Driver Mutation Analysis and PD-L1 Expression in Synchronous Double Primary Lung Cancer

Area of Science:

• Oncology
• Genetics
• Thoracic Surgery

Background:

• Synchronous double primary lung cancer (SDPLC) is increasingly detected.
• Limited understanding of SDPLC's genetic landscape, diagnostic markers, and prognostic factors hinders effective management.
• Comprehensive analysis of driver mutations and PD-L1 expression is crucial for advancing SDPLC care.

Purpose of the Study:

• To investigate the genetic profiles, including driver mutations (EGFR, KRAS, BRAF, EML4-ALK, ROS1) and PD-L1 expression, in SDPLC.
• To analyze clonality patterns among synchronous primary lung tumors.
• To correlate genetic findings and clinical factors with patient outcomes and guide targeted therapy decisions.

Main Methods:

• Analysis of 110 lesions from 55 surgically resected SDPLC patients.
• Detection of 5 known driver mutations (EGFR, KRAS, BRAF, EML4-ALK, ROS1) and PD-L1 expression.
• Assessment of tumor clonality and correlation with clinical parameters and survival data.

Main Results:

• EGFR mutations were present in 50% of tumors; EML4-ALK fusions in 4.55%; KRAS mutations in 8.18%. BRAF and ROS1 aberrations were not detected.
• 47 patients (85.5%) exhibited different clonality between primary tumors, while 4 (7.27%) showed the same clonality.
• EGFR mutations with same clonality were more frequent in patients over 65 (P=0.021). PD-L1 expression (14.54%) was higher in males, squamous cell carcinoma, and tumors >3 cm.

Conclusions:

• Evaluation of EGFR/KRAS mutations and EML4-ALK fusions is vital for SDPLC diagnosis and classification.
• Tumor clonality and specific mutations can inform prognosis and guide personalized treatment strategies.
• Identifying genetic markers and PD-L1 status aids in selecting appropriate targeted therapies for SDPLC patients.