Although liquid biopsy (blood) profiling to detect and characterize cancer from fragments of circulating tumor DNA continues to emerge as a clinically useful tool (PLoS1, NILE2, etc.), solid tissue profiling remains the gold standard and produces the most reliable results.

Concordance details of non-small-cell-lung-cancer (NSCLC) tissue biopsies performed by Caris over the last year vs. blood based cell-free (cfDNA) results as reported from multiple publication sources at the intent to treat level are outlined in the below diagram.

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Summary:

  • Solid tumor testing by Caris is reported at 92% for the intent to treat population, 84% for complete results and 16% for partial results returned (meaning not enough tissue to perform all assays ordered), which still contain actionable information.
    • Additional detail is provided for key actionable biomarkers such as ALK, ROS1, EGFR, BRAF and PD-L1 – all results are higher and more reliable than blood only profiling.
  • In the intent to treat population, cfDNA liquid biopsy success rate was 57%
    • Additional detail is provided for key biomarkers such as ALK, ROS1, EGFR, BRAF and PD-L1 – all results are lower and less reliable than solid tumor profiling and PD-L1 is not in tested for by blood.

Conclusion:
Caris tissue testing returns successful results in 92% of patients in an average of 10 days. The data presented demonstrated that testing by cfDNA returns results on 57% of patients in an advertised 9 days.2

  • Tissue testing remains the gold standard.
  • cfDNA can be a viable clinical tool in cases where tissue is not available or limited.
  • This data is consistent with numerous publications where researchers have concluded that cfDNA analysis is “not a replacement for histologic confirmation and immunohistochemistry from a diagnostic biopsy” but rather the “data thus supports a complementary role for plasma cfDNA NGS.”6

 

1. Lanman RB, Mortimer SA, Zill OA, Analytical and Clinical Validation of a Digital Sequencing Panel for Quantitative, Highly Accurate Evaluation of Cell-Free Circulating Tumor DNA. PLoS One. 2015 Oct 16;10(10) 2. Leighl, N, Page, R, Raymond, V: Clinical Utility of Comprehensive Cell-Free DNA Analysis to Identify Genomic Biomarkers in Patients with Newly Diagnosed Metastatic NSCLC. Clin Cancer Res. April 2019 3. Abbosh C, Birkbak NJ, Swanton C: Early stage NSCLC – challenges to implementing cfDNA-based screening and MRD detection. Nat Rev Clin Oncol. 2018 Sep; 15(9): 577-586. 4. Sacher AG, Komatsubara KM, Oxnard GR: Application of Plasma Genotyping Technologies in Non-Small Cell Lung Cancer: A Practical Review. J Thorac Oncol. 2017 Sep; 12(9): 1344-1356 5. Stetson, D, Ahmed, A, Xu, X: Orthogonal Comparison of Four Plasma NGS Tests With Tumor Suggests Technical Factors are a Major Source of Assay Discordance. JCO Precision Oncology, March 2019 6. Illumina Actionable Genome Consortium study 2019