原发性肺非霍奇金淋巴瘤的新型预后模型建立与疗效分析

李辉; 李建成; 刘锋; 吴迪; 陈传本; 李金銮

doi:10.11999/JEIT250874

原发性肺非霍奇金淋巴瘤的新型预后模型建立与疗效分析

doi: 10.11999/JEIT250874 cstr: 32379.14.JEIT250874

李辉¹,
李建成¹,
刘锋²,
吴迪³,
陈传本^1, ,,
李金銮^1, ,

1.
福建医科大学肿瘤临床医学院，福建省肿瘤医院福州 350014
2.
福建医科大学附属第一医院福州 350009
3.
福建省福州肺科医院福州 350008

基金项目: 福建省卫生健康中青年领军人才研修培养项目(2022)，福建省自然科学基金项目(2025J01221)，福建省肿瘤放射与免疫治疗临床医学研究中心(2020Y2012)

详细信息

作者简介:
李辉：男，博士生，研究方向为肿瘤相关预后研究、临床研究、横断面研究及分子细胞和动物层面的基础研究

李建成：男，主任医师，研究方向为胸部肿瘤(非小细胞肺癌、小细胞肺癌、食管癌、胸腺癌等)的前瞻性和回顾性临床研究以及相关基础实验研究

刘锋：男，主任医师，研究方向为胸部及腹部肿瘤(淋巴瘤、肺癌、乳腺癌、直肠癌、胃癌、肝癌、前列腺癌等)的前瞻性和回顾性临床研究以及相关基础实验研究

吴迪：男，主任医师，研究方向为肺部疾病(肺部肿瘤、肺结核、肺脓肿、肺结节等)的前瞻性和回顾性临床研究以及相关基础实验研究

陈传本：男，主任医师，研究方向为肿瘤(鼻咽癌、喉癌、淋巴瘤、肺癌、乳腺癌、直肠癌、胃癌、肝癌、前列腺癌、黑色素瘤、淋巴瘤、脑肿瘤等)的前瞻性和回顾性临床研究以及相关基础实验研究

李金銮：男，主任医师，研究方向为腹部肿瘤(乳腺癌、直肠癌、胃癌、肝癌、前列腺癌、黑色素瘤、淋巴瘤、脑肿瘤等)的前瞻性和回顾性临床研究以及相关基础实验研究

通讯作者:
陈传本　ccb@fjmu.edu.cn

李金銮　lijinluan@fjmu.edu.cn

中图分类号: XXXXX
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出版历程
- 收稿日期: 2025-08-31
- 修回日期: 2026-01-22
- 录用日期: 2026-01-22
- 网络出版日期: 2026-03-04

A Novel Prognostic Model Establishment and Treatment Efficacy Analysis for Primary Pulmonary Non-Hodgkin’s Lymphoma

LI Hui¹,
JIANCHENG Li¹,
FENG Liu²,
DI Wu³,
CHUANBEN Chen^{1
, ,},
JINLUAN Li^{1
, ,}

1.
Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital, Fuzhou 350014, China
2.
The First Affiliated Hospital of Fujian Medical University, Fuzhou 350009, China
3.
Fuzhou Pulmonary Hospital of Fujian, Fuzhou 350008, China

Funds: Fujian Research and Training Grants for Youth and Middle-aged Leaders in Healthcare, 2022, Natural Science Foundation of Fujian Province, 2025J01221, Fujian Provincial Clinical Research Center for Cancer Radiotherapy and Immunotherapy, 2020Y2012

摘要

摘要: 目的：本研究旨在建立并验证一种新的国际预后指数(International Prognostic Index, IPI)，并评估不同治疗方式对原发性肺非霍奇金淋巴瘤(Primary Pulmonary non-Hodgkin Lymphoma, PPL)患者的疗效。方法：本研究数据来源于美国癌症Surveillance, Epidemiology, and End Results数据库(SEER)以及三家中国医院的临床数据库。采用Cox回归分析筛选独立预后因素，并结合列线图和现有IPI模型构建了PPL-IPI，并通过一致性指数(Concordance-index, C指数)及校准曲线进行验证。在治疗效果评价中，采用逆概率加权法平衡组间差异，并通过Kaplan–Meier生存曲线及log-rank检验比较不同治疗方式的效果。结果：在SEER数据库中共纳入2000年至2019年确诊的4,313例患者，另有2010年至2021年确诊的107例来自中国外部验证队列的患者纳入本研究。PPL-IPI模型包含IPI的5个不良因素(年龄>60岁、血清乳酸脱氢酶高、Ann Arbor III/IV期、行为状态评分2 - 4分和结外侵犯数目超过1个)和Cox模型筛选的4个不良因素：性别(男性)、组织学类型(非黏膜相关淋巴组织［Mucosa-Associated Lymphoid Tissue, MALT］)、B症状(存在)、治疗(未接受)，并在原始IPI基础上显著提升预测效能(C-index, 0.932 vs. 0.834)。不同风险组3年生存率分别为：低危组(0–2个因素)96%，低中危组(3–4个因素)82%，高中危组(5个因素)50%，高危组(6–9个因素)11.11%(p<0.0001)。在治疗方面，化疗显著降低了原发性肺MALT淋巴瘤患者的肿瘤特异性生存率(p<0.001)；手术与放疗在原发性肺MALT淋巴瘤及弥漫大B细胞淋巴瘤患者中的疗效差异均无统计学意义(p>0.05)。结论：基于国际多中心大型队列建立的PPL-IPI具有优异的预后预测能力。对于原发性肺MALT淋巴瘤患者，化疗可能不利于生存；而在原发性肺MALT淋巴瘤和弥漫大B细胞淋巴瘤中，手术和放疗的疗效价值均无显著差别。
- 原发性肺非霍奇金淋巴瘤 /
- 新型预后指数 /
- 疗效分析 /
- 多中心研究 /
- 预后模型
Abstract: Objective At present, there are few related studies on primary pulmonary non-Hodgkin's lymphoma (PPL), mainly single-center and retrospective studies. Therefore, there is no widely used and recognized prognostic index and treatment decision for PPL. This study aims to establish and verify a novel International Prognostic Index (IPI) of PPL by using the data of cancer population in the United States and Chinese multi-centers, and to compare the curative effects of different treatment methods. So as to predict the clinical prognosis and to provide new and effective ideas for making treatment decisions of PPL. Methods In this study, the clinical data of patients diagnosed with PPL from 2000 to 2019 in the Surveillance, Epidemiology, and End Results (SEER) database of America and from 2010 to 2021 in 3 tertiary hospitals in China were included. Cox proportional hazards regression model was used to determine independent prognostic factors and a nomogram was established to predict cancer-specific survival (CSS). The model was validated using the Concordance-index (C-index) and calibration curve. Combining nomogram with IPI, a novel prognostic index was established, risk stratified and the 3-year overall survival (OS) rate was calculated. The inverse probability of treatment weighting (IPTW) was used to eliminate confounding factors, and Kaplan-Meier curve and Log-rank test were used for survival analysis. Results and Discussions Finally, a total of 4,313 cases from the SEER database and 107 cases from the Chinese multi-center were included this study. The multivariate Cox regression results showed that the independent prognostic factors of PPL included age (P<0.001; hazard ratio [HR], 1.078; 95% confidence interval [CI], 1.072–1.084), Ann Arbor stage (P<0.001), sex (P<0.001; HR, 0.719; 95% CI, 0.624–0.829), primary site (P=0.037), pathological type (P<0.001), B symptom (p=0.012; HR, 0.944; 95% CI, 0.773–0.997), surgery (P<0.001; HR, 1.453; 95% CI, 1.221–1.728), chemotherapy (P<0.001; HR, 0.742; 95% CI, 0.631–0.872), marital status (P<0.001). Based on these independent prognostic factors, a nomogram with 3, 5, and 10 years of CSS was established. By combining nomogram and IPI, we established a prognostic model of PPL, and its C-index was 0.932. By defining risk factors and stratifying the model, we established a novel prognostic index for PPL. The risk parameters were defined as: age > 60 years, Ann Arbor stage III/IV, serum LDH level >1 times normal level, performance status score >2, number of extranodal invasion >1, male, except mucosa-associated lymphoid tissue (MALT), positive B symptoms, and not receive cancer therapy; the definition of risk stratification and their 3-year OS rate were: low-risk group (0-2 risk factors) 96.97%, low-mediate risk group (3-4 risk factors) 82.61%, high-mediate risk group (5 risk factors) 50%, and high risk group (6-9 risk factors) 11.11%, (P<0.001). Regarding the efficacy comparison of treatment methods, both the American and Chinese data showed that chemotherapy significantly reduced the CSS of patients with primary pulmonary MALT lymphoma (P<0.001). There were no significant differences between the efficacy of surgery and radiotherapy both in primary pulmonary MALT lymphoma and diffuse large B-cell lymphoma (P>0.05). Conclusions First, this study established a novel prognostic index for PPL based on the data of the American cancer population and the Chinese multi-center cohort. The parameters were age, stage, serum LDH level, performance status score, and numbers of extranodal invasion. The index has excellent predictive ability and accuracy. Through risk stratification of this index, the 3-year OS rate of different risk groups were obtained. Finally, the efficacy analysis suggested that chemotherapy may be detrimental the CSS of patients with primary pulmonary MALT lymphoma. In addition, there was no significant difference of surgery and radiotherapy both in primary pulmonary MALT lymphoma and diffuse large B-cell lymphoma.
- Primary Pulmonary Non-Hodgkin’s Lymphoma /
- Novel prognostic index /
- Treatment efficacy /
- Multi-center analysis /
- Prognostic model

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图 1 研究对象纳入与排除的流程图

Figure 1. Flowchart of inclusion and exclusion of research subjects

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图 2 基于原发性肺非霍奇金淋巴瘤建立的nomogram

Figure 2. The nomogram for PPL. The total points projected on the bottom scales indicate the probabilities of the 3-, 5-, and 10-year CSS rates

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图 3 原发性肺非霍奇金淋巴瘤预后指数(PPL-IPI)危险分层的肿瘤特异性生存曲线与秩和检验

Figure 3. Clinical outcomes according to PPL-IPI risk group. Kaplan–Meier curve and log-rank test for CSS

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图 4 不同治疗方式下的肿瘤特异性生存曲线与秩和检验

Figure 4. Kaplan–Meier curve and log-rank test for CSS in different treatment methods.

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表 1 ：基于SEER数据库的原发性肺淋巴瘤患者的基线特征及预后因素的单因素与多因素Cox分析

参数	例数(4313例)	比例(%)	单因素Cox回归				多因素Cox回归
参数	例数(4313例)	比例(%)	p值	HR	95%CI		p值	HR	95%CI
年龄(岁)	65.6	-	<0.001	1.034	1.028	1.039	<0.001	1.078	1.072	1.084
性别(男性)	1944	45.1	0.001	0.804	0.705	0.918	<0.001	0.719	0.624	0.829
原发部位			0.001				0.037
主支气管	146	3.4	对照				对照
上叶	1226	28.4	0.177				0.207
中叶	329	7.6	0.002	0.664	0.514	0.859	0.022	0.694	0.507	0.950
下叶	1137	26.4	0.637				0.402
多发	86	2.0	0.013	1.195	1.039	1.374	0.790	1.470	0.956	2.262
未知	1389	32.2	0.137				0.825
组织学类型			<0.001				<0.001
NK/T细胞	390	9.0	对照				对照
DLBCL	1321	30.6	0.003	1.366	1.109	1.684	0.578	1.083	0.817	1.437
滤泡	178	4.1	0.036	0.718	0.527	0.979	0.046	0.648	0.422	0.993
MALT	1686	39.1	<0.001	0.383	0.302	0.486	<0.001	0.409	0.304	0.550
未知	607	14.1	0.129				0.362
确诊依据，病理	3560	82.5	0.003	0.748	0.619	0.905	0.677	0.958	0.782	1.173
Ann Arbor 分期			<0.001				<0.001
I期	1646	38.2	对照				对照
II期	588	13.6	<0.001	1.260	1.061	1.386	0.022	1.315	1.041	1.662
III期	167	3.9	0.355				<0.001	1.567	1.284	1.913
IV期	918	21.3	0.011	1.463	1.091	1.961	<0.001	1.773	1.293	2.432
未知	994	23.0	0.186				<0.001	1.714	1.351	2.174
B症状			<0.001				0.012
阳性	468	10.9	对照				对照
阴性	1992	46.2	<0.001	0.768	0.698	0.845	0.042	0.944	0.773	0.997
未知	1853	43.0	<0.001	1.277	1.128	1.445	0.573
手术	1306	30.3	<0.001	1.467	1.350	1.593	<0.001	1.453	1.221	1.728
放疗	580	13.4	0.266	0.948	0.863	1.041
化疗	2010	46.6	<0.001	0.734	0.686	0.786	<0.001	0.742	0.631	0.872
婚姻状态			<0.001				<0.001
丧偶	660	15.3	对照				对照
离异	408	9.5	0.093	0.808	0.630	1.036	0.048	0.747	0.559	0.997
已婚	2380	55.2	0.024	0.789	0.642	0.970	0.007	0.627	0.448	0.879
单身	611	14.2	0.490				0.565
未知	254	5.9	0.010	0.859	0.765	0.965	<0.001	0.680	0.564	0.819
是否第一原发，是	3321	77.0	0.036	1.088	1.005	1.176	0.932
注：SEER, Surveillance, Epidemiology, and End Results，美国癌症数据库；HR, Hazard Ratio，危险比；CI, Confident Interval，置信区间；NK/T细胞，Natural Killer T cells，自然杀伤T细胞；DLBCL, Diffuse Large B-cell Lymphoma，弥漫大B细胞淋巴瘤；MALT, Mucosa-associated Lymphoid Tissue，黏膜相关淋巴组织淋巴瘤。(HR/CI仅对显著项展示，参照组与不显著项不展示)

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表 2 多中心外部验证队列中原发性肺淋巴瘤患者的基线特征

参数	例数(107例)	比例(%)
年龄(<60岁)	51	47.7
性别(男性)	61	57.0
原发部位
主支气管	4	3.7
上叶	31	29.0
中叶	14	13.1
下叶	14	13.1
多发	37	34.6
未知	7	6.5
组织学类型
NK/T细胞	7	6.5
DLBCL	29	27.1
滤泡	2	1.9
MALT	57	53.3
未知	8	7.5
Ann Arbor分期
I/II期	48	44.9
III/IV期	48	44.9
未知	11	10.2
B症状
阳性	41	38.3
阴性	52	48.6
未知	14	13.1
手术	27	25.2
放疗	19	17.8
化疗	62	57.9
血清LDH水平，正常	82	76.6
行为状态评分，<2	96	89.7
结外侵犯数目， >1	31	29.0
注：NK/T细胞，Natural Killer T cells，自然杀伤T细胞；DLBCL, Diffuse Large B-cell Lymphoma，弥漫大B细胞淋巴瘤；MALT, Mucosa-associated Lymphoid Tissue，黏膜相关淋巴组织淋巴瘤。

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表 3 原发性肺非霍奇金淋巴瘤新型预后指数的定义与3年总生存率

	参数	定义	3年生存率
危险因素
	年龄	>60岁
	血清LDH水平	>正常
	Ann Arbor分期	III/IV期
	行为状态评分	2 - 4分
	结外侵犯数目	>1
	性别	男性
	组织学类型	除MALT外
	B症状	阳性
	抗肿瘤治疗	未治疗
危险分层
	低危组	0 ～ 2	96.97%
	中低危组	3 ～ 4	82.61%
	中高危组	5	50.00%
	高危组	6 ～ 9	11.11%
注： LDH, Lactate Dehydrogenase，乳酸脱氢酶；MALT, Mucosa-associated Lymphoid Tissue，黏膜相关淋巴组织淋巴瘤。

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