鼻咽癌调强放疗患者严重放射性口腔黏膜炎发生的影响因素分析

摘要/Abstract

摘要：

目的探讨鼻咽癌调强放疗患者放疗前、后及放疗期间口腔唾液流量、pH值和菌群3项指标的动态变化，并分析严重放射性口腔黏膜炎发生的影响因素。方法选取2021年6月2日至2022年12月30日山东省肿瘤防治研究院头颈放疗病区收治的首次接受放疗的100例鼻咽癌患者为研究对象。测定鼻咽癌患者放疗前、放疗15次、放疗35次、放疗后1个月、放疗后3个月5个时间点的口腔唾液流量、pH值和菌群，分析3个指标各时刻的动态变化。对鼻咽癌放疗患者放疗15次时严重放射性口腔黏膜炎发生的因素进行单因素及多因素logistic回归分析。结果鼻咽癌放疗患者放疗前、放疗15次、放疗35次、放疗后1个月、放疗后3个月唾液流量分别为（16.51±1.29）、（8.64±1.31）、（5.15±1.14）、（4.78±1.36）、（5.67±1.27） ml，差异有统计学意义（F=2 171.94，P<0.001），唾液流量在放疗后1个月降至最低后回升（均P<0.05）。鼻咽癌放疗患者放疗前、放疗15次、放疗35次、放疗后1个月、放疗后3个月口腔pH值分别为8.28±0.67、5.87±0.53、5.32±0.55、6.04±0.83、6.74±0.63，差异有统计学意义（F=370.43，P<0.001），pH值在放疗15次、放疗35次依次下降，放疗后1个月、放疗后3个月逐渐升高（均P<0.05）。鼻咽癌放疗患者放疗前（6%，6/100）、放疗15次（62%，62/100）、放疗35次（60%，60/100）、放疗后1个月（40%，40/100）、放疗后3个月（29%，29/100）病原菌检出率差异有统计学意义（χ²=18.24，P<0.001），与放疗前相比，放疗15次、放疗35次病原菌检出率差异均有统计学意义（χ²=1.90，P=0.001；χ²=1.63，P=0.005）；放疗15次与放疗35次病原菌检出率差异无统计学意义（χ²=0.27，P=0.644）；与放疗前相比，放疗后1个月、放疗后3个月病原菌检出率差异均无统计学意义（χ²=1.30，P=0.024；χ²=0.83，P=0.149）。100例鼻咽癌放疗患者中，70例患者发生严重放射性口腔黏膜炎（≥3级）。不同吸烟史（χ²=8.84，P=0.003）、饮酒史（χ²=23.94，P<0.001）、化疗史（χ²=40.41，P<0.001）、口腔卫生条件（χ²=8.16，P=0.004）、口腔pH值（χ²=16.83，P<0.001）、口腔病原菌（χ²=8.80，P=0.003）鼻咽癌放疗患者发生严重放射性口腔黏膜炎差异均有统计学意义。多因素分析显示，饮酒史（OR=2.23，95%CI为1.98~6.04，P=0.006）、化疗史（OR=3.13，95%CI为2.62~6.87，P<0.001）、口腔病原菌（OR=3.11，95%CI为1.04~9.31，P=0.043）均是鼻咽癌放疗患者严重放射性口腔黏膜炎发生的独立影响因素。结论鼻咽癌放疗患者唾液流量自放疗开始后逐渐降低，在放疗后1个月降至最低后回升。口腔pH值自放疗开始后至放疗35次逐渐下降，放疗后1个月至放疗后3个月逐渐升高。病原菌检出率放疗开始至放疗15次迅速增高，而放疗15次到35次增速较稳定，放疗后1个月趋于正常。饮酒史、化疗史、口腔病原菌均是严重放射性口腔黏膜炎发生的独立影响因素。

关键词:鼻咽肿瘤,放射治疗计划，计算机辅助,口炎,肿瘤微环境

Abstract:

ObjectiveTo investigate the dynamic changes of oral saliva flow， pH value， and bacterial flora before and after radiotherapy in patients with nasopharyngeal carcinoma （NPC） treated with intensity modulated radiotherapy， and to analyze the influencing factors of severe radioactive oral mucositis.MethodsOne hundred NPC patients who received radiotherapy for the first time in the Head and Neck Radiotherapy Ward of Shandong Cancer Hospital and Institute from June 2， 2021 to December 30， 2022 were selected. Oral saliva flow， pH value and bacterial flora were measured at 5 time points， namely before radiotherapy， 15 times of radiotherapy， 35 times of radiotherapy， 1 month and 3 months after radiotherapy in patients with NPC， and the dynamic changes of 3 indicators were analyzed at each time. The factors of the occurrence of severe radioactive oral mucositis in patients with NPC were analyzed by univariate and multivariate logistic regression 15 times of radiotherapy.ResultsThe saliva flow of patients with NPC before radiotherapy， 15 times of radiotherapy， 35 times of radiotherapy， 1 month after and 3 months after radiotherapy were （16.51±1.29），（8.64±1.31），（5.15±1.14），（4.78±1.36） and （5.67±1.27） ml， respectively， with a statistically significant difference （F=2 171.94，P<0.001）. Oral saliva flow decreased to the lowest level 1 month after radiotherapy and then increased （allP<0.05）. The pH values of patients with NPC before radiotherapy， 15 times of radiotherapy， 35 times of radiotherapy， 1 month after and 3 months after radiotherapy were 8.28±0.67， 5.87±0.53， 5.32±0.55， 6.04±0.83， 6.74±0.63， respectively， with a statistically significant difference （F=370.43，P<0.001）. The pH value decreased successively after 15 and 35 times of radiotherapy， and gradually increased 1 month and 3 months after radiotherapy （allP<0.05）. There was a statistically significant difference （χ²=18.24，P<0.001） in the detection rate of pathogenic bacteria in patients with NPC before radiotherapy （6%， 6/100）， 15 times of radiotherapy （62%， 62/100）， 35 times of radiotherapy （60%， 60/100）， 1 month after radiotherapy （40%， 40/100） and 3 months after radiotherapy （29%， 29/100）. Compared with before radiotherapy， there were statistically significant differences in the detection rates of pathogenic bacteria between 15 times of radiotherapy and 35 times of radiotherapy （χ²=1.90，P=0.001；χ²=1.63，P=0.005）. There was no statistically significant difference in the detection rate of pathogenic bacteria between 15 times of radiotherapy and 35 times of radiotherapy （χ²=0.27，P=0.644）. Compared with before radiotherapy， there was no statistically significant difference in the detection rate of pathogenic bacteria 1 month after radiotherapy and 3 months after radiotherapy （χ²=1.30，P=0.024；χ²=0.83，P=0.149）. Of 100 cases of NPC radiotherapy， 70 patients developed severe radiation oral mucositis （≥ grade 3）. There were statistically significant differences in severe radioactive oral mucositis among patients with different smoking history （χ²=8.84，P=0.003）， alcohol drinking （χ²=23.94，P<0.001）， chemotherapy （χ²=40.41，P<0.001）， oral hygiene （χ²=8.16，P=0.004）， oral pH （χ²=16.83，P<0.001） and oral pathogens （χ²=8.80，P=0.003）. Multivariate analysis showed that， alcohol drinking （OR=2.23， 95%CI： 1.98-6.04，P=0.006）， chemotherapy （OR=3.13， 95%CI： 2.62-6.87，P<0.001） and oral pathogens （OR=3.11， 95%CI： 1.04-9.31，P=0.043） were independent influencing factors for the occurrence of severe radioactive oral mucositis in NPC patients with radiotherapy.ConclusionThe oral saliva flow of patients with NPC decreases gradually from the beginning of radiotherapy to the lowest 1 month after radiotherapy and then increases. The pH value gradually decreases from the beginning of radiotherapy to 35 times of radiotherapy， and gradually increases from 1 month to 3 months after radiotherapy. The detection rate of pathogenic bacteria increases rapidly from the beginning of radiotherapy to 15 times of radiotherapy， and the growth rate is stable from 15 times of radiotherapy to 35 times of radiotherapy， and tended to be normal 1 month after radiotherapy. Drinking history， chemotherapy history and oral pathogens are independent risk factors influencing the occurrence of severe radioactive oral mucositis.

Key words:Nasopharyngeal neoplasms,Radiotherapy planning， computer-assisted,Stomatitis,Tumor microenvironment

安伟, 袁芳, 尚美美, 李媛媛, 刘惠君, 侯爱, 徐娟. 鼻咽癌调强放疗患者严重放射性口腔黏膜炎发生的影响因素分析[J]. 国际肿瘤学杂志, 2024, 51(12): 737-742.

An Wei, Yuan Fang, Shang Meimei, Li Yuanyuan, Liu Huijun, Hou Ai, Xu Juan. Analysis of influencing factors of severe radioactive oral mucositis in patients with nasopharyngeal carcinoma undergoing intensity-modulated radiotherapy[J]. Journal of International Oncology, 2024, 51(12): 737-742.

图/表4

指标	放疗前	放疗15次	放疗35次	放疗后1个月	放疗后3个月	F值	P值
唾液流量（ml）	16.51±1.29	8.64±1.31^a	5.15±1.14^ab	4.78±1.36^abc	5.67±1.27^abcd	2 171.94	<0.001
pH值	8.28±0.67	5.87±0.53^a	5.32±0.55^ab	6.04±0.83^ac	6.74±0.63^abcd	370.43	<0.001

表1

表2

100例鼻咽癌放疗患者放疗前、后及放疗期间各类口腔菌群的检出情况（例）"

病原菌	放疗前	放疗 15次	放疗 35次	放疗后 1个月	放疗后 3个月
肺炎克雷伯菌	3	17	15	8	7
鲍曼不动杆菌	0	13	10	4	1
铜绿假单胞菌	0	35	33	25	15
其他克雷伯菌	0	1	0	0	0
阴沟肠杆菌	0	0	0	1	2
大肠埃希菌	2	6	5	4	2
其他假单胞菌	0	0	0	0	0
其他革兰氏阴性杆菌	0	0	0	0	0
链球菌属	0	0	3	1	1
金黄色葡萄球菌	0	12	10	5	3
肠球菌	1	3	0	1	0
表皮葡萄球菌	0	0	1	0	0
其他葡萄球菌	0	0	0	0	1
假丝酵母菌	0	1	3	5	2

表2

表3

影响100例鼻咽癌放疗患者（放疗15次）严重放射性口腔黏膜炎发生的单因素分析（例）"

因素	例数	放射性口腔黏膜炎	χ²值	P值
性别
女	22	18	1.88	0.171
男	78	52	1.88	0.171
年龄（岁）
≤60	66	44	1.03	0.311
>60	34	26	1.03	0.311
吸烟史
有	35	31	8.84	0.003
无	65	39	8.84	0.003
饮酒史
有	57	51	23.94	<0.001
无	43	19	23.94	<0.001
化疗史
有	66	60	40.41	<0.001
无	34	10	40.41	<0.001
病理分型
未分化癌	73	52	0.20	0.658
分化型鳞状细胞癌	27	18	0.20	0.658
临床分期
Ⅰ~Ⅱ期	48	36	1.10	0.295
Ⅲ~Ⅳ期	52	34	1.10	0.295
口腔卫生条件
较好	34	30	8.16	0.004
较差	66	40	8.16	0.004
口腔pH值
≤6.5	92	70	16.83	<0.001
>6.5	8	0	16.83	<0.001
口腔病原菌
有	62	50	8.80	0.003
无	38	20	8.80	0.003
唾液流量（ml）
≤7	10	10	3.31	0.069
>7	90	60	3.31	0.069
黏膜保护剂
使用	78	58	3.21	0.073
未使用	22	12	3.21	0.073

表3

因素	β值	SE值	Waldχ²值	OR值	95%CI	P值
吸烟史	0.95	0.90	1.12	2.59	0.44~15.11	0.290
饮酒史	2.35	0.85	7.62	2.23	1.98~6.04	0.006
化疗史	3.23	0.77	10.73	3.13	2.62~6.87	<0.001
口腔卫生条件	-1.58	0.95	2.76	0.21	0.03~1.33	0.097
口腔pH值	-0.74	1.86	0.16	0.48	0.01~18.25	0.478
口腔病原菌	1.13	0.56	4.10	3.11	1.04~9.31	0.043

表4

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