构建并验证nomogram模型预测ⅠA期肺腺癌肺泡间转移

doi:10.19401/j.cnki.1007-3639.2022.12.009

中国癌症杂志 ›› 2022, Vol. 32 ›› Issue (12): 1210-1217.doi: 10.19401/j.cnki.1007-3639.2022.12.009

构建并验证nomogram模型预测ⅠA期肺腺癌肺泡间转移

张龙富¹^,²(), 刘洁², 倪筝³, 路新源⁴, 胡斌¹, 汪灏⁵, 冯明祥⁵, 张勇²()

1.上海市徐汇区中心医院呼吸与危重症医学科，上海 200031
2.复旦大学附属中山医院呼吸与危重症医学科，上海 200032
3.复旦大学附属中山医院病理科，上海 200032
4.复旦大学公共卫生学院公共卫生安全教育部重点实验室，上海 200032
5.复旦大学附属中山医院胸外科，上海 200032

收稿日期:2022-09-10 修回日期:2022-11-05 出版日期:2022-12-30 发布日期:2023-02-02
通信作者: 张勇
作者简介:张龙富（ORCID: 0000-0002-6657-2664），硕士，主治医师。
基金资助:
上海市医学重点专科建设计划(ZK2019C14);徐汇区医学科研项目(SHXH202113)

Development and validation of a nomogram for predicting spread through air spaces in stage ⅠA lung adenocarcinoma

ZHANG Longfu¹^,²(), LIU Jie², NI Zheng³, LU Xinyuan⁴, HU Bin¹, WANG Hao⁵, FENG Mingxiang⁵, ZHANG Yong²()

1. Department of Pulmonary and Critical Care Medicine, Central Hospital of Xuhui District, Shanghai 200031, China
2. Department of Pulmonary and Critical Care Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
3. Department of Pathology, Zhongshan Hospital, Fudan University, Shanghai 200032, China
4. School of Public Health, Key Laboratory of Public Health Safety, Ministry of Education, Fudan University, Shanghai 200032, China
5. Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai 200032, China

Received:2022-09-10 Revised:2022-11-05 Published:2022-12-30 Online:2023-02-02
Contact: ZHANG Yong

摘要/Abstract

摘要：

背景和目的：肺泡间转移（spread through air spaces，STAS）是早期肺腺癌的不良预后因素，尤其是楔形切除的患者，术前预测STAS有助于选择更佳的手术方式。本研究旨在建立并验证基于术前临床和影像学特征的列线图（nomogram）来预测ⅠA期肺腺癌的STAS。方法：回顾性分析2017年1月—2018年12月在复旦大学附属中山医院接受手术治疗的595例ⅠA期肺腺癌患者，通过4%的甲醛溶液固定石蜡包埋组织切片评估STAS结果。基于术前临床资料和胸部计算机体层成像（computed tomography，CT），4种临床特征和11种影像学特征纳入分析。通过logistic回归筛选临床和影像学特征中预测STAS的独立预测因素并构建nomogram模型。通过一致性指数（concordance index，C-index）、受试者工作特征（receiver operating characteristic，ROC）曲线的曲线下面积（area under curve，AUC）、校准图来评估模型的效能。结果：在595例ⅠA期肺腺癌患者中，STAS阳性为87例（14.6%）。单因素及多因素logistic回归结果显示分叶征（OR = 8.156，95% CI：1.021 ~ 65.099）、毛刺征（OR = 5.258，95% CI：2.506 ~ 11.032）和实性成分占比（consolidation tumor ratio，CTR）（0.50<CTR≤0.75，OR = 16.955，95% CI：3.579 ~ 80.309；0.75 <CTR≤1.00，OR = 20.793，95% CI：4.383 ~ 98.636）是STAS阳性的独立预测因素。基于这些预测因素建立的nomogram模型，对于STAS有较好的预测效能；C-index为0.901，AUC为0.897，且校准曲线拟合良好。结论：本研究建立并验证了预测ⅠA 期肺腺癌STAS的nomogram模型。本模型操作简单，有较好的预测效能，有利于术前选择合理的手术方式。

关键词: 肺腺癌, 肺泡间隙转移, 列线图

Abstract:

Background and purpose: Spread through air spaces (STAS) is a poor prognostic factor for early lung adenocarcinoma, especially in patients with wedge resection. Preoperative prediction of STAS is helpful to select a better surgical treatment. This study aimed to develop and validate a nomogram based on preoperative clinical and computed tomography (CT) characteristics to predict STAS in stage ⅠA lung adenocarcinoma. Methods: A total of 595 patients with stage ⅠA lung adenocarcinoma who underwent surgical treatment in Zhongshan Hospital Fudan University from January 2017 to December 2018 were retrospectively analyzed. The results of STAS were evaluated by paraffin embedded tissues fixed with 4% formaldehyde solution. Based on preoperative clinical data and chest CT, 4 clinical characteristics and 11 CT characteristics were analyzed. The independent predictors of STAS in clinical and CT characteristics were identified by logistic regression analysis and then used to build a nomogram. Concordance index (C-index), area under the curve (AUC) of receiver operating characteristic (ROC) and calibration plots were used to evaluate the performance of the model. Results: Among the 595 stage ⅠA lung adenocarcinoma patients, 87 patients (14.6%) were STAS positive. Univariate and multivariate logistic regression analyses showed that lobulation (OR=8.156, 95% CI: 1.021-65.099), spiculation (OR=5.258, 95% CI: 2.506-11.032) and consolidation tumor ratio (CTR) (0.50<CTR≤0.75; OR=16.955, 95% CI: 3.579-80.309; 0.75<CTR≤1.00; OR=20.793, 95% CI: 4.383-98.636) were independent predictors of STAS positivity. The nomogram based on these predictors achieved good predictive performance for STAS with a C-index of 0.901, an AUC of 0.897 and a well-fitted calibration curve. Conclusion: This study developed and validated a nomogram for predicting STAS in stage ⅠA lung adenocarcinoma. This model is simple to operate and has good predictive performance, which is conducive to the selection of reasonable surgical methods before operation.

Key words: Lung adenocarcinoma, Spread through air space, Nomogram

中图分类号:

R734.2

张龙富, 刘洁, 倪筝, 路新源, 胡斌, 汪灏, 冯明祥, 张勇. 构建并验证nomogram模型预测ⅠA期肺腺癌肺泡间转移[J]. 中国癌症杂志, 2022, 32(12): 1210-1217.

ZHANG Longfu, LIU Jie, NI Zheng, LU Xinyuan, HU Bin, WANG Hao, FENG Mingxiang, ZHANG Yong. Development and validation of a nomogram for predicting spread through air spaces in stage ⅠA lung adenocarcinoma[J]. China Oncology, 2022, 32(12): 1210-1217.

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参考文献 21

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Characteristics	Positive (N=87)	Negative (N=508)	P value	Characteristics	Positive (N=87)	Negative (N=508)	P value
Age/year			<0.001	CTR			<0.001
<65	47	340		CTR≤0.50	3	324
≥65	40	168		0.50<CTR≤0.75	12	60
Gender			<0.001	0.75<CTR≤1.00	72	124
Male	50	182		Emphysema			<0.001
Female	37	326		Absent	63	451
Smoke			<0.001	Present	24	57
Ever	44	89		Lobulation			<0.001
Never	43	419		Absent	1	179
CEA			0.002	Present	86	329
Normal	76	488		Spiculation			<0.001
High	11	20		Absent	11	365
Lesion location			0.337	Present	76	143
Upper and middle lobe	54	342		Pleural retraction			0.124
Lower lobe	33	166		Absent	43	296
Nodule pattern			<0.001	Present	44	212
Pure GGN	1	97		Vacuole sign			0.853
Mixed GGN	28	335		Absent	57	338
Solid	58	76		Present	30	170
Tumor sizeD/cm			0.007	Vascular change			0.095
D≤1	5	83		Normal	8	82
1<D≤2	49	296		Convergent	79	426
1<D≤3	33	129		Nodule-pleural types			0.160
				No connection	57	292
				Attachment	30	216

Variable	OR	95% CI	P value	Variable	OR	95% CI	P value
Age/year				CTR
<65	1.000	-	-	CTR≤0.50	1.000	-	-
≥65	1.722	1.086-2.729	0.021	0.50<CTR≤0.75	21.599	5.917-78.845	<0.001
Gender				0.75<CTR≤1.00	62.709	19.398-202.721	<0.001
Female	1.000	-	-	Emphysema
Male	2.420	1.524-3.842	<0.001	Absent	1.000	-	-
Smoke				Present	3.014	1.747-5.197	<0.001
Never	1.000	-	-	Lobulation
Ever	4.817	2.985-7.773	<0.001	Absent	1.000	-	-
CEA				Present	46.790	6.462-338.792	<0.001
Normal	1.000	-	-	Spiculation
High	3.531	1.627-7.661	0.001	Absent	1.000	-	-
Lesion location				Present	17.635	9.103-34.160	<0.001
Lower lobe	1.000	-	-	Pleural retraction
Upper and middle lobe	0.794	0.495-1.272	0.338	Absent	1.000	-	-
Nodule pattern				Present	1.428	0.905-2.253	0.125
Pure GGN	1.000	-	-	Vacuole sign
Mixed GGN	8.107	1.089-60.352	0.041	Absent	1.000	-	-
Solid	74.026	10.023-546.687	<0.001	Present	1.046	0.648-1.689	0.853
Tumor sizeD/cm				Vascular change
D≤1	1.000	-	-	Normal	1.000	-	-
1<D≤2	2.740	1.061-7.118	0.037	Convergent	1.900	0.884-4.083	0.100
2<D≤3	4.246	1.593-11.316	0.004	Nodule-pleural types
				No connection	1.000	-	-
				Attachment	0.711	0.442-1.145	0.161

Variable	OR	95% CI	P value
Age/year
<65	1.000	—	—
≥65	1.095	0.606-1.977	0.763
Gender
Female	1.000	—	—
Male	0.631	0.221-1.8	0.390
Smoke
Never	1.000	—	—
Ever	2.460	0.870-6.949	0.089
CEA
Normal	1.000	—	—
High	1.916	0.693-5.296	0.210
Nodule pattern
Pure GGN	1.000	—	—
Mixed GGN	0.285	0.022-3.568	0.330
Solid	0.679	0.041-8.108	0.685
Tumor sizeD/cm
D≤1	1.000	—	—
1<D≤2	1.004	0.311- 3.238	0.994
2<D≤3	0.923	0.274- 3.104	0.897
CTR
CTR≤0.50	1.000	—	—
0.50<CTR≤0.75	16.955	3.579- 80.309	<0.001
0.75<CTR≤1.00	20.793	4.383-98.636	<0.001
Emphysema
Absent	1.000	—	—
Present	0.851	0.384- 1.882	0.691
Lobulation
Absent	1.000	—	—
Present	8.156	1.021-65.099	0.048
Spiculation
Absent	1.000	—	—
Present	5.258	2.506-11.032	<0.001

构建并验证nomogram模型预测ⅠA期肺腺癌肺泡间转移

Development and validation of a nomogram for predicting spread through air spaces in stage ⅠA lung adenocarcinoma

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