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Clin Lung Cancer. 2019 Jan;20(1):30-36.e3. doi: 10.1016/j.cllc.2018.08.020. Epub 2018 Sep 5.

Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations.

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The University of Texas MD Anderson Cancer Center, Houston, TX.
Guardant Health Inc, Redwood City, CA.
Davidoff Cancer Center, Rabin Medical Center and Tel Aviv University, Petach Tikva, Israel.
The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:
The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address:



Major guidelines do not recommend routine molecular profiling of lung squamous-cell carcinoma (LUSC) because the prevalence of actionable alterations is thought to be low. Increased utilization of next-generation sequencing (NGS), particularly with cell-free circulating tumor DNA, facilitates reevaluation of this premise. PATIENTS AND METHODS: We retrospectively evaluated the prevalence of actionable alterations in 2 distinct LUSC cohorts totaling 492 patients. A total of 410 consecutive patients with stage 3B or 4 LUSC were tested with a targeted cell-free circulating DNA NGS assay, and 82 patients with LUSC of any stage were tested with a tissue NGS cancer panel.


In the overall cohort, 467 patients (94.9%) had a diagnosis of LUSC, and 25 patients (5.1%) had mixed histology with a squamous component. A total of 10.5% of the LUSC subgroup had somatic alterations with therapeutic relevance, including in EGFR (2.8%), ALK/ROS1 (1.3%), BRAF (1.5%), and MET amplification or exon 14 skipping (5.1%). Sixteen percent of patients with mixed histology had an actionable alteration. In the LUSC subgroup, 3 evaluable patients were treated with targeted therapy for an actionable alteration; all of them experienced partial response.


In this large, real-world LUSC cohort, we observed a clinically significant prevalence of actionable alterations. Accurate local histopathologic assessment in advanced-stage LUSC can be challenging. Further evaluation of the genomic landscape in this setting is warranted to potentially identify underappreciated treatment options.


Genomics; Guardant360; Lung cancer; Targeted therapy; cfDNA

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