Expert consensus on diagnosis and treatment of radiation-induced skin injury (2024 version)
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摘要: 放射性皮肤损伤是皮肤组织受到大剂量电离辐射作用后引起的损伤,是肿瘤局部放射治疗最常见的并发症,在核事故、放射事故和长期职业暴露等条件下也可发生。目前,国内外对于放射性皮肤损伤的诊断尚未统一标准,对其预防和治疗缺乏有效手段,亟待更多循证医学研究探索。结合国内外文献、国家职业卫生标准和现有临床经验,该共识编写组组织国内外相关领域专家,反复研讨制订针对当前放射性皮肤损伤诊断和治疗的专家共识,供临床使用参考。Abstract: Radiation-induced skin injury refers to damage caused to skin tissue after exposure to large doses of ionizing radiation. It is the most common complication in localized radiation therapy for tumors and can also occur under conditions such as nuclear accident, radiation accident, and long-term occupational exposure. Currently, there is no uniform standard for the diagnosis of radiation-induced skin injury both domestically and internationally, and there is a lack of effective methods for the prevention and treatment, necessitating more evidence-based medical researches to explore. Combining domestic and international literature, national occupational health standards, and existing clinical experience, the consensus writing group organized experts in related fields at home and abroad to repeatedly discuss and formulate an expert consensus for the diagnosis and treatment of radiation-induced skin injury, serving as a reference for clinical use.
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Key words:
- Radiation, ionizing /
- Skin /
- Ulcer /
- Diagnosis /
- Treatment /
- Expert consensus
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参考文献
(69) [1] 中华人民共和国国家卫生健康委员会 GBZ 106-2020 职业性放射性皮肤疾病诊断 2020 中华人民共和国国家卫生健康委员会. GBZ 106-2020 职业性放射性皮肤疾病诊断[S]. 2020.
[2] RosenthalA,IsrailevichR,MoyR.Management of acute radiation dermatitis: a review of the literature and proposal for treatment algorithm[J].J Am Acad Dermatol,2019,81(2):558-567.DOI: 10.1016/j.jaad.2019.02.047. [3] SorianoJL,CalpenaAC,SoutoEB,et al.Therapy for prevention and treatment of skin ionizing radiation damage: a review[J].Int J Radiat Biol,2019,95(5):537-553.DOI: 10.1080/09553002.2019.1562254. [4] ChinMS,Siegel-ReamerL,FitzGeraldGA,et al.Association between cumulative radiation dose, adverse skin reactions, and changes in surface hemoglobin among women undergoing breast conserving therapy[J].Clin Transl Radiat Oncol,2017,4:15-23.DOI: 10.1016/j.ctro.2017.03.003. [5] TaoY, AuperinA, SireC, et al. Multicenter randomized double-blind, placebo-controlled trial GORTEC (Groupe Oncologie Radiotherapie Tete et Cou) 2009-01 evaluating the effect of the regenerating agent on radiodermatitis of head and neck cancer patients[J]. Int J Radiat Oncol Biol Phys, 2017, 99(3): 590-595.DOI: 10.1016/j.ijrobp.2017.07.019. [6] 中华人民共和国国家卫生和计划生育委员会 GBZ/T 244-2017 电离辐射所致皮肤剂量估算方法 2017 中华人民共和国国家卫生和计划生育委员会.GBZ/T 244-2017 电离辐射所致皮肤剂量估算方法[S]. 2017.
[7] BehroozianT,GoldshteinD,Ryan WolfJ,et al.MASCC clinical practice guidelines for the prevention and management of acute radiation dermatitis: part 1) systematic review[J].EClinicalMedicine,2023,58:101886.DOI: 10.1016/j.eclinm.2023.101886. [8] MillerRC,SchwartzDJ,SloanJA,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[J].Int J Radiat Oncol Biol Phys,2011,79(5):1460-1466.DOI: 10.1016/j.ijrobp.2010.01.031. [9] ShawSZ, NienHH, WuCJ, et al. 3M Cavilon No-Sting Barrier Film or topical corticosteroid (mometasone furoate) for protection against radiation dermatitis: a clinical trial[J]. J Formos Med Assoc, 2015, 114(5): 407-414. DOI: 10.1016/j.jfma.2013.04.003. [10] GinexPK, BacklerC, CrosonE, et al. Radiodermatitis in patients with cancer: systematic review and meta-analysis [J]. Oncol Nurs Forum, 2020, 47(6): E225-E236.DOI: 10.1188/20.ONF.E225-E236. [11] HindleyA,ZainZ,WoodL,et al.Mometasone furoate cream reduces acute radiation dermatitis in patients receiving breast radiation therapy: results of a randomized trial[J].Int J Radiat Oncol Biol Phys,2014,90(4):748-755.DOI: 10.1016/j.ijrobp.2014.06.033. [12] ErridgeSC,McCabeM,PorterMK,et al.Prospective audit showing improved patient-assessed skin toxicity with use of betamethasone cream for those at high risk of radiation dermatitis[J].Radiother Oncol,2016,121(1):143-147.DOI: 10.1016/j.radonc.2016.07.005. [13] MenonA,PremSS,KumariR.Topical betamethasone valerate as a prophylactic agent to prevent acute radiation dermatitis in head and neck malignancies: a randomized, open-label, phase 3 trial[J].Int J Radiat Oncol Biol Phys,2021,109(1):151-160.DOI: 10.1016/j.ijrobp.2020.08.040. [14] UlffE,MarotiM,SerupJ,et al.A potent steroid cream is superior to emollients in reducing acute radiation dermatitis in breast cancer patients treated with adjuvant radiotherapy. A randomised study of betamethasone versus two moisturizing creams[J].Radiother Oncol,2013,108(2):287-292.DOI: 10.1016/j.radonc.2013.05.033. [15] ShariatiL,AmouheidariA,Naji EsfahaniH,et al.Protective effects of doxepin cream on radiation dermatitis in breast cancer: a single arm double-blind randomized clinical trial[J].Br J Clin Pharmacol,2020,86(9):1875-1881.DOI: 10.1111/bcp.14238. [16] CensabellaS,ClaesS,OrlandiniM,et al.Retrospective study of radiotherapy-induced skin reactions in breast cancer patients: reduced incidence of moist desquamation with a hydroactive colloid gel versus dexpanthenol[J].Eur J Oncol Nurs,2014,18(5):499-504.DOI: 10.1016/j.ejon.2014.04.009. [17] CensabellaS,ClaesS,OrlandiniM,et al.Efficacy of a hydroactive colloid gel versus historical controls for the prevention of radiotherapy-induced moist desquamation in breast cancer patients[J].Eur J Oncol Nurs,2017,29:1-7.DOI: 10.1016/j.ejon.2017.04.003. [18] RobijnsJ,BecheriniC,CainiS,et al.Natural and miscellaneous agents for the prevention of acute radiation dermatitis: a systematic review and meta-analysis[J].Support Care Cancer,2023,31(3):195.DOI: 10.1007/s00520-023-07656-z. [19] HeydariradG,AhadiB,Molavi VardanjaniH,et al.Herbal medicines for treatment of radiodermatitis: a systematic review and meta-analysis[J].J Altern Complement Med,2021,27(12):1098-1104.DOI: 10.1089/acm.2021.0166. [20] ZhaoH,ZhuW,ZhaoX,et al.Efficacy of epigallocatechin-3-gallate in preventing dermatitis in patients with breast cancer receiving postoperative radiotherapy: a double-blind, placebo-controlled, phase 2 randomized clinical trial[J].JAMA Dermatol,2022,158(7):779-786.DOI: 10.1001/jamadermatol.2022.1736. [21] ZhaoH,ZhuW,JiaL,et al.Phase I study of topical epigallocatechin-3-gallate (EGCG) in patients with breast cancer receiving adjuvant radiotherapy[J].Br J Radiol,2016,89(1058):20150665.DOI: 10.1259/bjr.20150665. [22] DiggelmannKV,ZytkoviczAE,TuaineJM,et al.Mepilex Lite dressings for the management of radiation-induced erythema: a systematic inpatient controlled clinical trial[J].Br J Radiol,2010,83(995):971-978.DOI: 10.1259/bjr/62011713. [23] SchmeelLC,KochD,StumpfS,et al.Prophylactically applied Hydrofilm polyurethane film dressings reduce radiation dermatitis in adjuvant radiation therapy of breast cancer patients[J].Acta Oncol,2018,57(7):908-915.DOI: 10.1080/0284186X.2018.1441542. [24] SchmeelLC,KochD,SchmeelFC,et al.Hydrofilm polyurethane films reduce radiation dermatitis severity in hypofractionated whole-breast irradiation: an objective, intra-patient randomized dual-center assessment[J].Polymers (Basel),2019,11(12):2112.DOI: 10.3390/polym11122112. [25] RobijnsJ,AquilanoM,BanerjeeS,et al.Barrier films and dressings for the prevention of acute radiation dermatitis: a systematic review and meta-analysis[J].Support Care Cancer,2023,31(4):219.DOI: 10.1007/s00520-023-07671-0. [26] MøllerPK,OllingK,BergM,et al.Breast cancer patients report reduced sensitivity and pain using a barrier film during radiotherapy - a Danish intra-patient randomized multicentre study[J].Tech Innov Patient Support Radiat Oncol,2018,7:20-25.DOI: 10.1016/j.tipsro.2018.05.004. [27] HerstPM, BennettNC, SutherlandAE, et al. Prophylactic use of Mepitel Film prevents radiation-induced moist desquamation in an intra-patient randomised controlled clinical trial of 78 breast cancer patients [J]. Radiother Oncol, 2014, 110(1): 137-143. DOI: 10.1016/j.radonc.2014.01.005. [28] WoodingH,YanJ,YuanL,et al.The effect of Mepitel Film on acute radiation-induced skin reactions in head and neck cancer patients: a feasibility study[J].Br J Radiol,2018,91(1081):20170298.DOI: 10.1259/bjr.20170298. [29] Fernández-CastroM, Martín-GilB, Peña-GarcíaI, et al. Effectiveness of semi-permeable dressings to treat radiation-induced skin reactions. a systematic review[J]. Eur J Cancer Care (Engl), 2017, 26(6):1-8. DOI: 10.1111/ecc.12685. [30] WanBA,ChanS,HerstP,et al.Mepitel Film and Mepilex Lite for the prophylaxis and treatment of skin toxicities from breast radiation[J].Breast,2019,46:87-89.DOI: 10.1016/j.breast.2019.05.012. [31] NiaziTM,VuongT,AzoulayL,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[J].Int J Radiat Oncol Biol Phys,2012,84(3):e305-310.DOI: 10.1016/j.ijrobp.2012.03.062. [32] HematiS,AsnaashariO,SarvizadehM,et al.Topical silver sulfadiazine for the prevention of acute dermatitis during irradiation for breast cancer[J].Support Care Cancer,2012,20(8):1613-1618.DOI: 10.1007/s00520-011-1250-5. [33] KangHC,AhnSD,ChoiDH,et al.The safety and efficacy of EGF-based cream for the prevention of radiotherapy-induced skin injury: results from a multicenter observational study[J].Radiat Oncol J,2014,32(3):156-162.DOI: 10.3857/roj.2014.32.3.156. [34] KongM,HongSE.Topical use of recombinant human epidermal growth factor (EGF)-based cream to prevent radiation dermatitis in breast cancer patients: a single-blind randomized preliminary study[J].Asian Pac J Cancer Prev,2013,14(8):4859-4864.DOI: 10.7314/apjcp.2013.14.8.4859. [35] LiuS,WangYL,ShiST,et al.The effect of recombinant human epidermal growth factor on radiation dermatitis in rectal and anal cancer patients: a self-controlled study[J].BMC Cancer,2022,22(1):1140.DOI: 10.1186/s12885-022-10226-x. [36] KouvarisJR,KoulouliasVE,PlataniotisGA,et al.Topical granulocyte-macrophage colony-stimulating factor for radiation dermatitis of the vulva[J].Br J Dermatol,2001,144(3):646-647.DOI: 10.1046/j.1365-2133.2001.04115.x. [37] MakkonenTA,MinnH,JekunenA,et al.Granulocyte macrophage-colony stimulating factor (GM-CSF) and sucralfate in prevention of radiation-induced mucositis: a prospective randomized study[J].Int J Radiat Oncol Biol Phys,2000,46(3):525-534.DOI: 10.1016/s0360-3016(99)00452-6. [38] SaarilahtiK,KajantiM,JoensuuT,et al.Comparison of granulocyte-macrophage colony-stimulating factor and sucralfate mouthwashes in the prevention of radiation-induced mucositis: a double-blind prospective randomized phase III study[J].Int J Radiat Oncol Biol Phys,2002,54(2):479-485.DOI: 10.1016/s0360-3016(02)02935-8. [39] KinodaJ,IshiharaM,NakamuraS,et al.Protective effect of FGF-2 and low-molecular-weight heparin/protamine nanoparticles on radiation-induced healing-impaired wound repair in rats[J].J Radiat Res,2018,59(1):27-34.DOI: 10.1093/jrr/rrx044. [40] ViswanathL,BindhuJ,KrishnamurthyB,et al.Granulocyte-colony stimulating factor (G-CSF) accelerates healing of radiation induced moist desquamation of the skin[J].Klin Onkol,2012,25(3):199-205. [41] HomDB, ManivelJC. Promoting healing with recombinant human platelet-derived growth factor--BB in a previously irradiated problem wound[J]. Laryngoscope, 2003, 113(9): 1566-1571. DOI: 10.1097/00005537-200309000-00029. [42] GujralMS,PatnaikPM,KaulR,et al.Efficacy of hydrolytic enzymes in preventing radiation therapy-induced side effects in patients with head and neck cancers[J].Cancer Chemother Pharmacol,2001,47 Suppl:S23-28.DOI: 10.1007/s002800170005. [43] DalePS,TamhankarCP,GeorgeD,et al.Co-medication with hydrolytic enzymes in radiation therapy of uterine cervix: evidence of the reduction of acute side effects[J].Cancer Chemother Pharmacol,2001,47 Suppl:S29-34.DOI: 10.1007/s002800170006. [44] RyanJL,HecklerCE,LingM,et al.Curcumin for radiation dermatitis: a randomized, double-blind, placebo-controlled clinical trial of thirty breast cancer patients[J].Radiat Res,2013,180(1):34-43.DOI: 10.1667/RR3255.1. [45] Ryan WolfJ,HecklerCE,GuidoJJ,et al.Oral curcumin for radiation dermatitis: a URCC NCORP study of 686 breast cancer patients[J].Support Care Cancer,2018,26(5):1543-1552.DOI: 10.1007/s00520-017-3957-4. [46] FinkelsteinS,KaneeL,BehroozianT,et al.Comparison of clinical practice guidelines on radiation dermatitis: a narrative review[J].Support Care Cancer,2022,30(6):4663-4674.DOI: 10.1007/s00520-022-06829-6. [47] FurusawaM,BabaY,MurakamiR,et al.Azelastine: its clinical application for radiation dermatitis[J].Radiat Med,1996,14(3):151-154. [48] RobijnsJ, LodewijckxJ, ClaesS, et al. Photobiomodulation therapy for the prevention of acute radiation dermatitis in head and neck cancer patients (DERMISHEAD trial)[J]. Radiother Oncol, 2021, 158: 268-275. DOI: 10.1016/j.radonc.2021.03.002. [49] RobijnsJ, LodewijckxJ, PutsS, et al. Photobiomodulation therapy for the prevention of acute radiation dermatitis in breast cancer patients undergoing hypofractioned whole-breast irradiation (LABRA trial) [J]. Lasers Surg Med, 2022, 54(3): 374-383.DOI: 10.1002/lsm.23475. [50] SchindlA,SchindlM,SchindlL,et al.Increased dermal angiogenesis after low-intensity laser therapy for a chronic radiation ulcer determined by a video measuring system[J].J Am Acad Dermatol,1999,40(3):481-484.DOI: 10.1016/s0190-9622(99)70503-7. [51] DeLandMM,WeissRA,McDanielDH,et al.Treatment of radiation-induced dermatitis with light-emitting diode (LED) photomodulation[J].Lasers Surg Med,2007,39(2):164-168.DOI: 10.1002/lsm.20455. [52] CensabellaS, ClaesS, RobijnsJ, et al. Photobiomodulation for the management of radiation dermatitis: the DERMIS trial, a pilot study of MLS® laser therapy in breast cancer patients[J]. Support Care Cancer, 2016, 24(9): 3925-3933. DOI: 10.1007/s00520-016-3232-0. [53] RobijnsJ,CensabellaS,ClaesS,et al.Biophysical skin measurements to evaluate the effectiveness of photobiomodulation therapy in the prevention of acute radiation dermatitis in breast cancer patients[J].Support Care Cancer,2019,27(4):1245-1254.DOI: 10.1007/s00520-018-4487-4. [54] ZhangX,LiH,LiQ,et al.Application of red light phototherapy in the treatment of radioactive dermatitis in patients with head and neck cancer[J].World J Surg Oncol,2018,16(1):222.DOI: 10.1186/s12957-018-1522-3. [55] BenderitterM,GourmelonP,BeyE,et al.New emerging concepts in the medical management of local radiation injury[J].Health Phys,2010,98(6):851-857.DOI: 10.1097/HP.0b013e3181c9f79a. [56] LatailladeJJ,DoucetC,BeyE,et al.New approach to radiation burn treatment by dosimetry-guided surgery combined with autologous mesenchymal stem cell therapy[J].Regen Med,2007,2(5):785-794.DOI: 10.2217/17460751.2.5.785. [57] PortasM,MansillaE,DragoH,et al.Use of human cadaveric mesenchymal stem cells for cell therapy of a chronic radiation-induced skin lesion: a case report[J].Radiat Prot Dosimetry,2016,171(1):99-106.DOI: 10.1093/rpd/ncw206. [58] TangH,HeY,LiangZ,et al.The therapeutic effect of adipose-derived stem cells on soft tissue injury after radiotherapy and their value for breast reconstruction[J].Stem Cell Res Ther,2022,13(1):493.DOI: 10.1186/s13287-022-02952-7. [59] LynnJV,RanganathanK,LubyAO,et al.Therapeutic efficacy of adipose-derived stem cells versus bone marrow stromal cells for irradiated mandibular fracture repair[J].Ann Plast Surg,2022,89(4):459-464.DOI: 10.1097/SAP.0000000000003301. [60] HuayllaniMT,Ruiz-GarciaH,BoczarD,et al.Adipose-derived stem cells therapy for radiation-induced skin injury[J].Ann Plast Surg,2021,87(6):639-649.DOI: 10.1097/SAP.0000000000003039. [61] FangZ,ChenP,TangS,et al.Will mesenchymal stem cells be future directions for treating radiation-induced skin injury?[J].Stem Cell Res Ther,2021,12(1):179.DOI: 10.1186/s13287-021-02261-5. [62] RigottiG,MarchiA,GalièM,et al.Clinical treatment of radiotherapy tissue damage by lipoaspirate transplant: a healing process mediated by adipose-derived adult stem cells[J].Plast Reconstr Surg,2007,119(5):1409-1422.DOI: 10.1097/01.prs.0000256047.47909.71. [63] YuD,ZhangS,MoW,et al.Transplantation of the stromal vascular fraction (SVF) mitigates severe radiation-induced skin injury[J].Radiat Res,2021,196(3):250-260.DOI: 10.1667/RADE-20-00156.1. [64] DongW,ZhangX,LuoX,et al.Regional flap: a reliable coverage for post-radiation ulcer[J].Int Wound J,2023,20(6):2224-2232.DOI: 10.1111/iwj.14103. [65] 程琳, 杜伟力, 张颖, 等.骶尾部慢性放射性溃疡的分期修复策略[J]. 中华烧伤杂志, 2021, 37(3): 225-231. DOI: 10.3760/cma.j.cn501120-20210104-00003. [66] TuanHT,VinhVQ,AnhTV,et al.Flap application in reconstructive surgery to manage severe radiation-induced ulcers: a case series[J].Wounds,2023,35(1):E7-E13.DOI: 10.25270/wnds/21090. [67] DiH,XiaTY,ZhangM,et al.Reconstruction of giant defects due to electrical and radiation burns in the lower leg with free anterolateral thigh flaps[J].J Plast Reconstr Aesthet Surg,2022,75(5):1596-1601.DOI: 10.1016/j.bjps.2021.11.115. [68] ChanDCW,WongHCY,RiadMA,et al.Prevention of radiation dermatitis with skin hygiene and washing: a systematic review and meta-analysis[J].Support Care Cancer,2023,31(5):294.DOI: 10.1007/s00520-023-07720-8. [69] WuL,ChenL,LiH,et al.Nocardia rubra cell-wall skeleton mitigates whole abdominal irradiation-induced intestinal injury via regulating macrophage function[J/OL].Burns Trauma,2024,12:tkad045[2024-01-26].https://pubmed.ncbi.nlm.nih.gov/38444637/.DOI: 10.1093/burnst/tkad045. -
Table 1. 牛津大学循证医学中心证据分级标准
证据级别 具体描述 Ⅰa 基于多个RCT的系统评价,且文献的同质性好 Ⅰb 单个RCT研究,且可信区间窄 Ⅰc 全或无的病例系列研究 Ⅱa 基于多个队列研究的系统评价 Ⅱb 单个队列研究或质量较差的RCT Ⅱc 结局研究或病因学研究 Ⅲa 病例对照研究的系统评价 Ⅲb 病例对照研究 Ⅳ 单个病例系列研究 Ⅴ 专家意见 注:RCT为随机对照试验 Table 2. 急性放射性皮肤损伤分度诊断标准
分度 初期反应期 假愈期 症状明显期 参考剂量(Gy) Ⅰ — — 毛囊丘疹、暂时脱毛 ≥3 Ⅱ 红斑 2~6周 脱毛、红斑 ≥5 Ⅲ 红斑、烧灼感 1~3周 二次红斑、水泡 ≥10 Ⅳ 红斑、麻木、瘙痒、水肿、刺痛 数小时~10 d 二次红斑、水泡、坏死、溃疡 ≥20 注:该表引自《职业性放射性皮肤疾病诊断》(GBZ 106-2020)[1];“—”表示无此项 Table 3. 慢性放射性皮肤损伤分度诊断标准
分度 临床表现 参考剂量(Gy) 急性迁延 慢性累积 Ⅰ 皮肤色素沉着或脱失、粗糙,指甲灰暗或纵嵴色条甲 ≥5 ≥15 Ⅱ 皮肤角化过度,皲裂或萎缩变薄,毛细血管扩张,指甲增厚变形 ≥10 ≥30 Ⅲ 坏死溃疡,角质突起,指端角化融合,肌腱挛缩,关节变形,功能障碍(具有其中1项即可) ≥20 ≥45 注:该表引自《职业性放射性皮肤疾病诊断》(GBZ 106-2020)[1]