The Radiological Characteristics, Tertiary Lymphoid Structures, and Survival Status Associated with EGFR Mutation in Patients with Subsolid Nodules Like Stage I-II LUAD

Overview

Journal BMC Cancer

Publisher Biomed Central

Specialty Oncology

Date 2024 Mar 26

PMID 38528507

Authors

Mei Xie

Jie Gao

Xidong Ma

Jialin Song

Chongchong Wu

Yangyu Zhou

Tianjiao Jiang

Yiran Liang

Chen Yang

Xinyu Bao

Xin Zhang

Jie Yao

Ying Jing

Jianlin Wu

Jianxin Wang

Xinying Xue

Affiliations

Soon will be listed here.

Abstract

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) recommended for the patients with subsolid nodule in early lung cancer stage is not routinely. The clinical value and impact in patients with EGFR mutation on survival outcomes is further needed to be elucidated to decide whether the application of EGFR-TKIs was appropriate in early lung adenocarcinoma (LUAD) stage appearing as subsolid nodules.

Materials And Methods: The inclusion of patients exhibiting clinical staging of IA-IIB subsolid nodules. Clinical information, computed tomography (CT) features before surgical resection and pathological characteristics including tertiary lymphoid structures of the tumors were recorded for further exploration of correlation with EGFR mutation and prognosis.

Results: Finally, 325 patients were enrolled into this study, with an average age of 56.8 ± 9.8 years. There are 173 patients (53.2%) harboring EGFR mutation. Logistic regression model analysis showed that female (OR = 1.944, p = 0.015), mix ground glass nodule (OR = 2.071, p = 0.003, bubble-like lucency (OR = 1.991, p = 0.003) were significant risk factors of EGFR mutations. Additionally, EGFR mutations were negatively correlated with TLS presence and density. Prognosis analysis showed that the presence of TLS was associated with better recurrence-free survival (RFS)(p = 0.03) while EGFR mutations were associated with worse RFS(p = 0.01). The RFS in patients with TLS was considerably excel those without TLS within EGFR wild type group(p = 0.018). Multivariate analyses confirmed that EGFR mutation was an independent prognostic predictor for RFS (HR = 3.205, p = 0.037).

Conclusions: In early-phase LUADs, subsolid nodules with EGFR mutation had specific clinical and radiological signatures. EGFR mutation was associated with worse survival outcomes and negatively correlated with TLS, which might weaken the positive impact of TLS on prognosis. Highly attention should be paid to the use of EGFR-TKI for further treatment as agents in early LUAD patients who carrying EGFR mutation.

Citing Articles

A novel hybrid model for predicting tertiary lymphoid structures and targeted immunotherapy outcomes in hepatocellular carcinoma: a multicenter retrospective study.

Li Y, Li X, Xiao X, Cheng J, Li Q, Liu C Eur Radiol. 2024; .

PMID: 39658681 DOI: 10.1007/s00330-024-11255-9.

Inflammation, tertiary lymphoid structures, and lung cancer: a bibliometric analysis.

Liu X, Liu H, Huang L, Lin L, Cai Q, Xiang Y Transl Lung Cancer Res. 2024; 13(10):2636-2648.

PMID: 39507023 PMC: 11535850. DOI: 10.21037/tlcr-24-350.

References

Zhang G, Zhang J, Cao Y, Zhao Z, Li S, Deng L . Nomogram based on preoperative CT imaging predicts the EGFR mutation status in lung adenocarcinoma. Transl Oncol. 2020; 14(1):100954. PMC: 7691609. DOI: 10.1016/j.tranon.2020.100954. View

Koch A, Vellanki P, Drezner N, Li X, Mishra-Kalyani P, Shen Y . FDA Approval Summary: Osimertinib for Adjuvant Treatment of Surgically Resected Non-Small Cell Lung Cancer, a Collaborative Project Orbis Review. Clin Cancer Res. 2021; 27(24):6638-6643. DOI: 10.1158/1078-0432.CCR-21-1034. View

Hirsch F, Suda K, Wiens J, Bunn Jr P . New and emerging targeted treatments in advanced non-small-cell lung cancer. Lancet. 2016; 388(10048):1012-24. DOI: 10.1016/S0140-6736(16)31473-8. View

Tsuboi M, Weder W, Escriu C, Blakely C, He J, Dacic S . Neoadjuvant osimertinib with/without chemotherapy versus chemotherapy alone for -mutated resectable non-small-cell lung cancer: NeoADAURA. Future Oncol. 2021; 17(31):4045-4055. PMC: 8530153. DOI: 10.2217/fon-2021-0549. View

Yoshioka H, Shimokawa M, Seto T, Morita S, Yatabe Y, Okamoto I . Final overall survival results of WJTOG3405, a randomized phase III trial comparing gefitinib versus cisplatin with docetaxel as the first-line treatment for patients with stage IIIB/IV or postoperative recurrent EGFR mutation-positive.... Ann Oncol. 2019; 30(12):1978-1984. DOI: 10.1093/annonc/mdz399. View

Yang L, He Y, Dong S, Wei X, Chen Z, Zhang B . Single-cell transcriptome analysis revealed a suppressive tumor immune microenvironment in EGFR mutant lung adenocarcinoma. J Immunother Cancer. 2022; 10(2). PMC: 8830346. DOI: 10.1136/jitc-2021-003534. View

Gao J, Rizzo S, Ma L, Qiu X, Warth A, Seki N . Pulmonary ground-glass opacity: computed tomography features, histopathology and molecular pathology. Transl Lung Cancer Res. 2017; 6(1):68-75. PMC: 5344841. DOI: 10.21037/tlcr.2017.01.02. View

Chen P, Liu Y, Wen Y, Zhou C . Non-small cell lung cancer in China. Cancer Commun (Lond). 2022; 42(10):937-970. PMC: 9558689. DOI: 10.1002/cac2.12359. View

Lindeman N, Cagle P, Aisner D, Arcila M, Beasley M, Bernicker E . Updated Molecular Testing Guideline for the Selection of Lung Cancer Patients for Treatment With Targeted Tyrosine Kinase Inhibitors: Guideline From the College of American Pathologists, the International Association for the Study of Lung Cancer,.... Arch Pathol Lab Med. 2018; 142(3):321-346. DOI: 10.5858/arpa.2017-0388-CP. View

10.

Papadimitrakopoulou V, Mok T, Han J, Ahn M, Delmonte A, Ramalingam S . Osimertinib versus platinum-pemetrexed for patients with EGFR T790M advanced NSCLC and progression on a prior EGFR-tyrosine kinase inhibitor: AURA3 overall survival analysis. Ann Oncol. 2020; 31(11):1536-1544. DOI: 10.1016/j.annonc.2020.08.2100. View

11.

Zhai H, Zhong W, Yang X, Wu Y . Neoadjuvant and adjuvant epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy for lung cancer. Transl Lung Cancer Res. 2015; 4(1):82-93. PMC: 4367710. DOI: 10.3978/j.issn.2218-6751.2014.11.08. View

12.

Lee C, Davies L, Wu Y, Mitsudomi T, Inoue A, Rosell R . Gefitinib or Erlotinib vs Chemotherapy for EGFR Mutation-Positive Lung Cancer: Individual Patient Data Meta-Analysis of Overall Survival. J Natl Cancer Inst. 2017; 109(6). DOI: 10.1093/jnci/djw279. View

13.

Schumacher T, Thommen D . Tertiary lymphoid structures in cancer. Science. 2022; 375(6576):eabf9419. DOI: 10.1126/science.abf9419. View

14.

Suda K, Mitsudomi T, Shintani Y, Okami J, Ito H, Ohtsuka T . Clinical Impacts of EGFR Mutation Status: Analysis of 5780 Surgically Resected Lung Cancer Cases. Ann Thorac Surg. 2020; 111(1):269-276. DOI: 10.1016/j.athoracsur.2020.05.041. View

15.

Friedlaender A, Addeo A, Russo A, Gregorc V, Cortinovis D, Rolfo C . Targeted Therapies in Early Stage NSCLC: Hype or Hope?. Int J Mol Sci. 2020; 21(17). PMC: 7504271. DOI: 10.3390/ijms21176329. View

16.

Wu Y, Tsuboi M, He J, John T, Grohe C, Majem M . Osimertinib in Resected -Mutated Non-Small-Cell Lung Cancer. N Engl J Med. 2020; 383(18):1711-1723. DOI: 10.1056/NEJMoa2027071. View

17.

Pi C, Xu C, Zhang M, Peng X, Wei X, Gao X . EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China. Thorac Cancer. 2018; 9(7):814-819. PMC: 6026603. DOI: 10.1111/1759-7714.12651. View

18.

Nicholson A, Tsao M, Beasley M, Borczuk A, Brambilla E, Cooper W . The 2021 WHO Classification of Lung Tumors: Impact of Advances Since 2015. J Thorac Oncol. 2021; 17(3):362-387. DOI: 10.1016/j.jtho.2021.11.003. View

19.

Saito M, Suzuki H, Kono K, Takenoshita S, Kohno T . Treatment of lung adenocarcinoma by molecular-targeted therapy and immunotherapy. Surg Today. 2017; 48(1):1-8. DOI: 10.1007/s00595-017-1497-7. View

20.

Sautes-Fridman C, Petitprez F, Calderaro J, Fridman W . Tertiary lymphoid structures in the era of cancer immunotherapy. Nat Rev Cancer. 2019; 19(6):307-325. DOI: 10.1038/s41568-019-0144-6. View