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1.青岛大学附属医院乳腺外科,山东青岛
2.青岛大学第一临床医学院,山东青岛
3.滨州医学院临床医学院,山东烟台
4.烟台毓璜顶医院普外科,山东烟台
马中良,E-mail:zhongliangma@qdu.edu.cn
收稿:2025-03-24,
修回:2025-11-23,
录用:2025-11-25,
纸质出版:2025-12-15
移动端阅览
王鸿彬,贺薇,陈逸菲,等.胃腺癌继发第二原发性恶性肿瘤临床特征分析及预后模型建立[J].陆军军医大学学报,2025,47(23):2979-2990.DOI:10.16016/j.2097-0927.202503071.
WANG H B,HE W,CHEN Y F,et al.Clinical characterization and prognostic modeling of second primary malignancies following gastric adenocarcinoma: a SEER database-based study[J].J Army Med Univ,2025,47(23):2979-2990.DOI:10.16016/j.2097-0927.202503071.
王鸿彬,贺薇,陈逸菲,等.胃腺癌继发第二原发性恶性肿瘤临床特征分析及预后模型建立[J].陆军军医大学学报,2025,47(23):2979-2990.DOI:10.16016/j.2097-0927.202503071. DOI:
WANG H B,HE W,CHEN Y F,et al.Clinical characterization and prognostic modeling of second primary malignancies following gastric adenocarcinoma: a SEER database-based study[J].J Army Med Univ,2025,47(23):2979-2990.DOI:10.16016/j.2097-0927.202503071. DOI:
目的
2
分析影响胃腺癌(gastric adenocarcinoma,GAC)继发第二原发性恶性肿瘤(second primary malignancy,SPM)患者生存结局的临床特征,构建预测模型和网络计算器。
方法
2
收集监测、流行病学和结果数据库(Surveillance, Epidemiology, and End Results,SEER)2010年1月至2017年12月被诊断为GAC的患者(
n
=24 085),对比非SPM患者(
n
=22 963)与SPM患者(
n
=1 122)的临床特征。按照3∶1的比例将SPM患者随机分为训练组(
n
=842)和内部验证组(
n
=280),使用单因素及多因素Cox回归分析筛选与预后相关的影响因素,基于筛选因素建立预后模型。受试者工作特征曲线(receiver operating characteristic,ROC)、校准曲线及决策曲线(decision curve analysis,DCA)被用于模型的评价。使用DynNom包将列线图发布至网络中并开发网络计算器。使用2010年1月至2017年12月在烟台毓璜顶医院普外科诊断为GAC后继发SPM的患者(
n
=192)进行外部验证。
结果
2
使用
χ²
检验对比SPM组与非SPM组患者基线数据,相较于非SPM组患者,SPM组患者高龄(56.3%)更多,T分期更倾向于早期,T1(29.2%)、T2(10.5%),GAC原发部位多见于贲门(43.7%),发生远处转移的患者更少(12.3%),接受放疗(32.5%)和手术(77.2%)的比例更高,结果有显著差异(
P
<
0.05)。经单因素及多因素Cox分析显示GAC的原发部位、T分期、SEER分期、放疗史、手术史,以及SPM的分级、分期、放疗史、化疗史、手术史是预测患者生存的显著变量(
P
<
0.05)。ROC曲线显示,训练集中,1年、3年和5年的AUC值分别为0.771(95%
CI
: 722~0.820)、0.839(95%
CI
:0.796~0.882)和0.836(95%
CI
:0.792~0.879)。而在内部验证集中,AUC值分别为0.751(95%
CI
:0.700~0.801)、0.746(95%
CI
:0.695~0.797)和0.772(95%
CI
:0.723~0.821)。外部验证集的AUC值分别为0.713(95%
CI
:0.648~0.778)、0.805(95%
CI
:0.749~0.861)和0.851(95%
CI
:0.801~0.901)。校准曲线的预测值与实际值具有较高吻合度,决策曲线表明了模型的优秀临床净收益。开发了可用于在线公开验证的网络平台(
https://kunma697.shinyapps.io/dynnomapp-1/
https://kunma697.shinyapps.io/dynnomapp-1/
)。
结论
2
依照GAC和SPM临床特征建立的预测模型和网络计算器可以有效评估SPM患者的预后。
Objective
2
To analyze clinical characteristics affecting survival outcomes in gastric adenocarcinoma (GAC) patients with second primary malignancies (SPM) and construct a predictive model with a web-based calculator.
Methods
2
Patients diagnosed with GAC between January 2010 and December 2017 in the SEER database (
n
=24 085) were analyzed
comparing non-SPM (
n
=22 963) and SPM cohorts (
n
=1 122). SPM patients were randomized (3:1) into training (
n
=842) and internal validation cohorts (
n
=280). Univariate/multivariate Cox regression identified prognostic factors for model construction. Model performance was evaluated via ROC curves
calibration plots
and decision curve analysis (DCA). A web-based calculator was deployed using DynNom (
https://kunma697.shinyapps.io/dynnomapp-1/
https://kunma697.shinyapps.io/dynnomapp-1/
). External validation used 192 SPM patients diagnosed at Yantai Yuhuangding Hospital (2010-2017).
Results
2
χ²
tests revealed SPM patients had higher age (56.3%)
earlier T-stage (T1:29.2%; T2:10.5%)
predominant gastric cardia involvement (43.7%)
fewer distant metastases (12.3%)
and higher rates of radiotherapy (32.5%) and surgery (77.2%)
vs
. non-SPM (
P
<
0.05). Cox analyses identified GAC primary site
T-stage
SEER stage
radiotherapy/surgery history
plus SPM grade/stage/treatment history as significant predictors (
P
<
0.05). AUCs in the training cohort were 0.771 (95%
CI
:0.722~0.820)
0.839 (95%
CI
:0.796~0.882)
and 0.836 (95%
CI
: 0.792~0.879) for 1-/3-/5-year survival; internal validation showed 0.751 (95%
CI
: 0.700~0.801)
0.746 (95%
CI
: 0.695~0.797)
and 0.77
2 (95%
CI
: 0.723~0.821); external validation yielded 0.713 (95%
CI
: 0.648~0.778)
0.805 (95%
CI
: 0.749~0.861)
and 0.851 (95%
CI
: 0.801~0.901). Calibration indicated high prediction-actuality concordance; DCA confirmed clinical utility.
Conclusion
2
The model and web calculator incorporating GAC/SPM characteristics effectively predict SPM patient prognosis.
ZENG H M , CHEN W Q , ZHENG R S , et al . Changing cancer survival in China during 2003-15: a pooled analysis of 17 population-based cancer registries [J]. Lancet Glob Health , 2018 , 6 ( 5 ): e555 - e567 . DOI: 10.1016/S2214-109X(18)30127-X http://dx.doi.org/10.1016/S2214-109X(18)30127-X .
BATENI S B , COBURN N G , LAW C H L , et al . Incidence and predictors of second primary cancers in patients with neuroendocrine tumors [J]. JAMA Oncol , 2021 , 7 ( 11 ): 1718 - 1720 . DOI: 10.1001/jamaoncol.2021.4531 http://dx.doi.org/10.1001/jamaoncol.2021.4531 .
TRAVIS L B . The epidemiology of second primary cancers [J]. Cancer Epidemiol Biomarkers Prev , 2006 , 15 ( 11 ): 2020 - 2026 . DOI: 10.1158/1055-9965.EPI-06-0414 http://dx.doi.org/10.1158/1055-9965.EPI-06-0414 .
CHEUNG K S , CHAN E W , WONG A Y S , et al . Long-term proton pump inhibitors and risk of gastric cancer development after treatment for Helicobacter pylori : a population-based study [J]. Gut , 2018 , 67 ( 1 ): 28 - 35 . DOI: 10.1136/gutjnl-2017-314605 http://dx.doi.org/10.1136/gutjnl-2017-314605 .
OH C M , WON Y J , JUNG K W , et al . Cancer statistics in Korea: incidence, mortality, survival, and prevalence in 2013 [J]. Cancer Res Treat , 2016 , 48 ( 2 ): 436 - 450 . DOI: 10.4143/crt.2016.089 http://dx.doi.org/10.4143/crt.2016.089 .
TURCOTTE L M , LIU Q , YASUI Y , et al . Temporal trends in treatment and subsequent neoplasm risk among 5-year survivors of childhood cancer, 1970-2015 [J]. JAMA , 2017 , 317 ( 8 ): 814 - 824 . DOI: 10.1001/jama.2017.0693 http://dx.doi.org/10.1001/jama.2017.0693 .
LEE J S , DUBOIS S G , COCCIA P F , et al . Increased risk of second malignant neoplasms in adolescents and young adults with cancer [J]. Cancer , 2016 , 122 ( 1 ): 116 - 123 . DOI: 10.1002/cncr.29685 http://dx.doi.org/10.1002/cncr.29685 .
ZHENG G Q , SUNDQUIST K , SUNDQUIST J , et al . Second primary cancers after gastric cancer, and gastric cancer as second primary cancer [J]. Clin Epidemiol , 2021 , 13 : 515 - 525 . DOI: 10.2147/CLEP.S304332 http://dx.doi.org/10.2147/CLEP.S304332 .
WANG B , LIU L . Clinical characteristics and prognostic nomogram analysis of patients with dual primary cancers with first gastric cancer: a retrospective study in China [J]. PeerJ , 2023 , 11 : e15278 . DOI: 10.7717/peerj.15278 http://dx.doi.org/10.7717/peerj.15278 .
SHAH B K , KHANAL A , HEWETT Y . Second primary malignancies in adults with gastric cancer—a US population-based study [J]. Front Oncol , 2016 , 6 : 82 . DOI: 10.3389/fonc.2016.00082 http://dx.doi.org/10.3389/fonc.2016.00082 .
SHI J X , PENG B , WANG C H , et al . Development and validation of a nomogram for predicting overall survival of resected N 2 non-small cell lung cancer patients undergoing neoadjuvant radiotherapy [J]. J Cancer Res Clin Oncol , 2023 , 149 ( 13 ): 11779 - 11790 . DOI: 10.1007/s00432-023-05073-7 http://dx.doi.org/10.1007/s00432-023-05073-7 .
BALACHANDRAN V P , GONEN M , SMITH J J , et al . Nomograms in oncology: more than meets the eye [J]. Lancet Oncol , 2015 , 16 ( 4 ): e173-80 . DOI: 10.1016/S1470-2045(14)71116-7 http://dx.doi.org/10.1016/S1470-2045(14)71116-7 .
NIEDER C , MEHTA M P , GEINITZ H , et al . Prognostic and predictive factors in patients with brain metastases from solid tumors: a review of published nomograms [J]. Crit Rev Oncol Hematol , 2018 , 126 : 13 - 18 . DOI: 10.1016/j.critrevonc.2018.03.018 http://dx.doi.org/10.1016/j.critrevonc.2018.03.018 .
ŁAWNICZAK M , GAWIN A , JAROSZEWICZ-HEIGELMANN H , et al . Synchronous and metachronous neoplasms in gastric cancer patients: a 23-year study [J]. World J Gastroenterol , 2014 , 20 ( 23 ): 7480 - 7487 . DOI: 10.3748/wjg.v20.i23.7480 http://dx.doi.org/10.3748/wjg.v20.i23.7480 .
MORAIS S , ANTUNES L , BENTO M J , et al . Risk of second primary cancers among patients with a first primary gastric cancer: a population-based study in North Portugal [J]. Cancer Epidemiol , 2017 , 50 ( Pt A ): 85 - 91 . DOI: 10.1016/j.canep.2017.08.007 http://dx.doi.org/10.1016/j.canep.2017.08.007 .
CRONIN K A , RIES L A G , EDWARDS B K . The surveillance, epidemiology, and end results (SEER) program of the national cancer institute [J]. Cancer , 2014 , 120 ( Suppl 23 ): 3755 - 3757 . DOI: 10.1002/cncr.29049 http://dx.doi.org/10.1002/cncr.29049 .
MYSURU SHIVANNA L , UROOJ A . A review on dietary and non-dietary risk factors associated with gastrointestinal cancer [J]. J Gastrointest Cancer , 2016 , 47 ( 3 ): 247 - 254 . DOI: 10.1007/s12029-016-9845-1 http://dx.doi.org/10.1007/s12029-016-9845-1 .
PACHECO-FIGUEIREDO L , LUNET N . Health status, use of healthcare, and socio-economic implications of cancer survivorship in Portugal: results from the Fourth National Health Survey [J]. J Cancer Surviv , 2014 , 8 ( 4 ): 611 - 617 . DOI: 10.1007/s11764-014-0370-6 http://dx.doi.org/10.1007/s11764-014-0370-6 .
YANG J , ANTIN P , BERX G , et al . Guidelines and definitions for research on epithelial-mesenchymal transition [J]. Nat Rev Mol Cell Biol , 2020 , 21 ( 6 ): 341 - 352 . DOI: 10.1038/s41580-020-0237-9 http://dx.doi.org/10.1038/s41580-020-0237-9 .
HANISCH E , BATSIS C . Clinicopathologic characteristics of colorectal cancer patients with synchronous and metachronous gastric cancer [J]. World J Surg , 2011 , 35 ( 3 ): 700 - 701 . DOI: 10.1007/s00268-010-0868-7 http://dx.doi.org/10.1007/s00268-010-0868-7 .
IM C , SHARAFELDIN N , YUAN Y , et al . Polygenic risk and chemotherapy-related subsequent malignancies in childhood cancer survivors: a childhood cancer survivor study and ST Jude lifetime cohort study report [J]. J Clin Oncol , 2023 , 41 ( 27 ): 4381 - 4393 . DOI: 10.1200/JCO.23.00428 http://dx.doi.org/10.1200/JCO.23.00428 .
ISHIGAKI T , YOSHIMASU T , OURA S , et al . Surgical treatment for metachronous second primary lung cancer after radical resection of primary lung cancer [J]. Ann Thorac Cardiovasc Surg , 2013 , 19 ( 5 ): 341 - 344 . DOI: 10.5761/atcs.oa.12.01921 http://dx.doi.org/10.5761/atcs.oa.12.01921 .
YANG J , LIU M , FAN J , et al . Surgical treatment of metachronous second primary lung cancer [J]. Ann Thorac Surg , 2014 , 98 ( 4 ): 1192 - 1198 . DOI: 10.1016/j.athoracsur.2014.05.050 http://dx.doi.org/10.1016/j.athoracsur.2014.05.050 .
NICKOLOFF J A , SHARMA N , TAYLOR L . Clustered DNA double-strand breaks: biological effects and relevance to cancer radiotherapy [J]. Genes , 2020 , 11 ( 1 ): 99 . DOI: 10.3390/genes11010099 http://dx.doi.org/10.3390/genes11010099 .
李传红 , 胡鹏 , 欧晏娇 , 等 . 预测小肝癌患者生存率列线图的建立和验证 [J]. 第三军医大学学报 , 2020 , 42 ( 20 ): 2046 - 2056 . DOI: 10.16016/j.1000-5404.202007005 http://dx.doi.org/10.16016/j.1000-5404.202007005 .
LI C H , HU P , OU Y J , et al . Development and validation of nomogram for predicting survival outcomes in patients with small hepatocellular carcinoma [J]. J Third Mil Med Univ , 2020 , 42 ( 20 ): 2046 - 2056 . DOI: 10.16016/j.1000-5404.202007005 http://dx.doi.org/10.16016/j.1000-5404.202007005 .
TONG Y L , ZHAO Y , SHAN Z X , et al . CA724 predicts overall survival in locally advanced gastric cancer patients with neoadjuvant chemotherapy [J]. BMC Cancer , 2021 , 21 ( 1 ): 4 . DOI: 10.1186/s12885-020-07666-8 http://dx.doi.org/10.1186/s12885-020-07666-8 .
CHAFT J E , RIMNER A , WEDER W , et al . Evolution of systemic therapy for stages Ⅰ~Ⅲ non-metastatic non-small-cell lung cancer [J]. Nat Rev Clin Oncol , 2021 , 18 ( 9 ): 547 - 557 . DOI: 10.1038/s41571-021-00501-4 http://dx.doi.org/10.1038/s41571-021-00501-4 .
RODRIGUES G , CHOY H , BRADLEY J , et al . Adjuvant radiation therapy in locally advanced non-small cell lung cancer: executive summary of an American Society for Radiation Oncology (ASTRO) evidence-based clinical practice guideline [J]. Pract Radiat Oncol , 2015 , 5 ( 3 ): 149 - 155 . DOI: 10.1016/j.prro.2015.02.013 http://dx.doi.org/10.1016/j.prro.2015.02.013 .
CHAFT J E , SHYR Y , SEPESI B , et al . Preoperative and postoperative systemic therapy for operable non-small-cell lung cancer [J]. J Clin Oncol , 2022 , 40 ( 6 ): 546 - 555 . DOI: 10.1200/JCO.21.01589 http://dx.doi.org/10.1200/JCO.21.01589 .
HOSTEIN I , FAUR N , PRIMOIS C , et al . BRAF mutation status in gastrointestinal stromal tumors [J]. Am J Clin Pathol , 2010 , 133 ( 1 ): 141 - 148 . DOI: 10.1309/AJCPPCKGA2QGBJ1R http://dx.doi.org/10.1309/AJCPPCKGA2QGBJ1R .
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