American Society of Clinical Oncology (ASCO) recommends liquid biopsy.
"Even if patients can use traditional tissue biopsy detection, a liquid biopsy may be safer, faster, and more convenient, even can provide more information."
Common scene in clinical setting:
To determine whether there is a suitable target drug for a lung cancer patient, traditionally he/she will undergo a tissue biopsy (either through endoscopic biopsy or coarse needle biopsy) to take a tiny piece of tumor so he can take the genetic testing to find out if there is a treatable target for him. However, very often there is too little tissue available for a complete genetic test, patient may need a re-biopsy to obtain more tissue to be tested again. This puts a lot of psychological pressure on the patient.
Fortunately, now patients learned that the new sequencing technology could detect minute circulating tumor DNA (ctDNA) through simple blood sampling to find whether they have specific actionable gene mutation and the corresponding drug.
| 30-50% | 11-18% |
|---|---|
| Of lung cancer biopsies have insufficient/unavailable tissue for comprehensive genomic profiling1 | Is the frequency of the guideline-recommended alterations in NSCLC that are EXCLUDED in limited gene tests2 |
Reference:
- Thompson et a, 2016. Clinical Cancer Research. Villaflor et al, 2016. Oncotarget. Hegemann et al, 2015. Cancer.
- Compared to a test that only includes EGFR hotspots (L858R and Exon 19 deletion) and ALK fusions. Based on a population frequency in NSCLC for the following alterations associated with guideline-recommended alterations – 5% for EGFR G719A, G719C and S768I mutations, 1% for ROS-1 fusions, 1% for RET fusions, 1-3% for BRAF mutations, 2-4% for HER2 mutations, and 1-4% for MET amplifications. Lovly C., L Horn, W. Pao. 2016. Molecular Profiling of Lung Cancer. My Cancer Genome.
| ALK | AR | BRAF | EGFR | ERBB2 | FGFR1 | FGFR3 | KRAS |
| MET | NRAS | NTRK1 | PIK3CA | PTEN | RET | ROS1 | SMAD4 |
| TP53 | MSI |
| Variant types | Detection range | Sensitivity (%) | Specificity (%) | PPV (%) | Accuracy (%) |
|---|---|---|---|---|---|
| SNVs | 0.1-0.2%%VAF | 86.263 | 99.999 | 95.763 | 99.999 |
| >0.2% VAF | 100 | 100 | 100 | 100 | |
| Indels | 0.1-0.2%%VAF | 83.333 | 99.999 | 90.909 | 99.998 |
| >0.2% VAF | 100 | 100 | 100 | 100 | |
| Fusions | >0.5% VAF | 100 | 100 | 100 | 100 |
| CNVs | >4.5 copies | 100 | 100 | 100 | 100 |
| MSI | 2-100% VAF | 100 | 100 | 100 | 100 |
The table shows statistical performance parameters such as sensitivity, specificity, positive predictive value (PPV) and accuracy for specific detection ranges. A summary of the results used to calculate analytical performance is provided in the electronic supplementary material, supplementary Table S1.
CNV copy number variant, ideals insertions and deletions, MSI microsatellite instability, VAF variant allele fraction, SNV single-nucleotide variant.
Molecular Diagnosis & Therapy 2019 June.
