----------------------------------+ | Growth Factors | Growth factors can play a | | | significant role in the healing | | | of RSI and cRSI. They are known | | | to similar the proliferation of | | | skin cells, promote the formation | | | of blood vessels, enhance the | | | production of collagen, reduce | | | inflammation, enhance cellular | | | migration and reduce the overall | | | risk of infection. Some growth | | | factor examples may include: | | | | | | - [Epidermal Growth | | | Factor]: Induces | | | proliferation of fibroblasts, | | | epidermal stem cells and | | | keratinocytes. | | | | | | - [Granulocyte | | | Macrophage-Colony Stimulating | | | Factor] hampers | | | the progress of macrophages. | | | Combined with steroids, | | | decreases risk of RSI and | | | reduces pain burden | | | | | | - [Pentoxifylline]: | | | a non-selective | | | phosphodiesterase inhibitor | | | that reduces inflammatory | | | markers | | | | | | - [Plasma:] | | | enhances cellular function, | | | increases skin regeneration | | | | | | - [Interleukins:] | | | Proinflammatory cytokines | | | that inhibits the expression | | | of inflammatory factors | | | | | | - [Superoxide | | | Dismutase:] an | | | enzymatic antioxidant that | | | may reduce incidents of | | | RSI/cRSI | | | | | | (Simman et al., 2023) | +-----------------------------------+-----------------------------------+ | Surgical Intervention | There is a consensus that | | | surgical intervention appears to | | | be the first line management of | | | cRSI as it eliminates damaged | | | tissue, promotes wound healing | | | and reduces the risk of | | | recurrence due to the abnormal | | | tissue growth caused by radiation | | | treatment. Some these surgical | | | interventions may include: | | | | | | - Skin grafting after full | | | removal of damaged area | | | (otherwise, the skin graft | | | will eventually die.) | | | | | | - Plasty technique with random | | | flap (limited to area, | | | direction and rotation of | | | flap) | | | | | | - Plasty technique and expander | | | flap (not applicable to | | | ulcers with hard base | | | | | | - Plasty technique with | | | seamless pedicle flap | | | | | | - Perforator skin flap | | | | | | - Free flap transfer with | | | vascular microsurgery. | | | | | | (Hoang Thanh Tuan, 2023) | | | | | | (Simman et al., 2023) | +-----------------------------------+-----------------------------------+ **Conclusion:** Radiation induced skin injuries is a prominent, debilitating symptom of radiation therapy. One the biggest challenge faced by clinicians is the lack of standardization on assessing and treating RSI and cRSI. Analysing the literature available, its easy to see that there are some similarities among the preventative measures and the treatment options available to treat these kinds of injures, but yet, there is no standardization of assessment or terminology or treatment. eviQ (Cancer Institute NSW, 2023), used by NSW Government to guide clinicians in mitigating and treating RSI, provides guidance for clinicians to prevent RSI that are validated by current best evidence. Understanding the pathophysiology of RSI is crucial for developing effective management strategies. Acute and chronic RSIs present with varying degrees of severity, from mild erythema to severe ulceration and necrosis. Preventative measures, such as patient education, proper skin care regimens, and advanced radiation techniques, play a vital role in minimizing skin damage. Generally, it is accepted that proper skin care and personal hygiene, the application of topical corticosteroids and the application of specific dressings that match wound exudate is the standard treatment but there is no consensus on what types of topical ointments are most effective, which dressing regime are most effective at which level of injury. Management of acute RSI includes the use of topical corticosteroids, barrier protection, and advanced radiation techniques, and appears to be able to be managed easily without advanced wound care knowledge. Chronic RSI is intrinsic, debilitating and difficult to treat, and there is minimal evidence to support a standard treatment strategy. Looking at the pathogenesis of cRSI, the damage to tissue structure radiation causes, the lack of oxygen and evidence available seems to point towards initiating surgical interventions prior to commencement of implementation of wound regimes, or wound palliation. However, all other avenues of treatment must be exhausted prior to seeking surgical treatment, meaning that there are patients must suffer debilitating side effects that can affect their quality of life. Reflecting on an example of this, patients have reported that if they had been told about the risk of cRSI, they would have never taken the radiation treatment, indicating that there is a lack of patient and clinician understanding of the impact of cRSI. Continued research and the development of standardized treatment protocols are essential to improve patient outcomes and quality of life.