LAUSR

We read with interest the review by Pisapia et al about perspectives on ALK and ROS1 testing for cytologic lung cancer samples. In addition to fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC), we agree that next-generation sequencing (NGS) and the nCounter system are promising tools for diagnosing ALK and ROS1 rearrangements and other EGFR, KRAS, BRAF, RET, and MET molecular alterations. Nevertheless, the financial implications of the different methods must be discussed for different health care systems as, for example, in this letter from a French point of view. Taking into account the proposed prices of cancerrelated molecular tests in France and our national guidelines focusing on EGFR, KRAS, ALK, and ROS1 testing in patients with advanced non–small cell lung cancer (NSCLC), we compared the costs of different strategies for searching for these molecular alterations. An NGS analysis using a gene-panel approach has been proposed at the cost of e882.9 in France. This price can include EGFR, KRAS, ALK, and ROS1 analyses and results in a cost of e88,290 to analyze 100 NSCLC samples. An analysis restricted to EGFR and KRAS and using non-NGS molecular methods has been proposed at the cost of e459. As for ALK and ROS1, each FISH test costs e110.7, whereas ALK and ROS1 IHC costs e56. In this manner, in addition to NGS methods, combining an EGFR-KRAS analysis with ALK and ROS1 testing would cost e680.4 per sample with FISH testing or e515 per sample with IHC. French guidelines now recommend first-line ALK and ROS1 IHC followed by the corresponding FISH test only in cases of ambiguous ALK IHC results (ie, a score of 1 1 or 21, which occurs in less than 5% of NSCLC cases in our experience) or any ROS1 IHC–positive results (ie, a score of 1 1 to 31, which occurs in less than 10% of NSCLC cases in our experience) to confirm the oncogenic rearrangements. Following these guidelines and combining non-NGS EGFRKRAS testing with ALK and ROS1 testing to analyze 100 NSCLC samples (ie, 100 ALK and ROS1 IHC analyses followed by 5 ALK FISH tests and 10 ROS1 FISH tests) would cost approximately e69,700 and would remain cheaper than NGS analyses to date. Another advantage of non-NGS methods is that some of them can easily be implemented in the daily practice of many pathology laboratories without the need for centralized, expensive, and time-consuming analyses in units expert at molecular pathology. In conclusion, we believe that because of the actual costs of NGS analyses, non-NGS methods are still valuable and cost-effective methods for analyzing NSCLC samples.