Concurrent versus sequential whole brain radiotherapy and TKI in EGFR-mutated NSCLC patients with brain metastasis

Chen, Hualin; Wu, Aibing; Tao, Hua; Yang, Donghong; Luo, Yiping; Li, Shujun; Yang, Zhijian; Chen, Ming

doi:10.1097/md.0000000000013014

Cited by 16 publications

(16 citation statements)

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“…Then we conducted the influence analysis of the included data ( Figures S1,S2), and founded out that Jiang et al, Ke et al and Magnuson (SRS) et al were the main origins which influenced the pooling outcome (26,29,32). The heterogeneity was effectively decreased or removed after exclusion of these three studies (I 2 =0.0%, P=0.680); Moreover, I 2 of iPFS was decreased to 38.5% (P=0.107) after removal of the three studies (byeon et al, Jiang et al and Chen et al) (23,26,27) which were considered as the culprit of heterogeneity by sensitivity analysis. The Egger's and Begg's test of included studies suggested no significant publication bias (P>0.05).…”

Section: Tki + Brain Rt Vs Tki Alone On Os and Ipfsmentioning

confidence: 97%

“…Then, 9 papers were excluded by screening the type of article, including 2 comment, 3 case report, 1 letter and 3 conference abstracts. 16 candidates were fully reviewed and finally 12 papers meeting inclusive criteria and were selected for meta-analysis (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34). The flow diagram of our literature inclusion scheme was shown in Figure 1.…”

Section: Study Selectionmentioning

confidence: 99%

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EGFR-TKI plus brain radiotherapy versus EGFR-TKI alone in the management of EGFR-mutated NSCLC patients with brain metastases

Dong¹,

Liang²,

Zhao³

et al. 2019

Transl. Lung Cancer Res

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Background: It has been confirmed that epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) presented better efficacy than brain radiotherapy (brain RT) in the treatment of brain metastasis (BM) in EGFR mutated NSCLC patients. However, whether the combination of EGFR-TKIs and brain RT is better than EGFR-TKIs alone remains unclear. We aim to compare the outcomes of adding brain RT to EGFR-TKIs and to screen for the beneficial population by a meta-analysis of currently available data. Methods: A systematic search for relevant articles was conducted in six databases. The outcomes were overall survival (OS) and intracranial progression-free survival (iPFS) between groups, both were measured as hazard ratios (HRs). Meta-regression and dominant subgroup analysis were used to explore advantageous subgroups. Results: A total of 12 retrospective studies involving 1,553 EGFR mutated patients with BM at the first diagnosis were included. EGFR-TKIs plus brain RT showed a significant prolonged OS (HR =0.64, 95%

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Section: Tki + Brain Rt Vs Tki Alone On Os and Ipfsmentioning

confidence: 97%

Section: Study Selectionmentioning

confidence: 99%

EGFR-TKI plus brain radiotherapy versus EGFR-TKI alone in the management of EGFR-mutated NSCLC patients with brain metastases

Dong¹,

Liang²,

Zhao³

et al. 2019

Transl. Lung Cancer Res

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“…Many meta-analyses and retrospective studies regarding the combination of EGFR-TKIs with radiotherapy have yielded conflicting results. Some studies have reported the superior efficacy and survival benefit of upfront radiotherapy or radiotherapy plus EGFR-TKIs over EGFR-TKIs alone [18][19][20][21][22]. However, others have reported no survival benefit [23][24][25][26].…”

Section: Discussionmentioning

confidence: 99%

Complete Remission of Multiple Brain Metastases in a Patient with EGFR-Mutated Non-Small-Cell Lung Cancer Treated with First-Line Osimertinib without Radiotherapy

Ameku¹,

Higa

2020

Case Reports in Oncological Medicine

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Osimertinib has demonstrated efficacy against stable or asymptomatic central nervous system (CNS) metastases of epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC) in phase 2 and 3 clinical trials that allowed prior CNS radiotherapy. However, the efficacy of osimertinib only or the optimal treatment combination or sequence of radiotherapy has not been investigated. A 74-year-old woman diagnosed with T4N1M1c Stage IVB lung adenocarcinoma with EGFR mutation presented with a left upper lobe mass and multiple bilateral lung metastases. A total of more than 20 asymptomatic multiple brain metastases with a maximum diameter of 12 mm were diagnosed simultaneously. Osimertinib was administered as first-line treatment. Whole brain radiotherapy was deferred because she had no neurological symptoms. After 5 weeks, the multiple brain metastases disappeared completely, together with the response in the lung lesions. This case demonstrated that first-line treatment with osimertinib could even achieve complete remission of multiple brain metastases comprising as many as twenty lesions of EGFR-mutated NSCLC without radiation therapy. Radiation therapy for brain metastases can be deferred or even withheld. A new treatment strategy for EGFR mutated NSCLC with CNS metastases should be investigated using osimertinib, especially regarding optimal combination or sequence of radiotherapy.

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“…WBRT can significantly reduce the intracranial progression rate and prolong the median iPFS and median OS; these results are consistent with those of previous studies. 22,24,25,29 Multivariate analysis showed that WBRT (P=0.016) is an independent prognostic factor in patients with multiple BM from NSCLC under EGFR-TKI targeted therapy. According to our study, a comprehensive treatment model of EGFR-TKI and WBRT in lung cancer patients with multiple BM can significantly prolong the survival of patients and further consolidate the position of WBRT in BM of lung cancer.…”

Section: Discussionmentioning

confidence: 99%

“…22 Chen H and other studies have shown that simultaneous treatment of EGFR-TKI and WBRT improves patients' short-and longterm benefits compared with sequential or separate use. 29 Liu et al showed that in EGFR-mutant NSCLC patients with BM, the timing of brain RT has no effect on OS. 30 The optimal timing of brain RT for EGFR-TKI-treated lung cancer patients with BM is still inconclusive in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

<p>Whole-Brain Radiotherapy Can Improve the Survival of Patients with Multiple Brain Metastases from Non-Small Cell Lung Cancer Treated by Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors</p>

Chen¹,

Wu²,

Liu³

et al. 2020

CMAR

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To observe whether whole-brain radiotherapy (WBRT) can bring survival benefits to patients with multiple brain metastases (BM) from non-small cell lung cancer (NSCLC) treated by epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) and determine the best time for WBRT intervention. Methods: A retrospective analysis was performed on 148 patients diagnosed with EGFR gene-mutated NSCLC. All patients had multiple BM and received EGFR-TKI targeted therapy, which was performed to observe whether WBRT can bring survival benefits, and whether the choice of WBRT timing affects the survival of patients. Results: Among the 148 patients with NSCLC treated with EGFR-TKI, 76 received WBRT; 72 were without WBRT. WBRT can reduce the intracranial progression rate in the patients (19.7% vs 33.3%, P=0.040), thus improving the intracranial progression-free survival (iPFS) (median iPFS: 11.9 months versus 10.2 months, P=0.039) and overall survival (OS) (median OS: 21.0 months versus 16.7 months, P=0.043). Multivariate analysis showed that WBRT (HR=0.606; 95% CI: 0.403-0.912, P=0.016) and the low Eastern Cooperative Oncology Group performance status (HR=1.884; 95% CI: 1.120-3.170, P=0.017) are independent prognostic factors in all patients. Further subgroup analysis showed that the choice of WBRT time had no effect on patient survival. Conclusion: WBRT can improve the survival of patients with multiple BM from NSCLC receiving EGFR-TKI targeted therapy and is an independent prognostic factor. The choice of RT time has no effect on patient survival.

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Concurrent versus sequential whole brain radiotherapy and TKI in EGFR-mutated NSCLC patients with brain metastasis

Cited by 16 publications

References 50 publications

EGFR-TKI plus brain radiotherapy versus EGFR-TKI alone in the management of EGFR-mutated NSCLC patients with brain metastases

EGFR-TKI plus brain radiotherapy versus EGFR-TKI alone in the management of EGFR-mutated NSCLC patients with brain metastases

Complete Remission of Multiple Brain Metastases in a Patient with EGFR-Mutated Non-Small-Cell Lung Cancer Treated with First-Line Osimertinib without Radiotherapy

<p>Whole-Brain Radiotherapy Can Improve the Survival of Patients with Multiple Brain Metastases from Non-Small Cell Lung Cancer Treated by Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors</p>

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