共识
ENGLISH ABSTRACT
放射性口腔黏膜炎辐射防护专家共识
中国抗癌协会肿瘤放射防护专业委员会
中华预防医学会放射卫生专业委员会
作者及单位信息
·
DOI: 10.3760/cma.j.cn113030-20240105-00006
Expert consensus on prevention and treatment of radiotherapy-induced oral mucositis
The Cancer Radiation Protection Committee of China Anti-Cancer Association
The Radiation Health Committee of Chinese Preventive Medicine Association
Yuan Xianglin
Zhang Zhen
Fan Saijun
Authors Info & Affiliations
The Cancer Radiation Protection Committee of China Anti-Cancer Association
The Radiation Health Committee of Chinese Preventive Medicine Association
Yuan Xianglin
Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China
Zhang Zhen
Fudan University Shanghai Cancer Center, Shanghai 200032, China
Fan Saijun
Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China
·
DOI: 10.3760/cma.j.cn113030-20240105-00006
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摘要

放射性口腔黏膜炎(RIOM)是头颈肿瘤放疗中最常见的不良反应之一,可导致营养不良、贫血、免疫力下降、放疗中断等不良后果,严重影响患者的生活质量及治疗效果,亟需采取积极有效的预防及治疗措施,降低患者RIOM的发生率及严重程度。为进一步加强RIOM的规范化管理,由中国抗癌协会肿瘤放射防护专业委员会和中华预防医学会放射卫生专业委员会联合牵头,组织肿瘤放射治疗及放射防护领域的多位专家学者,参考国内外相关文献及临床证据制定本共识,详细阐述RIOM的临床表现、诊断、评估及危险因素,进一步细化RIOM的防治策略,旨在为临床诊疗实践提供重要参考。

放射疗法;放射性口腔黏膜炎;预防;治疗;共识
ABSTRACT

Radiotherapy-induced oral mucositis (RIOM) is one of the most common toxicities of radiotherapy for patients with head and neck tumors, resulting in malnutrition, anemia, decreased immunity and interruption of radiotherapy, which seriously interfere with the quality of life and therapeutic effect of patients. Active and effective strategies are urgently needed to reduce the incidence and severity of RIOM. To further promote standardized management of RIOM, the Cancer Radiation Protection Committee of China Anti-Cancer Association and the Radiation Health Committee of Chinese Preventive Medicine Association organized experts of radiation therapy and radiation protection to formulate this consensus by referring to relevant domestic and international literature and clinical evidence. This consensus elaborates the clinical manifestations, diagnosis, evaluation, risk factors, and further refines the prevention and treatment strategy of RIOM, providing important reference for clinical practice.

Radiotherapy;Radiotherapy-induced oral mucositis;Prevention;Treatment;Consensus
Yuan Xianglin, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China, Email: nc.defudabe.tsuhnilgnaixnauy
Zhang Zhen, Fudan University Shanghai Cancer Center, Shanghai 200032, China, Email: nc.defudabe.nadufgnahz_nehz
Fan Saijun, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Tianjin 300192, China, Email: nc.defcaab.smac-mrinujiasnaf
引用本文

中国抗癌协会肿瘤放射防护专业委员会,中华预防医学会放射卫生专业委员会. 放射性口腔黏膜炎辐射防护专家共识[J]. 中华放射肿瘤学杂志,2024,33(04):296-306.

DOI:10.3760/cma.j.cn113030-20240105-00006

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放射性口腔黏膜炎(radiotherapy-induced oral mucositis,RIOM)是电离辐射干扰口腔上皮细胞的正常更新而导致的急性黏膜损伤,是头颈肿瘤放射治疗中最常见的不良反应之一 1。RIOM是放射治疗过程中最痛苦的不良反应,几乎发生于所有头颈肿瘤放射治疗患者。临床实践中,放射治疗常常与化疗、靶向治疗、免疫治疗等其他治疗手段联合应用,不同程度增加了RIOM的发生率和严重程度,甚至导致放射治疗中断。RIOM继发引起营养不良、贫血、免疫力下降、睡眠障碍、抑郁等严重不良反应,极大降低了患者的生活质量和治疗效果,增加了患者住院率和社会经济负担。因此,采取积极有效的策略,降低患者RIOM的发生率及严重程度,改善患者的生活质量,并最终提高患者的放疗疗效,是头颈肿瘤放疗临床实践中非常重要的工作。
为进一步加强RIOM的规范化管理,中国抗癌协会肿瘤放射防护专业委员会和中华预防医学会放射卫生专业委员会联合牵头,组织肿瘤放射治疗和放射防护领域的多位专家学者,参考国内外相关文献,编写了本共识,进一步细化RIOM的防治策略,为临床诊疗提供有效可行的帮助。
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附录
附录1 临床口腔黏膜炎评估量表

临床口腔黏膜炎评估量表见 附表1

分级标准 0级 1级 2级 3级 4级 5级
WHO标准 无口腔黏膜炎 红斑,伴有疼痛,无溃疡形成 溃疡形成,能进食固体食物 溃疡形成,广泛红斑,进食流质食物 溃疡形成,无法进食 -
NCI CTCAE - 无症状或症状轻微,无需干预 中度疼痛或溃疡,不影响进食,可调整饮食 严重疼痛,影响进食 可能危及生命,需紧急处理 死亡
RTOG标准 - 红斑,充血,可有轻度疼痛,无需镇痛药 片状黏膜炎或有炎性血清血液分泌物,或有中度疼痛 融合的纤维性黏膜炎,可伴重度疼痛 溃疡,出血,坏死 -
临床口腔黏膜炎评估量表
附录2 放射性口腔黏膜炎病理生理5阶段

1.损伤起始阶段:放疗引发基底上皮细胞以及黏膜下层细胞的DNA链断裂造成细胞损伤,进而导致细胞周期中断及细胞凋亡(直接导致细胞死亡)。此外,放射线激发活性氧的产生,启动损伤级联反应,此阶段并未对黏膜功能造成损害。

2.初级损伤阶段:放疗、活性氧启动级联和相互作用的生物学事件,包括NF-κB、Wnt、p53等炎症信号通路的激活,导致一系列促炎细胞因子的产生,包括TNF-α、白介素(interleukin)-1β和IL-6等,这些过程可能协同参与黏膜和内皮的初级损伤。

3.信号放大阶段:初级损伤阶段诱导的分子,如TNF-α和IL-1β等放大初级信号或激活其他细胞中的NF-κB,放大其反应,促进丝裂原激活蛋白激酶(mitogen-activated protein kinase,MAPK)、环氧合酶2(cyclooxygenase 2,COX2)等炎症因子的转录,进而导致上皮和固有层细胞中基质金属蛋白酶(matrix metalloproteinase,MMP)1和MMP3的激活,最终造成组织损伤和黏膜破坏。研究发现,口腔微生物可以通过激活转录因子如NF-κB启动炎症级联反应 [ 93 ] 。这些促炎细胞因子的释放诱导了一个正反馈回路,保持了NF-κB介导的炎症反应的激活 [ 94 ]

4.溃疡形成阶段:黏膜完整性的破坏逐步导致溃疡的形成,溃疡一旦形成,革兰氏阳性和革兰氏阴性口腔细菌定植,并释放出细胞壁产物,加重和延长黏膜损伤。专性和兼性厌氧革兰氏阴性杆菌与≥2级黏膜炎正相关 [ 95 ]

5.溃疡愈合阶段:在大多数情况下,放疗引起黏膜炎是一种急性过程,待其损伤信号消失后,黏膜会逐步自行愈合。但修复后的黏膜对外部损伤的防御能力下降,继续放化疗会增加复发黏膜炎的概率。

附录3 基础口腔护理措施

1.患者教育:放疗前应该帮助患者理解口腔护理的重要性,鼓励患者保持良好的口腔卫生,同时每天对口腔黏膜情况进行自我监测,及时报告口腔变化,还应建议患者戒烟、戒酒,避免食用如西红柿、柑橘类水果和辛辣、热、生或较硬的食物。同时向患者强调在放疗期间摄入足够能量及营养对于治疗的意义,要求患者提高依从性,配合专业人员进行营养评估并接受必要的营养支持。

2.口腔准备:在放疗前或期间应积极寻求口腔专科人员的帮助,全面评估患者的口腔情况,包括口腔卫生状况、龋齿、金属修复材料、义齿等,并对需干预的情况进行临床处理,包括取出金属充填物或将其改为非金属充填物、拆除不良修复体、拔除患牙、处理龋齿、洁牙等 [ 7596 ]

3.牙齿及牙龈的清洁:根据Bass或改良Bass方法( 附录4 ),每天对牙齿、牙龈和舌头进行2~4次清洁,最好是在饭后和睡前 [ 75 ] 。推荐使用软毛牙刷或棉签,以降低黏膜出血的风险。使用牙刷后用清水将其彻底冲洗干净,并将刷头朝上存放在杯子中,每个月更换一支新的软毛牙刷。使用含轻度氟化物(1 000×10 -6~1 500×10 -6)的非研磨性牙膏保护牙釉质,部分头颈部患者需更高含量的氟化物(>1 500×10 -6[ 97 ] 。使用牙线、牙签、牙刷每天清洁齿间区域减少菌斑的形成。有血小板或凝血功能障碍的患者应谨慎使用以上清洁工具。

4.漱口:用不含酒精的漱口水,在醒来后和刷牙后每天至少4次漱口,每次15 ml,时间≥1 min。在漱口后的半小时内,避免进食和饮水 [ 75 ]

5.义齿护理:保证义齿与口腔适配,以避免义齿运动导致黏膜破坏。在进行口腔清洁前应先取出义齿,再用牙刷和牙膏清洁,最后用清水冲洗,如果有条件的话,可以将义齿浸泡在抗菌溶液(如0.2%氯己定)后再佩戴 [ 7597 ] 。放疗过程中,尽可能少佩戴义齿,直到口腔黏膜愈合。

6.保持口腔和唇部湿润:患者应饮用足量液体以保持口腔湿润,还可使用生理盐水喷雾剂、pH中性或含氟化物唾液替代物(人工唾液)、雾化治疗 [ 97 ] 。用无菌凡士林或白色石蜡、润唇膏润滑唇部黏膜。

附录4 水平颤动拂刷法(改良Bass刷牙法)

1.后牙颊面:将牙刷以45°角轻放在牙齿和牙龈的交界处,刷毛朝向牙龈(上颌向上、下颌向下),轻轻加压,使刷毛作短距离的水平颤动,然后拂刷牙面。。

2.后牙舌面:将牙刷保持45°角轻放在牙齿和牙龈的交界处,以同样方法刷牙舌面。

3.前牙舌面:将牙刷直立放到牙面上,上排牙齿向下,下排牙齿向上提拉轻刷。

4.牙齿咬合面:将牙刷刷毛垂直于咬合面,进行前后短距离颤动轻刷。可多角度地对牙齿和牙龈进行全面清洁,每次刷2~3颗牙,反复刷8~10次。

5.轻刷舌头表面:由内向外轻轻去除食物残渣及细菌,保持口气清新。

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备注信息
A
袁响林,华中科技大学同济医学院附属同济医院,武汉 430030,Email: nc.defudabe.tsuhnilgnaixnauy
B
章真,复旦大学附属肿瘤医院,上海 200032,Email: nc.defudabe.nadufgnahz_nehz
C
樊赛军,中国医学科学院放射医学研究所,天津 300192,Email: nc.defcaab.smac-mrinujiasnaf
D
中国抗癌协会肿瘤放射防护专业委员会, 中华预防医学会放射卫生专业委员会. 放射性口腔黏膜炎辐射防护专家共识[J]. 中华放射肿瘤学杂志, 2024, 33(4): 296-306. DOI: 10.3760/cma.j.cn113030-20240105-00006.
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