2609005261
  • Open Access
  • Review

Research Progress on AI-Driven Biomarker Prediction in Non-Small Cell Lung Cancer

  • Baihua Zhang 1,2,*,   
  • Jing Teng 1,3 and 
  • Siyuan Lu 2

Received: 15 March 2026 | Revised: 26 August 2026 | Accepted: 22 September 2026 | Published: 22 October 2026

Abstract

This study overviews the application of artificial intelligence (AI) in the prediction of biomarkers for non-small cell lung cancer (NSCLC). Different from recent reviews on AI-driven radiogenomics that adopt clinical or imaging-based classification, this work innovatively takes AI model architecture as the core classification framework. By analyzing multimodal data (mainly CT) and modeling paradigms (radiomics, deep learning and fusion models), it reveals the current research status centered on EGFR mutation prediction. In terms of technological evolution, prediction models are evolving from traditional radiomics to end-to-end learning, Transformer architecture and multimodal perception-driven deep learning paradigms. This study deeply analyzes the performance differences among different models, fills the application gaps in existing reviews, and provides an important benchmark reference for the clinical optimization of AI-assisted tools and the promotion of standardized precise diagnosis and treatment of NSCLC.

References 

  • 1.

    Siegel, R.L.; Miller, K.D.; Wagle, N.S.; et al. Cancer statistics, 2023. CA Cancer J. Clin. 2023, 73, 17–48. https://doi.org/10.3322/caac.21763.

  • 2.

    Global Burden of Disease Cancer Collaboration; Fitzmaurice, C.; Akinyemiju, T.F.; et al. Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2016: A Systematic Analysis for the Global Burden of Disease Study. JAMA Oncol. 2018, 4, 1553–1568. https://doi.org/10.1001/jamaoncol.2018.2706.

  • 3.

    Liu, X.; Jiang, G.; Sun, X.; et al. Relationship between driver gene mutations and clinical pathological characteristics in older lung adenocarcinoma. Front. Oncol. 2023, 13, 1275575. https://doi.org/10.3389/fonc.2023.1275575.

  • 4.

    Keegan, A.; Ricciuti, B.; Garden, P.; et al. Plasma IL-6 changes correlate to PD-1 inhibitor responses in NSCLC. J. Immunother. Cancer 2020, 8, e000678. https://doi.org/10.1136/jitc-2020-000678.

  • 5.

    Choi, C.M.; Kim, M.Y.; Hwang, H.J.; et al. Advanced adenocarcinoma of the lung: Comparison of CT characteristics of patients with anaplastic lymphoma kinase gene rearrangement and those with epidermal growth factor receptor mutation. Radiology 2015, 275, 272–279. https://doi.org/10.1148/radiol.14140848.

  • 6.

    Cao, D.; Xu, H.; Xu, X.; et al. A reliable and feasible way to predict the benefits of Nivolumab in patients with non-small cell lung cancer: A pooled analysis of 14 retrospective studies. Oncoimmunology 2018, 7, e1507262. https://doi.org/10.1080/2162402x.2018.1507262.

  • 7.

    Kurose, K.; Sakaeda, K.; Fukuda, M.; et al. Immune checkpoint therapy and response biomarkers in non-small-cell lung cancer: Serum NY-ESO-1 and XAGE1 antibody as predictive and monitoring markers. Adv. Clin. Chem. 2023, 112, 155–204. https://doi.org/10.1016/bs.acc.2022.09.004.

  • 8.

    Ni, S.; Liang, Q.; Jiang, X.; et al. Prognostic models for immunotherapy in non-small cell lung cancer: A comprehensive review. Heliyon 2024, 10, e29840. https://doi.org/10.1016/j.heliyon.2024.e29840.

  • 9.

    Sacher, A.G.; Dahlberg, S.E.; Heng, J.; et al. Association between Younger Age and Targetable Genomic Alterations and Prognosis in Non-Small-Cell Lung Cancer. JAMA Oncol. 2016, 2, 313–320. https://doi.org/10.1001/jamaoncol.2015.4482.

  • 10.

    Alfranca, Y.L.; Garcia, M.E.O.; Rueda, A.G.; et al. Blood Biomarkers of Response to Immune Checkpoint Inhibitors in Non-Small Cell Lung Cancer. J. Clin. Med. 2022, 11, 3245. https://doi.org/10.3390/jcm11113245.

  • 11.

    Imyanitov, E.N.; Iyevleva, A.G.; Levchenko, E.V. Molecular testing and targeted therapy for non-small cell lung cancer: Current status and perspectives. Crit. Rev. Oncol. Hematol. 2021, 157, 103194. https://doi.org/10.1016/j.critrevonc.2020.103194.

  • 12.

    Liu, Y.; Kim, J.; Qu, F.; et al. CT Features Associated with Epidermal Growth Factor Receptor Mutation Status in Patients with Lung Adenocarcinoma. Radiology 2016, 280, 271–280. https://doi.org/10.1148/radiol.2016151455.

  • 13.

    Rivière, A.; Lecuyer, A.I.; Laurent, E.; et al. 1-year mortality in lung cancer in France according to key timepoints of care pathways. ERJ Open Res. 2022, 8, 00157-2022. https://doi.org/10.1183/23120541.00157-2022.

  • 14.

    Onimaru, R.; Onishi, H.; Ogawa, G.; et al. Final report of survival and late toxicities in the Phase I study of stereotactic body radiation therapy for peripheral T2N0M0 non-small cell lung cancer (JCOG0702). Jpn. J. Clin. Oncol. 2018, 48, 1076–1082. https://doi.org/10.1093/jjco/hyy141.

  • 15.

    Wang, S.; Yu, H.; Gan, Y.; et al. Mining whole-lung information by artificial intelligence for predicting EGFR genotype and targeted therapy response in lung cancer: A multicohort study. Lancet Digit. Health 2022, 4, e309–e319. https://doi.org/10.1016/s2589-7500(22)00024-3.

  • 16.

    Chen, Q.; Li, Y.; Cheng, Q.; et al. EGFR Mutation Status and Subtypes Predicted by CT-Based 3D Radiomic Features in Lung Adenocarcinoma. Onco Targets Ther. 2022, 15, 597–608. https://doi.org/10.2147/ott.s352619.

  • 17.

    Sleeman, W.C.; Kapoor, R.; Ghosh, P. Multimodal classification: Current landscape, taxonomy and future directions. ACM Comput. Surv. 2023, 55, 1–31. https://doi.org/10.1145/3543848.

  • 18.

    HajiEsmailPoor, Z.; Tabnak, P.; Baradaran, B.; et al. Diagnostic performance of CT scan–based radiomics for prediction of lymph node metastasis in gastric cancer: A systematic review and meta-analysis. Front. Oncol. 2023, 13, 1185663. https://doi.org/10.3389/fonc.2023.1185663.

  • 19.

    Liu, X.; Xu, T.; Wang, S.; et al. CT-based radiomic phenotypes of lung adenocarcinoma: A preliminary comparative analysis with targeted next-generation sequencing. Front. Med. 2023, 10, 1191019. https://doi.org/10.3389/fmed.2023.1191019.

  • 20.

    Mino-Kenudson, M.; Schalper, K.; Cooper, W.; et al. Predictive Biomarkers for Immunotherapy in Lung Cancer: Perspective from the International Association for the Study of Lung Cancer Pathology Committee. J. Thorac. Oncol. 2022, 17, 1335–1354. https://doi.org/10.1016/j.jtho.2022.09.109.

  • 21.

    Gao, Q.; Yang, L.; Lu, M.; et al. The artificial intelligence and machine learning in lung cancer immunotherapy. J. Hematol. Oncol. 2023, 16, 55. https://doi.org/10.1186/s13045-023-01456-y.

  • 22.

    Zhou, G.; Xu, S.; Liu, X.; et al. Relationship between the image characteristics of artificial intelligence and EGFR gene mutation in lung adenocarcinoma. Front. Genet. 2023, 13, 1090180. https://doi.org/10.3389/fgene.2022.1090180.

  • 23.

    She, Y.; Jin, Z.; Wu, J.; et al. Development and Validation of a Deep Learning Model for Non–Small Cell Lung Cancer Survival. JAMA Netw. Open 2020, 3, e205842. https://doi.org/10.1001/jamanetworkopen.2020.5842.

  • 24.

    Lai, Y.H.; Chen, W.N.; Hsu, T.C.; et al. Overall survival prediction of non-small cell lung cancer by integrating microarray and clinical data with deep learning. Sci. Rep. 2020, 10, 4679. https://doi.org/10.1038/s41598-020-61588-w.

  • 25.

    De Fauw, J.; Ledsam, J.R.; Romera-Paredes, B.; et al. Clinically applicable deep learning for diagnosis and referral in retinal disease. Nat. Med. 2018, 24, 1342–1350. https://doi.org/10.1038/s41591-018-0107-6.

  • 26.

    Mu, W.; Jiang, L.; Zhang, J.; et al. Non-invasive decision support for NSCLC treatment using PET/CT radiomics. Nat. Commun. 2020, 11, 5228. https://doi.org/10.1038/s41467-020-19116-x.

  • 27.

    Sun, K.; Zheng, Y.; Yang, X.; et al. A novel transformer-based aggregation model for predicting gene mutations in lung adenocarcinoma. Med. Biol. Eng. Comput. 2024, 62, 1427–1440. https://doi.org/10.1007/s11517-023-03004-9.

  • 28.

    Jiang, Y.; Ma, S.; Xiao, W.; et al. Predicting EGFR gene mutation status in lung adenocarcinoma based on multifeature fusion. Biomed. Signal Process. Control. 2023, 84, 104786. https://doi.org/10.1016/j.bspc.2023.104786.

  • 29.

    Wang, C.; Xu, X.; Shao, J.; et al. Deep Learning to Predict EGFR Mutation and PD-L1 Expression Status in Non-Small-Cell Lung Cancer on Computed Tomography Images. J. Oncol. 2021, 2021, 5499385. https://doi.org/10.1155/2021/5499385.

  • 30.

    Wang, C.; Ma, J.; Shao, J.; et al. Non-Invasive Measurement Using Deep Learning Algorithm Based on Multi-Source Features Fusion to Predict PD-L1 Expression and Survival in NSCLC. Front. Immunol. 2022, 13, 828560. https://doi.org/10.3389/fimmu.2022.828560.

  • 31.

    Liao, J.; Li, X.; Gan, Y.; et al. Artificial intelligence assists precision medicine in cancer treatment. Front. Oncol. 2023, 12, 998222. https://doi.org/10.3389/fonc.2022.998222.

  • 32.

    Chen, M.; Copley, S.J.; Viola, P.; et al. Radiomics and artificial intelligence for precision medicine in lung cancer treatment. Semin. Cancer Biol. 2023, 93, 97–113. https://doi.org/10.1016/j.semcancer.2023.05.004.

  • 33.

    Li, M.S.C.; Mok, K.K.S.; Mok, T.S.K. Developments in targeted therapy & immunotherapy—How non-small cell lung cancer management will change in the next decade: A narrative review. Ann. Transl. Med. 2023, 11, 358. https://doi.org/10.21037/atm-22-4444.

  • 34.

    Atmakuru, A.; Chakraborty, S.; Faust, O.; et al. Deep learning in radiology for lung cancer diagnostics: A systematic review of classification, segmentation, and predictive modeling techniques. Expert Syst. Appl. 2024, 255, 124665. https://doi.org/10.1016/j.eswa.2024.124665.

  • 35.

    Zheng, J.; Xu, S.; Wang, G.; et al. Applications of CT-based radiomics for the prediction of immune checkpoint markers and immunotherapeutic outcomes in non-small cell lung cancer. Front. Immunol. 2024, 15, 1434171. https://doi.org/10.3389/fimmu.2024.1434171.

  • 36.

    Arango-Argoty, G.; Bikiel, D.E.; Sun, G.J.; et al. AI-driven predictive biomarker discovery with contrastive learning to improve clinical trial outcomes. Cancer Cell 2025, 43, 875–890.e8. https://doi.org/10.1016/j.ccell.2025.03.029.

  • 37.

    Bonci, E.A.; Bandura, A.; Dooley, A.; et al. Artificial intelligence in NSCLC management for revolutionizing diagnosis, prognosis, and treatment optimization: A systematic review. Crit. Rev. Oncol. Hematol. 2025, 216, 104929. https://doi.org/10.1016/j.critrevonc.2025.104929.

  • 38.

    Dehkharghanian, T.; Bidgoli, A.A.; Riasatian, A.; et al. Biased data, biased AI: Deep networks predict the acquisition site of TCGA images. Diagn. Pathol. 2023, 18, 67. https://doi.org/10.1186/s13000-023-01355-3.

  • 39.

    Fu, Y.; Jung, A.W.; Torne, R.V.; et al. Pan-cancer computational histopathology reveals mutations, tumor composition and prognosis. Nat. Cancer 2020, 1, 800–810. https://doi.org/10.1038/s43018-020-0085-8.

  • 40.

    Noorbakhsh, J.; Farahmand, S.; Foroughi pour, A.; et al. Deep learning-based cross-classifications reveal conserved spatial behaviors within tumor histological images. Nat. Commun. 2020, 11, 6367. https://doi.org/10.1038/s41467-020-20030-5.

  • 41.

    Huang, K.; Mo, Z.; Zhu, W.; et al. Prediction of Target-Drug Therapy by Identifying Gene Mutations in Lung Cancer With Histopathological Stained Image and Deep Learning Techniques. Front. Oncol. 2021, 11, 642945. https://doi.org/10.3389/fonc.2021.642945.

  • 42.

    Rączkowska, A.; Paśnik, I.; Kukiełka, M.; et al. Deep learning-based tumor microenvironment segmentation is predictive of tumor mutations and patient survival in non-small-cell lung cancer. BMC Cancer 2022, 22, 1001. https://doi.org/10.1186/s12885-022-10081-w.

  • 43.

    Chen, Z.; Li, X.; Yang, M.; et al. Optimization of deep learning models for the prediction of gene mutations using unsupervised clustering. J. Pathol. Clin. Res. 2023, 9, 3–17. https://doi.org/10.1002/cjp2.302.

  • 44.

    Morel, L.O.; Derangère, V.; Arnould, L.; et al. Preliminary evaluation of deep learning for first-line diagnostic prediction of tumor mutational status. Sci. Rep. 2023, 13, 6927. https://doi.org/10.1038/s41598-023-34016-y.

  • 45.

    Chen, Y.; Zhou, C.; Zhang, X.; et al. Construction of a novel radioresistance-related signature for prediction of prognosis, immune microenvironment and anti-tumour drug sensitivity in non-small cell lung cancer. Ann. Med. 2025, 57, 2447930. https://doi.org/10.1080/07853890.2024.2447930.

  • 46.

    Lu, M.Y.; Chen, B.; Williamson, D.F.K.; et al. A multimodal generative AI copilot for human pathology. Nature 2024, 634, 466–473. https://doi.org/10.1038/s41586-024-07618-3.

  • 47.

    Jia, L.; Wu, W.; Hou, G.; et al. Residual neural network with mixed loss based on batch training technique for identification of EGFR mutation status in lung cancer. Multimed. Tools Appl. 2023, 82, 33443–33463. https://doi.org/10.1007/s11042-023-14876-2.

  • 48.

    Zhao, W.; Chen, W.; Li, G.; et al. GMILT: A Novel Transformer Network That Can Noninvasively Predict EGFR Mutation Status. IEEE Trans. Neural Netw. Learn. Syst. 2024, 35, 7324–7338. https://doi.org/10.1109/tnnls.2022.3190671.

  • 49.

    Tomita, N.; Tafe, L.J.; Suriawinata, A.A.; et al. Predicting oncogene mutations of lung cancer using deep learning and histopathologic features on whole-slide images. Transl. Oncol. 2022, 24, 101494. https://doi.org/10.1016/j.tranon.2022.101494.

  • 50.

    Yong, M.P.; Hum, Y.C.; Lai, K.W.; et al. Histopathological Cancer Detection Using Intra-Domain Transfer Learning and Ensemble Learning. IEEE Access 2024, 12, 1434–1457. https://doi.org/10.1109/access.2023.3343465.

  • 51.

    Zhang, H.; He, M.; Wan, R.A.; et al. Establishment and Evaluation of EGFR Mutation Prediction Model Based on Tumor Markers and CT Features in NSCLC. J. Healthc. Eng. 2022, 2022, 8089750. https://doi.org/10.1155/2022/8089750.

  • 52.

    Liu, Y.; Zhou, J.; Wu, J.; et al. Development and Validation of Machine Learning Models to Predict Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Cancer: A Multi-Center Retrospective Radiomics Study. Cancer Control 2022, 29, 10732748221092926. https://doi.org/10.1177/10732748221092926.

  • 53.

    Yang, C.; Chen, W.; Gong, G.; et al. Application of CT radiomics features to predict the EGFR mutation status and therapeutic sensitivity to TKIs of advanced lung adenocarcinoma. Transl. Cancer Res. 2020, 9, 6683–6690. https://doi.org/10.21037/tcr-20-1216.

  • 54.

    Dang, Y.; Wang, R.; Qian, K.; et al. Clinical and radiological predictors of epidermal growth factor receptor mutation in nonsmall cell lung cancer. J. Appl. Clin. Med. Phys. 2021, 22, 271–280. https://doi.org/10.1002/acm2.13107.

  • 55.

    Zhang, G.; Cao, Y.; Zhang, J.; et al. Predicting EGFR mutation status in lung adenocarcinoma: Development and validation of a computed tomography-based radiomics signature. Am. J. Cancer Res. 2021, 11, 546–560.

  • 56.

    Chen, W.; Hua, Y.; Mao, D.; et al. A Computed Tomography-Derived Radiomics Approach for Predicting Uncommon EGFR Mutation in Patients With NSCLC. Front. Oncol. 2021, 11, 722106. https://doi.org/10.3389/fonc.2021.722106.

  • 57.

    Jiang, M.; Yang, P.; Li, J.; et al. Computed tomography-based radiomics quantification predicts epidermal growth factor receptor mutation status and efficacy of first-line targeted therapy in lung adenocarcinoma. Front. Oncol. 2022, 12, 985284. https://doi.org/10.3389/fonc.2022.985284.

  • 58.

    Dong, Y.; Jiang, Z.; Li, C.; et al. Development and validation of novel radiomics-based nomograms for the prediction of EGFR mutations and Ki-67 proliferation index in non-small cell lung cancer. Quant. Imaging Med. Surg. 2022, 12, 2658–2671. https://doi.org/10.21037/qims-21-980.

  • 59.

    Njoto, E.N.; Jasminarti Dwi Kusumawardani, I.A.; Rai, I.B.N. Predicting EGFR Mutation in Lung Adenocarcinoma: Development and Validation of the EGFR Mutation Predictive Score (EMPS) in Bali, Indonesia. Asian Pac. J. Cancer Prev. 2023, 24, 2903–2910. https://doi.org/10.31557/apjcp.2023.24.8.2903.

  • 60.

    Wu, S.; Shen, G.; Mao, J.; et al. CT Radiomics in Predicting EGFR Mutation in Non-small Cell Lung Cancer: A Single Institutional Study. Front. Oncol. 2020, 10, 542957. https://doi.org/10.3389/fonc.2020.542957.

  • 61.

    Zhu, H.; Song, Y.; Huang, Z.; et al. Accurate prediction of epidermal growth factor receptor mutation status in early-stage lung adenocarcinoma, using radiomics and clinical features. Asia-Pac. J. Clin. Oncol. 2022, 18, 586–594. https://doi.org/10.1111/ajco.13641.

  • 62.

    Hou, D.; Li, W.; Wang, S.; et al. Different Clinicopathologic and Computed Tomography Imaging Characteristics of Primary and Acquired EGFR T790M Mutations in Patients with Non-Small-Cell Lung Cancer. Cancer Manag. Res. 2021, 13, 6389–6401. https://doi.org/10.2147/cmar.s323972.

  • 63.

    Ninomiya, K.; Arimura, H.; Chan, W.Y.; et al. Robust radiogenomics approach to the identification of EGFR mutations among patients with NSCLC from three different countries using topologically invariant Betti numbers. PLoS ONE 2021, 16, e0244354. Correction in: PLoS ONE 2024, 19, e0316496. https://doi.org/10.1371/journal.pone.0244354.

  • 64.

    Rossi, G.; Barabino, E.; Fedeli, A.; et al. Radiomic Detection of EGFR Mutations in NSCLC. Cancer Res. 2021, 81, 724–731. https://doi.org/10.1158/0008-5472.can-20-0999.

  • 65.

    Weng, Q.; Hui, J.; Wang, H.; et al. Radiomic Feature-Based Nomogram: A Novel Technique to Predict EGFR-Activating Mutations for EGFR Tyrosine Kinase Inhibitor Therapy. Front. Oncol. 2021, 11, 590937. https://doi.org/10.3389/fonc.2021.590937.

  • 66.

    Zhu, Y.; Guo, Y.B.; Xu, D.; et al. A computed tomography (CT)-derived radiomics approach for predicting primary co-mutations involving TP53 and epidermal growth factor receptor (EGFR) in patients with advanced lung adenocarcinomas (LUAD). Ann. Transl. Med. 2021, 9, 545. https://doi.org/10.21037/atm-20-6473.

  • 67.

    Cheng, B.; Deng, H.; Zhao, Y.; et al. Predicting EGFR mutation status in lung adenocarcinoma presenting as ground-glass opacity: Utilizing radiomics model in clinical translation. Eur. Radiol. 2022, 32, 5869–5879. https://doi.org/10.1007/s00330-022-08673-y.

  • 68.

    Chen, Z.; Lu, H.; Liu, A.; et al. TRANS: A prediction model for EGFR mutation status in NSCLC based on radiomics and clinical features. Respir. Res. 2025, 26, 211. https://doi.org/10.1186/s12931-025-03287-6.

  • 69.

    Hong, D.; Xu, K.; Zhang, L.; et al. Radiomics Signature as a Predictive Factor for EGFR Mutations in Advanced Lung Adenocarcinoma. Front. Oncol. 2020, 10, 28. https://doi.org/10.3389/fonc.2020.00028.

  • 70.

    Lu, X.; Li, M.; Zhang, H.; et al. A novel radiomic nomogram for predicting epidermal growth factor receptor mutation in peripheral lung adenocarcinoma. Phys. Med. Biol. 2020, 65, 055012. https://doi.org/10.1088/1361-6560/ab6f98.

  • 71.

    Lu, J.; Ji, X.; Wang, L.; et al. Machine Learning-Based Radiomics for Prediction of Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma. Dis. Markers 2022, 2022, 2056837. https://doi.org/10.1155/2022/2056837.

  • 72.

    Kawazoe, Y.; Shiinoki, T.; Fujimoto, K.; et al. Investigation of the combination of intratumoral and peritumoral radiomic signatures for predicting epidermal growth factor receptor mutation in lung adenocarcinoma. J. Appl. Clin. Med. Phys. 2023, 24, e13980. https://doi.org/10.1002/acm2.13980.

  • 73.

    Omura, K.; Murakami, Y.; Hashimoto, K.; et al. Detection of EGFR mutations in early-stage lung adenocarcinoma by machine learning-based radiomics. Transl. Cancer Res. 2023, 12, 837–847. https://doi.org/10.21037/tcr-22-2683.

  • 74.

    Shang, Y.; Chen, W.; Li, G.; et al. Computed Tomography-derived intratumoral and peritumoral radiomics in predicting EGFR mutation in lung adenocarcinoma. Radiol. Med. 2023, 128, 1483–1496. https://doi.org/10.1007/s11547-023-01722-6.

  • 75.

    Chen, Z.; Gao, S.; Ding, C.; et al. CT-based non-invasive identification of the most common gene mutation status in patients with non-small cell lung cancer. Med. Phys. 2024, 51, 1872–1882. https://doi.org/10.1002/mp.16744.

  • 76.

    Ma, J.W.; Jiang, X.; Wang, Y.M.; et al. Dual-energy CT-based radiomics in predicting EGFR mutation status non-invasively in lung adenocarcinoma. Heliyon 2024, 10, e24372. https://doi.org/10.1016/j.heliyon.2024.e24372.

  • 77.

    Chen, C.; Liu, X.; Li, A.; et al. Non-invasive prediction of EGFR gene mutations in non-small cell lung cancer by multi-parameter CT perfusion imaging. Front. Med. 2025, 12, 1660923. https://doi.org/10.3389/fmed.2025.1660923.

  • 78.

    Li, S.; Luo, T.; Ding, C.; et al. Detailed identification of epidermal growth factor receptor mutations in lung adenocarcinoma: Combining radiomics with machine learning. Med. Phys. 2020, 47, 3458–3466. https://doi.org/10.1002/mp.14238.

  • 79.

    Liu, G.; Xu, Z.; Ge, Y.; et al. 3D radiomics predicts EGFR mutation, exon-19 deletion and exon-21 L858R mutation in lung adenocarcinoma. Transl. Lung Cancer Res. 2020, 9, 1212–1224. https://doi.org/10.21037/tlcr-20-122.

  • 80.

    Kawazoe, Y.; Shiinoki, T.; Fujimoto, K.; et al. Comparison of the radiomics-based predictive models using machine learning and nomogram for epidermal growth factor receptor mutation status and subtypes in lung adenocarcinoma. Phys. Eng. Sci. Med. 2023, 46, 395–403. https://doi.org/10.1007/s13246-023-01232-9.

  • 81.

    Huo, J.W.; Luo, T.Y.; Diao, L.; et al. Using combined CT-clinical radiomics models to identify epidermal growth factor receptor mutation subtypes in lung adenocarcinoma. Front. Oncol. 2022, 12, 846589. https://doi.org/10.3389/fonc.2022.846589.

  • 82.

    Hao, P.; Deng, B.Y.; Huang, C.T.; et al. Predicting anaplastic lymphoma kinase rearrangement status in patients with non-small cell lung cancer using a machine learning algorithm that combines clinical features and CT images. Front. Oncol. 2022, 12, 994285. https://doi.org/10.3389/fonc.2022.994285.

  • 83.

    Xiong, W.; Yu, X.; Zhou, T.; et al. A Radiomics-clinical Nomogram based on CT Radiomics to Predict Acquired T790M Mutation Status in Non-small Cell Lung Cancer Patients. Curr. Med. Imaging 2024, 20, e15734056283623. https://doi.org/10.2174/0115734056283623240215102037.

  • 84.

    Yang, X.; Fang, C.; Li, C.; et al. Can CT Radiomics Detect Acquired T790M Mutation and Predict Prognosis in Advanced Lung Adenocarcinoma with Progression After First- or Second-Generation EGFR TKIs? Front. Oncol. 2022, 12, 904983. https://doi.org/10.3389/fonc.2022.904983.

  • 85.

    Le, N.Q.K.; Kha, Q.H.; Nguyen, V.H.; et al. Machine Learning-Based Radiomics Signatures for EGFR and KRAS Mutations Prediction in Non-Small-Cell Lung Cancer. Int. J. Mol. Sci. 2021, 22, 9254. https://doi.org/10.3390/ijms22179254.

  • 86.

    Zhang, X.; Zhang, G.; Qiu, X.; et al. Non-invasive decision support for clinical treatment of non-small cell lung cancer using a multiscale radiomics approach. Radiother. Oncol. 2024, 191, 110082. https://doi.org/10.1016/j.radonc.2024.110082.

  • 87.

    Ninomiya, K.; Arimura, H.; Tanaka, K.; et al. Three-dimensional topological radiogenomics of epidermal growth factor receptor Del19 and L858R mutation subtypes on computed tomography images of lung cancer patients. Comput. Methods Programs Biomed. 2023, 236, 107544. https://doi.org/10.1016/j.cmpb.2023.107544.

  • 88.

    Ma, D.N.; Gao, X.Y.; Dan, Y.B.; et al. Evaluating Solid Lung Adenocarcinoma Anaplastic Lymphoma Kinase Gene Rearrangement Using Noninvasive Radiomics Biomarkers. Onco Targets Ther. 2020, 13, 6927–6935. https://doi.org/10.2147/OTT.S257798.

  • 89.

    Song, L.; Zhu, Z.; Mao, L.; et al. Clinical, Conventional CT and Radiomic Feature-Based Machine Learning Models for Predicting ALK Rearrangement Status in Lung Adenocarcinoma Patients. Front. Oncol. 2020, 10, 369. https://doi.org/10.3389/fonc.2020.00369.

  • 90.

    Choe, J.; Lee, S.M.; Kim, W.; et al. CT radiomics-based prediction of anaplastic lymphoma kinase and epidermal growth factor receptor mutations in lung adenocarcinoma. Eur. J. Radiol. 2021, 139, 109710. https://doi.org/10.1016/j.ejrad.2021.109710.

  • 91.

    Li, X.; Chen, J.; Zhang, C.; et al. Application value of CT radiomic nomogram in predicting T790M mutation of lung adenocarcinoma. BMC Pulm. Med. 2023, 23, 339. https://doi.org/10.1186/s12890-023-02609-y.

  • 92.

    Lu, J.; Ji, X.; Liu, X.; et al. Machine learning-based radiomics strategy for prediction of acquired EGFR T790M mutation following treatment with EGFR-TKI in NSCLC. Sci. Rep. 2024, 14, 446. https://doi.org/10.1038/s41598-023-50984-7.

  • 93.

    Li, J.; Xu, R.; Wang, D.; et al. Non-invasive identification of TKI-resistant NSCLC: A multi-model AI approach for predicting EGFR/TP53 co-mutations. BMC Pulm. Med. 2025, 25, 336. https://doi.org/10.1186/s12890-025-03805-8.

  • 94.

    Zhang, T.; Xu, Z.; Liu, G.; et al. Simultaneous Identification of EGFR, KRAS, ERBB2, and TP53 Mutations in Patients with Non-Small Cell Lung Cancer by Machine Learning-Derived Three-Dimensional Radiomics. Cancers 2021, 13, 1814. https://doi.org/10.3390/cancers13081814.

  • 95.

    Jiang, Z.; Dong, Y.; Yang, L.; et al. CT-Based Hand-crafted Radiomic Signatures Can Predict PD-L1 Expression Levels in Non-small Cell Lung Cancer: A Two-Center Study. J. Digit. Imaging 2021, 34, 1073–1085. https://doi.org/10.1007/s10278-021-00484-9.

  • 96.

    Wen, Q.; Yang, Z.; Dai, H.; et al. Radiomics Study for Predicting the Expression of PD-L1 and Tumor Mutation Burden in Non-Small Cell Lung Cancer Based on CT Images and Clinicopathological Features. Front. Oncol. 2021, 11, 620246. https://doi.org/10.3389/fonc.2021.620246.

  • 97.

    Bracci, S.; Dolciami, M.; Trobiani, C.; et al. Quantitative CT texture analysis in predicting PD-L1 expression in locally advanced or metastatic NSCLC patients. Radiol. Med. 2021, 126, 1425–1433. https://doi.org/10.1007/s11547-021-01399-9.

  • 98.

    Shiinoki, T.; Fujimoto, K.; Kawazoe, Y.; et al. Predicting programmed death-ligand 1 expression level in non-small cell lung cancer using a combination of peritumoral and intratumoral radiomic features on computed tomography. Biomed. Phys. Eng. Express 2022, 8, 025008. https://doi.org/10.1088/2057-1976/ac4d43.

  • 99.

    Chen, Y.; Xu, T.; Jiang, C.; et al. CT-based radiomics signature to predict CD8+ tumor infiltrating lymphocytes in non-small-cell lung cancer. Acta Radiol. 2023, 64, 1390–1399. https://doi.org/10.1177/02841851221126596.

  • 100.

    Sun, R.; Sundahl, N.; Hecht, M.; et al. Radiomics to predict outcomes and abscopal response of patients with cancer treated with immunotherapy combined with radiotherapy using a validated signature of CD8 cells. J. Immunother. Cancer 2020, 8, e001429. https://doi.org/10.1136/jitc-2020-001429.

  • 101.

    Sun, Z.; Hu, S.; Ge, Y.; et al. Radiomics study for predicting the expression of PD-L1 in non-small cell lung cancer based on CT images and clinicopathologic features. J. X-Ray Sci. Technol. 2020, 28, 449–459. https://doi.org/10.3233/xst-200642.

  • 102.

    Yoon, J.; Suh, Y.J.; Han, K.; et al. Utility of CT radiomics for prediction of PD-L1 expression in advanced lung adenocarcinomas. Thorac. Cancer 2020, 11, 993–1004. https://doi.org/10.1111/1759-7714.13352.

  • 103.

    Liu, P.M.; Feng, B.; Shi, J.F.; et al. A deep-learning model using enhanced chest CT images to predict PD-L1 expression in non-small-cell lung cancer patients. Clin. Radiol. 2023, 78, e689–e697. https://doi.org/10.1016/j.crad.2023.05.010.

  • 104.

    Fu, Y.; Zhang, H.; Xue, P.; et al. Qualitative analysis of PD-L1 expression in non-small-cell lung cancer based on chest CT radiomics. Biomed. Signal Process. Control. 2023, 84, 104815. https://doi.org/10.1016/j.bspc.2023.104815.

  • 105.

    Montoya, C.; Spieler, B.; Welford, S.M.; et al. Predicting response to immunotherapy in non-small cell lung cancer- from bench to bedside. Front. Oncol. 2023, 13, 1225720. https://doi.org/10.3389/fonc.2023.1225720.

  • 106.

    Iwatate, Y.; Hoshino, I.; Yokota, H.; et al. Radiogenomics for predicting p53 status, PD-L1 expression, and prognosis with machine learning in pancreatic cancer. Br. J. Cancer 2020, 123, 1253–1261. https://doi.org/10.1038/s41416-020-0997-1.

  • 107.

    Park, C.; Jeong, D.Y.; Choi, Y.; et al. Tumor-infiltrating lymphocyte enrichment predicted by CT radiomics analysis is associated with clinical outcomes of non-small cell lung cancer patients receiving immune checkpoint inhibitors. Front. Immunol. 2023, 13, 1038089. https://doi.org/10.3389/fimmu.2022.1038089.

  • 108.

    Chen, M.; Lu, H.; Copley, S.J.; et al. A Novel Radiogenomics Biomarker for Predicting Treatment Response and Pneumotoxicity From Programmed Cell Death Protein or Ligand-1 Inhibition Immunotherapy in NSCLC. J. Thorac. Oncol. 2023, 18, 718–730. https://doi.org/10.1016/j.jtho.2023.01.089.

  • 109.

    Wu, S.; Zhan, W.; Liu, L.; et al. Pretreatment radiomic biomarker for immunotherapy responder prediction in stage IB–IV NSCLC (LCDigital-IO Study): A multicenter retrospective study. J. Immunother. Cancer 2023, 11, e007369. https://doi.org/10.1136/jitc-2023-007369.

  • 110.

    Yolchuyeva, S.; Giacomazzi, E.; Tonneau, M.; et al. A Radiomics-Clinical Model Predicts Overall Survival of Non-Small Cell Lung Cancer Patients Treated with Immunotherapy: A Multicenter Study. Cancers 2023, 15, 3829. https://doi.org/10.3390/cancers15153829.

  • 111.

    Yolchuyeva, S.; Ebrahimpour, L.; Tonneau, M.; et al. Multi-institutional prognostic modeling of survival outcomes in NSCLC patients treated with first-line immunotherapy using radiomics. J. Transl. Med. 2024, 22, 42. https://doi.org/10.1186/s12967-024-04854-z.

  • 112.

    Wu, S.; Pan, J.; Zheng, Y.; et al. Integration of Machine Learning, Bioinformatics, and Experimental Validation to Identify Novel Diagnostic and Prognostic Biomarkers Associated with Succinylation in Lung Adenocarcinoma. Drug Dev. Res. 2025, 86, e70184. https://doi.org/10.1002/ddr.70184.

  • 113.

    Zhang, J.; Zhao, X.; Zhao, Y.; et al. Value of pre-therapy 18F-FDG PET/CT radiomics in predicting EGFR mutation status in patients with non-small cell lung cancer. Eur. J. Nucl. Med. Mol. Imaging 2020, 47, 1137–1146. https://doi.org/10.1007/s00259-019-04592-1.

  • 114.

    Yang, B.; Ji, H.S.; Zhou, C.S.; et al. 18F-fluorodeoxyglucose positron emission tomography/computed tomography-based radiomic features for prediction of epidermal growth factor receptor mutation status and prognosis in patients with lung adenocarcinoma. Transl. Lung Cancer Res. 2020, 9, 563–574. https://doi.org/10.21037/tlcr-19-592.

  • 115.

    Shiri, I.; Amini, M.; Nazari, M.; et al. Impact of feature harmonization on radiogenomics analysis: Prediction of EGFR and KRAS mutations from non-small cell lung cancer PET/CT images. Comput. Biol. Med. 2022, 142, 105230. https://doi.org/10.1016/j.compbiomed.2022.105230.

  • 116.

    Li, H.; Gao, C.; Sun, Y.; et al. Radiomics Analysis to Enhance Precise Identification of Epidermal Growth Factor Receptor Mutation Based on Positron Emission Tomography Images of Lung Cancer Patients. J. Biomed. Nanotechnol. 2021, 17, 691–702. https://doi.org/10.1166/jbn.2021.3056.

  • 117.

    Wang, C.; Zhang, R.; Sun, X.; et al. Prediction of epidermal growth factor receptor mutation status by textural features in stage IV lung adenocarcinoma. Memo-Mag. Eur. Med. Oncol. 2024, 17, 100–106. https://doi.org/10.1007/s12254-024-00961-1.

  • 118.

    Liu, Z.; Zhang, T.; Lin, L.; et al. Applications of radiomics-based analysis pipeline for predicting epidermal growth factor receptor mutation status. Biomed. Eng. Online 2023, 22, 17. Correction in: Biomed. Eng. Online 2023, 22, 32. https://doi.org/10.1186/s12938-022-01049-9.

  • 119.

    Koyasu, S.; Nishio, M.; Isoda, H.; et al. Usefulness of gradient tree boosting for predicting histological subtype and EGFR mutation status of non-small cell lung cancer on 18F FDG-PET/CT. Ann. Nucl. Med. 2020, 34, 49–57. https://doi.org/10.1007/s12149-019-01414-0.

  • 120.

    Agüloğlu, N.; Aksu, A.; Akyol, M.; et al. Importance of pretreatment 18F-FDG PET/CT texture analysis in predicting EGFR and ALK mutations in patients with non-small-cell lung cancer. Nuklearmedizin 2022, 61, 433–439. https://doi.org/10.1055/a-1868-4918.

  • 121.

    Li, S.; Hu, Y.; Tian, C.; et al. Prediction of EGFR-TP53 genes co-mutations in patients with lung adenocarcinoma (LUAD) by 18F-FDG PET/CT radiomics. Clin. Transl. Oncol. 2025, 27, 1506–1515. https://doi.org/10.1007/s12094-024-03685-0.

  • 122.

    Zhang, M.; Bao, Y.; Rui, W.; et al. Performance of 18F-FDG PET/CT Radiomics for Predicting EGFR Mutation Status in Patients with Non-Small Cell Lung Cancer. Front. Oncol. 2020, 10, 568857. https://doi.org/10.3389/fonc.2020.568857.

  • 123.

    Aide, N.; Weyts, K.; Lasnon, C. Prediction of the Presence of Targetable Molecular Alteration(s) with Clinico-Metabolic 18 F-FDG PET Radiomics in Non-Asian Lung Adenocarcinoma Patients. Diagnostics 2022, 12, 2448. https://doi.org/10.3390/diagnostics12102448.

  • 124.

    Li, S.; Li, Y.; Zhao, M.; et al. Combination of 18F-Fluorodeoxyglucose PET/CT Radiomics and Clinical Features for Predicting Epidermal Growth Factor Receptor Mutations in Lung Adenocarcinoma. Korean J. Radiol. 2022, 23, 921–930. https://doi.org/10.3348/kjr.2022.0295.

  • 125.

    Zhao, H.Y.; Su, Y.X.; Zhang, L.H.; et al. Prediction model based on 18F-FDG PET/CT radiomic features and clinical factors of EGFR mutations in lung adenocarcinoma. Neoplasma 2022, 69, 233–241. https://doi.org/10.4149/neo_2021_201222n1388.

  • 126.

    Gao, J.; Niu, R.; Shi, Y.; et al. The predictive value of [18F]FDG PET/CT radiomics combined with clinical features for EGFR mutation status in different clinical staging of lung adenocarcinoma. EJNMMI Res. 2023, 13, 26. https://doi.org/10.1186/s13550-023-00977-4.

  • 127.

    Liu, Q.; Sun, D.; Li, N.; et al. Predicting EGFR mutation subtypes in lung adenocarcinoma using 18F-FDG PET/CT radiomic features. Transl. Lung Cancer Res. 2020, 9, 549–562. https://doi.org/10.21037/tlcr.2020.04.17.

  • 128.

    Chang, C.; Zhou, S.; Yu, H.; et al. A clinically practical radiomics-clinical combined model based on PET/CT data and nomogram predicts EGFR mutation in lung adenocarcinoma. Eur. Radiol. 2021, 31, 6259–6268. https://doi.org/10.1007/s00330-020-07676-x.

  • 129.

    Nair, J.K.R.; Saeed, U.A.; McDougall, C.C.; et al. Radiogenomic Models Using Machine Learning Techniques to Predict EGFR Mutations in Non-Small Cell Lung Cancer. Can. Assoc. Radiol. J. 2021, 72, 109–119. https://doi.org/10.1177/0846537119899526.

  • 130.

    Tan, J.L.; Xia, L.; Sun, S.G.; et al. Prediction of EGFR mutation status in lung adenocarcinoma based on 18F-FDG PET/CT radiomic features. Am. J. Nucl. Med. Mol. Imaging 2023, 13, 230–244.

  • 131.

    Zhang, T.; Liu, Z.; Lin, L.; et al. Detection of the gene mutation of epidermal growth factor receptor in lung adenocarcinoma by radiomic features from a small amount of PET data. Nucl. Med. Commun. 2023, 44, 795–802. https://doi.org/10.1097/mnm.0000000000001718.

  • 132.

    Ruan, D.; Fang, J.; Teng, X. Efficient 18F-fluorodeoxyglucose positron emission tomography/computed tomography-based machine learning model for predicting epidermal growth factor receptor mutations in non-small cell lung cancer. Q. J. Nucl. Med. Mol. Imaging 2024, 68, 70–83. https://doi.org/10.23736/s1824-4785.22.03441-0.

  • 133.

    Wang, Y.; Yang, G.; Gao, X.; et al. Subregion-specific 18F-FDG PET-CT radiomics for the pre-treatment prediction of EGFR mutation status in solid lung adenocarcinoma. Am. J. Nucl. Med. Mol. Imaging 2024, 14, 134–143. https://doi.org/10.62347/ddrr4923.

  • 134.

    Chang, C.; Sun, X.; Wang, G.; et al. A Machine Learning Model Based on PET/CT Radiomics and Clinical Characteristics Predicts ALK Rearrangement Status in Lung Adenocarcinoma. Front. Oncol. 2021, 11, 603882. https://doi.org/10.3389/fonc.2021.603882.

  • 135.

    Wang, J.; Lv, X.; Huang, W.; et al. Establishment and Optimization of Radiomics Algorithms for Prediction of KRAS Gene Mutation by Integration of NSCLC Gene Mutation Mutual Exclusion Information. Front. Pharmacol. 2022, 13, 862581. https://doi.org/10.3389/fphar.2022.862581.

  • 136.

    Zhang, R.; Shi, K.; Hohenforst-Schmidt, W.; et al. Ability of 18F-FDG Positron Emission Tomography Radiomics and Machine Learning in Predicting KRAS Mutation Status in Therapy-Naive Lung Adenocarcinoma. Cancers 2023, 15, 3684. https://doi.org/10.3390/cancers15143684.

  • 137.

    Hinzpeter, R.; Kulanthaivelu, R.; Kohan, A.; et al. Predictive [18F]-FDG PET/CT-Based Radiogenomics Modelling of Driver Gene Mutations in Non-small Cell Lung Cancer. Acad. Radiol. 2024, 31, 5314–5323. https://doi.org/10.1016/j.acra.2024.06.038.

  • 138.

    Li, J.; Ge, S.; Sang, S.; et al. Evaluation of PD-L1 Expression Level in Patients with Non-Small Cell Lung Cancer by 18F-FDG PET/CT Radiomics and Clinicopathological Characteristics. Front. Oncol. 2021, 11, 789014. https://doi.org/10.3389/fonc.2021.789014.

  • 139.

    Zhang, R.; Hohenforst-Schmidt, W.; Steppert, C.; et al. Standardized 18F-FDG PET/CT radiomic features provide information on PD-L1 expression status in treatment-naïve patients with non-small cell lung cancer. Nuklearmedizin 2022, 61, 385–393. https://doi.org/10.1055/a-1816-6950.

  • 140.

    Jiang, M.; Sun, D.; Guo, Y.; et al. Assessing PD-L1 Expression Level by Radiomic Features From PET/CT in Nonsmall Cell Lung Cancer Patients: An Initial Result. Acad. Radiol. 2020, 27, 171–179. https://doi.org/10.1016/j.acra.2019.04.016.

  • 141.

    Kiss, F.J.; Járó, A.I.; Máthé, D.; et al. Predicting PD-L1 expression status in NSCLC using radiomic analysis of 18 F-FDG-PET/CT images. Eur. J. Nucl. Med. Mol. Imaging 2026, 53, 800–811. https://doi.org/10.1007/s00259-025-07453-2.

  • 142.

    Ji, Y.; Cui, K.; Zhang, J.; et al. Noninvasive Prediction of Programmed Cell Death Protein-Ligand 1 Expression in Locally Advanced Non-small Cell Lung Cancer by 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography-Based Metabolic Habitats: A Multicenter Radiomic and Biological Study. Ann. Surg. Oncol. 2025, 32, 10094–10107. https://doi.org/10.1245/s10434-025-18139-2.

  • 143.

    Lim, C.H.; Koh, Y.W.; Hyun, S.H.; et al. A Machine Learning Approach Using PET/CT-based Radiomics for Prediction of PD-L1 Expression in Non-small Cell Lung Cancer. Anticancer Res. 2022, 42, 5875–5884. https://doi.org/10.21873/anticanres.16096.

  • 144.

    Wang, Y.B.; He, X.; Song, X.; et al. The radiomic biomarker in non-small cell lung cancer: 18F-FDG PET/CT characterisation of programmed death-ligand 1 status. Clin. Radiol. 2023, 78, e732–e740. https://doi.org/10.1016/j.crad.2023.06.003.

  • 145.

    Wang, Y.; Zhao, N.; Wu, Z.; et al. New insight on the correlation of metabolic status on 18F-FDG PET/CT with immune marker expression in patients with non-small cell lung cancer. Eur. J. Nucl. Med. Mol. Imaging 2020, 47, 1127–1136. https://doi.org/10.1007/s00259-019-04500-7.

  • 146.

    Wu, L.; Liu, J.; Wang, S.; et al. Negative Correlation Between 18F-RGD Uptake via PET and Tumoral PD-L1 Expression in Non-Small Cell Lung Cancer. Front. Endocrinol. 2022, 13, 913631. https://doi.org/10.3389/fendo.2022.913631.

  • 147.

    Wang, L.; Ruan, M.; Lei, B.; et al. The potential of 18F-FDG PET/CT in predicting PDL1 expression status in pulmonary lesions of untreated stage IIIB-IV non-small-cell lung cancer. Lung Cancer 2020, 150, 44–52.

  • 148.

    Zhou, J.; Zou, S.; Cheng, S.; et al. Correlation Between Dual-Time-Point FDG PET and Tumor Microenvironment Immune Types in Non-Small Cell Lung Cancer. Front. Oncol. 2021, 11, 559623. https://doi.org/10.3389/fonc.2021.559623.

  • 149.

    Cui, Y.; Lin, Y.; Zhao, Z.; et al. Comprehensive 18F-FDG PET-based radiomics in elevating the pathological response to neoadjuvant immunochemotherapy for resectable stage III non-small-cell lung cancer: A pilot study. Front. Immunol. 2022, 13, 994917. https://doi.org/10.3389/fimmu.2022.994917.

  • 150.

    Yang, M.; Li, X.; Cai, C.; et al. [18F]FDG PET-CT radiomics signature to predict pathological complete response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer: A multicenter study. Eur. Radiol. 2024, 34, 4352–4363. https://doi.org/10.1007/s00330-023-10503-8.

  • 151.

    Ahn, S.J.; Kwon, H.; Yang, J.J.; et al. Contrast-enhanced T1-weighted image radiomics of brain metastases may predict EGFR mutation status in primary lung cancer. Sci. Rep. 2020, 10, 8905. https://doi.org/10.1038/s41598-020-65470-7.

  • 152.

    Meißner, A.K.; Gutsche, R.; Galldiks, N.; et al. Radiomics for the non-invasive prediction of PD-L1 expression in patients with brain metastases secondary to non-small cell lung cancer. J. Neurooncol. 2023, 163, 597–605. https://doi.org/10.1007/s11060-023-04367-7.

  • 153.

    Hu, Y.; Geng, Y.; Wang, H.; et al. Improved Prediction of Epidermal Growth Factor Receptor Status by Combined Radiomics of Primary Nonsmall-Cell Lung Cancer and Distant Metastasis. J. Comput. Assist. Tomogr. 2024, 48, 780–788. https://doi.org/10.1097/rct.0000000000001591.

  • 154.

    Zhang, G.; Man, Q.; Shang, L.; et al. Using Multi-phase CT Radiomics Features to Predict EGFR Mutation Status in Lung Adenocarcinoma Patients. Acad. Radiol. 2024, 31, 2591–2600. https://doi.org/10.1016/j.acra.2023.12.024.

  • 155.

    Song, J.; Ding, C.; Huang, Q.; et al. Deep learning predicts epidermal growth factor receptor mutation subtypes in lung adenocarcinoma. Med. Phys. 2021, 48, 7891–7899. https://doi.org/10.1002/mp.15307.

  • 156.

    Deng, K.; Wang, L.; Liu, Y.; et al. A deep learning-based system for survival benefit prediction of tyrosine kinase inhibitors and immune checkpoint inhibitors in stage IV non-small cell lung cancer patients: A multicenter, prognostic study. EClinicalMedicine 2022, 51, 101541. https://doi.org/10.1016/j.eclinm.2022.101541.

  • 157.

    Xu, N.; Wang, J.; Dai, G.; et al. EfficientNet-Based System for Detecting EGFR-Mutant Status and Predicting Prognosis of Tyrosine Kinase Inhibitors in Patients with NSCLC. J. Imaging Inform. Med. 2024, 37, 1086–1099. https://doi.org/10.1007/s10278-024-01022-z.

  • 158.

    Dong, Y.; Hou, L.; Yang, W.; et al. Multi-channel multi-task deep learning for predicting EGFR and KRAS mutations of non-small cell lung cancer on CT images. Quant. Imaging Med. Surg. 2021, 11, 2354–2375. https://doi.org/10.21037/qims-20-600.

  • 159.

    Song, Z.; Liu, T.; Shi, L.; et al. The deep learning model combining CT image and clinicopathological information for predicting ALK fusion status and response to ALK-TKI therapy in non-small cell lung cancer patients. Eur. J. Nucl. Med. Mol. Imaging 2021, 48, 361–371. https://doi.org/10.1007/s00259-020-04986-6.

  • 160.

    Xiao, Z.; Cai, H.; Wang, Y.; et al. Deep learning for predicting epidermal growth factor receptor mutations of non-small cell lung cancer on PET/CT images. Quant. Imaging Med. Surg. 2023, 13, 1286–1299. https://doi.org/10.21037/qims-22-760.

  • 161.

    Zhang, B.; Qi, S.; Pan, X.; et al. Deep CNN Model Using CT Radiomics Feature Mapping Recognizes EGFR Gene Mutation Status of Lung Adenocarcinoma. Front. Oncol. 2021, 10, 598721. https://doi.org/10.3389/fonc.2020.598721.

  • 162.

    Zhang, G.; Shang, L.; Cao, Y.; et al. Prediction of epidermal growth factor receptor (EGFR) mutation status in lung adenocarcinoma patients on computed tomography (CT) images using 3-dimensional (3D) convolutional neural network. Quant. Imaging Med. Surg. 2024, 14, 6048–6059. https://doi.org/10.21037/qims-24-33.

  • 163.

    Shao, X.; Ge, X.; Gao, J.; et al. Transfer learning–based PET/CT three-dimensional convolutional neural network fusion of image and clinical information for prediction of EGFR mutation in lung adenocarcinoma. BMC Med. Imaging 2024, 24, 54. https://doi.org/10.1186/s12880-024-01232-5.

  • 164.

    Yoon, H.J.; Choi, J.; Kim, E.; et al. Deep learning analysis to predict EGFR mutation status in lung adenocarcinoma manifesting as pure ground-glass opacity nodules on CT. Front. Oncol. 2022, 12, 951575. https://doi.org/10.3389/fonc.2022.951575.

  • 165.

    Huang, X.; Sun, Y.; Tan, M.; et al. Three-Dimensional Convolutional Neural Network-Based Prediction of Epidermal Growth Factor Receptor Expression Status in Patients with Non-Small Cell Lung Cancer. Front. Oncol. 2022, 12, 772770. https://doi.org/10.3389/fonc.2022.772770.

  • 166.

    Mahajan, A.; Kania, V.; Agarwal, U.; et al. Deep-Learning-Based Predictive Imaging Biomarker Model for EGFR Mutation Status in Non-Small Cell Lung Cancer from CT Imaging. Cancers 2024, 16, 1130. https://doi.org/10.3390/cancers16061130.

  • 167.

    Yin, G.; Wang, Z.; Song, Y.; et al. Prediction of EGFR Mutation Status Based on 18F-FDG PET/CT Imaging Using Deep Learning-Based Model in Lung Adenocarcinoma. Front. Oncol. 2021, 11, 709137. https://doi.org/10.3389/fonc.2021.709137.

  • 168.

    Silva, F.; Pereira, T.; Morgado, J.; et al. EGFR Assessment in Lung Cancer CT Images: Analysis of Local and Holistic Regions of Interest Using Deep Unsupervised Transfer Learning. IEEE Access 2021, 9, 58667–58676. https://doi.org/10.1109/access.2021.3070701.

  • 169.

    Tian, P.; He, B.; Mu, W.; et al. Assessing PD-L1 expression in non-small cell lung cancer and predicting responses to immune checkpoint inhibitors using deep learning on computed tomography images. Theranostics 2021, 11, 2098–2107. https://doi.org/10.7150/thno.48027.

  • 170.

    He, B.; Dong, D.; She, Y.; et al. Predicting response to immunotherapy in advanced non-small-cell lung cancer using tumor mutational burden radiomic biomarker. J. Immunother. Cancer 2020, 8, e000550. https://doi.org/10.1136/jitc-2020-000550.

  • 171.

    Yuan, L.; Wang, Q.; Sun, F.; et al. Deep learning and inflammatory markers predict early response to immunotherapy in unresectable NSCLC: A multicenter study. Biomol. Biomed. 2025, 25, 2252–2268. https://doi.org/10.17305/bb.2025.12324.

  • 172.

    Zhu, Y.; Liu, Y.L.; Feng, Y.; et al. A CT-derived deep neural network predicts for programmed death ligand-1 expression status in advanced lung adenocarcinomas. Ann. Transl. Med. 2020, 8, 930. https://doi.org/10.21037/atm-19-4690.

  • 173.

    Liang, C.; Zheng, M.; Zou, H.; et al. Deep learning-based image analysis predicts PD-L1 status from 18F-FDG PET/CT images in non-small-cell lung cancer. Front. Oncol. 2024, 14, 1402994. https://doi.org/10.3389/fonc.2024.1402994.

  • 174.

    Saad, M.B.; Hong, L.; Aminu, M.; et al. Predicting benefit from immune checkpoint inhibitors in patients with non-small-cell lung cancer by CT-based ensemble deep learning: A retrospective study. Lancet Digit. Health 2023, 5, e404–e420. Correction in: Lancet Digit. Health 2023, 5, e403. https://doi.org/10.1016/s2589-7500(23)00082-1.

  • 175.

    Mu, W.; Jiang, L.; Shi, Y.; et al. Non-invasive measurement of PD-L1 status and prediction of immunotherapy response using deep learning of PET/CT images. J. Immunother. Cancer 2021, 9, e002118.

  • 176.

    Huang, X.; Huang, X.; Xie, Y.; et al. Integrative habitat analysis and multi-instance deep learning for predictive model of PD-1/PD-L1 immunotherapy efficacy in NSCLC patients: A dual-center retrospective study. BMC Med. Imaging 2025, 25, 288. https://doi.org/10.1186/s12880-025-01828-5.

  • 177.

    Pao, J.J.; Biggs, M.; Duncan, D.; et al. Predicting EGFR mutational status from pathology images using a real-world dataset. Sci. Rep. 2023, 13, 4404. https://doi.org/10.1038/s41598-023-31284-6.

  • 178.

    Zhao, D.; Zhao, Y.; He, S.; et al. High accuracy epidermal growth factor receptor mutation prediction via histopathological deep learning. BMC Pulm. Med. 2023, 23, 244. https://doi.org/10.1186/s12890-023-02537-x.

  • 179.

    Zanoletti, M.; Ugolini, F.; El Bachiri, L.; et al. EGFR Mutation Detection in Whole Slide Images of Non-Small Cell Lung Cancers Using a Two-Stage Deep Transfer Learning Approach. Cancer Med. 2025, 14, e71249. https://doi.org/10.1002/cam4.71249.

  • 180.

    Zhang, W.; Wang, W.; Xu, Y.; et al. Prediction of Epidermal Growth Factor Receptor Mutation Subtypes in Non–Small Cell Lung Cancer from Hematoxylin and Eosin–Stained Slides Using Deep Learning. Lab. Invest. 2024, 104, 102094. https://doi.org/10.1016/j.labinv.2024.102094.

  • 181.

    Terada, Y.; Takahashi, T.; Hayakawa, T.; et al. Artificial Intelligence–Powered Prediction of ALK Gene Rearrangement in Patients with Non–Small-Cell Lung Cancer. JCO Clin. Cancer Inform. 2022, 6, e2200070. Erratum in: JCO Clin. Cancer Inform. 2022, 6, e2200157. https://doi.org/10.1200/cci.22.00070.

  • 182.

    Wang, X.; Zhao, J.; Marostica, E.; et al. A pathology foundation model for cancer diagnosis and prognosis prediction. Nature 2024, 634, 970–978. https://doi.org/10.1038/s41586-024-07894-z.

  • 183.

    Cheng, G.; Zhang, F.; Xing, Y.; et al. Artificial Intelligence-Assisted Score Analysis for Predicting the Expression of the Immunotherapy Biomarker PD-L1 in Lung Cancer. Front. Immunol. 2022, 13, 893198. https://doi.org/10.3389/fimmu.2022.893198.

  • 184.

    Wu, J.; Liu, C.; Liu, X.; et al. Artificial intelligence-assisted system for precision diagnosis of PD-L1 expression in non-small cell lung cancer. Mod. Pathol. 2022, 35, 403–411. https://doi.org/10.1038/s41379-021-00904-9.

  • 185.

    Jain, M.S.; Massoud, T.F. Predicting tumour mutational burden from histopathological images using multiscale deep learning. Nat. Mach. Intell. 2020, 2, 356–362. https://doi.org/10.1038/s42256-020-0190-5.

  • 186.

    Sadhwani, A.; Chang, H.W.; Behrooz, A.; et al. Comparative analysis of machine learning approaches to classify tumor mutation burden in lung adenocarcinoma using histopathology images. Sci. Rep. 2021, 11, 16605. https://doi.org/10.1038/s41598-021-95747-4.

  • 187.

    Mayer, C.; Ofek, E.; Fridrich, D.E.; et al. Direct identification of ALK and ROS1 fusions in non-small cell lung cancer from hematoxylin and eosin-stained slides using deep learning algorithms. Mod. Pathol. 2022, 35, 1882–1887. https://doi.org/10.1038/s41379-022-01141-4.

  • 188.

    Niu, Y.; Wang, L.; Zhang, X.; et al. Predicting Tumor Mutational Burden From Lung Adenocarcinoma Histopathological Images Using Deep Learning. Front. Oncol. 2022, 12, 927426. https://doi.org/10.3389/fonc.2022.927426.

  • 189.

    Dammak, S.; Cecchini, M.J.; Breadner, D.; et al. Using deep learning to predict tumor mutational burden from scans of H&E-stained multicenter slides of lung squamous cell carcinoma. J. Med. Imaging 2023, 10, 017502. https://doi.org/10.1117/1.jmi.10.1.017502.

  • 190.

    Ishii, S.; Takamatsu, M.; Ninomiya, H.; et al. Machine learning-based gene alteration prediction model for primary lung cancer using cytologic images. Cancer Cytopathol. 2022, 130, 812–823. https://doi.org/10.1002/cncy.22609.

  • 191.

    Hondelink, L.M.; Hüyük, M.; Postmus, P.E.; et al. Development and validation of a supervised deep learning algorithm for automated whole-slide programmed death-ligand 1 tumour proportion score assessment in non-small cell lung cancer. Histopathology 2022, 80, 635–647. https://doi.org/10.1111/his.14571.

  • 192.

    Choi, S.; Cho, S.I.; Ma, M.; et al. Artificial intelligence–powered programmed death ligand 1 analyser reduces interobserver variation in tumour proportion score for non–small cell lung cancer with better prediction of immunotherapy response. Eur. J. Cancer 2022, 170, 17–26. https://doi.org/10.1016/j.ejca.2022.04.011.

  • 193.

    Liu, J.; Zheng, Q.; Mu, X.; et al. Automated tumor proportion score analysis for PD-L1 (22C3) expression in lung squamous cell carcinoma. Sci. Rep. 2021, 11, 15907. https://doi.org/10.1038/s41598-021-95372-1.

  • 194.

    Zhao, Y.; Xiong, S.; Ren, Q.; et al. Deep learning using histological images for gene mutation prediction in lung cancer: A multicentre retrospective study. Lancet Oncol. 2025, 26, 136–146. https://doi.org/10.1016/s1470-2045(24)00599-0.

  • 195.

    Wang, X.; Chen, P.; Ding, G.; et al. Dual-scale categorization based deep learning to evaluate programmed cell death ligand 1 expression in non-small cell lung cancer. Medicine 2021, 100, e25994. https://doi.org/10.1097/md.0000000000025994.

  • 196.

    Ligero, M.; Serna, G.; El Nahhas, O.S.M.; et al. Weakly Supervised Deep Learning Predicts Immunotherapy Response in Solid Tumors Based on PD-L1 Expression. Cancer Res. Commun. 2024, 4, 92–102. https://doi.org/10.1158/2767-9764.crc-23-0287.

  • 197.

    Kather, J.N.; Heij, L.R.; Grabsch, H.I.; et al. Pan-cancer image-based detection of clinically actionable genetic alterations. Nat. Cancer 2020, 1, 789–799. Correction in: Nat. Cancer 2020, 1, 1129. https://doi.org/10.1038/s43018-020-0087-6.

  • 198.

    Lu, M.Y.; Chen, T.Y.; Williamson, D.F.K.; et al. AI-based pathology predicts origins for cancers of unknown primary. Nature 2021, 594, 106–110. https://doi.org/10.1038/s41586-021-03512-4.

  • 199.

    Wang, Y.; Coudray, N.; Zhao, Y.; et al. HEAL: An automated deep learning framework for cancer histopathology image analysis. Bioinformatics 2021, 37, 4291–4295. https://doi.org/10.1093/bioinformatics/btab380.

  • 200.

    Huang, Z.; Chen, L.; Lv, L.; et al. A new AI-assisted scoring system for PD-L1 expression in NSCLC. Comput. Methods Programs Biomed. 2022, 221, 106829. https://doi.org/10.1016/j.cmpb.2022.106829.

  • 201.

    Campanella, G.; Kumar, N.; Nanda, S.; et al. Real-world deployment of a fine-tuned pathology foundation model for lung cancer biomarker detection. Nat. Med. 2025, 31, 3002–3010. https://doi.org/10.1038/s41591-025-03780-x.

  • 202.

    Li, Y.; Lv, X.; Chen, C.; et al. A deep learning model integrating multisequence MRI to predict EGFR mutation subtype in brain metastases from non-small cell lung cancer. Eur. Radiol. Exp. 2024, 8, 2. https://doi.org/10.1186/s41747-023-00396-z.

  • 203.

    You, S.; Fan, Y.; Yang, Z.; et al. Deep learning on brain metastasis for predicting EGFR genotype and EGFR-TKI therapy response in metastatic NSCLC: A multicenter study. Front. Bioeng. Biotechnol. 2025, 13, 1637095. https://doi.org/10.3389/fbioe.2025.1637095.

  • 204.

    Cao, P.; Jia, X.; Wang, X.; et al. Deep learning radiomics for the prediction of epidermal growth factor receptor mutation status based on MRI in brain metastasis from lung adenocarcinoma patients. BMC Cancer 2025, 25, 443. https://doi.org/10.1186/s12885-025-13823-8.

  • 205.

    Fang, Y.; Wang, M.; Song, Q.; et al. Tackling Tumor Heterogeneity Issue: Transformer-Based Multiple Instance Enhancement Learning for Predicting EGFR Mutation via CT Images. IEEE Trans. Med. Imaging 2025, 44, 4524–4535. https://doi.org/10.1109/TMI.2025.3578995.

  • 206.

    Xiang, J.; Wang, X.; Zhang, X.; et al. A vision–language foundation model for precision oncology. Nature 2025, 638, 769–778. https://doi.org/10.1038/s41586-024-08378-w.

  • 207.

    Shao, J.; Ma, J.; Zhang, S.; et al. Radiogenomic System for Non-Invasive Identification of Multiple Actionable Mutations and PD-L1 Expression in Non-Small Cell Lung Cancer Based on CT Images. Cancers 2022, 14, 4823. https://doi.org/10.3390/cancers14194823.

  • 208.

    Song, J.; Wang, L.; Ng, N.N.; et al. Development and Validation of a Machine Learning Model to Explore Tyrosine Kinase Inhibitor Response in Patients with Stage IV EGFR Variant–Positive Non–Small Cell Lung Cancer. JAMA Netw. Open 2020, 3, e2030442. https://doi.org/10.1001/jamanetworkopen.2020.30442.

  • 209.

    Zhao, S.; Li, W.; Liu, Z.; et al. End-to-End Prediction of EGFR Mutation Status with Denseformer. IEEE J. Biomed. Health Inform. 2024, 28, 54–65. https://doi.org/10.1109/jbhi.2023.3307295.

  • 210.

    Gui, D.; Song, Q.; Song, B.; et al. AIR-Net: A novel multi-task learning method with auxiliary image reconstruction for predicting EGFR mutation status on CT images of NSCLC patients. Comput. Biol. Med. 2022, 141, 105157. https://doi.org/10.1016/j.compbiomed.2021.105157.

  • 211.

    Feng, Y.; Song, F.; Zhang, P.; et al. Prediction of EGFR Mutation Status in Non–Small Cell Lung Cancer Based on Ensemble Learning. Front. Pharmacol. 2022, 13, 897597. https://doi.org/10.3389/fphar.2022.897597.

  • 212.

    Chen, S.; Han, X.; Tian, G.; et al. Using stacked deep learning models based on PET/CT images and clinical data to predict EGFR mutations in lung cancer. Front. Med. 2022, 9, 1041034. https://doi.org/10.3389/fmed.2022.1041034.

  • 213.

    Qin, R.; Wang, Z.; Qiao, K.; et al. Multi-Type Interdependent Feature Analysis Based on Hybrid Neural Networks for Computer-Aided Diagnosis of Epidermal Growth Factor Receptor Mutations. IEEE Access 2020, 8, 38517–38527. https://doi.org/10.1109/access.2020.2971281.

  • 214.

    Prelaj, A.; Galli, E.G.; Miskovic, V.; et al. Real-world data to build explainable trustworthy artificial intelligence models for prediction of immunotherapy efficacy in NSCLC patients. Front. Oncol. 2023, 12, 1078822. https://doi.org/10.3389/fonc.2022.1078822.

  • 215.

    Benfares, A.; Alami, B.; Boukansa, S.; et al. NSCLC EGFR Mutation Prediction via Random Forest Model: A Clinical–CT–Radiomics Integration Approach. Adv. Respir. Med. 2025, 93, 39. https://doi.org/10.3390/arm93050039.

  • 216.

    Qin, X.; Wang, H.; Hu, X.; et al. Predictive models for patients with lung carcinomas to identify EGFR mutation status via an artificial neural network based on multiple clinical information. J. Cancer Res. Clin. Oncol. 2020, 146, 767–775. https://doi.org/10.1007/s00432-019-03103-x.

  • 217.

    Wang, L.; Zhang, H.; Pan, C.; et al. Predicting Durable Responses to Immune Checkpoint Inhibitors in Non-Small-Cell Lung Cancer Using a Multi-Feature Model. Front. Immunol. 2022, 13, 829634. https://doi.org/10.3389/fimmu.2022.829634.

  • 218.

    Yao, X.; Zhu, Y.; Huang, Z.; et al. Fusion of shallow and deep features from 18F-FDG PET/CT for predicting EGFR-sensitizing mutations in non-small cell lung cancer. Quant. Imaging Med. Surg. 2024, 14, 5460–5472. https://doi.org/10.21037/qims-23-1028.

  • 219.

    Peng, J.; Zhang, J.; Zou, D.; et al. Deep learning to estimate durable clinical benefit and prognosis from patients with non-small cell lung cancer treated with PD-1/PD-L1 blockade. Front. Immunol. 2022, 13, 960459. https://doi.org/10.3389/fimmu.2022.960459.

  • 220.

    Zhang, X.; Zhang, G.; Qiu, X.; et al. Exploring non-invasive precision treatment in non-small cell lung cancer patients through deep learning radiomics across imaging features and molecular phenotypes. Biomark. Res. 2024, 12, 12. https://doi.org/10.1186/s40364-024-00561-5.

  • 221.

    Hao, P.; Yu, Y.; Huang, C.T.; et al. Advancing EGFR mutation subtypes prediction in NSCLC by combining 3D pretrained ConvNeXt, radiomics, and clinical features. Front. Oncol. 2024, 14, 1464555. https://doi.org/10.3389/fonc.2024.1464555.

  • 222.

    Gong, J.; Fu, F.; Ma, X.; et al. Hybrid deep multi-task learning radiomics approach for predicting EGFR mutation status of non-small cell lung cancer in CT images. Phys. Med. Biol. 2023, 68, 245021. https://doi.org/10.1088/1361-6560/ad0d43.

  • 223.

    Wu, J.; Meng, H.; Zhou, L.; et al. Habitat radiomics and deep learning fusion nomogram to predict EGFR mutation status in stage I non-small cell lung cancer: A multicenter study. Sci. Rep. 2024, 14, 15877. https://doi.org/10.1038/s41598-024-66751-1.

  • 224.

    Vanguri, R.S.; Luo, J.; Aukerman, A.T.; et al. Multimodal integration of radiology, pathology and genomics for prediction of response to PD-(L)1 blockade in patients with non-small cell lung cancer. Nat. Cancer 2022, 3, 1151–1164. https://doi.org/10.1038/s43018-022-00416-8.

  • 225.

    Kim, S.; Lim, J.H.; Kim, C.H.; et al. Deep learning–radiomics integrated noninvasive detection of epidermal growth factor receptor mutations in non-small cell lung cancer patients. Sci. Rep. 2024, 14, 922. https://doi.org/10.1038/s41598-024-51630-6.

  • 226.

    Huang, W.; Wang, J.; Wang, H.; et al. PET/CT Based EGFR Mutation Status Classification of NSCLC Using Deep Learning Features and Radiomics Features. Front. Pharmacol. 2022, 13, 898529. https://doi.org/10.3389/fphar.2022.898529.

  • 227.

    Zuo, Y.; Liu, Q.; Li, N.; et al. Optimal 18F-FDG PET/CT radiomics model development for predicting EGFR mutation status and prognosis in lung adenocarcinoma: A multicentric study. Front. Oncol. 2023, 13, 1173355. https://doi.org/10.3389/fonc.2023.1173355.

  • 228.

    Zuo, Y.; Liu, Q.; Li, N.; et al. Explainable 18F-FDG PET/CT radiomics model for predicting EGFR mutation status in lung adenocarcinoma: A two-center study. J. Cancer Res. Clin. Oncol. 2024, 150, 469. https://doi.org/10.1007/s00432-024-05998-7.

  • 229.

    Lu, Y.; Liu, F.; Yu, Y.; et al. AI-enabled molecular phenotyping and prognostic predictions in lung cancer through multimodal clinical information integration. Cell Rep. Med. 2025, 6, 102216. https://doi.org/10.1016/j.xcrm.2025.102216.

  • 230.

    Wang, C.; Ma, J.; Shao, J.; et al. Predicting EGFR and PD-L1 Status in NSCLC Patients Using Multitask AI System Based on CT Images. Front. Immunol. 2022, 13, 813072. https://doi.org/10.3389/fimmu.2022.813072.

  • 231.

    Wang, X.Y.; Wu, S.H.; Ren, J.; et al. Predicting Gene Comutation of EGFR and TP53 by Radiomics and Deep Learning in Patients with Lung Adenocarcinomas. J. Thorac. Imaging 2025, 40, e0817. https://doi.org/10.1097/rti.0000000000000817.

  • 232.

    Tan, X.; Li, Y.; Wang, S.; et al. Predicting EGFR mutation, ALK rearrangement, and uncommon EGFR mutation in NSCLC patients by driverless artificial intelligence: A cohort study. Respir. Res. 2022, 23, 132. https://doi.org/10.1186/s12931-022-02053-2.

  • 233.

    Ji, Y.; Ge, R.; Meng, W.; et al. Enhanced prediction of gene mutation and risk stratification in non-small-cell lung cancer through dual-pathway fusion of radiomics and pathomics. Front. Oncol. 2025, 15, 1646851. https://doi.org/10.3389/fonc.2025.1646851.

  • 234.

    Ai, X.; Jia, B.; He, Z.; et al. Noninvasive early identification of durable clinical benefit from immune checkpoint inhibition: A prospective multicenter study (NCT04566432). Signal Transduct. Target. Ther. 2024, 9, 350. https://doi.org/10.1038/s41392-024-02060-3.

  • 235.

    Mitra, J.; Ghose, S.; Thawani, R. Clinically Explainable Prediction of Immunotherapy Response Integrating Radiomics and Clinico-Pathological Information in Non-Small Cell Lung Cancer. Cancers 2025, 17, 2679. https://doi.org/10.3390/cancers17162679.

  • 236.

    Trivizakis, E.; Souglakos, J.; Karantanas, A.; et al. Deep Radiotranscriptomics of Non-Small Cell Lung Carcinoma for Assessing Molecular and Histology Subtypes with a Data-Driven Analysis. Diagnostics 2021, 11, 2383. https://doi.org/10.3390/diagnostics11122383.

  • 237.

    Shao, J.; Ma, J.; Zhang, Q.; et al. Predicting gene mutation status via artificial intelligence technologies based on multimodal integration (MMI) to advance precision oncology. Semin. Cancer Biol. 2023, 91, 1–15 https://doi.org/10.1016/j.semcancer.2023.02.006.

  • 238.

    Shao, J.; Ma, J.; Yu, Y.; et al. A multimodal integration pipeline for accurate diagnosis, pathogen identification, and prognosis prediction of pulmonary infections. Innovation 2024, 5, 100648. https://doi.org/10.1016/j.xinn.2024.100648.

  • 239.

    Liu, Z.; Lin, G.; Yan, Z.; et al. Predictive mutation signature of immunotherapy benefits in NSCLC based on machine learning algorithms. Front. Immunol. 2022, 13, 989275. https://doi.org/10.3389/fimmu.2022.989275.

  • 240.

    Shiri, I.; Maleki, H.; Hajianfar, G.; et al. Next-Generation Radiogenomics Sequencing for Prediction of EGFR and KRAS Mutation Status in NSCLC Patients Using Multimodal Imaging and Machine Learning Algorithms. Mol. Imaging Biol. 2020, 22, 1132–1148. https://doi.org/10.1007/s11307-020-01487-8.

  • 241.

    Wang, B.; Bao, C.; Wang, X.; et al. Inter-equipment validation of PET-based radiomics for predicting EGFR mutation statuses in patients with non-small cell lung cancer. Clin. Radiol. 2024, 79, 571–578. https://doi.org/10.1016/j.crad.2023.12.030.

  • 242.

    Yang, X.; Liu, M.; Ren, Y.; et al. Using contrast-enhanced CT and non-contrast-enhanced CT to predict EGFR mutation status in NSCLC patients—A radiomics nomogram analysis. Eur. Radiol. 2022, 32, 2693–2703. https://doi.org/10.1007/s00330-021-08366-y.

  • 243.

    Liu, H.; Shu, P.; Zhao, L.; et al. Machine learning approaches for EGFR mutation status prediction in NSCLC: An updated systematic review. Front. Oncol. 2025, 15, 1576461. https://doi.org/10.3389/fonc.2025.1576461.

  • 244.

    Li, B.; Su, J.; Liu, K.; et al. Deep learning radiomics model based on PET/CT predicts PD-L1 expression in non-small cell lung cancer. Eur. J. Radiol. Open 2024, 12, 100549. https://doi.org/10.1016/j.ejro.2024.100549.

  • 245.

    Yamazaki, M.; Yagi, T.; Tominaga, M.; et al. Role of intratumoral and peritumoral CT radiomics for the prediction of EGFR gene mutation in primary lung cancer. Br. J. Radiol. 2022, 95, 20220374. https://doi.org/10.1259/bjr.20220374.

  • 246.

    Cheng, Y.; Wang, H.; Yuan, W.; et al. Combined radiomics of primary tumour and bone metastasis improve the prediction of EGFR mutation status and response to EGFR-TKI therapy for NSCLC. Phys. Med. 2023, 116, 103177. https://doi.org/10.1016/j.ejmp.2023.103177.

  • 247.

    Rinaldi, L.; Guerini Rocco, E.; Spitaleri, G.; et al. Association between Contrast-Enhanced Computed Tomography Radiomic Features, Genomic Alterations and Prognosis in Advanced Lung Adenocarcinoma Patients. Cancers 2023, 15, 4553. https://doi.org/10.3390/cancers15184553.

  • 248.

    Yang, Y.; Yang, J.; Liang, Y.; et al. Identification and Validation of Efficacy of Immunological Therapy for Lung Cancer from Histopathological Images Based on Deep Learning. Front. Genet. 2021, 12, 642981. https://doi.org/10.3389/fgene.2021.642981.

  • 249.

    Hashimoto, K.; Murakami, Y.; Omura, K.; et al. Prediction of Tumor PD-L1 Expression in Resectable Non-Small Cell Lung Cancer by Machine Learning Models Based on Clinical and Radiological Features: Performance Comparison with Preoperative Biopsy. Clin. Lung Cancer 2024, 25, e26–e34.e6. https://doi.org/10.1016/j.cllc.2023.08.010.

  • 250.

    Chen, L.; Chen, L.; Ni, H.; et al. Prediction of CD3 T cells and CD8 T cells expression levels in non-small cell lung cancer based on radiomic features of CT images. Front. Oncol. 2023, 13, 1104316. https://doi.org/10.3389/fonc.2023.1104316.

  • 251.

    Fuster-Matanzo, A.; Picó-Peris, A.; Bellvís-Bataller, F.; et al. Prediction of oncogene mutation status in non-small cell lung cancer: A systematic review and meta-analysis with a special focus on artificial intelligence-based methods. Eur. Radiol. 2026, 36, 2157–2185. https://doi.org/10.1007/s00330-025-11962-x.

  • 252.

    Parra-Medina, R.; Guerron-Gomez, G.; Mendivelso-González, D.; et al. Deep learning in histopathology images for prediction of oncogenic driver molecular alterations in lung cancer: A systematic review and meta-analysis. Transl. Lung Cancer Res. 2025, 14, 1756–1769. https://doi.org/10.21037/tlcr-2024-1196.

  • 253.

    Zheng, T.; Li, X.; Zhou, L.; et al. Predictive value of machine learning for PD-L1 expression in NSCLC: A systematic review and meta-analysis. World J. Surg. Oncol. 2025, 23, 199. https://doi.org/10.1186/s12957-025-03847-6.

  • 254.

    Wang, T.W.; Hsu, M.S.; Lin, Y.H.; et al. Application of Radiomics in Prognosing Lung Cancer Treated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: A Systematic Review and Meta-Analysis. Cancers 2023, 15, 3542. https://doi.org/10.3390/cancers15143542.

  • 255.

    Singhal, K.; Azizi, S.; Tu, T.; et al. Large language models encode clinical knowledge. Nature 2023, 620, 172–180. Correction in: Nature 2023, 620, E19. https://doi.org/10.1038/s41586-023-06291-2.

  • 256.

    Jee, J.; Fong, C.; Pichotta, K.; et al. Automated real-world data integration improves cancer outcome prediction. Nature 2024, 636, 728–736. https://doi.org/10.1038/s41586-024-08167-5.

  • 257.

    Park, H.J.; Huh, J.Y.; Chae, G.; et al. Extraction of clinical data on major pulmonary diseases from unstructured radiologic reports using a large language model. PLoS ONE 2024, 19, e0314136. https://doi.org/10.1371/journal.pone.0314136.

Share this article:
How to Cite
Zhang, B.; Teng, J.; Lu, S. Research Progress on AI-Driven Biomarker Prediction in Non-Small Cell Lung Cancer. AI Medicine 2026, 3 (2), 11. https://doi.org/10.53941/aim.2026.100011.
RIS
BibTex
Copyright & License
article copyright Image
Copyright (c) 2026 by the authors.
Article Metrics
55
Article Views
0
Citations