TEST:

Oncomine™ Lung cfDNA Assay

No variants were observed in NRAS, ROS1, and MET genes. Our data showed that this commercial NGS panel could detect actionable mutations, enabling early detection, treatment monitoring, and disease surveillance.

Detectable ctDNA mutations were more frequent in patients with poorly differentiated tumors, and patients without detectable ctDNA mutations showed longer survival (medians of 10.5 months vs. 18 months, p = 0.019). The detection of circulating tumor DNA in pancreatic adenocarcinomas is correlated with worse survival outcomes.

The Oncomine Lung cfDNA Assay can be used to identify plasma EGFR mutations in patients with lung cancer, although further large-scale studies are required to evaluate the analytical validity for other types of aberrations and genes using clinical samples.

In addition, TP53 mutation status significantly predicts shorter overall survival (HR = 3.4 &lsqb;1.2-9.7]; p < 0.001). We demonstrated that TP53 mutation incidence as well as a cell-free DNA load can be used as biomarkers for NSCLC monitoring and can help to detect the disease progression prior to radiological confirmation of the status.

The NGS panel could successfully detect actionable mutations in liquid biopsies with a high concordance rate and sensitivity. The detection of variants in cfDNA, but not in tDNA, suggests a greater representativeness of the mutational tumor spectrum in samples of liquid biopsies opening perspectives for employing this approach in the routing setting. The NGS assay for liquid biopsy may decrease tissue biopsies and turnaround time for report release, accelerating therapeutic strategies for NSCLC patients.

Nearly one-third of NSCLC patients were found to have actionable mutations by liquid biopsy, and these were highly concordant with tissue. Oncomine cfDNA testing is predicted to provide similar results with lower cost and faster turnaround time.

Conclusions Front-line liquid biopsy might improve the management of symptomatic, hospitalized patients with lung cancer, potentially leading to early start of targeted therapy. Enrollment and longitudinal monitoring of oncogenic drivers with liquid biopsy are ongoing.

The patient was unfit for platin-based doublet chemotherapy but was offered Pemetrexed, continuing Osimertinib in standard doses...This variant is characteristic for neuroblastomas and known to be Crizotinib-resistant... Liquid biopsy-guided approach at progression in elderly patients with reduced PS may offer a feasible and effective therapy, as in this case by combining ALK- and EGFR-TKI. The treatment is ongoing and current progression-free survival is now 8 months, which is the longest under the whole treatment course. Effective combination of Osimertinib and Alectinib has been reported in single cases of disseminated EGFR-mutant NSCLC becoming resistant to Osimertinib through acquired ALK-fusions.

The addition of trametinib to panitumumab led to a high rate of tumor shrinkage in RAS/RAF wt metastatic colorectal cancer, with poor tolerability due to a high incidence of skin toxicity. Median PFS was similar to panitumumab alone in historical control data.

"The patient received stereotactic radiosurgery (SRS) against two intracranial processes followed by Erlotinib and achieved intra- and extracranial partial response (PR)...Based on these results no additional targeted treatment options were possible, and chemotherapy with Carboplatin/Pemetrexed was initiated while continuing Osimertinib, achieving only short-term stabilization of the disease. However, additional NGS analysis of RNA isolated from the hepatic metastasis showed ANK3-RET fusion on chromosome 10q (breakpoint chr10: 61994446, chr10: 43612032), and RET-TKI was initiated (Pralsetinib)...2. Complementary RNA-based testing is important to implement as a standard diagnostic strategy to better uncover the molecular evolution in advanced EGFR-mutated NSCLC and contribute to identification of further targeted treatment possibilities when progression during Osimertinib occur."

17 TP53 p.R249S 18 TP53 p.R158H 19 TP53 p.S215R 20 TP53 p.P278L 21 TP53 p.R283H 22 TP53 p.P278S; TP53 p.G279E; TP53 c.375+3_375+4insG; p.? 23 TP53 p.R267Q 24 TP53 p.C238F; TP53 p.C275S 25 TP53 p.Y163C 26 TP53 p.R248W 27 TP53 p.S241F 28 TP53 p.V272G Conclusion For patients in whom molecular analysis on tissue cannot be performed, NGS analysis of cfDNA in plasma provides an opportunity to detect driver mutations for subsequent targeted therapy.

P2/3 | "The IFCT-0703 randomized phase II trial failed to show a benefit of 6 months adjuvant pazopanib (P) vs... Post-operative ctDNA mutations are found in 26.0% of the pts but their positivity had no impact on DFS or OS . In contrast, DFS and OS were poorer in pts with increased plasma DNA concentration . ctDNA mutations status do not recapitulate the complexity of MRD characterization ."