2501 - Cranial Radiotherapy Improves Survival in Brain Metastatic NSCLC Patients Bearing EGFR and TP53 Mutations
Presenter(s)
L. L. WANG1, M. Sun Jr2, Y. Jiang3, D. Yang4, and W. Zhou5; 1Chongqing university cancer hospital, Chongqing, Chongqing, China, 2Chongqing university cancer hospital, Chongqing, China, 3Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China, 4Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China, China, 5Department of radiotherapy oncology, Chongqing University Cancer Hospital & Chongqing Cancer Institute & Chongqing Cancer Hospital, Chongqing, China
Purpose/Objective(s): Patients with non-small cell lung cancer (NSCLC) who have concurrent EGFR and TP53 mutations and brain metastases generally have a poor prognosis. The clinical characteristics, genetic mutation profiles, and the impact of radiotherapy on survival in these patients require further investigation. This study analyzes baseline characteristics, genetic mutation spectra, survival data, and the potential role of radiotherapy based on data from more than 150 patients.
Materials/Methods: A retrospective analysis was conducted on 152 brain metastatic NSCLC patients with EGFR and TP53 mutations. Baseline data (age, gender, smoking history, staging, etc.), genetic mutation types (EGFR subtypes, TP53 exons and mutation types), survival data (PFS, OS), and radiotherapy information were collected. Descriptive statistics and survival analysis (Kaplan-Meier method) were used for data processing.
Results: Median age was 58 years (range 32-83). Most patients were diagnosed at stage IV (95.4%), and brain metastases were mostly multifocal (67.8%) with an average lesion diameter of 1.4 cm. 72.4% of patients had a Karnofsky Performance Score (KPS) of =80, indicating that most patients had a relatively good performance status. EGFR mutations were predominantly in exon 19 Del (46.7%) and L858R (38.8%), with rare mutations accounting for 9.2%; EGFR amplification (CN=4) was present in 32.9%. TP53 mutations were concentrated in exons 5-8 (82.9%), with missense mutations (54.6%) and splice mutations (28.3%) being the most common; the median mutation frequency was 39.5%. Other concurrent mutations included MET amplification (18.4%), PIK3CA mutations (12.5%), and RB1 deletion (9.2%). The median overall survival (OS) was 19.2 months (95% CI 16.8-21.6), and the median progression-free survival (PFS) was 9.5 months (95% CI 8.1-10.9). In first-line treatment, third-generation EGFR-TKIs (osimertinib) significantly prolonged PFS compared to first/second-generation EGFR-TKIs (11.3 vs. 7.8 months, P=0.002). Patients receiving intracranial radiotherapy (whole-brain or stereotactic radiotherapy) had a median OS of 21.4 months, compared to 14.6 months for those who did not receive radiotherapy (P=0.013). The combination of radiotherapy and EGFR-TKI significantly improved intracranial control rates compared to EGFR-TKI alone (82.1% vs. 63.5%, P=0.004).
Conclusion: Patients with EGFR and TP53 mutations in NSCLC with brain metastases have distinct clinical and molecular features. The combination of third-generation EGFR-TKI and intracranial radiotherapy significantly extends survival. TP53 mutations may accelerate disease progression by promoting genomic instability. Future studies should explore combination therapies targeting TP53 to improve prognosis.