Whole brain radiation therapy does not improve the overall survival of EGFR-mutant NSCLC patients with leptomeningeal metastasis

Abstract

Background Leptomeningeal metastasis (LM) is a devastating and terminal complication of advanced non-small-cell lung cancer (NSCLC), especially in patients harboring epidermal growth factor receptor (EGFR) mutations. The role of whole brain radiation therapy (WBRT) in the treatment of EGFR-mutant NSCLC patients with LM is not conclusive. Therefore, we conducted a retrospective study to evaluate the therapeutic effect of WBRT in this setting. Methods EGFR-mutant NSCLC patients with LM, who had previously received treatment at the Shandong Cancer Hospital and Institute from July 2014 to March 2018 were reviewed retrospectively. LM was diagnosed by positive CSF cytology and/or leptomeningeal-enhanced magnetic resonance imaging (MRI). Survival was estimated using the Kaplan-Meier method. Results In total, 51 EGFR-mutated NSCLC patients with LM were eligible for analysis, subdivided into 26 in the WBRT group and 25 in the non-WBRT group. No significant differences were observed in intracranial ORR (15.4% vs. 16%, p = 0.952) and DCR (34.7% vs. 28%, p = 0.611) between the two groups. The median iPFSLM and OSLM for the entire cohort were 3.3 months (95% CI: 2.77–3.83) and 12.6 months (95% CI: 9.66–15.54), respectively. No difference in iPFSLM was observed between the WBRT and non-WBRT groups (median 3.9 vs. 2.8 months; HR = 0.506, p = 0.052). The median OSLM was 13.6 months in the WBRT group, compared with 5.7 months in the non-WBRT group (HR = 0.454, p = 0.022). Multivariate analyses of OSLM showed that KPS ≥ 80 at the time of LM diagnosis (HR = 0.428, 95% CI: 0.19–0.94; p = 0.034) and the administration of EGFR-TKIs (HR = 0.258, 95% CI: 0.11–0.58; p = 0.001) were independent predictors of survival, but WBRT (HR = 0.49, 95% CI: 0.24–1.01; p = 0.54) was not. Toxicities associated with WBRT or other treatment were rare. Conclusion For EGFR-mutated NSCLC patients with LM, WBRT did not improve intracranial treatment response and survival statistically.

Whole brain radiotherapy (WBRT) for leptomeningeal metastasis from NSCLC in the era of targeted therapy: a retrospective study

“…Our subgroup analysis reported that 49 patients with definite EGFR mutation gained almost no benefit from WBRT. This agrees with Yan et al who found that WBRT did not improve the overall survival of EGFR-mutated patients with LM [11]. We further reported that the overall survival in wild type patients with LM is noticeably enhanced.…”

“…There have been a few retrospective studies evaluating the prognosis of LM from NSCLC in the EGFR mutation subgroup. The median overall survival of these studies varies from 3 to 4 months [ 9 , 10 ] to 9–12 months [ 11 , 12 ].…”

“…Local-regional treatments including whole brain radiotherapy (WBRT), intrathecal chemotherapy (ITC), and ventriculoperitoneal (VP) shunt operations play a critical role in relieving neurological symptoms caused by intracranial hypertension in LM [ 13 – 15 ]. Although non-invasive whole brain radiotherapy (WBRT) seems to be effective in palliating neurologic signs and symptoms [ 13 ], WBRT has not been widely accepted for treating LM due to its plausible amelioration in survivals at the expense of potentially neurocognitive toxicity [ 11 , 16 ]. Several important questions have yet to be answered: 1) whether WBRT has an impact on survival outcomes; 2) if so, which sub-population will benefit from WBRT; 3) what are the optimal doses of WBRT for patients with different clinical and biological backgrounds.…”

Osimertinib combined with bevacizumab for leptomeningeal metastasis from EGFR‐mutation non‐small cell lung cancer: A phase II single‐arm prospective clinical trial

“…Although WBRT is an effective treatment for patients with brain metastasis (BM), its therapeutic effect in LM patients with EGFR mutations has not been fully evaluated. In a retrospective analysis of 51 EGFRm NSCLC patients with LM, the median LM PFS was 3.3 months (95% CI: 2.77–3.83), and no difference in LM PFS was observed between the WBRT and non‐WBRT groups (median 3.9 vs. 2.8 months; HR = 0.506, P = 0.052) 28 . A previous study showed that WBRT could play a role in symptom control; however, the authors did not find that it influenced the survival of LM from EGFRm NSCLC 30 .…”

“…The median survival time after LM treatment is 3–6 months 6,9,26,27 . Currently, the treatment for LM consists of EGFR‐TKIs, WBRT, systemic/intrathecal chemotherapy, ventriculoperitoneal shunt (VP shunt) and immune checkpoint inhibitors (ICIs) 6,28,29 . However, the survival benefits of these treatments remain poorly established.…”