1. Clinical Value of Upfront Cranial Radiation Therapy in Osimertinib-Treated Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer With Brain Metastases
- Author
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Yuan Li, Zhengfei Zhu, Yang Zhao, Wanqin Zeng, Xiao Chu, Jianjiao Ni, Tiantian Guo, Wen Yu, Liqing Zou, Shengping Wang, Q. Liu, Yue Zhou, Yida Li, Luxi Ye, Ya Zeng, Li Chu, Shuyan Li, Xi Yang, and Fan Yu
- Subjects
Oncology ,Cancer Research ,medicine.medical_specialty ,Lung Neoplasms ,medicine.drug_class ,medicine.medical_treatment ,Population ,Radiosurgery ,Tyrosine-kinase inhibitor ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,0302 clinical medicine ,Carcinoma, Non-Small-Cell Lung ,Internal medicine ,medicine ,Humans ,Radiology, Nuclear Medicine and imaging ,Osimertinib ,Epidermal growth factor receptor ,Lung cancer ,education ,Protein Kinase Inhibitors ,Retrospective Studies ,Acrylamides ,education.field_of_study ,Aniline Compounds ,Radiation ,biology ,Brain Neoplasms ,business.industry ,medicine.disease ,ErbB Receptors ,Clinical trial ,Radiation therapy ,030220 oncology & carcinogenesis ,biology.protein ,Cranial Irradiation ,business - Abstract
Purpose As a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), osimertinib has a powerful ability to penetrate the blood-brain barrier and a high potency for controlling brain metastases (BMs) from EGFR-mutant non-small cell lung cancer (NSCLC). The clinical value of cranial radiation therapy in osimertinib-treated NSCLC with BMs remains largely unknown. Methods and Materials Patients with NSCLC and BMs and receiving osimertinib treatment as the standard of care were retrospectively enrolled from 2 institutions. Cranial radiation therapy (RT; whole-brain radiation therapy [WBRT] or/and stereotactic radiosurgery [SRS]) performed before disease progression (PD) to osimertinib was categorized as upfront cranial radiation therapy (ucRT group), excluding those treatments performed during prior EGFR-TKI treatment. Overall survival (OS), progression-free survival (PFS), and the time to intracranial progression (iTTP) were compared between the 2 groups, with adjustment by covariates in propensity-score matched (PSM) analyses. The state of having 1 to 3 BM lesions, with a maximal size of ≤3 cm, was defined as having oligo-BM; otherwise; the cases were defined as having multiple BMs. Results Of the 205 patients enrolled, osimertinib was used as first-line therapy in 74 and second-line therapy in 131. There were 48 patients who received ucRTs, including WBRT in 24 and SRS in 24. All patients with oligo-BM in the ucRT group received SRS alone (n = 17), whereas most (n = 28; 90.3%) patients with multiple BMs received WBRT. Failure pattern analyses indicated that in the non-ucRT group, 40.2% of the initial PD involved the brain and 76.9% of the cranial PD involved the original sites, indicating the potential roles of ucRT. Indeed, the iTTP was significantly prolonged (P = .010) in the ucRT group among the whole population. In the PSM oligo-BM cohort, the ucRT group showed superior PFS (P = .033) and OS (P = .026) compared with the non-ucRT group, and the differences remained after multivariate Cox analyses. No such differences were observed in the subpopulation with multiple BMs. Conclusions In osimertinib-treated NSCLC patients with BMs, oligo-BM status could be used as a potential factor to select patients for upfront cranial RT. Further investigation by well-designed clinical trials is warranted.
- Published
- 2021