Prevention and treatment of acute radiation-induced skin reactions: a systematic review and meta-analysis of randomized controlled trials

Raymond Javan Chan, Joan Webster, Bryan Chung, Louise Marquart, Muhtashimuddin Ahmed, Stuart Garantziotis, Raymond Javan Chan, Joan Webster, Bryan Chung, Louise Marquart, Muhtashimuddin Ahmed, Stuart Garantziotis

Abstract

Background: Radiation-induced skin reaction (RISR) is a common side effect that affects the majority of cancer patients receiving radiation treatment. RISR is often characterised by swelling, redness, pigmentation, fibrosis, and ulceration, pain, warmth, burning, and itching of the skin. The aim of this systematic review was to assess the effects of interventions which aim to prevent or manage RISR in people with cancer.

Methods: We searched the following databases up to November 2012: Cochrane Skin Group Specialised Register, CENTRAL (2012, Issue 11), MEDLINE (from 1946), EMBASE (from 1974), PsycINFO (from 1806), CINAHL (from 1981) and LILACS (from 1982). Randomized controlled trials evaluating interventions for preventing or managing RISR in cancer patients were included. The primary outcomes were development of RISR, and levels of RISR and symptom severity. Secondary outcomes were time taken to develop erythema or dry desquamation; quality of life; time taken to heal, a number of skin reaction and symptom severity measures; cost, participant satisfaction; ease of use and adverse effects. Where appropriate, we pooled results of randomized controlled trials using mean differences (MD) or odd ratios (OR) with 95% confidence intervals (CI).

Results: Forty-seven studies were included in this review. These evaluated six types of interventions (oral systemic medications; skin care practices; steroidal topical therapies; non-steroidal topical therapies; dressings and other). Findings from two meta-analyses demonstrated significant benefits of oral Wobe-Mugos E for preventing RISR (OR 0.13 (95% CI 0.05 to 0.38)) and limiting the maximal level of RISR (MD -0.92 (95% CI -1.36 to -0.48)). Another meta-analysis reported that wearing deodorant does not influence the development of RISR (OR 0.80 (95% CI 0.47 to 1.37)).

Conclusions: Despite the high number of trials in this area, there is limited good, comparative research that provides definitive results suggesting the effectiveness of any single intervention for reducing RISR. More research is required to demonstrate the usefulness of a wide range of products that are being used for reducing RISR. Future efforts for reducing RISR severity should focus on promising interventions, such as Wobe-Mugos E and oral zinc.

Figures

Figure 1
Figure 1
Study flow diagram.
Figure 2
Figure 2
Number of included studies by country or region.
Figure 3
Figure 3
Number of included studies sample size.
Figure 4
Figure 4
Risk of bias summary: review authors’ judgements about each risk of bias item for each included study.
Figure 5
Figure 5
Forest plot of comparison: Whole-Mugos E vs usual care (no medication), Outcome: Development of RISR (Yes/No).
Figure 6
Figure 6
Forest plot of comparison: Deodorant vs non-deodorant, Outcome: Development of a RISR.
Figure 7
Figure 7
Forest plot of comparison: Wobe-Mugos E vs usual care (no medication), Outcome: Maximum levels of skin toxicity as measure by EORTC/RTOG, with a possible range of 0-4.
Figure 8
Figure 8
Forest plot of comparison: trolamine vs control. Outcome: Maximum levels of skin toxicity as measure by EORTC/RTOG, with a possible range of 0-4.

References

    1. Maduro JH, Pras E, Willemse PH, de Vries EG. Acute and long-term toxicity following radiotherapy alone or in combination with chemotherapy for locally advanced cervical cancer. Cancer Treat Rev. 2003;29(6):471–488. doi: 10.1016/S0305-7372(03)00117-8.
    1. Vaz A, Pinto-Neto A, Conde D, Costa-Paiva L, Morais S, Esteves S. Quality of life of women with gynecologic cancer: associated factors. Arch Gynecol Obstet. 2007;276(6):583–589. doi: 10.1007/s00404-007-0397-2.
    1. Porock D. Factors influencing the severity of radiation skin and oral mucosal reactions: development of a conceptual framework. Eur J Cancer Care (Engl) 2002;11(1):33–43. doi: 10.1046/j.1365-2354.2002.00287.x.
    1. Sitton E. Early and late radiation-induced skin alterations. Part II: Nursing care of irradiated skin. Oncol Nurs Forum. 1992;19(6):907–912.
    1. Hymes SR, Strom EA, Fife C. Radiation dermatitis: clinical presentation, pathophysiology, and treatment 2006. J Am Acad Dermatol. 2006;54(1):28–46. doi: 10.1016/j.jaad.2005.08.054.
    1. Noble-Adams R. Radiation-induced reactions 1: an examination of the phenomenon. Br J Nurs. 1999;8(17):1134–1140.
    1. Naylor W, Mallett J. Management of acute radiotherapy induced skin reactions: a literature review. Eur J Oncol Nurs. 2001;5(4):221–223. doi: 10.1054/ejon.2001.0145.
    1. Glean E, Edwards S, Faithfull S, Meredith C, Richards C, Smith M. et al.Intervention for acute radiotherapy induced skin reactions in cancer patients: the development of a clinical guideline recommended for use by the college of radiographers. J Radiother Prac. 2001;2:75–84.
    1. de Ruyck K, van Eijkeren M, Claes K, Morthier R, de Paepe A, Vral A. et al.Radiation-induced damage to normal tissues after radiotherapy in patients treated for gynecologic tumors: association with single nucleotide polymorphisms in XRCC1, XRCC3, and OGG1 genes and in vitro chromosomal radiosensitivity in lymphocytes. Int J Radiat Oncol Biol Phys. 2005;62(4):1140–1149. doi: 10.1016/j.ijrobp.2004.12.027.
    1. Bolderston A. Skin care recommendations during radiotherapy: a survey of Canadian practice. Can J Med Radiat Tech. 2002;34:3–11.
    1. Wells M, Macmillan M, Raab G, MacBride S, Bell N, MacKinnon K. et al.Does aqueous or sucralfate cream affect the severity of erythematous radiation skin reactions? A randomised controlled trial. Radiother Oncol. 2004;73(2):153–162. doi: 10.1016/j.radonc.2004.07.032.
    1. McFerran TA. A Dictionary of Nursing. Cambridge: Oxford University Press; 1998.
    1. Huda W. Review of Radiologic Physics. Balltimore: Lippincott, Williams & Wilkins; 2009.
    1. McQuestion M. Evidence-based skin care management in radiation therapy. Semin Oncol Nurs. 2006;22(3):163–173. doi: 10.1016/j.soncn.2006.04.004.
    1. Cohn AB, Lang PO, Agarwal JP, Peng SL, Alizadeh K, Stenson KM. et al.Free-flap reconstruction in the doubly irradiated patient population. Plast Surg Nurs. 2008;122:125–132.
    1. Boot-Vickers M, Eaton K. Skin care for patients receiving radiotherapy. Prof Nurse. 1999;14(10):706–708.
    1. Bolderston A, Lloyd NS, Wong RK, Holden L, Robb-Blenderman L. The prevention and management of acute skin reactions related to radiation therapy: a systematic review and practice guideline. Support Care Cancer. 2006;14(8):802–817. doi: 10.1007/s00520-006-0063-4.
    1. Butcher K, Williamson K. Management of erythema and skin presevation; advice forpatients receiving radical radiotherapy to the breast: a systematic literature review. J Radiother Prac. 2012;11(1):44–54. doi: 10.1017/S1460396910000488.
    1. Kedge E. A systematic review to investigate the effectiveness and acceptability ofinterventions of moist desquamation in radiotherapy patients. Radiography. 2009;15:247–257. doi: 10.1016/j.radi.2008.08.002.
    1. Koukourakis GV, Kelekis N, Kouvaris J. et al.Therapeutics interventions with antiinflammatorycreams in post radiation acute skin reactions: a systematic review of mostimportant clinical trials. Recent Pat Inflamm Allergy Drug Discov. 2010;4:149–158. doi: 10.2174/187221310791163099.
    1. Richardson J, Smith JE, McIntyre M, Thomas R, Pilkington K. Aloe vera for preventing radiation-induced skin reactions: a systematic literature review. Clin Oncol (R Coll Radiol) 2005;17(6):478–484. doi: 10.1016/j.clon.2005.04.013.
    1. Salvo N, Barnes E, van Draanen J. et al.Prophylaxis and management of acute radiationinducedskin reactions: a systematic review of the literature. Curr Oncol. 2010;17:94–112.
    1. Zhang Y, Zhang S, Shao X. Topical agent therapy for prevention and treatment of radiodermatitis: a meta-analysis. Support Care Cancer. 2013;21(4):1025–1032. doi: 10.1007/s00520-012-1622-5.
    1. Chan R, Larsen E, Chan P. Re-examining the evidence in radiation dermatitis management literature: an overview and a critical appraisal of systematic reviews. Int J Radiat Oncol Biol Phys. 2012;84(3):e357–e362. doi: 10.1016/j.ijrobp.2012.05.009.
    1. Chan R. Response to “Topical agent therapy for preventionand treatment of radiodermatitis: a meta-analysis”. Support Care Cancer. 2013;21(7):1801–1802. doi: 10.1007/s00520-013-1737-3.
    1. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. The Atrium, Southern Gate, Chichester, West Sussex PO19 8SQ, England: John Wiley & Sons Ltd; 2008.
    1. Ryan R, Hill S, Broclain D, Horey D, Oliver S, Prictor M, Cochrane C, Communication Review Group. Study quality guide. 2007. (accessed 10 March 2009)
    1. Parmar MK, Torri V, Stewart L. Extracting summary statistics to perform meta-analysis of the published literature for survival endpoints. Stat Med. 1998;17(24):2814–2815.
    1. Merchant T, Bosley C, Smith J, Barratti P, Pritchard D, Davis T, Li C, Xiong X. A phase III trial comparing an anionic phospholipid-based cream and aloe vera-based gel in the prevention of radiation dermatitis in pediatric patients. J Radiat Oncol. 2007;2(45):1–8.
    1. Aygenc E, Celikkanat S, Kaymakci M, Aksaray F, Ozdem C. Prophylactic effect of pentoxifylline on radiotherapy complications: a clinical study. Otolaryngol Head Neck Surg. 2004;130(3):351–356. doi: 10.1016/j.otohns.2003.08.015.
    1. Bairati I, Meyer F, Ge’linas M, Fortin A, Nabid A. et al.Randomized trial of antioxidant vitamins to prevent acute adverse effects of radiation therapy in head and neck cancer patients. J Clin Oncol. 2005;23(24):5805–5813. doi: 10.1200/JCO.2005.05.514.
    1. Dale PS, Tamhankar CP, George D, Daftary GV. Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects. Cancer Chemother Pharmacol. 2001;47 Suppl:S29–S34.
    1. Gujral MS, Patnaik PM, Kaul R, Parikh HK, Conradt C, Tamhankar CP. et al.Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers. Cancer Chemother Pharmacol. 2001;47 Suppl:S23–S28.
    1. Lievens Y, Haustermans K, van den Weyngaert D, van den Bogaert W, Scalliet P, Hutsebaut L. et al.Does sucralfate reduce the acute side-effects in head and neck cancer treated with radiotherapy? A double-blind randomised trial. Radiother Oncol. 1998;47(2):149–153. doi: 10.1016/S0167-8140(97)00231-4.
    1. Lin LC, Que J, Lin LK, Lin FC. Zinc supplementation to improve mucositis and dermatitis in patients after radiotherapy for head-and-neck cancers: a double-blind, randomised study. Int J Radiat Oncol Biol Phys. 2006;65(3):745–750. doi: 10.1016/j.ijrobp.2006.01.015.
    1. Campbell IR, Illingworth MH. Can patients wash during radiotherapy to the breast or chest wall? A randomised controlled trial. Clin Oncol. 1992;4(2):78–82. doi: 10.1016/S0936-6555(05)80971-9.
    1. Roy I, Fortin A, Larochelle M. The impact of skin washing with water and soap during breast irradiation: a randomised study. Radiother Oncol. 2001;58(3):333–339. doi: 10.1016/S0167-8140(00)00322-4.
    1. Bennett C. An investigation into the use of a non-metallic deodorant during radiotherapy treatment: a randomised controlled trial. J Radiother Prac. 2009;8(1):3–9. doi: 10.1017/S146039690800647X.
    1. Gee A, Churn M, Errington RD. A randomised controlled trial to test a non-metallic deodorant used during a course of radiotherapy. J Radiother Prac. 2000;1:205–212. doi: 10.1017/S1460396999000321.
    1. Théberge V, Harel F, Dagnault A. Use of axillary deodorant and effect on acute skin toxicity during radiotherapy for breast cancer: a prospective randomised noninferiority trial. Int J Radiat Oncol Biol Phys. 2009;75(4):1048–1052. doi: 10.1016/j.ijrobp.2008.12.046.
    1. Watson LC, Gies D, Thompson E, Thomas B. Randomized control trial: evaluating aluminum-based antiperspirant use, axilla skin toxicity, and reported quality of life in women receiving external beam radiotherapy for treatment of Stage 0, I, and II breast cancer. Int J Radiat Oncol Biol Phys. 2012;83:e29–e34. doi: 10.1016/j.ijrobp.2011.12.006.
    1. Glees JP, Mameghan-Zadeh H, Sparkes CG. Effectiveness of topical steroids in the control of radiation dermatitis: a randomised trial using 1% hydrocortisone cream and 0.05% clobetasone butyrate (Eumovate) Clin Radiol. 1979;30(4):397–403. doi: 10.1016/S0009-9260(79)80217-2.
    1. Halnan KE. The effect of corticosteroids on the radiation skin reaction. A random trial to assess the value of local application of Prednisolone and Neomycin ointment after X-ray treatment of basal cell carcinoma. Br J Radiol. 1962;35:403–408. doi: 10.1259/0007-1285-35-414-403.
    1. Miller RC, Schwartz DJ, Sloan JA, Griffin PC, Deming RL, Anders JC. et al.Mometasone furoate effect on acute skin toxicity in breast cancer patients receiving radiotherapy: a phase III double-blind, randomized trial from the North Central Cancer Treatment Group N06C4. Int J Radiat Oncol Biol Phys. 2011;79:1460–1466. doi: 10.1016/j.ijrobp.2010.01.031.
    1. Omidvari S, Saboori H, Mohammadianpanah M, Mosalaei A, Ahmadloo N, Mosleh-Shirazi MA. et al.Topical betamethasone for prevention of radiation dermatitis. Indian J Dermatol Venereol Leprol. 2007;73(3):209–219.
    1. Schmuth M, Wimmer MA, Hofer S, Sztankay A, Weinlich G, Linder DM. et al.Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomised, double-blind study. Br J Dermatol. 2002;146(6):983–991. doi: 10.1046/j.1365-2133.2002.04751.x.
    1. Delaney G, Fisher R, Hook C, Barton M. Sucralfate cream in the management of moist desquamation during radiotherapy. Australas Radiol. 1997;41(3):270–275. doi: 10.1111/j.1440-1673.1997.tb00672.x.
    1. Elliott EA, Wright JR, Swann RS, Nguyen-T + ón F, Takita C, Bucci MK. et al.Phase III Trial of an emulsion containing trolamine for the prevention of radiation dermatitis in patients with advanced squamous cell carcinoma of the head and neck: results of Radiation Therapy Oncology Group Trial 99–13. J Clin Oncol. 2006;24(13):2092–2097. doi: 10.1200/JCO.2005.04.9148.
    1. Fisher J, Scott C, Stevens R, Marconi B, Champion L, Freedman GM. et al.Randomized phase III study comparing Best Supportive Care to Biafine as a prophylactic agent for radiation-induced skin toxicity for women undergoing breast irradiation: Radiation Therapy Oncology Group (RTOG) 97–13. Int J Radiat Oncol Biol Phys. 2000;48(5):1307–1310. doi: 10.1016/S0360-3016(00)00782-3.
    1. Garibaldi E, Gatti M, Gardes MP, Raiteri E, Delmastro E, Bona C. et al.Randomized trial on the efficacy of two non steroidal drugs in the prevention of skin damage induced by radiotherapy. J Plastic Dermatol. 2009;5(3):233–239.
    1. Gosselin TK, Schneider SM, Plambeck MA, Rowe K. A prospective randomized, placebo-controlled skin care study in women diagnosed with breast cancer undergoing radiation therapy. Oncol Nurs Forum. 2010;37(5):619–626. doi: 10.1188/10.ONF.619-626.
    1. Heggie S, Bryant GP, Tripcony L, Keller J, Rose P, Glendenning M. et al.A phase III study on the efficacy of topical aloe vera gel on irradiated breast tissue. Cancer Nurs. 2002;25(6):442–451. doi: 10.1097/00002820-200212000-00007.
    1. Jensen JM, Gau T, Schultze J, Lemmnitz G, Folster-Holst R, Abels C, Abels C, Proksch E. Strahlenther Onkol. vol. 187. Luebeck Germany; 2011. Treatment of Acute Radiodermatitis with an oil-in-water emulsion following radiation therapy for breast cancer; pp. 378–384.
    1. Kirova YM, Fromantin I, de Ricke Y, Fourquet A, Movan E, Padiglione S, Ealcou MC, Campana F, Bollet MA. Can we decrease the skin reaction in breast cancer patients using hyluronic acid during radiation therapy? results of phase III randomised trial. Radiother Oncol. 2011;100:205–209. doi: 10.1016/j.radonc.2011.05.014.
    1. Leonardi MC, Gariboldi S, Ivaldi GB, Ferrari A, Serafini F, Didier F. et al.A double-blind, randomised, vehicle-controlled clinical study to evaluate the efficacy of MAS065D in limiting the effects of radiation on the skin: interim analysis. Eur J Dermatol. 2008;18(3):317–321.
    1. Liguori V, Guillemin C, Pesce GF, Mirimanoff RO, Bernier J. Double-blind, randomised clinical study comparing hyaluronic acid cream to placebo in patients treated with radiotherapy. Radiother Oncol. 1997;42(2):155–161. doi: 10.1016/S0167-8140(96)01882-8.
    1. Ma H, Zhang X, Bai M, Wang X. Clinical effects of lianbai liquid in prevention and treatment of dermal injury caused by radiotherapy. J Tradit Chin Med. 2007;27(3):193–196.
    1. Maiche A, Isokangas OP, Gröhn P. Skin protection by sucralfate cream during electron beam therapy. Acta Oncol. 1994;33(2):201–203. doi: 10.3109/02841869409098406.
    1. Olsen DL, Raub W Jr, Bradley C, Johnson M, Macias JL, Love V. et al.The effect of aloe vera gel/mild soap versus mild soap alone in preventing skin reactions in patients undergoing radiation therapy. Oncol Nurs Forum. 2001;28(3):543–547.
    1. Pommier P, Gomez F, Sunyach MP, D’Hombres A, Carrie C, Montbarbon X. Phase III randomised trial of Calendula officinalis compared with trolamine for the prevention of acute dermatitis during irradiation for breast cancer. J Clin Oncol. 2004;22(8):1447–1453. doi: 10.1200/JCO.2004.07.063.
    1. Primavera G, Carrera M, Berardesca E, Pinnaró P, Messina M, Arcangeli G. A double-blind, vehicle-controlled clinical study to evaluate the efficacy of MAS065D (XClair), a hyaluronic acid-based formulation, in the management of radiation-induced dermatitis. Cutan Ocul Toxicol. 2006;25(3):165–171. doi: 10.1080/15569520600860009.
    1. Ribet V, Salas S, Levecq JM, Bastit L, Alfonsi M, de Rauglaudre G. et al.[Interest of a sterilised anti-burning gel in radiation dermatitis: results of a comparative study] Ann Dermatol. 2008;Spec No 1:5–10.
    1. Rizza L, D’Agostino A, Girlando A, Puglia C. Evaluation of the effect of topical agents on radiation-induced skin disease by reflectance spectrophotometry. J Pharm Pharmacol. 2010;62(6):779–785.
    1. Wheat J, Currie G, Coulter K. Wheatgrass extract as a topical skin agent for acute radiation skin toxicity in breast radiation therapy: a randomised controlled trial. J Aust Tradit Med Soc. 2006;12(3):135–137.
    1. Wheat J, Currie G, Coulter K. Management of acute radiation skin toxicity with wheatgrass extract in breast radiation therapy: pilot study. Aust J Med Herbal. 2007;19(2):77–80.
    1. Williams MS, Burk M, Loprinzi CL, Hill M, Schomberg PJ, Nearhood K. et al.Phase III double-blind evaluation of an aloe vera gel as a prophylactic agent for radiation-induced skin toxicity. Int J Radiat Oncol Biol Phys. 1996;36(2):345–349. doi: 10.1016/S0360-3016(96)00320-3.
    1. Zhang J, Zhang L, Zhang L. Effect of trolamine (biafine) in preventing and treating radiation-indcued dermal injury in head and neck carinoma patients. J Pract Oncol. 2011;26(3):269–271.
    1. Aquino-Parsons C, Lomas S, Smith K, Hayes J, Lew S, Bates A, Macdonald AG. Phase III study of silver leaf nylon dressing vs standard care for reduction of inframammary moist desquamation in patients undergoing adjuvant whole breast radiation therapy. J Med Imag Radiat Sci. 2008;4:215–221.
    1. Gollins S, Gaffney C, Slade S, Swindell R. RCT on gentian violet versus a hydrogel dressing for radiotherapy-induced moist skin desquamation. J Wound Care. 2008;17(6):268–270. 272, 274–265.
    1. Mak SS, Zee CY, Molassiotis A, Chan SJ, Leung SF, Mo KF. et al.A comparison of wound treatments in nasopharyngeal cancer patients receiving radiation therapy. Cancer Nurs. 2005;28(6):436–445. doi: 10.1097/00002820-200511000-00005.
    1. Niazi TM, Vuong T, Azoulay L, Marijnen C, Bujko K, Nasr E. et al.Silver clear nylon dressing is effective in preventing radiation-induced dermatitis in patients with lower gastrointestinal cancer: results from a phase III study. Int J Radiat Oncol Biol Phys. 2012;84:e305–e310. doi: 10.1016/j.ijrobp.2012.03.062.
    1. Paterson DB, Poonam P, Bennett N, Peszynski R, van Beekhuizen M, Jasperse M, Herst PM. Randomized intra-patient controlled trial of mepilex lite dressings versus aqueous cream in managing radiation-induced skin reactions post-mastectomy. J Cancer Sci Ther. 2012;4(11):347–356.
    1. Shell JA, Stanutz F, Grimm J. Comparison of moisture vapor permeable (MVP) dressings to conventional dressings for management of radiation skin reactions. Oncol Nurs Forum. 1986;13(1):11–16.
    1. Fife D, Rayhan DJ, Behnam S, Ortiz A, Elkeeb L, Aquino L. et al.A randomized, controlled, double-blind study of light emitting diode photomodulation for the prevention of radiation dermatitis in patients with breast cancer. Dermatol Surg. 2010;36:1921–1927. doi: 10.1111/j.1524-4725.2010.01801.x.
    1. Graham PH, Plant N, Graham JL, Browne L, Borg M, Capp A, Delaney GP, Harvey J, Kenny L, Francis M. et al.A paired, double-blind, randomized comparison of a moisturizing durable barrier cream to 10% glycerine cream in the prophylactic management of postmastectomy irradiation skin care: trans Tasman Radiation Oncology Group (TROG) 04.01. Int J Radiat Oncol Biol Phys. 2013;86(1):45–50. doi: 10.1016/j.ijrobp.2012.12.009.
    1. Sharp L, Finnila K, Johansson H, Abrahamsson M, Hatschek T, Bergenmar M. No differences between Calendula cream and aqueous cream in the prevention of acute radiation skin reactions–results from a randomised blinded trial. Eur J Oncol Nurs. 2013;17(4):429–435. doi: 10.1016/j.ejon.2012.11.003.
    1. Zhong WH, Tang QF, Hu LY, Feng HX. Mepilex Lite dressings for managing acute radiation dermatitis in nasopharyngeal carcinoma patients: a systematic controlled clinical trial. Medical oncology. 2013;30(4):761.

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