Evidence-Based Skin Care Management in Radiation Therapy

Seminars in Oncology Nursing, Vol 22, No 3 (August), 2006: pp 163–173 163

OBJECTIVES: To review published studies evaluating interventions for the prevention and management of radi- EVIDENCE-BASED ation skin reactions/dermatitis. DATA SOURCES: SKIN CARE Research studies, review articles, and clinical practice guidelines. CONCLUSION: MANAGEMENT IN There is insufficient evidence in the literature to recommend specific topical or oral agents in the preven- RADIATION tion or management of skin reactions. Recent limited evidence sug- gests that the use of calendula cream may reduce the incidence of THERAPY grade 2 and 3 reactions in women with breast cancer. Additionally, early studies evaluating the use of barrier films or creams may im- MAURENE MCQUESTION prove moist desquamation. IMPLICATIONS FOR NURSING ADIATION treatment may cause a variety of physical PRACTICE: skin reactions and contributes to pain, discomfort, Oncology nurses need to increase irritation, itching, and burning. Radiation skin their awareness of the evidence or changes can affect activities of daily living and qual- lack of evidence when recom- ity of life. Individuals may experience difficulties mending interventions to their Rwith wearing or managing their usual clothing, restriction in the patients. Further research is re- movement of a limb or affected area, visible reactions from others, quired to evaluate interventions loss of independence and self care, and incur costs in managing some in the prevention and manage- skin reactions. Skin changes can be experienced by up to 95% of 1 ment of radiation dermatitis. patients. For some, skin changes may have a dose-limiting impact. It is imperative that nurses be knowledgeable about the assessment and management of skin reactions caused by radiation. Goals of care related to the management of radiation skin reactions include maintaining skin integrity, cleanliness, comfort, and the reduction of pain, From the Radiation Medicine Program, protection from trauma, prevention and management of infection, Princess Margaret Hospital, Toronto, On- and the promotion of a moist wound healing environment. If re- tario, Canada. quired, goals will also include the control of bleeding, management of Maurene McQuestion, RN, BA, BScN, CON(C), MSc: Advanced Practice Nurse, Ra- exudate, and odor control. diation Medicine Program, Princess Marga- This article addresses the normal tissue response to radiation ret Hospital University Health Network, To- therapy, factors that affect the degree of reaction, and evidence-based ronto, Ontario, Canada. Address correspondence to Maurene Mc- skin care management in radiation therapy. The goal is to assist Question, RN, BA, BScN, CON(C), MSc, Ra- nurses in making decisions about the care of patients with radiation diation Medicine Program, Princess Marga- skin reactions. ret Hospital, 610 University Ave, Room 15- 609, Toronto, Ontario M5G 2M9; e-mail: [email protected] SKIN ANATOMY AND PHYSIOLOGY

© 2006 Elsevier Inc. All rights reserved. ormal skin is composed of the epidermis and the dermis. The 0749-2081/06/2203-$30.00/0 N epidermis, which includes the outer corniﬁed layer and the doi:10.1016/j.soncn.2006.04.004 deeper basal layer, is continually being renewed through a bal- 164 M. McQUESTION

anced production of new cells from the basal layer TYPES AND SEVERITY OF SKIN REACTIONS in response to the normal shedding of the cornified layer. The basal layer of the epidermis con- arly radiation skin reactions occur within 1 to tains germinal or stem cells that divide and differ- E4 weeks of treatment and may persist for 2 to entiate into mature skin cells. Approximately 10% 4 weeks following treatment. They are identified of basal cells undergo mitosis each day. As the and graded by severity along a continuum ranging outer cells of the cornified layer shed or detach, from erythema and dry desquamation to moist they are replaced by newly differentiated cells desquamation and in more severe cases, ulcer- from the basal layer. This normal process involves ation. During the first 2 weeks of treatment, with both the proliferation and differentiation or mat- a daily fractionated dose of 1.8 to 2.0 Gy, the uration of skin cells to completely replace the patient generally does not experience any discom- epidermal layer approximately every 4 weeks. The fort. Transient erythema may occur within 24 dermis, underlying the epidermis, contains the hours of beginning treatment and is visibly local- support structures including blood vessels, nerves, ized to the treatment field after 2 to 3 weeks of 2,3 glands, and hair follicles. radiation. The skin appears red, warm, and may Following an initial dose of radiation, a fixed have a rashy appearance. Patients may describe 3 percentage of basal cells are destroyed. The re- their skin as feeling sensitive and tight. maining cells become cornified and shed more Hyperpigmentation occurs after 2 to 4 weeks of quickly, thus resulting in a disruption in the bal- treatment. With the cumulative dose reaching 20 ance between the normal production of cells at Gy the patient may experience dryness, pruritus, the basal layer of the skin and the destruction of or flaking of the skin or dry desquamation.8 This is cells at the skin surface. Although non-cycling a result of the decreased ability of the basal layer basal cells are then stimulated into a cycling to replace surface layers, shedding of the epider- phase, continued destruction of basal cells occurs mis, and decreased functioning of the sweat and from ongoing radiation treatment. Additionally, sebaceous glands. At doses of 30 to 40 Gy, extra- an inflammatory response with the secretion of capillary cell damage occurs with increased capil- histamine and serotonin occurs as well as a vas- lary blood flow, hyperemia, and edema. If severe, cular response with extracapillary cell injury and there is epilation leading to moist desquamation capillary dilation. Erythema begins as a result of that can occur at doses of 45 to 60 Gy. With moist capillary dilatation in the dermis accompanied by desquamation, the dermis is exposed. The treat- edema because of increased vascularity and ob- ment field is moist, tender, and red with oozing struction.3,4 Changes in pigmentation are caused and leaking of serous fluid. It can also be accom- by the migration of melanin to the more superfi- panied by light or heavy exudate and crusting.3 cial layers of the epidermis. Hair growth is inter- rupted as hair follicles revert to a resting phase of their cell cycle and hair follicles shed new hairs. Factors Affecting Skin Reactions Complete hair loss can occur at doses greater than Factors affecting the degree of skin reaction 55 Gy, with regrowth occurring approximately 2 include both treatment-related factors and indi- months after the last dose of radiation. Sweat and vidual or patient-related factors. Patients at risk sebaceous glands can be permanently destroyed for skin reactions include patients receiving treat- after approximately 30 Gy in 15 treatments (ie, 2 ment to sites where two skin surfaces are in con- Gy per day) over a 3-week period.3 This can lead tact (eg, breast, perineum), areas where the epi- to reduced skin lubrication causing dryness and dermis is thin and smooth (eg, axilla, face, pruritus. perineum) or where the skin integrity has already Normal tissue repair results from a homeostatic been disrupted from surgery, burns, or lesions. stimulus or feedback mechanism with re-epitheli- Altered wound healing may occur in situations of alization with the proliferation and differentiation postoperative radiation or in surgical incisions of cells from the basal membrane and the migra- that are in the field of irradiated tissue.2 Patient tion of epithelial cells from outside the treatment risk factors also include: the individual’s usual field. Re-epithelialization usually begins in about skin routine, concurrent chemotherapy, immuno- 10 days.5 A moist wound healing environment therapy or targeted therapies, associated medical supports the migration of these cells across the conditions or co-morbidities such as diabetes or wound area of the skin reaction.6,7 renal failure, older age, compromised nutritional SKIN CARE MANAGEMENT IN RADIATION THERAPY 165

status, previous lymphocele aspiration, chronic thereby reducing the skin reaction. Many cen- sun exposure, smoking, and environmental condi- ters11 now keep the uninvolved skin doses over tions.2,9 neck nodes to 55 Gy. Treatment-related risk factors for enhanced Peak skin reactions resulting from hyperfrac- skin reactions include the location of the tumor or tionated accelerated radiotherapy (more than one treatment field (eg, chest wall, head and neck, treatment per day, with a smaller dose per frac- facial, skin folds, breast, axilla, perineum), a larger tion) may not be observed until the end of treat- treatment volume/field, a larger total dose of radi- ment or following treatment because of the short ation, large fraction size (greater than 2.0 Gy per course of therapy. Late skin reactions are related fraction), longer duration of treatment, type of to a larger total dose and total treatment time.3 energy used with lower energy photon and elec- trons depositing a higher skin dose, and the use of REVIEW OF THE LITERATURE ON any bolus material. Megavoltage units such as linear accelerators, with higher energies deliver- MANAGEMENT INTERVENTIONS ing maximal doses of radiation to deeper tissues, 1.5 to 3.0 cm below the skin surface, depending on everal studies have been conducted assessing the energy of the particular unit (6 MV to 18 MV), Sthe outcome of interventions for the preven- thereby sparing the skin.2,9,10 Electron beams de- tion and management of radiation skin reactions. liver an increased dose to the skin because of their There continues to be a paucity of evidence to shorter wavelength, and are often used as a boost recommend many of the interventions or prod- or way of enhancing the dose to tumors or nodes ucts that have been or are being used in clinical closer to the skin surface. In comparison, older practice. Identified products used as interventions treatment units such as the Cobalt-60 unit, will in the literature include lotions, creams, oint- deposit the maximum delivery dose 0.5 cm below ments, and specialized dressings. Most studies the skin surface. have been prevention trials rather than manage- Newer techniques of treatment can potentially ment trials, with methodologic weaknesses mak- affect the incidence and severity of radiation skin ing it difficult to make comparisons across studies reactions, most notably in patients with head and to form recommendations for specific interven- neck cancer. Compared with contemporary con- tions. Other methodologic weaknesses include formal radiation delivery, traditional non-confor- small sample sizes, a wide variety of terms used to mal external beam radiation techniques have re- describe reactions, a variety of measurement sulted in a larger volume of normal tissue tools, and differential outcomes across studies. receiving high doses during a course of treatment. Some studies used the Radiation Therapy Oncol- Conformal radiation techniques and newer inten- ogy Group (RTOG) acute toxicity scale or a mod- sity-modulated radiation therapy (IMRT) have re- ified version of the RTOG scale, while others resulted in small volumes of normal tissue receiving port investigator-developed scales. Outcomes vary the full treatment dose. While in theory, this widely, including severity of skin reaction based should result in less skin dose and improvement in on time to erythema, mean and maximum ery- skin reactions; this has not always been observed. thema scores, mean severity scores, mean toxicity The requirement for multiple beams tangential to scores, time to dry desquamation, incidence and skin delivered through immobilization devices frequency of grades of skin reaction and pain, and (eg, in head and neck IMRT plans) can result in pruritus. increased skin dose and reactions. One potential A 2002 Canadian study12 involving a semi- solution might be to include skin over uninvolved structured telephone survey with 26 regional ra- neck nodes as an organ at risk during treatment diotherapy departments identified significant planning to reduce the dose to uninvolved skin practice differences across organizations and and thereby reduce the degree of skin reaction.11 within interdisciplinary teams.12 Historical prac- Planning for head and neck radiation doses are tices and individual opinions have often guided often 70 Gy, with the skin over neck nodes receiv- practice interventions. Only recently have organi- ing 60 to 70 Gy as well. Taking into consideration zations begun to develop practice guidelines based the skin as a sensitive structure and not including on data from randomized control trials or litera- the uninvolved skin over neck nodes in the con- ture reviews with organizational consensus for tour can reduce the dose to the skin by 6% to 7%, practice.13,14 166 M. McQUESTION

Many general interventions and recommenda- Skin assessments including a RTOG grading score tions are found in the literature. While individu- and evaluation of itching and pain were conducted ally these recommendations may not provide any during treatment and twice following end of treat- supporting evidence, they are often recommended ment. A significant reduction in itching scores at in practice based on clinical experience and that the end of treatment, and erythema and desqua- they do not cause harm. Patients may be advised mation scores following treatment (6 or 8 weeks), to wear loose clothing made of cotton or soft was found in patients who washed with soap and fabrics in areas of contact with the treatment field. water independent of any bolus dose. Tapes and adhesives are not applied to the treat- A similar study was conducted by Roy et al,16 ment area to prevent mechanical injury. Cosmetic with 99 patients randomized to washing with soap products (perfume, make up, or aftershave) and water or no washing. A higher incidence of should also be avoided in the treatment field to moist desquamation was found in the no-washing prevent or minimize sensitivity reactions and ir- group (33% vs 14%) and higher median scores for ritation. The use of heating pads or ice packs is pain, itching, and burning, although these results also not recommended to prevent thermal injury. were not statistically significant. There is insuffi- Electric razors should be used for any shaving in cient evidence to recommend any particular mild the treatment field. Patients should avoid swim- soap during treatment. A study by Frosch and ming in lakes or chlorinated swimming pools or Kligman,17 using a soap chamber method for de- using hot tubs once dry desquamation is present termining the irritancy of soaps, classified Dove or if the skin is no longer intact because of the (Unilever, London, UK) as the only mild soap drying and irritating potential of chemicals used in among 18 soaps tested. Washing and shampooing commercial pools and the risk of infections from of the hair are socially expected hygiene practices. lakes or the warm moist environment of a hot tub. Preventing patients from using these normal rou- A cool mist humidifier should be recommended if tines may add unnecessary distress without any humidification is required for other reasons. proven benefit.18 While saline soaks are recommended in many The use of deodorant within the treatment field clinical settings, they provide no proven benefit has created controversy in clinical settings be- with healing, but may provide comfort with a cause of concerns about an increase in surface cooling sensation with the ability to loosen and skin dose caused by a potential bolus effect from remove any crusting in the treatment field. Addi- deodorants, creams, or powders. Burch et al19 tionally, cost, information, and ability for self-care need to be considered when nurses make skin used an ionizing chamber to measure the surface care recommendations to patients and family care dose of 15 products including six deodorants (ie, providers. solids, roll-ons, and a spray). They compared a set of samples representing normal application thick- Washing ness with a set of samples of extremely thick Washing with lukewarm water and a mild soap application and reported no increase in surface is now recommended as routine care for all pa- dose with normal application. The samples repre- tients receiving radiation therapy. While several senting the thick application were five times the authors make this recommendation, only two ran- normal thickness of application and resulted in domized trials have been conducted assessing higher surface doses. Additionally, there was no washing routines. Campbell and Illingworth15 ran- difference between metallic and nonmetallic de- domized 99 women receiving adjuvant radiother- odorant or powder products, challenging previous apy for breast cancer to one of three groups com- assumptions that products containing magne- paring washing practices. The groups were no sium, aluminum, or zinc would cause an increased washing, washing with water alone, and washing dose and skin reaction. The authors concluded with soap and water. All women were receiving that any enhanced skin reaction with normal treatment to the breast (chest wall), axilla, and product use could be related to irritating chemical supraclavicular fossa for 20 fractions, with two ingredients in the product rather than because of tangential opposed fields usinga5MVlinear ac- an increased surface area and bolus effect with celerator. Approximately half of the women re- normal application of a product. Deodorant can be ceived a Vaseline (Chesebrough-Ponds, Green- applied on intact skin and can be used throughout wich, CT) bolus with 10 to 15 of the fractions. treatment. SKIN CARE MANAGEMENT IN RADIATION THERAPY 167

Lotions and Potions dose to the tumor bed and used the product start- A variety of lotions, creams, and ointments have ing 10 days before treatment. Neither study been recommended in the literature but there is a showed significant differences in the degree of paucity of randomized controlled trials with evi- skin reaction between products or no treatment, dence to support one product over another. nor a prophylactic radioprotective benefit with Aloe vera. Three randomized trials of aloe trolamine. vera gel have been conducted.20–22 Aloe vera is a A recent randomized trial compared Calendula green fleshy cactus plant containing a gel that has Officinalis (marigold plant) with trolamine in been used as a complementary treatment for dry women receiving radiation for breast cancer.27 skin, cuts, and burns. While the use of aloe vera Calendula is a cream derived from the marigold gel has been shown to be safe, none of the ran- plant. Outcome measures included the incidence domized trials showed any difference between of reaction by RTOG grade, pain, the relationship groups that would support the use of an aloe vera between pain and interference with daily living, product.23 Williams et al22 compared aloe vera gel the occurrence and reasons for any treatment with a placebo in 194 women receiving breast disruptions, and satisfaction with the ease of prod- radiation. There was no difference in scores for uct application. Results showed that calendula maximum dermatitis severity or in the time to cream was statistically significantly better in re- onset or duration of Ն grade 2 dermatitis. Olsen et ducing the occurrence of grade 2 or higher skin al21 randomized 73 patients receiving radiation to reaction, in reducing the associated pain with the the head and neck, chest, or abdomen/pelvis to skin reaction, and reducing the incidence of treat- use aloe vera gel and washing with soap or to ment interruption. While patients used the calen- washing with soap alone. At higher cumulative dula cream (84% adherence) and were satisfied doses (Ͼ27 Gy), a significant difference was found with pain relief, topical application of the cream in time to onset of skin changes. The authors was identified as difficult by 30% of patients. Al- concluded that aloe vera may provide a protective though this study is unique in offering a potential skin effect with increasing cumulative doses. Con- for a product to prevent grade 2 dermatitis, a versely, Heggie et al20 compared aloe vera gel with formulation that provides ease of application a topical aqueous cream, each applied three times would encourage the uptake of this evidence into a day during treatment and for 2 weeks following practice. treatment. They found that the cumulative prob- Hyaluronic acid cream. Only one human ability of dry desquamation was higher in the aloe study has been conducted assessing the prophy- vera group (70% vs 41%), as was the prevalence of lactic use of hyaluronic acid (HA) cream.28 Pa- dry desquamation after 3 weeks of therapy. Aloe tients receiving radiation treatment for head and vera gel has been described as having anti-inflam- neck cancer, breast, or pelvic carcinomas were matory and anti-bacterial properties, but is not a randomized to receive either HA 0.2% cream (Ialu- moisturizer.24 gen; IBSA, Lugano, Switzerland) or placebo, ap- Biafine (trolamine). Biafine (Genmedix Ltd, plied to the skin twice daily at the start of radia- France) is an oil-in-water emulsion that has been tion. HA is a polymer that has been shown to used in France for many years. It is reported to stimulate fibroblasts and fibrin development, have non-steroidal anti-inflammatory properties, thereby accelerating the granulation phase of and heal wounds by recruiting macrophages to the healing. In animal models, it has been hypothe- wound bed and promoting the production of gran- sized that HA destroys the oxygen free radicals ulation tissue. Two randomized non-blinded stud- associated with impairing wound healing.29 An ies compared trolamine with best supportive care institution-based rating scale for skin reaction was (ie, Aquaphor [Smith & Nephew, Inc, Little Rock, used with outcome measures including skin reac- AR] and aloe vera) or Lipiderm (G-Pharm Ltd, tion score, patient tolerability, and a subjective France), respectively.25,26 Both studies included a efficacy score by physician and patient. Results no-treatment arm. Both studies included women indicated a statistically significant improvement with breast cancer receiving similar treatments of in delaying the onset of skin reaction by the third 50 Gy to the whole breast. The intervention prod- week as well as reducing the intensity and dura- uct(s) used throughout treatment and for 2 weeks tion of reaction in the group using the HA cream. following treatment. Additionally, women in the No other studies have been conducted to replicate Fenig et al26 study received an additional 10 Gy and support or refute this finding. Although not 168 M. McQUESTION

significant, the mean dose of radiation was lower 0.2% hydrocortisone cream and a placebo in pain the group receiving the HA cream. tients with a variety of cancer diagnoses. Corticosteroids. Corticosteroids have often Sulcrafate. Studies investigating sulcrafate been prescribed in both the prevention and man- have included both prevention and management agement of radiation skin reactions caused by the trials as well as oral and topical routes of admin- anti-inflammatory effect in general dermatological istration. Sulcrafate has been shown to stimulate conditions. The effects in radiation skin reactions cell growth in rats and has been reported to have are thought to be a result of vasoconstriction, an anti-inflammatory effect on gastrointestinal reduced capillary permeability, and inhibition of mucosa.35,36 Two intraindividual prevention trials leukocyte migration.30 Although the studies have was conducted using patients as their own con- generally not found any significant differences or trols.37,38 Evensen et al37 assessed skin reactions benefits with a particular steroid cream, all have in patients with head and neck cancer random- compared different formulations of corticosteroid ized to receive either sodium sucrose octasulfate creams to each other or to an emollient cream. (Na SOS) or a placebo. These authors reported no Two randomized, double blind trials compared difference in erythema, but the placebo group had the prophylactic use of corticosteroid creams for less moist desquamation resulting. 38 the prevention of acute skin reactions in women Maiche et al randomized women with breast with breast cancer.31,32 Bostrom et al31 random- cancer to apply sucralfate cream or a base cream ized 49 women receiving radiation for node-nega- twice daily during 5 weeks of radiation therapy tive breast cancer to receive either mometasone and reported a significant reduction in the devel- furoate (MMF) or an emollient cream twice daily opment of grade 2 skin reactions with more rapid healing with the sucralfate cream. The conflicting from the start of radiation treatment until the results between these two trials may be related to twelfth treatment and then once daily until 3 the different patient groups and treatment doses weeks following treatment. Outcomes measured and the different formulations of the sucralfate included the degree of erythema and pigmentation cream used. using reflectance spectrophotometry, visual skin A later study by Wells et al39 randomized 357 assessment scores using a six-point investigator- patients with head and neck, breast, or anorectal developed scale, and subjective symptom experi- cancer to receive either aqueous cream, sucralfate ence. The patients receiving the emollient cream cream, or no cream from the start of treatment. had significantly higher skin reactions scores Outcome measures included the measurement of compared with those in the MMF group (60% grade acute skin toxicity or grade (modified RTOG ϭ IV reaction vs 25%, respectively; P .011) but no score), erythema readings using reflectance spec- significant difference in symptoms of pruritus or trophotometry, a quality-of-life score, and symp- 32 pain. While Schmuth et al suggested that the toms including pain, itching, burning, and sleep topical corticosteroid cream may be beneficial to disturbance. No significant differences were found patients receiving radiation for breast cancer, no between the treatment arms. The researchers significant differences were found in the trial. concluded that there was no benefit from a pro- Two earlier studies evaluated the use of steroid phylactic application of a cream to the treatment creams in the management of skin reactions in area. More significantly, the authors identified patients with breast cancer, head and neck, chest several risk factors related to more severe skin wall, and abdominal cancers, respectively.33,34 reactions, suggesting the need for further study in Glees et al33 reported a significant difference in patients at higher risk. intensity of skin reaction favoring a 1% hydrocor- Two studies assessing the effectiveness of oral tisone cream compared with clobetasone butyrate sucralfate found no benefit of the prophylactic use cream. Despite this finding, these authors did not of sucralfate in reducing the degree of skin reac- recommend either cream as a first choice treat- tions in patients receiving head and neck cancer ment because 96.4% of the patients using the or in reducing any late toxicity on the rectum in hydrocortisone cream and 88.5% of the patients patients receiving radiation for prostate can- using the clobetasone cream had a moderate to cer.40,41 Delaney et al42 stratified patients by can- maximum skin reaction. Potera et al34 reported no cer diagnosis and randomized patients to receive significant differences in the duration or intensity 10% sucralfate in sorbolene cream or sorbolene of skin reactions with the prophylactic use of a alone for the management of Ն grade 3 (RTOG SKIN CARE MANAGEMENT IN RADIATION THERAPY 169

criteria) moist desquamation. Sorbolene is a a low toxicity and hypersensitivity as well as a low cream composed of water and oils often contain- incidence of resistance. It should be avoided in ing 10% glycerin. No differences were found in the patients with sensitivity to sulfa drugs. No studies measurement of pain or in time to healing be- exist that assess the use and benefit of silver tween the two products, although the study was sulfadiazine ointment in radiation skin reactions. closed early because of limited accrual. The re- Antimicrobials should not be used as prophylactic searchers also identified that significant heteroge- management because of concerns about sensitiv- neity existed between the two treatment groups. ity or resistance with overuse.8 Barrier films. The use of barrier films or creams as a skin protector has been hypothesized Dressings to reduce trauma and retain moisture in the main- The use of dressings in the management of tenance of intact skin, thereby reducing radiation radiation skin reactions is based on the under- injury. Cavilon No-Sting barrier film (3M, St Paul, standing that a moist wound-healing environment MN) was evaluated as a prophylactic treatment in promotes the rate of re-epithelialization and the the prevention of moist desquamation.43 No-Sting migration of epithelial cells across the wound bed was compared to sorbolene in women receiving 50 and that wounds kept moist heal 50% faster.6,7 Gy in 25 fractions of radiation for breast cancer. Hydrophilic dressings. While a number of An internal control method was used randomizing authors have cited the use of dressings in the the products to either the medial or lateral aspect management of moist desquamation, few studies of the chest wall, applied from the start of radia- exist evaluating the effects of hydrocolloids, semi- tion to 2 weeks following treatment. No-Sting was permeable dressings, or hydrogels in the manage- applied twice weekly as it is designed to last sev- ment of radiation skin reactions. Further, the va- eral days, whereas the sorbolene cream was ap- riety of dressings on the market varies in plied twice daily based on standard practice. Irre- thickness, fluid handling or retention ability, per- spective of the frequency of application of the two meability, and conformability. The most com- products, the No-Sting showed a statistically sig- monly cited study evaluating moisture vapor per- nificant improvement in frequency and duration meable (MVP) dressings assessed the rate of of moist desquamation, but no difference in pain healing and patient comfort in 16 patients with or pruritus. dry and moist desquamation.46 Patients were ran- An earlier pilot study by See et al44 evaluated domized to use either a MVP (Tegaderm, 3M) the use of Dermofilm (Innovatec, Australia Pty dressing or hydrous lanolin gauze dressing to Ltd), a micro-thin emollient skin protector, con- manage skin reactions during radiation treat- taining hydrophilic and lipophilic agents, in 50 ment.46 patients receiving radiation to a variety of treat- Additionally, patients in the gauze-dressing ment sites. Although favorable results were re- group who had more severe reactions had the skin ported in reducing pain and skin irritation, a cleansed with a one quarter strength hydrogen larger randomized trial comparing Dermofilm peroxide solution followed by a saline rinse. Heal- with other products was recommended. ing time in the MVP group was 19 days versus 24 Table 1 describes trials on ointments and days for patients using the gauze dressing. Patient creams for the prevention and management of discomfort scores varied in both groups and were acute radiation skin reactions. associated with dressing changes. Despite no sta- Antimicrobials. Silver sulfadiazine (Silva- tistical difference being found between the two dene; King Pharmaceuticals Inc, Bristol, TN) and types of dressings, these authors suggest the po- other antibacterial agents have been used with tential for MVP dressings to be used in the man- radiation skin reactions because of their ability to agement of radiation skin reactions.46 reach a high concentration of the drug in the local Two studies evaluated the use of hydrocolloid area with minimal systemic absorption. Silver sul- dressings in patients who had completed radiation fadiazine, a sulfa drug, is a bacteriocidal agent treatment.47,48 Margolin et al47 evaluated the use active against most gram-positive and gram-nega- of Duoderm (ConvaTec, Princeton, NJ) in a non- tive bacteria. It has generally been used in pa- comparative study with 18 patients who com- tients with burns or mild infections.45 While other pleted radiation. Mean healing time was 13 days drugs have been shown to be more effective in without any documented wound infections. Mak burns, silver sulfadiazine has been shown to have et al48 compared the effect of a hydrocolloid dress- 170 M. McQUESTION

TABLE 1. Descriptions of Trials on Ointments and Creams for the Prevention and Management of Acute Radiation Skin Reactions

No. of Patients Per Outcomes Intervention Study Study Design Treatment Arm Measured Findings

Aloe vera Dudek et al23 Non-randomized 109 (3 different RTOG toxicity No difference between (2000) controlled commercial score, Acute Skin groups; Aloe vera products of aloe Reaction Index shown to be safe vera gel) - 25, (ASRI) 25, and 59 in each group Heggie et RCT 107 - aloe vera Skin toxicity, pain, Higher probability of al20 (2002) 101 - aqueous itching dry desquamation in cream aloe group; higher prevalence of dry desquamation in aloe group Olsen et al21 RCT 33 - mild soap ϩ Skin change and 69% pf patients (2001) aloe RTOG toxicity receiving aloe ϩ 40 - mild soap (erythema, skin soap had skin texture, skin itch, changes at Ͻ 27Gy tanning) vs 43 % of soap only (P Ͻ.034) Williams et RCT 194 - aloe vs Maximum dermatitis No difference in al22 (1996) placebo severity, time to scores for all 108 - aloe vs no onset of Ն grade measures treatment 2 dermatitis, duration of Ն grade 2 dermatitis Trolamine Fisher, et al25 RCT 66 – biafine RN and RT grading No difference in (2000) 74 - best of skin reaction degree of skin supportive care reaction between groups Fenig et al26 RCT 25 - biafine Maximum skin No difference in (2001) 24 - lipiderm reaction score, degree of skin 25 - no treatment time to grade 2 reaction between toxicity, duration groups of dermatitis Calendula Pommier et RCT 126 - calendula Incidence, RTOG Reduced grade 2 or cream al27 (2004) 128 - trolamine score, pain, pain higher skin reactions (biafine) and interference (P Ͻ.001); reduced with ADL, pain (P ϭ .03) with treatment calendula cream interruptions, product satisfaction Hyaluronic acid Liguori et al28 RCT 76 - hyaluronic Skin reaction scale Delayed onset of skin cream (1997) acid 0.2% (institution based), reaction by week 3; 76 - placebo patient tolerability, reduced intensity efficacy score by and duration of skin physician and reaction with patient hyaluronic acid weeks 3-7, 8 and 10 Corticosteroids Bostrom et RCT 25 - MMF Degree of erythema, 60% grade IV skin al31 (2001) 25 - emollient pigmentation, reaction in emollient cream visual skin group vs 35% MMF assessment group, P ϭ .011; no (investigator difference in pain or developed tool), pruritis symptom rating SKIN CARE MANAGEMENT IN RADIATION THERAPY 171

TABLE 1. Descriptions of Trials on Ointments and Creams for the Prevention and Management of Acute Radiation Skin Reactions (Cont’d)

No. of Patients Per Outcomes Intervention Study Study Design Treatment Arm Measured Findings

Schmuth et RCT 11 - 0.5% Mean severity No differences al32 (2002) dexpanthenol score, adverse between groups cream effects (itching, 10 – 0.1% MPA burning), Skindex 15 – control group Sulcrafate Evensen et RCT (patients as 60–NaSOSvs Erythema, No significant al37 (2001) own control) placebo desquamation, differences pain, itching Maiche et RCT (internal 44 – sulcrafate vs Incidence of grade Significant reduction in al38 (1994) control base cream 2 reaction grade 2 skin method) reaction, more rapid healing with sulcrafate cream Wells et al39 RCT 120 - Aqueous Skin toxicity, No difference in (2004) cream (modified RTOG), treatment arms 122 - Sulcrafate erythema, quality cream of life, symptoms 124 - No cream (itching, pain, sunburn, sleep disturbances, erythema, desquamation) Delaney et RCT 20 - 10% RTOG toxicity, pain, No difference in pain al42 (1997) sulcrafate in healing or healing of moist sorbolene cream desquamation 19 - Sorbolene cream Barrier Films Graham et RCT (internal 61 - No-Sting vs RTOG score, pain, Reduction in al43 (2004) control sorbolene (30 pruritis frequency and method) medial duration of moist application, 30 desquamation and lateral) pruritis in No-Sting group

Abbreviations: RCT, randomized controlled trial; MMF, mometasone furoate; MPA, methylprednisolone aceponate cream; Na SOS, sodium sucrose octasulfate; RTOG, Radiation Therapy Oncology Group; RN, registered nurse; RT, radiation therapist; ADL, activities of daily living.

ing changed every 2 days with the twice-daily Several other dressings have been used in clin- application of gentian violet, an antifungal and ical practice or described in the literature, includ- antiseptic agent, on moist desquamation in 42 ing hydrogels for wound hydration, absorbent patients. The study was conducted despite evi- dressings for exudates management, foam dress- dence in animal models indicating that gentian ings, and alginates, among others, but none have violet interfered with wound healing. Although the been studied in patients with radiation skin reac- effect on human wound healing was not known, tions.6 Although one study was conducted evalu- toxicities were reported when gential violet was ating Mepitel (Mölnlycke Health Care, Göteborg, used on blisters in mucosal tissue. No signiﬁcant Sweden), a non-adhering dressing, the study eval- differences existed between the two groups in uated the potential bolus effect to the skin rather wound healing time, although dressing comfort than the effect on wound healing. and aesthetics was statistically signiﬁcant for the Silver dressings. Silver dressings have been hydrocolloid dressing. used in the treatment of burns, venous ulcers, and 172 M. McQUESTION

chronic wounds requiring an antibacterial.49,50 The management of radiation skin reactions. Early dressing is a non-adherent rayon and polyester ma- data supports the use of calendula cream to terial coated with manocrystaline silver. In patients decrease the incidence of moist desquamation. with burns, silver leaf nylon dressings (SLND) have Further evaluation is required with consider- been shown to be more effective than topical agents, ation to the formulation for ease of application. including silver sulfadiazine. SLND have only been Barrier films or creams may also be an interven- recently considered in the management of radiation tion that will prove beneficial, but further re- skin reactions. Vuong et al51 evaluated the dressings search is also required. Because of limited with 15 consecutive patients receiving radiation to evidence for prevention and management, sec- the perineum for anal canal or gynecologic cancers. ondary outcomes such as comfort, symptom Patients wore the dressing from the beginning of relief, ease of application, and cost may be more treatment and for 2 weeks post-treatment. Historical important. Larger, multi-site trials need to be controls were used for comparison. All patients re- conducted using consistent and validated ceived radiation and chemotherapy. While the inci- outcome measures. Outcomes directed at re- dence of grade 3 and 4 reactions in this group of ducing the onset and duration of skin reactions patients is typically 43% to 78%, the SLND reduced this incidence significantly, with only three grade 3 in addition to incidence need to be cons- scores and no grade 4 scores in patients using the idered. SLND compared with 92 grade 3 and 4 scores in the Several trials evaluating topical agents have control group. This study highlighted the role and raised the question whether any product will benefit of using an antibacterial dressing in patients actually prevent or promote the healing of radi- receiving radiation for anal canal and gynecologic ation skin reactions. Given that radiation skin cancers. reactions are a result of damage to the dermal layer of the skin and the resultant imbalance RECOMMENDATIONS FOR FUTURE RESEARCH between the normal production of cells at the basal layer of the skin and the destruction of here remains a paucity of literature and cells at the skin surface, other interventions Twell-designed studies evaluating the effec- may need to be developed aimed at affecting the tiveness of interventions for the prevention and underlying physiologic mechanisms.

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