Abstract 5960
Background
Next generation sequencing (NGS) of cfDNA in NSCLC is entering in clinical practice. Several commercially available platforms using NGS report wide variety of somatic aberrations. Vendors also include therapeutic suggestions to guide oncologists. In addition, new levels of evidence tools are now available for tissue results, but not still used in LB.
Methods
Advanced NSCLC pts underwent commercial 73-gene cfDNA NGS analysis. ESMO Scale for Clinical Actionability (ESCAT) and OncoKB were used to grade levels of evidence for categorize aberrations and compared with variant allele frequency (VAF), treatment decisions, and vendor suggestions.
Results
77 samples from 73 advanced NSCLC pts (73% adenocarcinoma, 27% squamous cell carcinoma) at the time of diagnosis (49%) or during disease course (51%) were analyzed. Median turnaround time was 8 days (range 5-17), with no genotyping failures. There were 323 unique somatic alternations identified: Sequence mutations (254), amplifications (43), synonymous mutations (23), and fusions (3). Median cfDNA % was 0.7 (range 0.05-49.5); 7 samples had no detectable genetic alterations. Variants of unknown significance were 33% of point mutations. We detected 87 and 88 potentially actionable genetic alterations according to ESCAT (IA-IV) and OncoKB (1-4), respectively, and 26% received a matched targeted drug. Discrepancies between these two tools and vendor suggestions were reported in 4 cases. We performed a subset analysis of 64 samples: Median VAF was 4.37 % (range 0.16-43.05) and a VAF < 1% was reported in 16 samples; 45% of alterations (excluding amplifications) were clonal events (cfDNA% divided by VAF > 0.5). Among EGFR and ALK positive samples median VAF was 7.98% (range 0.29-41.2); 3/17 samples presented a VAF below 1%, with no detrimental effect on treatment response.
Conclusions
The application of ESCAT and OncoKB is feasible in LB. Driver mutations with low VAF are amenable to receive treatment. VAF could be included as complementary tool to grading systems to better understand the significance of aberrations.Discrepancies between vendor therapeutic suggestions and evidence-based grading systems requests caution in the use of information outside the molecular tumor board.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C.D. Rolfo: Honoraria (self), personal fees : Novartis; Honoraria (self), personal fees : MSD; Non-remunerated activity/ies, non-financial support : OncoDNA; Honoraria (self), personal fees and non-financial support : GuardantHealth. All other authors have declared no conflicts of interest.
Resources from the same session
5011 - LCSCAF1 maintains cancer stem-like traits by stabilizing c-Myc protein and promotes metastasis and recurrence in lung cancer
Presenter: Tao Guo
Session: Poster Display session 1
Resources:
Abstract
4955 - XAF1 Enhances Temozolomide Induced Autophagic Cell Death through AMPK signaling pathway
Presenter: Mingoo Lee
Session: Poster Display session 1
Resources:
Abstract
5616 - The effect of cortisol on methylation patterns in breast cancer cell lines
Presenter: Haya Intabli
Session: Poster Display session 1
Resources:
Abstract
4649 - Global and sex-specific epigenome-wide association studies for the identification of the main methylated loci related to smoking in a Mediterranean population
Presenter: Judith Begona Ramirez Sabio
Session: Poster Display session 1
Resources:
Abstract
4984 - Whole transcriptomics analyses of mimicking Circulating Tumor Cells (CTCs) by single-cell RNA sequencing (scRNAseq)
Presenter: Jessica Garcia
Session: Poster Display session 1
Resources:
Abstract
5926 - Comparison of enzymatic- and bisulfite conversion to map the plasma cell-free methylome in cancer
Presenter: Nicole Lambert
Session: Poster Display session 1
Resources:
Abstract
5454 - Detection of low mutations in hepatocellular carcinoma by using circulating tumor DNA
Presenter: Esl Kim
Session: Poster Display session 1
Resources:
Abstract
4428 - Variants in the JAK1 and JAK2 genes in the risk and prognosis of patients with cutaneous melanoma
Presenter: Bruna Carvalho
Session: Poster Display session 1
Resources:
Abstract
4409 - P-Rex1 expression in breast cancer patients.
Presenter: Angela Lara Montero
Session: Poster Display session 1
Resources:
Abstract
4185 - Modulation of Risk of Cutaneous Melanoma Patients by Variants in STAT3 Gene and Functional Analysis
Presenter: Gabriela Gomez
Session: Poster Display session 1
Resources:
Abstract