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Primary Tumor Radiotherapy During EGFR-TKI Disease Control Improves Survival of Treatment Naïve Advanced EGFR-Mutant Lung Adenocarcinoma Patients

Authors Hsu KH, Huang JW, Tseng JS, Chen KW, Weng YC, Yu SL, Yang TY, Huang YH, Chen JJW, Chen KC, Chang GC

Received 3 January 2021

Accepted for publication 10 March 2021

Published 25 March 2021 Volume 2021:14 Pages 2139—2148

DOI https://doi.org/10.2147/OTT.S300267

Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Professor Gaetano Romano


Kuo-Hsuan Hsu,1,2,* Jing-Wen Huang,2,3,* Jeng-Sen Tseng,2,4,5 Kuan-Wen Chen,6 Yih-Chyang Weng,7 Sung-Liang Yu,8– 12 Tsung-Ying Yang,4,5 Yen-Hsiang Huang,2,4 Jeremy JW Chen,2 Kun-Chieh Chen,4,13– 15 Gee-Chen Chang2,4,5,13– 15

1Division of Critical Care and Respiratory Therapy, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 2Institute of Biomedical Sciences, College of Life Sciences, National Chung Hsing University, Taichung, Taiwan; 3Department of Radiation Oncology, Taichung Veterans General Hospital, Taichung, Taiwan; 4Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 5Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; 6Department of Radiation Oncology, Taichung Tzu-Chi Hospital, Buddhist Tzu-Chi Medical Foundation, Taichung, Taiwan; 7Radiation Oncology, Nantou Hospital of Ministry of Health and Welfare, Nantou City, Taiwan; 8Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan; 9Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan; 10Center of Genomic Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; 11Department of Pathology and Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan; 12Center for Optoelectronic Biomedicine, College of Medicine, National Taiwan University, Taipei, Taiwan; 13Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan; 14Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 15School of Medicine, Chung Shan Medical University, Taichung, Taiwan

*These authors contributed equally to this work

Correspondence: Gee-Chen Chang; Kun-Chieh Chen
Division of Pulmonary Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, No. 110, Sec. 1, Jianguo N. Road, Taichung, 402, Taiwan, Republic of China
Tel +886-4-24739595 ext. 34412
Fax +886-4-24739595 #34710
Email [email protected]; [email protected]

Background: Whether radiotherapy only for primary lung tumor (RTPLT) after epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI) therapy improves survival of treatment naïve advanced EGFR-mutant lung adenocarcinoma (LAD) patients with/without polymetastasis.
Materials and Methods: This was a retrospective, single-center, observational study. Patients with stage IIIB-IV EGFR-mutant LAD with disease control by EGFR-TKI therapy were divided into curative RTPLT, and control, without radiotherapy (WRTPLT) groups.
Results: A total of 138 patients were enrolled; 46 in the RTPLT group and 92 in the WRTPLT group. Amongst them, 37% had oligometastasis, and 26.1% brain metastasis. The RTPLT group had both significantly longer progression-free survival (PFS) (27.5 months [95% CI 18.1– 36.9] vs 10.9 months [95% CI 6.3– 15.5], P< 0.001) and overall survivor (OS) (NR [95% CI NR-NR] vs 38.0 months [95% CI 31.2– 44.8], P< 0.001), respectively, when compared to the WRTPLT group. In multivariate analysis, the adjusted HR of radiotherapy on PFS was 0.30 (0.19– 0.47) and on OS, 0.11 (0.04– 0.30). Patients with oligometastasis had significantly longer PFS than those with polymetastasis with an HR of 0.35 (0.14– 0.85), P=0.02. Patients with either oligometastasis or polymetastasis had significant longer PFS when undergoing radiotherapy than those without (both P< 0.05). An EGFR-TKI to radiotherapy interval < 24 weeks seemed more beneficial (P=0.097). Radiation pneumonitis comprised 32 (69.6%), 12 (26.1%), and two (4.3%) cases of common terminology criteria grade I, II, and III, respectively.
Conclusion: Curative RTPLT can prolong survival in patients with LAD following EGFR-TKI disease control, both involving oligometastasis and polymetastasis. RTPLT within 24 weeks after EGFR-TKI initiation appeared to be more beneficial with tolerable radiation pneumonitis.

Keywords: radiotherapy to primary lung tumor, RTPLT, EGFR-TKI, lung adenocarcinoma, oligometastasis, polymetastasis

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