非小细胞肺癌患者放疗后肺部侵袭性真菌病发生危险因素及预测模型构建

doi:10.3760/cma.j.cn371439-20240422-00082

摘要/Abstract

摘要：

目的探讨原发非小细胞肺癌（NSCLC）患者放疗后肺部侵袭性真菌病（IFD）发生危险因素并构建预测模型。方法回顾性纳入2020年1月至2024年1月于四川省宜宾市第二人民医院接受放疗的298例原发NSCLC患者为研究对象。分析患者放疗后肺部IFD发生情况，对原发NSCLC患者放疗后肺部IFD发生危险因素行单因素及多因素分析，依据多因素分析结果构建logistic预测模型，并通过受试者操作特征（ROC）曲线评估各指标的预测效能。结果 298例接受放疗的原发NSCLC患者，61例发生肺部IFD，发生率为20.47%；其中检出真菌73株，包括假丝酵母菌属57株和曲霉菌属16株。IFD患者与非IFD患者年龄（χ²=23.13，P<0.001）、是否合并2型糖尿病（χ²=19.28，P<0.001）、是否接受侵入性操作（χ²=17.49，P<0.001）及同步放化疗（χ²=18.48，P<0.001）差异均有统计学意义。多因素分析显示，年龄≥65岁（OR=4.64，95%CI为2.12~10.13，P<0.001）、合并2型糖尿病（OR=5.63，95%CI为2.19~14.48，P<0.001）、同步放化疗（OR=3.73，95%CI为1.74~8.02，P=0.001）及接受侵入性操作（OR=5.11，95%CI为2.33~11.19，P<0.001）均是原发NSCLC患者放疗后肺部IFD发生的独立危险因素。基于以上指标构建logistic预测模型为logit（P）=-4.59+1.53×年龄+1.73×合并2型糖尿病+1.32×同步放化疗+1.63×接受侵入性操作（R²=0.852）。ROC曲线分析显示，年龄≥65岁、合并2型糖尿病、接受侵入性操作、同步放化疗、回归模型P值预测原发NSCLC患者放疗后肺部IFD发生的曲线下面积分别为0.68、0.63、0.68、0.68、0.82。结论年龄、合并2型糖尿病、接受侵入性操作及同步放化疗均是原发NSCLC患者放疗后肺部IFD发生的独立危险因素，利用以上4个因素构建的预测模型对于患者肺部IFD预测具有良好的效能。

关键词: 癌, 非小细胞肺, 放射疗法, 侵袭性真菌感染, 危险因素, 预测模型

Abstract:

Objective To investigate the risk factors of pulmonary invasive fungal disease （IFD） in patients with primary non-small cell lung cancer （NSCLC） after radiotherapy and to construct predictive model. Methods A total of 298 patients with primary NSCLC who received radiotherapy in the Second People's Hospital of Yibin of Sichuan from January 2020 to January 2024 were retrospectively included as the study objects. The incidence of pulmonary IFD after radiotherapy was analyzed. Univariate and multivariate analyses were performed on the risk factors of pulmonary IFD in patients with primary NSCLC after radiotherapy. A logistic prediction model was constructed according to the results of multivariate analysis，and the predictive efficacy of each index was evaluated by receiver operator characteristic （ROC） curve. Results There were 61 cases with pulmonary IFD after radiotherapy in all 298 patients，with the incidence of 20.47%. And 73 strains fungi were detected，including 57 strains for Candida and 16 strains for Aspergillus. There were statistically significant differences in age （χ²=23.13，P<0.001），whether they had type 2 diabetes （χ²=19.28，P<0.001），whether they underwent invasive procedures （χ²=17.49，P<0.001），and concurrent chemoradiotherapy （χ²=18.48，P<0.001） between IFD patients and non-IFD patients. Multivariate analysis showed that age≥65 years （OR=4.64，95%CI：2.12-10.13，P<0.001），combined type 2 diabetes （OR=5.63，95%CI：2.19-14.48，P<0.001），concurrent chemoradiotherapy （OR=3.73，95%CI：1.74-8.02，P=0.001） and invasive procedures （OR=5.11，95%CI：2.33-11.19，P<0.001） were independent risk factors for pulmonary IFD in patients with primary NSCLC after radiotherapy. Based on the above indexes，the logistic prediction model was constructed as follows：logit（P）=-4.59+1.53×age+1.73×combined type 2 diabetes+1.32×concurrent chemoradiotherapy+ 1.63×acceptance of invasive procedures （R²=0.852）. ROC curve analysis showed that the area under the curve of pulmonary IFD in patients with primary NSCLC who were≥65 years old，combined with type 2 diabetes，receiving invasive procedures，concurrent chemoradiotherapy，and regression model P value were 0.68，0.63，0.68，0.68，0.82，respectively. Conclusion The incidence of pulmonary IFD in patients with primary NSCLC after radiotherapy is independently related to age，type 2 diabetes，invasive procedures and concurrent chemoradiotherapy. The prediction model constructed by using the above four factors has good efficacy in predicting IFD in patients' lungs.

Key words: Carcinoma, non-small-cell lung, Radiotherapy, Invasive fungal infections, Risk factors, Prediction model

吕俊, 熊昊, 郑燕秋, 董礼. 非小细胞肺癌患者放疗后肺部侵袭性真菌病发生危险因素及预测模型构建[J]. 国际肿瘤学杂志, 2024, 51(8): 493-497.

Lyu Jun, Xiong Hao, Zheng Yanqiu, Dong Li. Risk factors and prediction model construction of pulmonary IFD in patients with NSCLC after radiotherapy[J]. Journal of International Oncology, 2024, 51(8): 493-497.

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参考文献 19

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指标	IFD患者（n=61）	非IFD患者（n=237）	χ²/t值	P值
年龄（岁）
≥65	51（83.61）	117（49.37）	23.13	<0.001
<65	10（16.39）	120（50.63）	23.13	<0.001
性别
男性	32（52.46）	130（54.85）	0.11	0.738
女性	29（47.54）	107（45.15）	0.11	0.738
体质量指数（kg/m²）	23.44±3.19	23.60±3.38	-0.33	0.739
高血压
是	15（24.59）	70（29.54）	0.58	0.446
否	46（75.41）	167（70.46）	0.58	0.446
2型糖尿病
是	15（24.59）	14（5.91）	19.28	<0.001
否	46（75.41）	223（94.09）	19.28	<0.001
冠心病
是	10（16.39）	51（21.52）	0.78	0.376
否	51（83.61）	186（78.48）	0.78	0.376
肝功能不全
是	2（3.28）	9（3.80）	<0.01	>0.999
否	59（96.72）	228（96.20）	<0.01	>0.999
肾功能不全
是	3（4.92）	12（5.06）	<0.01	>0.999
否	58（95.08）	225（94.94）	<0.01	>0.999
吸烟
是	12（19.67）	43（18.14）	0.08	0.784
否	49（80.33）	194（81.86）	0.08	0.784
饮酒
是	12（19.67）	61（25.74）	0.97	0.326
否	49（80.33）	176（74.26）	0.97	0.326
病理组织学类型
腺癌	45（73.77）	172（72.57）	0.04	0.851
鳞状细胞癌	16（26.23）	65（27.43）	0.04	0.851
TNM分期
Ⅰ~Ⅱ期	28（45.90）	91（38.40）	1.14	0.286
Ⅲ~Ⅳ期	33（54.10）	146（61.60）	1.14	0.286
同步放化疗
有	50（81.97）	122（51.48）	18.48	<0.001
无	11（18.03）	115（48.52）	18.48	<0.001
侵入性操作
有	52（85.25）	133（56.12）	17.49	<0.001
无	9（14.75）	104（43.88）	17.49	<0.001

影响因素	β值	SE值	Wald χ²值	OR值	95%CI	P值
年龄(≥65岁/<65岁)	1.53	0.40	14.80	4.64	2.12~10.13	<0.001
合并2型糖尿病（是/否）	1.73	0.48	12.88	5.63	2.19~14.48	<0.001
同步放化疗（是/否）	1.32	0.39	11.40	3.73	1.74~8.02	0.001
接受侵入性操作（是/否）	1.63	0.40	16.61	5.11	2.33~11.19	<0.001
常量	-4.59	0.55	69.62	0.01		<0.001

项目	最佳截断值	曲线下面积	敏感性（%）	特异性（%）	约登指数（%）
年龄≥65岁	0.50	0.68	83.61	52.74	36.35
2型糖尿病	0.50	0.63	31.15	94.09	25.24
同步放化疗	0.50	0.68	81.97	54.01	35.98
侵入性操作	0.50	0.68	83.61	52.74	36.35
回归模型P值	0.34	0.82	63.93	86.92	50.85