Real-World Evidence of EGFR Targeted Therapy in NSCLC- A Brief Report of Decade Long Single Center Experience.

The significance of EGFR targeted therapy in the lung adenocarcinoma is paramount. Several controlled clinical trials have reported considerable survival of EGFR mutation positive patients on receiving the EGFR tyrosine kinase inhibitor (TKI). However, the real-world evidence of benefits of EGFR TKI would be further useful to understand how the designated therapeutic regimen benefits the patients. In this study, we report a decade long real-world evidence of EGFR molecular testing in lung cancer at Tata Memorial Hospital (Mumbai, India). Laboratory and hospital records containing basic demographic details, clinical characteristics, treatment regimen, survival outcome were collected retrospectively. Statistical association and survival analysis were performed using the R programming. The cohort includes 9,053 lung cancer patients tested for EGFR mutations during 2011 to 2019. Baseline T790M and compound mutations were the only mutations observed co-occurring while all other EGFR mutations were mutually exclusive. Furthermore, the baseline T790M were also observed to be associated with TTF1 positivity, smoking and local metastasis. Overall survival of the patients harboring co-occurring compound mutations was significantly lesser than the other EGFR positive patients. Overall, our study suggests that EGFR TKI may provide real-world benefit to the lung cancer patients harboring mutually exclusive EGFR mutations. On the other hand, further systematic study is essential to develop better therapeutic regimen for co-occurring baseline EGFR T790M and other compound mutations.

Comprehensive Development and Implementation of Good Laboratory Practice for NGS Based Targeted Panel on Solid Tumor FFPE Tissues in Diagnostics.

The speed, accuracy, and increasing affordability of next-generation sequencing (NGS) have revolutionized the advent of precision medicine. To date, standardized validation criteria for diagnostic accreditation do not exist due to variability across the multitude of NGS platforms and within NGS processes. In molecular diagnostics, it is necessary to ensure that the primary material of the FFPE sample has good quality and optimum quantity for the analysis, otherwise the laborious and expensive NGS test may result in unreliable information. Therefore, stringent quality control of DNA and RNA before, during, and after library preparation is an essential parameter. Considering the various challenges with the FFPE samples, we aimed to set a benchmark in QC metrics that can be utilized by molecular diagnostic laboratories for successful library preparation and high-quality NGS data output. In total, 144 DNA and 103 RNA samples of various cancer types with a maximum storage of 2 years were processed for 52 gene focus panels. During the making of DNA and RNA libraries, extensive QC check parameters were imposed at different checkpoints. The decision tree approach can be set as a benchmark for FFPE samples and as a guide to establishing a good clinical laboratory practice for targeted NGS panels.