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Expert consensus on prevention and control strategy of radiotherapy-induced oral mucositis (2019) Chinese Society of Radiation Oncology of Chinese Medical Association
Abstract Radiotherapy-induced oral mucositis (RTOM) is a category of oral mucosal injury caused by radiotherapy,which is the most common complication of radiotherapy in patients with head and neck tumors. Severe RTOM may interrupt the treatment and lower the clinical efficacy. In recent years,new accomplishment on the prevention and treatment of RTOM has been reported. Nevertheless,unified standards and guidelines are still lacking in China. This expert consensus refers to clinical practice guideline abroad,reviews and summarizes the prevention and management of RTOM at home and abroad,aiming to provide recommendations and suggestions for the prevention and treatment of RTOM in patients with head and neck tumors in China.
$author.xingMing_EN. Expert consensus on prevention and control strategy of radiotherapy-induced oral mucositis (2019) Chinese Society of Radiation Oncology of Chinese Medical Association[J]. Chinese Journal of Radiation Oncology, 2019, 28(9): 641-647.
$author.xingMing_EN. Expert consensus on prevention and control strategy of radiotherapy-induced oral mucositis (2019) Chinese Society of Radiation Oncology of Chinese Medical Association[J]. Chinese Journal of Radiation Oncology, 2019, 28(9): 641-647.
[1] Vera-Llonch M,Oster G,Hagiwara M,et al. Oral mucositis in patients undergoing radiation treatment for head and neck carcinoma[J]. Cancer,2006,106(2):329-336. DOI:10.1002/cncr.21622. [2] 陈谦明. 口腔黏膜病学[M].3版. 北京:人民卫生出版社,2008:77-78. Chen QM. Oral mucosology[M].3ed. Beijing:People's health publishing house,2008:77-78. [3] Popovtzer A,Eisbruch A. Advances in radiation therapy of head and neck cancer[J]. Exp Rev Anticancer Ther,2008,8(4):633-644. DOI:10.1586/14737140.8.4.633. [4] Elting LS,Cooksley CD,Chambers MS,et al. Risk,outcomes,and costs of radiation-induced oral mucositis among patients with head-and-neck malignancies[J]. Int J Radiat Oncol Biol Phys,2007,68(4):1110-1120. DOI:10.1016/j.ijrobp.2007.01.053. [5] Etiz D,Orhan B,Demirustu C,et al. Comparison of radiation-induced oral mucositis scoring systems[J]. Tumori,2002,88(5):379-384. [6] Riesenbeck D,Dorr W Documentation of radiation-induced oral mucositis. Scoring systems[J]. Strahlenther Onkol,1998,174(Suppl 3):44-46. [7] Sonis ST,Eilers JP,Epstein JB,et al. Validation of a new scoring system for the assessment of clinical trial research of oral mucositis induced by radiation or chemotherapy[J]. Cancer,1999,85(10):2103-2113. [8] National cancer institute. Common toxicity criteria. Version2.0.(1999)[DB/OL][2019-07-02].https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/ctcv204-30-992.pdf. [9] Rubenstein EB,Peterson DE,Schubert M,et al. Clinical practice guidelines for the prevention and treatment of cancer therapy-induced oral and gastrointestinal mucositis[J]. Cancer,2004,100(9 Suppl):2026-2046. DOI:10.1002/cncr.20163. [10] Lalla RV,Bowen J,Barasch A,et al. MASCC/ISOO clinical practice guidelines for the management of mucositis secondary to cancer therapy[J]. Cancer,2014,120(10):1453-1461. DOI:10.1002/cncr.28592. [11] Peterson DE,Boers-Doets CB,Bensadoun RJ,et al. Management of oral and gastrointestinal mucosal injury:ESMO Clinical Practice Guidelines for diagnosis,treatment,and follow-up[J]. Ann Oncol,2015,26(Suppl 5):v139-51. DOI:10.1093/annonc/mdv202. [12] Shankar A,Roy S,Bhandari M,et al. Current trends in management of oral mucositis in cancer treatment[J]. As Pac J Cancer Prev,2017,18(8):2019-2026. DOI:10.22034/APJCP.2017.18.8.2019. [13] Eilers J,Million R. Prevention and management of oral mucositis in patients with cancer[J]. Semin Oncol Nurs,2007,23(3):201-212. DOI:10.1016/j.soncn.2007.05.005. [14] Sonis ST Mucositis:the impact,biology and therapeutic opportunities of oral mucositis[J]. Oral Oncol,2009,45(12):1015-1020. DOI:10.1016/j.oraloncology.2009.08.006. [15] Khaw A,Logan R,Keefe D,et al. Radiation-induced oral mucositis and periodontitis—proposal for an inter-relationship[J]. Oral Dis. 2014 Apr;20(3):e7-18. doi:10.1111/odi.12199. [16] Hsiung CY,Ting HM,Huang HY,et al. Parotid-sparing intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma:preserved parotid function after IMRT on quantitative salivary scintigraphy,and comparison with historical data after conventional radiotherapy[J]. Int J Radiat Oncol Biol Phys,2006,66(2):454-461. DOI:10.1016/j.ijrobp.2006.04.033. [17] Romesser PB,Cahlon O,Scher ED,et al. Proton beam reirradiation for recurrent head and neck cancer:multi-institutional report on feasibility and early outcomes[J]. Int J Radiat Oncol Biol Phys,2016,95(2):386-395. DOI:10.1016/j.ijrobp.2016.02.036. [18] Vogel J,Both S,Kirk M,et al. Proton therapy for pediatric head and neck malignancies[J]. Pediatr Blood Cancer. 2018 Feb;65(2). doi:10.1002/pbc.26858. [19] Romesser PB,Cahlon O,Scher E,et al. Proton beam radiation therapy results in significantly reduced toxicity compared with intensity-modulated radiation therapy for head and neck tumors that require ipsilateral radiation[J]. Radiother Oncol,2016,118(2):286-292. DOI:10.1016/j.radonc.2015.12.008. [20] Bourhis J,Lapeyre M,Tortochaux J,et al. Phase Ⅲ randomized trial of very accelerated radiation therapy compared with conventional radiation therapy in squamous cell head and neck cancer:a GORTEC trial[J]. J Clin Oncol,2006,24(18):2873-2878. DOI:10.1200/JCO.2006.08.057. [21] Fu KK,Pajak TF,Trotti A,et al. A radiation therapy oncology group (RTOG) phase Ⅲ randomized study to compare hyperfractionation and two variants of accelerated fractionation to standard fractionation radiotherapy for head and neck squamous cell carcinomas:first report of RTOG 9003[J]. Int J Radiat Oncol Biol Phys,2000,48(1):7-16. DOI:10.1016/s0360-3016(00)00663-5 [22] Xu T,Liu Y,Dou S,et al. Weekly cetuximab concurrent with IMRT aggravated radiation-induced oral mucositis in locally advanced nasopharyngeal carcinoma:Results of a randomized phase Ⅱ study[J]. Oral Oncol,2015,51(9):875-879. DOI:10.1016/j.oraloncology.2015.06.008. [23] Trotti A,Bellm LA,Epstein JB,et al. Mucositis incidence,severity and associated outcomes in patients with head and neck cancer receiving radiotherapy with or without chemotherapy:a systematic literature review[J]. Radiother Oncol,2003,66(3):253-262. DOI:https://doi.org/10.1016/S0167-8140(02)00404-8 [24] Mallick S,Benson R,Rath GK. Radiation induced oral mucositis:a review of current literature on prevention and management[J]. Eur Arch Otorhinolaryngol,2016,273(9):2285-2293. DOI:10.1007/s00405-015-3694-6. [25] Gupta T,Kannan S,Ghosh-Laskar S,et al. Systematic review and Meta-analysis of conventionally fractionated concurrent chemoradiotherapy versus altered fractionation Radiotherapy Alone in the Definitive Management of locoregionally advanced head and neck squamous cell carcinoma[J]. Clin Oncol (R Coll Radiol),2016,28(1):50-61. DOI:10.1016/j.clon.2015.09.002. [26] Narayan S,Lehmann J,Coleman MA,et al. Prospective evaluation to establish a dose response for clinical oral mucositis in patients undergoing head-and-neck conformal radiotherapy[J]. Int J Radiat Oncol Biol Phys,2008,72(3):756-762. DOI:10.1016/j.ijrobp.2008.01.060. [27] Wang ZH,Zhang SZ,Zhang ZY,et al. Protecting the oral mucosa in patients with oral tongue squamous cell carcinoma treated postoperatively with intensity-modulated radiotherapy:a randomized study[J]. Laryngoscope,2012,122(2):291-298. DOI:10.1002/lary.22434. [28] Khuntia D,Harris J,Bentzen S,et al. Increased oral mucositis after IMRT versus non-IMRT when combined with cetuximab and cisplatin or docetaxel for head and neck cancer:preliminary results of RTOG 0234[J]. Int J Radiat Oncol Biol Phys,2008,72(1):S33. DOI:10.1016/j.ijrobp.2008.06.839. [29] 殷蔚伯,申文江,王绿化. 放射治疗损伤[M]. 北京:中国医药科技出版社,2001:79-81. Yin WB,Shen WJ,Wang LH. Radiotherapy Injury[M]. Beijing:China medical science and technology press,2001:79-81. [30] Calais G,Alfonsi M,Bardet E,et al. Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma[J]. J Natl Cancer Inst,1999,91(24):2081-2086. [31] Olmi P,Crispino S,Fallai C,et al. Locoregionally advanced carcinoma of the oropharynx:conventional radiotherapy vs.accelerated hyperfractionated radiotherapy vs.concomitant radiotherapy and chemotherapy—a multicenter randomized trial[J]. Int J Radiat Oncol Biol Phys,2003,55(1):78-92. [32] Forastiere AA,Goepfert H,Maor M,et al. Concurrent chemotherapy and radiotherapy for organ preservation in advanced laryngeal cancer[J]. N Engl J Med,2003,349(22):2091-2098. DOI:10.1056/NEJMoa031317. [33] Cooper JS,Pajak TF,Forastiere AA,et al. Postoperative concurrent radiotherapy and chemotherapy for high-risk squamous-cell carcinoma of the head and neck[J]. N Engl J Med,2004,350(19):1937-44. DOI:10.1056/NEJMoa032646. [34] Bernier J,Domenge C,Ozsahin M,et al. Postoperative irradiation with or without concomitant chemotherapy for locally advanced head and neck cancer[J]. N Engl J Med,2004,350(19):1945-52. DOI:10.1056/NEJMoa032641. [35] Xu C,Zhang LH,Chen YP,et al. Chemoradiotherapy versus radiotherapy alone in stage Ⅱ nasopharyngeal carcinoma:a systemic review and Meta-analysis of 2138 patients[J]. J Cancer,2017,8(2):287-297. DOI:10.7150/jca.17317. [36] Blanchard P,Lee A,Marguet S,et al. Chemotherapy and radiotherapy in nasopharyngeal carcinoma:an update of the MAC-NPC meta-analysis[J]. Lancet Oncol,2015,16(6):645-655. DOI:10.1016/S1470-2045(15)70126-9. [37] Chen L,Hu CS,Chen XZ,et al. Concurrent chemoradiotherapy plus adjuvant chemotherapy versus concurrent chemoradiotherapy alone in patients with locoregionally advanced nasopharyngeal carcinoma:a phase 3 multicentre randomised controlled trial[J]. Lancet Oncol,2012,13(2):163-171. DOI:10.1016/S1470-2045(11)70320-5. [38] Li Y,Chen QY,Tang LQ,et al. Concurrent chemoradiotherapy with or without cetuximab for stage Ⅱ to Ⅳ b nasopharyngeal carcinoma:a case-control study[J]. BMC Cancer,2017,17(1):567. DOI:10.1186/s12885-017-3552-6. [39] Bjarnason GA,Mackenzie RG,Nabid A,et al. Comparison of toxicity associated with early morning versus late afternoon radiotherapy in patients with head-and-neck cancer:a prospective randomized trial of the National Cancer Institute of Canada Clinical Trials Group (HN3)[J]. Int J Radiat Oncol Biol Phys,2009,73(1):166-172. DOI:10.1016/j.ijrobp.2008.07.009. [40] Bensinger W,Schubert M,Ang KK,et al. NCCN task force report.prevention and management of mucositis in cancer care[J]. J Natl Compr Canc Netw,2008,6(Suppl 1):S1-21, S22-24. [41] Peterson DE,Bensadoun RJ,Roila F,et al. Management of oral and gastrointestinal mucositis:ESMO Clinical Practice Guidelines[J]. Ann Oncol,2011,22(Suppl 6):vi78-84. DOI:10.1093/annonc/mdr391. [42] McGuire DB,Fulton JS,Park J,et al. Systematic review of basic oral care for the management of oral mucositis in cancer patients[J]. Support Care Cancer,2013,21(11):3165-3177. DOI:10.1007/s00520-013-1942-0. [43] Ps SK,Balan A,Sankar A,et al. Radiation induced oral mucositis[J]. Indian J Palliat Care,2009,15(2):95-102. DOI:10.4103/0973-1075.58452. [44] Saarilahti K,Kajanti M,Joensuu T,Comparison of granulocyte-macrophage colony-stimulating factorand 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 Oct 1;54(2):479-85. DOI:10.1016/s0360-3016(02)02935-8 [45] Wagner W,Alfrink M,Haus U,Matt J. Treatment of irradiation-induced mucositis with growth factors (rhGM-CSF) in patients with head and neck cancer[J]. Anticancer Res,1999,19(1B):799-803. [46] Mantovani G,Massa E,Astara G,et al. Phase Ⅱ clinical trial of local use of GM-CSF for prevention and treatment of chemotherapy-and concomitant chemoradiotherapy-induced severe oral mucositis in advanced head and neck cancer patients:an evaluation of effectiveness,safety and costs[J]. Oncol Rep,2003,10(1):197-206. DOI:https://doi.org/10.3892/or.10.1.19?. [47] Ryu JK,Swann S,LeVeque F,et al. The impact of concurrent granulocyte macrophage-colony stimulating factor on radiation-induced mucositis in head and neck cancer patients:a double-blind placebo-controlled prospective phase Ⅲ study by Radiation Therapy Oncology Group 9901[J]. Int J Radiat Oncol Biol Phys,2007,67(3):643-650. DOI:10.1016/j.ijrobp.2006.09.043. [48] Hoffman KE,Pugh SL,James JL,et al. The impact of concurrent granulocyte-macrophage colony-stimulating factor on quality of life in head and neck cancer patients:results of the randomized,placebo-controlled Radiation Therapy Oncology Group 9901 trial[J]. Qual Life Res,2014,23(6):1841-1858. DOI:10.1007/s11136-014-0628-5. [49] Judith E,Raber-Durlacher I,von Bültzingslwen S. Systematic review of cytokines and growth factors for the management of oral mucositis in cancer patients[J]. Support Care Cancer,2013,21(2):343-355. DOI:10.1007/s00520-012-1594-5. [50] 李素艳,高黎,殷蔚伯,等. 金因肽对急性放射性黏膜炎及皮炎的作用[J]. 中华放射肿瘤学杂志,2002,11(1):30-32. Li SY,Gao L,Yin WB,et al. Effects of ginin on acute radiation mucositis and dermatitis[J]. Chin J Radiat Oncol,2002,11(1):30-32. [51] Wu HG,Song SY,Kim YS,et al. Therapeutic effect of recombinant human epidermal growth factor (RhEGF) on mucositis in patients undergoing radiotherapy,with or without chemotherapy,for head and neck cancer:a double-blind placebo-controlled prospective phase 2 multi-institutional clinical trial[J]. Cancer,2009,115(16):3699-3708. DOI:10.1002/cncr.24414. [52] Nicolatou-Galitis O,Sarri T,Bowen J,et al. Systematic review of amifostine for the management of oral mucositis in cancer patients[J]. Support Care Cancer,2013,21(1):357-364. DOI:10.1007/s00520-012-1613-6. [53] Tsujimoto T,Yamamoto Y,Wasa M,et al. L-glutamine decreases the severity of mucositis induced by chemoradiotherapy in patients with locally advanced head and neck cancer:a double-blind,randomized,placebo-controlled trial[J]. Oncol Rep,2015,33(1):33-39. DOI:10.3892/or.2014.3564. [54] Quinn B. Efficacy of a supersaturated calcium phosphate oral rinse for the prevention and treatment of oral mucositis in patients receiving high-dose cancer therapy:a review of current data[J]. Eur J Cancer Care (Engl),2013,22(5):564-579. DOI:10.1111/ecc.12073. [55] Lambrecht M,Mercier C,Geussens Y,et al. The effect of a supersaturated calcium phosphate mouth rinse on the development of oral mucositis in head and neck cancer patients treated with (chemo) radiation:a single-center,randomized,prospective study of a calcium phosphate mouth rinse+ standard of care versus standard of care[J]. Support Care Cancer,2013,21(10):2663-2670. DOI:10.1007/s00520-013-1829-0. [56] Sironi M,Milanese C,Vecchi A,et al. Benzydamine inhibits the release of tumor necrosis factor-alpha and monocyte chemotactic protein-1 by Candida albicans-stimulated human peripheral blood cells[J]. Int J Clin Lab Res,1997,27(2):118-122. [58] Sironi M,Pozzi P,Polentarutti N,et al. Inhibition of inflammatory cytokine production and protection against endotoxin toxicity by benzydamine[J]. Cytokine,1996,8(9):710-716. [58] Epstein JB,Silverman S Jr,Paggiarino DA,et al. Benzydamine HCl for prophylaxis of radiation-induced oral mucositis:results from a multicenter,randomized,double-blind,placebo-controlled clinical trial[J]. Cancer,2001,92(4):875-885. [59] Kazemian A,Kamian S,Aghili M,et al. Benzydamine for prophylaxis of radiation-induced oral mucositis in head and neck cancers:a double-blind placebo-controlled randomized clinical trial[J]. Eur J Cancer Care (Engl),2009,18(2):174-178. DOI:10.1111/j.1365-2354.2008.00943.x. [60] Nicolatou-Galitis O,Sarri T,Bowen J,et al. Systematic review of anti-inflammatory agents for the management of oral mucositis in cancer patients[J]. Support Care Cancer,2013,21(11):3179-3189. DOI:10.1007/s00520-013-1847-y. [61] Saunders DP,Epstein JB,Elad S,et al. Systematic review of antimicrobials,mucosal coating agents,anesthetics,and analgesics for the management of oral mucositis in cancer patients[J]. Support Care Cancer,2013,21(11):3191-3207. DOI:10.1007/s00520-013-1871-y. [62] 林冰,郎锦义,张鹏. 放化疗全程配合不同中药组方治疗鼻咽癌的临床观察[J]. 四川中医,2014,32(9):71-73. Lin B,Lang JY,Zhang P. Clinical observation on the treatment of nasopharyngeal carcinoma by radiotherapy and chemotherapy combined with different traditional chinese medicine formulas[J]. Sichuan Tradit Chin Med,2014,32(9):71-73. [63] Zheng B,Zhu X,Liu M,et al. Randomized,double-blind,placebo-controlled trial of Shuanghua Baihe tablets to prevent oral mucositis in patients with nasopharyngeal cancer undergoing chemoradiation therapy[J]. Int J Radiat Oncol Biol Phys,2018,100(2):418-426. DOI:10.1016/j.ijrobp.2017.10.013. [64] Kong M,Hwang DS,Yoon SW,et al. The effect of clove-based herbal mouthwash on radiation-induced oral mucositis in patients with head and neck cancer:a single-blind randomized preliminary study[J]. Onco Targets Ther,2016,9:4533-4538. DOI:10.2147/OTT. S108769. [65] Luo Y,Feng M,Fan Z,et al. Effect of Kangfuxin solution on chemo/radiotherapy-induced mucositis in nasopharyngeal carcinoma patients:a multicenter,prospective randomized phase Ⅲ clinical study[J]. Evid Based Complement Alternat Med,2016,2016:8692343. DOI:10.1155/2016/8692343. [66] Mose S,Adamietz IA,Saran F,et al. Can prophylactic application of immunoglobulin decrease radiotherapy-induced oral mucositis?[J]. Am J Clin Oncol,1997,20(4):407-411. [67] Ahmadi A. Potential prevention:Aloe vera mouthwash may reduce radiation-induced oral mucositis in head and neck cancer patients[J]. Chin J Integr Med,2012,18(8):635-640. DOI:10.1007/s11655-012-1183-y. [68] Santos-Silva AR,Rosa GB,Eduardo CP,et al. Increased risk for radiation-related caries in cancer patients using topical honey for the prevention of oral mucositis[J]. Int J Oral Maxillofac Surg,2011,40(11):1335-1336. DOI:10.1016/j.ijom.2011.05.006. [69] Lin BM,Starmer HM,Gourin CG. The relationship between depressive symptoms,quality of life,and swallowing function in head and neck cancer patients 1 year after definitive therapy[J]. Laryngoscope,2012,122(7):1518-1525. DOI:10.1002/lary.23312. [70] Basso FG,Pansani TN,Soares DG,et al. Biomodulation of inflammatory cytokines related to oral mucositis by low-level laser therapy[J]. Photochem Photobiol,2015,91(4):952-956. DOI:10.1111/php.12445. [71] Kannan V,Bapsy PP,Anantha N,et al. Efficacy and safety of granulocyte macrophage-colony stimulating factor (GM-CSF) on the frequency and severity of radiation mucositis in patients with head and neck carcinoma[J]. Int J Radiat Oncol Biol Phys,1997,37(5):1005-1010. [72] McAleese JJ,Bishop KM,A'Hern R,et al. Randomized phase Ⅱ study of GM-CSF to reduce mucositis caused by accelerated radiotherapy of laryngeal cancer[J]. Br J Radiol,2006,79(943):608-613. DOI:https://doi.org/10.1259/ bjr/55190439. [73] Sprinzl GM,Galvan O,de Vries A,et al. Local application of granulocytemacrophage colony stimulating factor (GM-CSF) for the treatment of oral mucositis[J]. Eur J Cancer,2001,37(16):2003-2009. DOI:10.1016/s0959-8049(01)00170-8. [74] Nishii1 M,Soutome S,Kawakita A. Factors associated with severe oral mucositis and candidiasis in patients undergoing radiotherapy for oral and oropharyngeal carcinomas:a retrospective multicenter study of 326 patients[J]. Support Care Cancer. 2019 Jun 8. DOI:10.1007/s00520-019-04885-z. [75] Pillsbury HC Ⅲ,Webster WP,Rosenman J. Prostaglandin inhibitorand radiotherapy in advanced head and neck cancers[J]. Arch Otolaryngol Head Neck Surg,1986,112(5):552-553. DOI:10.1007/s00520-019-04885-z.
2019, Vol. 28 
