Effect of timing, technique and molecular features on brain control with local therapies in oncogene-driven lung cancer

ESMO Open

article

R.A. El Shafie¹  K. Seidensaal¹  F. Bozorgmehr⁴  D. Kazdal⁵  T. Eichkorn¹  M. Elshiaty⁴  D. Weber⁷  M. Allgäuer⁵  L. König¹  K. Lang¹  T. Forster¹  N. Arians¹  S. Rieken¹  C.-P. Heussel³  F.J. Herth⁵  M. Thomas⁴  A. Stenzinger⁵  J. Debus¹  P. Christopoulos⁴ 

[1] Department of Radiation Oncology, Heidelberg University Hospital;National Center for Radiation Oncology ,(NCRO), Heidelberg Institute for Radiation Oncology;Department of Radiology and Nuclear Medicines, Thoraxklinik at Heidelberg University Hospital;Department of Thoracic Oncology, Thoraxklinik at Heidelberg University Hospital;Translational Lung Research Center Heidelberg ,(TLRC-H), Member of the German Center for Lung Research;Institute of Pathology, Heidelberg University Hospital;Institute of Medical Biometry and Informatics ,(IMBI), Heidelberg University Hospital;University Medical Center Göttingen, Department of Radiation Oncology;Department of Pneumology, Thoraxklinik at Heidelberg University Hospital;National Center for Tumor Diseases;Clinical Cooperation Unit Radiation Oncology ,(E050), German Cancer Research Center;Deutsches Konsortium für Translationale Krebsforschung ,(DKTK), Partner Site Heidelberg, German Cancer Research Center;Heidelberger Ionenstrahltherapie-Zentrum

关键词: EGFR+ NSCLC;    ALK+ NSCLC;    brain metastases;    whole-brain radiotherapy;    stereotactic radiotherapy;   

DOI  :  10.1016/j.esmoop.2021.100161

学科分类：社会科学、人文和艺术（综合）

来源: BMJ Publishing Group

【 摘 要 】

Background The improved efficacy of tyrosine kinase inhibitors (TKI) mandates reappraisal of local therapy (LT) for brain metastases (BM) of oncogene-driven non-small-cell lung cancer (NSCLC).Patients and methods This study included all epidermal growth factor receptor-mutated (EGFR+, n = 108) and anaplastic lymphoma kinase-rearranged (ALK+, n = 33) TKI-naive NSCLC patients diagnosed with BM in the Thoraxklinik Heidelberg between 2009 and 2019. Eighty-seven patients (62%) received early LT, while 54 (38%) received delayed (n = 34; 24%) or no LT (n = 20; 14%). LT comprised stereotactic (SRT; n = 40; 34%) or whole-brain radiotherapy (WBRT; n = 77; 66%), while neurosurgical resection was carried out in 19 cases.Results Median overall survival (OS) was 49.1 months for ALK+ and 19.5 months for EGFR+ patients (P = 0.001), with similar median intracranial progression-free survival (icPFS) (15.7 versus 14.0 months, respectively; P = 0.80). Despite the larger and more symptomatic BM (P < 0.001) of patients undergoing early LT, these experienced longer icPFS [hazard ratio (HR) 0.52; P = 0.024], but not OS (HR 1.63; P = 0.12), regardless of the radiotherapy technique (SRT versus WBRT) and number of lesions. High-risk oncogene variants, i.e. non-del19 EGFR mutations and ‘short' EML4-ALK fusions (mainly variant 3, E6:A20), were associated with earlier intracranial progression (HR 2.97; P = 0.001). The longer icPFS with early LT was also evident in separate analyses of the EGFR+ and ALK+ subsets.Conclusions Despite preferential use for cases with poor prognostic factors, early LT prolongs the icPFS, but not OS, in TKI-treated EGFR+/ALK+ NSCLC. Considering the lack of survival benefit, and the neurocognitive effects of WBRT, patients presenting with polytopic BM may benefit from delaying radiotherapy, or from radiosurgery of multiple or selected lesions. For SRT candidates, the improved tumor control with earlier radiotherapy should be weighed against the potential toxicity and the enhanced intracranial activity of newer TKI. High-risk EGFR/ALK variants are associated with earlier intracranial failure and identify patients who could benefit from more aggressive management.

【 授权许可】

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