The prognostic and predictive value of solid subtype in invasive lung adenocarcinoma

Yang Zhang, Jing Li, Rui Wang, Yuan Li, Yunjian Pan, Deng Cai, Haichuan Hu, Hang Li, Ting Ye, Xiaoyang Luo, Yiliang Zhang, Bin Li, Lei Shen, Yihua Sun, Haiquan Chen, Yang Zhang, Jing Li, Rui Wang, Yuan Li, Yunjian Pan, Deng Cai, Haichuan Hu, Hang Li, Ting Ye, Xiaoyang Luo, Yiliang Zhang, Bin Li, Lei Shen, Yihua Sun, Haiquan Chen

Abstract

A total of 1039 stage I-III invasive lung adenocarcinoma including 186 solid subtype patients who have undergone radical resection were assessed for clinicopathologic characteristics, status of common driver mutations, pattern of recurrence, recurrence-free survival (RFS), overall survival (OS), post-recurrence survival (PRS) and predictive value for adjuvant chemotherapy and EGFR tyrosine kinase inhibitors (TKIs). Solid predominant adenocarcinomas were more likely to have initial distant recurrences than non-solid subtype invasive adenocarcinomas (P = 0.018). In univariate analysis, solid predominant adenocarcinoma patients had significantly worse RFS (P < 0.001), OS (P < 0.001) and PRS (P = 0.010). Multivariate analysis adjusting for clinicopathologic variables and mutational status showed that solid subtype was an independent poor prognostic factor (odds ratio = 1.876, 95% confidence interval: 1.291-3.158; P = 0.003) and an independent negative predictor for stage II-III patients undergoing adjuvant chemotherapy (odds ratio = 2.020, 95% confidence interval: 1.291-3.158; P = 0.002). In EGFR-mutated solid predominant lung adenocarcinoma patients who experienced disease recurrence, the response rate to EGFR TKIs was only 37.5%. In radically resected invasive lung adenocarcinoma, solid subtype was an independent poor prognostic factor and negative predictor for adjuvant chemotherapy.

Figures

Figure 1. Recurrence-free survival (RFS) and overall…
Figure 1. Recurrence-free survival (RFS) and overall survival (OS) of all patients (A and B), stage I patients (C and D), stage II-III patients (E and F) and stage II-III patients undergoing postoperative adjuvant chemotherapy (G and H) between solid and non-solid predominant lung adenocarcinoma.
Figure 2. Post-recurrence survival (PRS) between solid…
Figure 2. Post-recurrence survival (PRS) between solid and non-solid predominant lung adenocarcinoma.

References

    1. Travis W. D. et al. International association for the study of lung cancer/american thoracic society/european respiratory society international multidisciplinary classification of lung adenocarcinoma. J Thorac Oncol 6, 244–285 (2011).
    1. Hung J. J. et al. Predictive Value of the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society Classification of Lung Adenocarcinoma in Tumor Recurrence and Patient Survival. J Clin Oncol (2014).
    1. Campos-Parra A. D. et al. Relevance of the novel IASLC/ATS/ERS classification of lung adenocarcinoma in advanced disease. Eur Respir J 5, 1439–1447 (2014).
    1. Yoshizawa A. et al. Validation of the IASLC/ATS/ERS lung adenocarcinoma classification for prognosis and association with EGFR and KRAS gene mutations: analysis of 440 Japanese patients. J Thorac Oncol 8, 52–61 (2013).
    1. Russell P. A. et al. Correlation of mutation status and survival with predominant histologic subtype according to the new IASLC/ATS/ERS lung adenocarcinoma classification in stage III (N2) patients. J Thorac Oncol 8, 461–468 (2013).
    1. Hung J. J. et al. Prognostic value of the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society lung adenocarcinoma classification on death and recurrence in completely resected stage I lung adenocarcinoma. Ann Surg 258, 1079–1086 (2013).
    1. Warth A. et al. The novel histologic International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society classification system of lung adenocarcinoma is a stage-independent predictor of survival. J Clin Oncol 30, 1438–1446 (2012).
    1. Yoshizawa A. et al. Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases. Mod Pathol 24, 653–664 (2011).
    1. Zhang Y. et al. Frequency of driver mutations in lung adenocarcinoma from female never-smokers varies with histologic subtypes and age at diagnosis. Clin Cancer Res 18, 1947–1953 (2012).
    1. Cha M. J. et al. Micropapillary and solid subtypes of invasive lung adenocarcinoma: clinical predictors of histopathology and outcome. J Thorac Cardiovasc Surg 147, 921–928 e922 (2014).
    1. Xu L., Tavora F. & Burke A. Histologic features associated with metastatic potential in invasive adenocarcinomas of the lung. Am J Surg Pathol 37, 1100–1108 (2013).
    1. Russell P. A. et al. Does lung adenocarcinoma subtype predict patient survival?: A clinicopathologic study based on the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society international multidisciplinary lung adenocarcinoma classification. J Thorac Oncol 6, 1496–1504 (2011).
    1. Sakurai H. et al. Differences in the prognosis of resected lung adenocarcinoma according to the histological subtype: a retrospective analysis of Japanese lung cancer registry data. Eur J Cardiothorac Surg 45, 100–107 (2014).
    1. Yoshida T. et al. Solid predominant histology predicts EGFR tyrosine kinase inhibitor response in patients with EGFR mutation-positive lung adenocarcinoma. J Cancer Res Clin Oncol 139, 1691–1700 (2013).
    1. Woo T. et al. Prognostic value of the IASLC/ATS/ERS classification of lung adenocarcinoma in stage I disease of Japanese cases. Pathol Int 62, 785–791 (2012).
    1. de Bruin E. C. et al. Reduced NF1 expression confers resistance to EGFR inhibition in lung cancer. Cancer Discov 4, 606–619 (2014).
    1. Cancer Genome Atlas Research N. Comprehensive molecular profiling of lung adenocarcinoma. Nature 511, 543–550 (2014).
    1. Detterbeck F. C., Boffa D. J. & Tanoue L. T. The new lung cancer staging system. Chest 136, 260–271 (2009).
    1. Pan Y. et al. ALK, ROS1 and RET fusions in 1139 lung adenocarcinomas: A comprehensive study of common and fusion pattern-specific clinicopathologic, histologic and cytologic features. Lung Cancer 2, 121–126 (2014).
    1. Wang R. et al. RET fusions define a unique molecular and clinicopathologic subtype of non-small-cell lung cancer. J Clin Oncol 30, 4352–4359 (2012).

Source: PubMed

Szponzorok és közreműködők

Egészségi állapot

Kábítószer-beavatkozások

3
Iratkozz fel