Risk factors of metachronous brain metastasis in patients with EGFR-mutated advanced non-small cell lung cancer

被引:20
作者
Ouyang, Wen [1 ]
Yu, Jing [1 ]
Zhou, Yan [1 ]
Hu, Jing [1 ]
Huang, Zhao [1 ]
Zhang, Junhong [1 ,2 ,3 ]
Xie, Conghua [1 ,2 ,3 ]
机构
[1] Wuhan Univ, Dept Radiat & Med Oncol, Zhongnan Hosp, 169 Donghu Rd, Wuhan 430071, Hubei, Peoples R China
[2] Wuhan Univ, Hubei Key Lab Tumor Biol Behav, Zhongnan Hosp, Wuhan, Peoples R China
[3] Wuhan Univ, Hubei Clin Canc Study Ctr, Zhongnan Hosp, Wuhan, Peoples R China
基金
中国国家自然科学基金;
关键词
Non-small cell lung cancer; Epidermal growth factor receptor; Brain metastases; Risk factor; OSIMERTINIB; THERAPY; TKI; INHIBITORS; GEFITINIB; ERLOTINIB; FAILURE; RTOG; RPA;
D O I
10.1186/s12885-020-07202-8
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BackgroundNSCLC patients with EGFR mutation were at a higher incidence of developing brain metastasis (BM). Patients with BM are associated with high mortality. Reducing BM incidence becomes increasingly significant for NSCLC patients to achieve prolonged survival. The aim of the study was to explore the possible risk factors of developing metachronous BM during EGFR-TKIs treatment, and to identify the potential candidates for prophylactic cranial irradiation (PCI) or the first-line Osimertinib treatment.MethodsA total of 157 consecutive EGFR-mutated advanced NSCLC patients without BM at initial diagnosis in our institution from 2012 and 2018 were retrospectively reviewed. Comparisons of OS were performed based on BM status. The cumulative incidence of metachronous BM was calculated by the Kaplan-Meier method, and the independent risk factors of metachronous BM were investigated by multivariate analysis.ResultsPatients developing metachronous BM had worse survival (mOS: 22.1months) than patients not-developing BM (mOS: 44.8months). Moreover, the multivariate analysis indicated that age <= 49years (P=0.035), number of extracranial metastases (P=0.013), and malignant pleural effusion (P=0.002) were independent risk factors of metachronous BM. Furthermore, the 1-year actuarial incidence of developing metachronous BM in patients with no risk factor (n=101), 1 risk factor (n=46), and 2 risk factors (n=10) were 7.01, 14.61, and 43.75%, respectively (P<0.001).ConclusionsPatients developing metachronous BM during EGFR-TKIs treatment have worse outcomes. Our results suggested that EGFR-mutated advanced NSCLC patients with <greater than or equal to>1 risk factors were candidates for PCI or the first-line Osimertinib treatment.
引用
收藏
页数:11
相关论文
共 35 条
[1]   Risk factors for brain metastases in patients with non-small-cell lung cancer [J].
An, Ning ;
Jing, Wang ;
Wang, Haoyi ;
Li, Ji ;
Liu, Yang ;
Yu, Jinming ;
Zhu, Hui .
CANCER MEDICINE, 2018, 7 (12) :6357-6364
[2]   Long-term survival in patients with non-small cell lung cancer and synchronous brain metastasis treated with whole-brain radiotherapy and thoracic chemoradiation [J].
Arrieta, Oscar ;
Villarreal-Garza, Cynthia ;
Zamora, Jesus ;
Blake-Cerda, Monika ;
de la Mata, Maria D. ;
Zavala, Diego G. ;
Muniz-Hernandez, Sae ;
de la Garza, Jaime .
RADIATION ONCOLOGY, 2011, 6
[3]   Brain metastasis development and poor survival associated with carcinoembryonic antigen (CEA) level in advanced non-small cell lung cancer: a prospective analysis [J].
Arrieta, Oscar ;
Saavedra-Perez, David ;
Kuri, Roberto ;
Aviles-Salas, Alejandro ;
Martinez, Luis ;
Mendoza-Posada, Daniel ;
Castillo, Patricia ;
Astorga, Alma ;
Guzman, Enrique ;
De la Garza, Jaime .
BMC CANCER, 2009, 9
[4]   Preclinical Comparison of Osimertinib with Other EGFR-TKIs in EGFR-Mutant NSCLC Brain Metastases Models, and Early Evidence of Clinical Brain Metastases Activity [J].
Ballard, Peter ;
Yates, James W. T. ;
Yang, Zhenfan ;
Kim, Dong-Wan ;
Yang, James Chih-Hsin ;
Cantarini, Mireille ;
Pickup, Kathryn ;
Jordan, Angela ;
Hickey, Mike ;
Grist, Matthew ;
Box, Matthew ;
Johnstrom, Peter ;
Varnas, Katarina ;
Malmquist, Jonas ;
Thress, Kenneth S. ;
Janne, Pasi A. ;
Cross, Darren .
CLINICAL CANCER RESEARCH, 2016, 22 (20) :5130-5140
[5]   Routine molecular profiling of patients with advanced non-small-cell lung cancer: results of a 1-year nationwide programme of the French Cooperative Thoracic Intergroup (IFCT) [J].
Barlesi, Fabrice ;
Mazieres, Julien ;
Merlio, Jean-Philippe ;
Debieuvre, Didier ;
Mosser, Jean ;
Lena, Herve ;
Ouafik, L'Houcine ;
Besse, Benjamin ;
Rouquette, Isabelle ;
Westeel, Virginie ;
Escande, Fabienne ;
Monnet, Isabelle ;
Lemoine, Antoinette ;
Veillon, Remi ;
Blons, Helene ;
Audigier-Valette, Clarisse ;
Bringuier, Pierre-Paul ;
Lamy, Regine ;
Beau-Faller, Michele ;
Pujol, Jean-Louis ;
Sabourin, Jean-Christophe ;
Penault-Llorca, Frederique ;
Denis, Marc G. ;
Lantuejoul, Sylvie ;
Morin, Franck ;
Quan Tran ;
Missy, Pascale ;
Langlais, Alexandra ;
Milleron, Bernard ;
Cadranel, Jacques ;
Soria, Jean-Charles ;
Zalcman, Gerard .
LANCET, 2016, 387 (10026) :1415-1426
[6]  
Bhatt VR, 2017, J GLOB ONCOL, V3, P208, DOI 10.1200/JGO.2016.003392
[7]  
Camp Robert L, 2004, Clin Cancer Res, V10, P7252
[8]   Serum Tumor Markers CEA, CYFRA21-1, and CA-125 Are Associated With Worse Prognosis In Advanced Non-Small-Cell Lung Cancer (NSCLC) [J].
Cedres, Susana ;
Nunez, Isaac ;
Longo, Marina ;
Martinez, Pablo ;
Checa, Eva ;
Torrejon, Davis ;
Felip, Enriqueta .
CLINICAL LUNG CANCER, 2011, 12 (03) :172-179
[9]   Brain metastases in locally advanced nonsmall cell lung carcinoma after multimodality treatment -: Risk factors analysis [J].
Ceresoli, GL ;
Reni, M ;
Chiesa, G ;
Carretta, A ;
Schipani, S ;
Passoni, P ;
Bolognesi, A ;
Zannini, P ;
Villa, E .
CANCER, 2002, 95 (03) :605-612
[10]   AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer [J].
Cross, Darren A. E. ;
Ashton, Susan E. ;
Ghiorghiu, Serban ;
Eberlein, Cath ;
Nebhan, Caroline A. ;
Spitzler, Paula J. ;
Orme, Jonathon P. ;
Finlay, M. Raymond V. ;
Ward, Richard A. ;
Mellor, Martine J. ;
Hughes, Gareth ;
Rahi, Amar ;
Jacobs, Vivien N. ;
Brewer, Monica Red ;
Ichihara, Eiki ;
Sun, Jing ;
Jin, Hailing ;
Ballard, Peter ;
Al-Kadhimi, Katherine ;
Rowlinson, Rachel ;
Klinowska, Teresa ;
Richmond, Graham H. P. ;
Cantarini, Mireille ;
Kim, Dong-Wan ;
Ranson, Malcolm R. ;
Pao, William .
CANCER DISCOVERY, 2014, 4 (09) :1046-1061