Improving the turnaround time of molecular profiling for advanced non-small cell lung cancer: Outcome of a new algorithm integrating multiple approaches

Background: Molecular tumor profiling to identify oncogenic drivers and actionable mutations has a profound impact on how lung cancer is treated. Especially in the subgroup of non-small cell lung cancer (NSCLC), molecular testing for certain mutations is crucial in daily clinical practice and is recommended by international guidelines. To date, a standardized approach to identify druggable genetic alterations are lacking. We have developed and implemented a new diagnostic algorithm to harmonize the molecular testing of NSCLC.

Patients and methods: In this retrospective analysis, we reviewed 119 patients diagnosed with NSCLC at the University Hospital Zurich. Tumor samples were analyzed using our standardized diagnostic algorithm: After the histological diagnosis was made, tissue samples were further analyzed by immunohistochemical stainings as well as the real-time PCR test Idylla™. Extracted DNA was further utilized for comprehensive genomic profiling (FoundationOne®CDx, F1CDx).

Results: Out of the 119 patients were included in this study, 100 patients were diagnosed with non-squamous NSCLC (nsqNSCLC) and 19 with squamous NSCLC (sqNSCLC). The samples from the nsqNSCLC patients underwent testing by Idylla™ and were evaluated by immunohistochemistry (IHC). F1CDx analysis was run on 67 samples and 46 potentially actionable genomic alterations were detected. Ten patients received the indicated targeted treatment. The median time to test results was 4 days for the Idylla test, 5 days for IHC and 13 days for the F1CDx.

Conclusion: In patients with NSCLC, the implementation of a standardized molecular testing algorithm provided information on predictive markers for NSCLC within a few working days. The implementation of broader genomic profiling led to the identification of actionable targets, which would otherwise not have been discovered.