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

Vincent Lam, Hai T. Tran, Kimberly C. Banks, Richard B. Lanman, Waree Rinsurongkawong, Nir Peled, Jeff Lewis, J. Jack Lee, Jack Roth, Emily B. Roarty, Stephen Swisher, Amir Ali Talasaz, P. Andrew Futreal, Vassiliki Papadimitrakopoulou, John V. Heymach, Jianjun Zhang

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)30-36.e3
JournalClinical Lung Cancer
Volume20
Issue number1
DOIs
StatePublished - Jan 1 2019
Externally publishedYes

Fingerprint

DNA Sequence Analysis
Squamous Cell Carcinoma
Lung
Neoplasms
Histology
Circulating Neoplastic Cells
DNA
Exons
Therapeutics
Guidelines

Keywords

  • cfDNA
  • Genomics
  • Guardant360
  • Lung cancer
  • Targeted therapy

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations. / Lam, Vincent; Tran, Hai T.; Banks, Kimberly C.; Lanman, Richard B.; Rinsurongkawong, Waree; Peled, Nir; Lewis, Jeff; Lee, J. Jack; Roth, Jack; Roarty, Emily B.; Swisher, Stephen; Talasaz, Amir Ali; Futreal, P. Andrew; Papadimitrakopoulou, Vassiliki; Heymach, John V.; Zhang, Jianjun.

In: Clinical Lung Cancer, Vol. 20, No. 1, 01.01.2019, p. 30-36.e3.

Research output: Contribution to journalArticle

Lam, V, Tran, HT, Banks, KC, Lanman, RB, Rinsurongkawong, W, Peled, N, Lewis, J, Lee, JJ, Roth, J, Roarty, EB, Swisher, S, Talasaz, AA, Futreal, PA, Papadimitrakopoulou, V, Heymach, JV & Zhang, J 2019, 'Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations', Clinical Lung Cancer, vol. 20, no. 1, pp. 30-36.e3. https://doi.org/10.1016/j.cllc.2018.08.020
Lam, Vincent ; Tran, Hai T. ; Banks, Kimberly C. ; Lanman, Richard B. ; Rinsurongkawong, Waree ; Peled, Nir ; Lewis, Jeff ; Lee, J. Jack ; Roth, Jack ; Roarty, Emily B. ; Swisher, Stephen ; Talasaz, Amir Ali ; Futreal, P. Andrew ; Papadimitrakopoulou, Vassiliki ; Heymach, John V. ; Zhang, Jianjun. / Targeted Tissue and Cell-Free Tumor DNA Sequencing of Advanced Lung Squamous-Cell Carcinoma Reveals Clinically Significant Prevalence of Actionable Alterations. In: Clinical Lung Cancer. 2019 ; Vol. 20, No. 1. pp. 30-36.e3.
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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.",
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AU - Lam, Vincent

AU - Tran, Hai T.

AU - Banks, Kimberly C.

AU - Lanman, Richard B.

AU - Rinsurongkawong, Waree

AU - Peled, Nir

AU - Lewis, Jeff

AU - Lee, J. Jack

AU - Roth, Jack

AU - Roarty, Emily B.

AU - Swisher, Stephen

AU - Talasaz, Amir Ali

AU - Futreal, P. Andrew

AU - Papadimitrakopoulou, Vassiliki

AU - Heymach, John V.

AU - Zhang, Jianjun

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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