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A foundation model-enhanced CT radiomics signature for the noninvasive assessment of tertiary lymphoid structures and prediction of therapy benefit in gastric cancer

Xianchun Gao, Zhe Li, Jun Yu, Jiangpeng Wei, Didi Wen, Ning Han, Linbin Lu, Yongxi Song, Qiong Xiao, Guangtao Wu, Kun Feng, Shibo Wang, Zhongyang Zhang, Dai Zhang, Ling Chen, Zengshan Li, Minwen Zheng, Yong Xia and Yongzhan Nie
Cancer Biology & Medicine April 2026, 20260076; DOI: https://doi.org/10.20892/j.issn.2095-3941.2026.0076
Xianchun Gao
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Zhe Li
2School of Computer Science and Engineering, Northwestern Polytechnical University, Xi’an 710068, China
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Jun Yu
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Jiangpeng Wei
3Department of Digestive Surgery, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Didi Wen
4Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Ning Han
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Linbin Lu
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Yongxi Song
5Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110100, China
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Qiong Xiao
5Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110100, China
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Guangtao Wu
5Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110100, China
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Kun Feng
5Department of Surgical Oncology and General Surgery, The First Hospital of China Medical University, Key Laboratory of Precision Diagnosis and Treatment of Gastrointestinal Tumors (China Medical University), Ministry of Education, Shenyang 110100, China
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Shibo Wang
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Zhongyang Zhang
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Dai Zhang
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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Ling Chen
6State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, China
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Zengshan Li
6State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Pathology, Xijing Hospital and School of Basic Medicine, Fourth Military Medical University, Xi’an 710032, China
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Minwen Zheng
4Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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  • For correspondence: zhengmw2007{at}163.com yxia{at}nwpu.edu.cn yongznie{at}fmmu.edu.cn
Yong Xia
2School of Computer Science and Engineering, Northwestern Polytechnical University, Xi’an 710068, China
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  • For correspondence: zhengmw2007{at}163.com yxia{at}nwpu.edu.cn yongznie{at}fmmu.edu.cn
Yongzhan Nie
1State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, National Clinical Research Center for Digestive Diseases, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, China
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  • ORCID record for Yongzhan Nie
  • For correspondence: zhengmw2007{at}163.com yxia{at}nwpu.edu.cn yongznie{at}fmmu.edu.cn
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    Figure 1

    Development, validation, and clinical utility of the FMRS for TLS prediction and survival stratification. (A) Overview of the study workflow, including patient selection, data collection, and cohort allocation. (B) Schematic illustration of the CT-based framework for predicting TLS status with the foundation model-enhanced radiomics signature (FMRS). (C, D) Receiver operating characteristic (ROC) curves demonstrating FMRS performance for TLS classification in the training cohort (C) and validation cohort (D). (E, F) Confusion matrices showing agreement between FMRS-predicted TLS status and histopathological assessment in the training cohort (E) and validation cohort (F); correctly classified cases are shown along the diagonal, and misclassifications are shown off the diagonal. (G–J) Kaplan–Meier survival analyses, stratified by FMRS status: overall survival (OS) in the training cohort (G) and validation cohort (H), and disease-free survival (DFS) in the training cohort (I) and validation cohort (J). (K–M) Kaplan–Meier curves for OS, comparing FMRS-high and FMRS-low groups in the internal neoadjuvant therapy cohorts: all patients (K), neoadjuvant chemotherapy subgroup (L), and neoadjuvant immunotherapy subgroup (M). (N) Kaplan–Meier analysis of OS according to FMRS status in the external neoadjuvant chemotherapy validation cohort. AUC, area under the curve; FMRS, foundation model-enhanced CT radiomics signature; H&E, hematoxylin–eosin staining; HR, hazard ratio; IHC, immunohistochemistry; TLS, tertiary lymphoid structure; WSI, whole slide scanning.

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    Table 1

    Baseline characteristics of patients in the training, internal, and external validation cohorts

    CharacteristicPatients, No. (%)
    Training cohort (n = 304)Internal validation cohort (n = 307)Internal neoadjuvant therapy cohort (n = 303)External neoadjuvant chemotherapy cohort (n = 90)
    Age, mean (SD), y59.4 (10.2)59.0 (9.6)60.4 (8.9)59.2 (10.1)
    Sex
     Male226 (74.3)250 (81.4)249 (82.2)64 (71.1)
     Female78 (25.7)57 (18.6)54 (17.8)26 (28.9)
    CEA, ng/mL
     <5234 (77.0)250 (81.4)198 (65.3)61 (67.8)
     ≥570 (23.0)57 (18.6)105 (34.7)29 (32.2)
    CA 19-9, U/mL
     <37229 (75.3)234 (76.2)230 (75.9)64 (71.1)
     ≥3775 (24.7)73 (23.8)73 (24.1)26 (28.9)
    Primary tumor location
     Proximal102 (33.6)104 (33.9)139 (45.9)21 (23.3)
     Body72 (23.7)72 (23.5)82 (27.1)25 (27.8)
     Antrum130 (42.8)131 (42.7)82 (27.1)44 (48.9)
    Pathologic T stage
     pT1–226 (8.6)36 (11.7)——
     pT3–4278 (91.4)271 (88.3)——
    Pathologic N stage
     pN0–1106 (34.9)105 (34.2)——
     pN2–3198 (65.1)202 (65.8)——
    Pathologic TNM stage
     pStage II85 (28.0)96 (31.3)——
     pStage III219 (72.0)211 (68.7)——
    Neoadjuvant therapy
     Chemotherapy——202 (66.7)90 (100)
     Immunotherapy——101 (33.3)0 (0)
    Adjuvant chemotherapy
     No54 (17.8)52 (16.9)——
     Yes250 (82.2)255 (83.1)——
    TRG
     0——33 (10.9)6 (6.7)
     1——36 (11.9)13 (14.4)
     2——112 (37.0)30 (33.3)
     3——122 (40.3)41 (45.6)
    TLS class
     Immature TLS173 (56.9)162 (52.8)——
     Mature TLS131 (43.1)145 (47.2)—

    No, number; SD, standard deviation; TRG, tumor regression grade; TLS, tertiary lymphoid structure.

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    Cancer Biology & Medicine: 23 (5)
    Cancer Biology & Medicine
    Vol. 23, Issue 5
    15 May 2026
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    A foundation model-enhanced CT radiomics signature for the noninvasive assessment of tertiary lymphoid structures and prediction of therapy benefit in gastric cancer
    Xianchun Gao, Zhe Li, Jun Yu, Jiangpeng Wei, Didi Wen, Ning Han, Linbin Lu, Yongxi Song, Qiong Xiao, Guangtao Wu, Kun Feng, Shibo Wang, Zhongyang Zhang, Dai Zhang, Ling Chen, Zengshan Li, Minwen Zheng, Yong Xia, Yongzhan Nie
    Cancer Biology & Medicine Apr 2026, 20260076; DOI: 10.20892/j.issn.2095-3941.2026.0076

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    A foundation model-enhanced CT radiomics signature for the noninvasive assessment of tertiary lymphoid structures and prediction of therapy benefit in gastric cancer
    Xianchun Gao, Zhe Li, Jun Yu, Jiangpeng Wei, Didi Wen, Ning Han, Linbin Lu, Yongxi Song, Qiong Xiao, Guangtao Wu, Kun Feng, Shibo Wang, Zhongyang Zhang, Dai Zhang, Ling Chen, Zengshan Li, Minwen Zheng, Yong Xia, Yongzhan Nie
    Cancer Biology & Medicine Apr 2026, 20260076; DOI: 10.20892/j.issn.2095-3941.2026.0076
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      • FMRS predicts TLS classification from CT images
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      • FMRS status predicts response and survival benefit from neoadjuvant therapy
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