Fan Yu1, Jianjiao Ni1, Wanqin Zeng2, Yue Zhou1, Tiantian Guo1, Ya Zeng1, Yang Zhao1, Shuyan Li1, Yida Li1, Xi Yang1, Liqing Zou1, Shengping Wang3, Quan Liu3, Yuan Li4, Li Chu1, Xiao Chu1, Luxi Ye1, Wen Yu5, Zhengfei Zhu6. 1. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China. 2. Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. 3. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, China. 4. Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China. 5. Department of Radiation Oncology, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, China. Electronic address: yuzhiwen0827@163.com. 6. Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China; Institute of Thoracic Oncology, Fudan University, Shanghai, China. Electronic address: fuscczzf@163.com.
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.
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.
Authors: Zhengfei Zhu; Jianjiao Ni; Xuwei Cai; Shengfa Su; Hongqing Zhuang; Zhenzhou Yang; Ming Chen; Shenglin Ma; Conghua Xie; Yaping Xu; Jiancheng Li; Hong Ge; Anwen Liu; Lujun Zhao; Chuangzhou Rao; Congying Xie; Nan Bi; Zhouguang Hui; Guangying Zhu; Zhiyong Yuan; Jun Wang; Lina Zhao; Wei Zhou; Chai Hong Rim; Arturo Navarro-Martin; Ben G L Vanneste; Dirk De Ruysscher; J Isabelle Choi; Jacek Jassem; Joe Y Chang; Lucyna Kepka; Lukas Käsmann; Michael T Milano; Paul Van Houtte; Rafal Suwinski; Alberto Traverso; Hiroshi Doi; Yang-Gun Suh; Georges Noël; Natsuo Tomita; Roman O Kowalchuk; Terence T Sio; Baosheng Li; Bing Lu; Xiaolong Fu Journal: Transl Lung Cancer Res Date: 2022-09