Abstract 224P
Background
Leptomeningeal metastasis (LM) is a devastating complication of advanced non-small cell lung cancer (NSCLC). Genetic profiling using cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) may serve as a novel method for monitoring of LM. Our study was designed to measure mutations in serially collected CSF specimens and investigate its correlation with clinical outcome in EGFR-mutated (EGFRm) NSCLC.
Methods
From March 2018 to June 2023, patients with cytology-confirmed LM who had EGFRm NSCLC were enrolled. All of them underwent EGFR tyrosine kinase inhibitor (TKI) plus intrathecal therapy as initial treatment for LM disease. cfDNA isolated from CSF was analyzed via gene-panel target-capture next-generation sequencing. Mutation abundance index (MAI) was defined as the average value of mutant allele fractions (AF) which are greater than 5%.
Results
35 patients were included in the final analysis. The median time from diagnosis of NSCLC to LM was 18.3 months (95% confidence interval (CI): 14.1-22.4). Intra- and extra-cranial ORR was 14.3% and 8.6% respectively. The median survival after diagnosis of LM was 18.1 months (95% CI: 11.0-19.4). cfDNA was detectable in all 76 CSF samples. Type of EGFR mutation, presence of TP53 mutation and baseline MAI (MAI 1) were not discriminating factors for OS. For each patient, MAI 2 was defined as the MAI measured while on treatment with EGFR TKI (1-2 months away from baseline). The pattern of MAI change was associated with clinical outcome. Neurological function improvement was identified in 72.7% (8/11) of cases with MAI decrease (MAI 2 < MAI 1, N=11). Patients with MAI decrease had significantly better OS than patients with stable or increased MAI (median OS, 21.3 vs. 14.4 months, p=0.012, HR=0.293).
Table: 224P
Baseline characteristics and treatment patterns of patients with LM in EGFRm NSCLC (N=35)
| Characteristics | N (%) |
| Age | |
| <65 | 13 (37.1) |
| ≥65 | 22 (62.9) |
| Sex | |
| Male | 12 (34.3) |
| Female | 23 (65.7) |
| Smoking status | |
| Former/current | 12 (34.3) |
| Never | 23 (65.7) |
| ECOG score | |
| 0-1 | 24 (68.6) |
| ≥2 | 11 (31.4) |
| History of surgery | |
| Yes | 12 (34.3) |
| No | 23 (65.7) |
| TNM stage at initial diagnosis | |
| Stage I-III | 13 (37.1) |
| Stage IV | 22 (62.9) |
| Type of EGFR mutation at baseline | |
| Exon 21 L858R | 17 (48.5) |
| Exon 19 deletion | 10 (28.6) |
| Compound mutations | 8 (22.9) |
| Coexisting intraparenchymal brain metastasis | |
| Yes | 27 (77.1) |
| No | 8 (22.9) |
| Previous lines of therapy before LM | |
| 0 | 3 (8.6) |
| 1 | 23 (65.7) |
| ≥2 | 9 (25.7) |
| Intra-cranial response | |
| CR/PR | 5 (14.3) |
| SD | 30 (85.7) |
| PD | 0 (0) |
| Extra-cranial response | |
| CR/PR | 3 (8.6) |
| SD | 32 (91.4) |
| PD | 0 (0) |
| Radiation therapy | |
| Yes | 6 (17.1) |
| No | 29 (82.9) |
Conclusions
CSF-based MAI might be used as a prognostic indicator in LM in EGFRm NSCLC.
Legal entity responsible for the study
National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.