Mutational Landscape and Treatment Response in Extensive-Stage Small-Cell Lung Cancer: A Single-Center Real-World...

Area of Science:

• Oncology
• Medical Genetics
• Clinical Research

Background:

• Small-cell lung cancer (SCLC) is aggressive, often diagnosed at the extensive stage (ES-SCLC).
• The 'cold' immune profile of SCLC limits the efficacy of chemoimmunotherapy (CIT).
• Chemotherapy (CT) alone is a standard treatment, but novel strategies are needed.

Purpose of the Study:

• To evaluate the real-world clinical efficacy of first-line CIT versus CT in ES-SCLC patients.
• To analyze the association between gene mutation characteristics and clinical indicators.
• To identify prognostic factors and potential personalized treatment pathways.

Main Methods:

• Retrospective analysis of 170 ES-SCLC patients treated between January 2020 and January 2024.
• Categorization by first-line treatment: CIT (n=115) versus CT (n=55).
• Genomic profiling for a subset of patients to correlate mutations with clinicopathological factors.

Main Results:

• CIT group showed a significantly higher objective response rate (76.5%) compared to CT (56.4%).
• Median progression-free survival was similar (6.0 vs. 5.8 months).
• Adrenal metastasis identified as an independent adverse prognostic factor; specific gene mutations (MYC, NTRK3, ALK, NTRK1) correlated with metastasis sites.

Conclusions:

• First-line CIT significantly improves initial response rates in ES-SCLC compared to CT.
• Baseline adrenal metastasis is a negative prognostic indicator.
• Genomic signatures correlate with clinical characteristics, supporting personalized treatment strategies for SCLC.