The most common adverse events of the 3 groups of patients during the treatment included headache, vomiting, hair loss, rash, diarrhea, and elevated transaminases, which were mostly grade 1 or 2. These symptoms improved after symptomatic treatment, and all the patients could tolerate these events.
Previous studies demonstrated that EGFR-TKIs can effectively improve the prognosis of NSCLC patients with sensitive EGFR mutation,[19–24] but the optimal timing of WBRT and EGFR-TKI remains controversial. Therefore, this retrospective study aimed to examine the outcomes of concurrent versus sequential WBRT and EGFR-TKI in NSCLC patients with EGFR mutation. The results suggest that the simultaneous application of EGFR-TKIs and WBRT can effectively improve the short- and long-term benefits of patients with brain metastasis of NSCLC carrying EGFR mutation, without additional adverse events.
Using EGFR-TKIs alone for the treatment of patients with brain metastases of NSCLC involves relatively high intracranial recurrence rate, and the PFS is also short. Park et al prospectively analyzed the data of using EGFR-TKIs alone for the treatment of brain metastases of lung cancer in 28 patients with EGFR mutation, and found tumor progression in 21 patients (13 patients with only intracranial progression, 4 with intra- and extracranial progression, and 4 with only extracranial progression). In addition, 14 of the 17 patients with intracranial progression received radiotherapy. The PFS of all the patients was 6.6 months, and OS was 15.9 months. The relatively long survival time in these patients was probably due to the radiotherapy after tumor progression. These findings highlight several drawbacks in using EGFR-TKIs alone for the treatment, which could be associated with the function of blood–brain barrier that restrict the transfer of EGFR-TKIs into brain, and therefore lead to low dose of EGFR-TKIs in the central nervous system. Yang et al reported that the median iPFS was 4.8 and 10.0 months for patients with brain metastasis of NSCLC carrying EGFR mutation in the WBRT and icotinib groups, respectively (P < .05), while the median OS was 20.5 and 18.0 months, respectively (P > .05). Therefore, treating brain metastases from NSCLC using TKI therapy alone seems insufficient. On the other hand, WBRT is not restricted by the blood–brain barrier and may facilitate the intracranial transfer of EGFR-TKIs. Previous studies have already demonstrated that using EGFR-TKIs could increase the sensitivity of tumor cells to radiotherapy[43–45] thus concurrent application might exert a synergistic effect between EGFR-TKIs and radiotherapy. Supporting our finding that concurrently using WBRT and EGFR-TKIs was the most effective treatment.
The present study is not without limitations. First, this was a retrospective study with a number of confounding factors. Secondly, the sample size was small. Thirdly, this study only included 2 clinically common EGFR mutations, and there was no comprehensive analysis of the EGFR mutations. In the future, more rigorous and prospective clinical studies with large sample size should be designed to further confirm the optimal timing, modes, and doses of WBRT and EGFR-TKI in the treatment of patients with brain metastasis of NSCLC with EGFR mutation, to provide a higher level of evidence-based treatment for those patients.
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