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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.

Author information

1
The University of Texas MD Anderson Cancer Center, Houston, TX.
2
Guardant Health Inc, Redwood City, CA.
3
Davidoff Cancer Center, Rabin Medical Center and Tel Aviv University, Petach Tikva, Israel.
4
The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: jheymach@mdanderson.org.
5
The University of Texas MD Anderson Cancer Center, Houston, TX. Electronic address: jzhang20@mdanderson.org.

Abstract

BACKGROUND:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

Genomics; Guardant360; Lung cancer; Targeted therapy; cfDNA

PMID:
30279110
DOI:
10.1016/j.cllc.2018.08.020
[Indexed for MEDLINE]
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