Molecular Adequacy of Image-Guided Rebiopsies for Molecular Retesting in Advanced Non-Small Cell Lung Cancer: A...

In the era of biomarker-driven systemic therapy for advanced NSCLC, the role of routine repeated biopsies for decision making outside EGFR-mutant disease remains unproven. We report our center's experience of safety and adequacy for molecular retesting of tumor material obtained from image-guided lung rebiopsies in NSCLC.

We performed a retrospective case note analysis of patients undergoing image-guided lung rebiopsies at a single cancer center between 2011 and 2014. The primary objective was to determine the pathological success rate. Secondary and exploratory objectives were to determine technical success rate, histological concordance, molecular adequacy, genotypes identified, and complication rate.

In all, 103 patients underwent transthoracic image-guided procedures. A total of 66 rebiopsies in NSCLC were identified and analyzed. The pathological success rate was 87.1%. A high histological discordance rate was observed (12 of 52 evaluable cases [23.1%]). Pretest molecular adequacy as determined by the lung pathologist was 78.8% (52 of 66). Of 52 adequate samples 51 were sent for molecular analysis, with a total of 209 genes analyzed (including EGFR, ALK receptor tyrosine kinase gene [ALK], KRAS, BRAF, dicoidin domain receptor tyrosine kinase 2 gene [DDR2], NRAS, ROS1, and rearranged during transfection proto-oncogene gene [RET]). The rate of postgenotyping molecular adequacy was 87.1% (182 of 209). Overall, 20 new potentially actionable mutations were identified, with 13 of 66 patients (19.7%) starting to receive new targeted treatment as a result. Overall, rebiopsies informed clinical decision making in 63.6% of cases. The rates of complications were 15% for pneumothorax, 3% for pneumothorax requiring chest drain, and 8% for hemoptysis.

We have validated the pathological and molecular adequacy rates of rebiopsies and demonstrated clinical utility in routine decision making.