Expanding Broad Molecular Reflex Testing in Non-Small Cell Lung Cancer to Squamous Histology

Area of Science:

• Oncology
• Molecular Diagnostics
• Thoracic Surgery

Background:

• Biomarker-driven targeted therapy has revolutionized non-small cell lung cancer (NSCLC) treatment.
• Molecular reflex testing is standard for non-squamous NSCLC but varies for squamous NSCLC (SCC).
• Current SCC testing guidelines sometimes exclude patients based on age or smoking history.

Purpose of the Study:

• To evaluate the clinical utility of molecular reflex testing in an unselected cohort of lung SCC patients.
• To determine the frequency of targetable molecular alterations in lung SCC.
• To propose an optimized molecular testing workflow for NSCLC.

Main Methods:

• Retrospective single-center study of 316 consecutive lung SCC cases.
• DNA- and RNA-based next-generation sequencing (NGS) was performed.
• Clinicopathological data were correlated with sequencing results.

Main Results:

• Targetable molecular alterations were identified in 6.6% (21/316) of lung SCC cases.
• Detected alterations included EGFR mutations, KRAS G12C mutations, ALK fusions, EGFR fusions, and METex14 skipping events.
• All patients with targetable alterations were over 50 years old and had significant smoking history (>15 pack-years).

Conclusions:

• Molecular reflex testing is valuable in lung SCC, revealing actionable targets in a notable proportion of patients.
• Restrictive testing strategies excluding patients by age or smoking status may miss opportunities for targeted therapy.
• Universal molecular reflex testing using NGS for all NSCLC, irrespective of histology, age, or smoking status, is recommended.