Efficacy Of Whole-Brain Radiotherapy For Leptomeningeal Metastasis From Lung Cancer

Treatment of leptomeningeal metastasis (LM) remains a significant clinical challenge. Craniospinal irradiation may be a reasonable treatment option, but it does not seem to be widely employed, considering the poor prognosis of the patients and time and effort required for the procedure. We assessed the impact of whole-brain radiotherapy (WBRT) without spinal irradiation for LM from lung cancer. Between October 2008 and January 2019, 93 patients were treated with WBRT for LM from lung cancer. LM was diagnosed using contrast-enhanced magnetic resonance imaging (MRI), but patients who were difficult to diagnose due to previous brain surgery were excluded. Contrast-enhanced MRI was performed at intervals of 1 to 3 months after WBRT. The median age was 67 years. Eighty-seven patients had histologically-proven non-small-cell lung carcinoma (adenocarcinoma in 72) and 11 patients had small cell carcinoma. Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) were used for 42 patients with adenocarcinoma. There were 52 patients with diffuse lesions on MRI and 41 with localized lesions. Sixty-three patients had a history of Gamma-knife radiosurgery (GK). WBRT was delivered alone in 45 patients, in combination with GK in 47, and in combination with tumorectomy in 1. GK was performed in 15 patients as salvage therapy for recurrence after WBRT. The median follow-up period was 4.6 months. Overall survival was 51% at 5 months. Of 74 dead patients, cause of death was identified in 58; 22 were considered to have died of the CNS disease. Multivariate analysis showed that age <65 years, female gender, KPS >70, and use of EGFR-TKI were associated with longer survival. There was no significant difference in survival due to the distribution of lesions on MRI. Post-WBRT MRI was performed in 62 patients, of which 46 patients (65%) showed tumor shrinkage on MRI. Among 35 evaluable patients treated with EGFR-TKI, improvements were observed in 27 (83%). Seven (41%) of 17 adenocarcinoma patients receiving no EGFR-TKI and 5 (71%) of 7 small cell carcinoma patients showed improvements. The cumulative incidence of intracranial recurrence after WBRT was significantly lower in patients receiving EGFR-TKI. Of 44 patients observed on MRI for more than 3 months after WBRT, 8 patients (18%) showed Grade 2 leukoencephalopathy and 4 (9%) showed Grade 2 brain necrosis. There was no grade 3 or greater toxicity. Although the use of EGFR-TKI may have a strong impact on outcome, some patients improved after WBRT on MRI. WBRT may be chosen after considering the patient’s prognosis and neurological symptoms.