In the US, lung cancer will add 224,210 new cases and cause 159,260 deaths in 2014. Non- small cell lung cancer (NSCLC) accounts for 80% of lung cancer. The availability of targeted therapies directed to driver oncogenes such as EGFR mutations and gene fusions (e.g., EML4- ALK) in recent years has transformed the management of NSCLC. These advances have also created an unprecedented challenge to conduct multiple molecular testing using limited diagnostic materials. In many settings, 40-50% of NSCLC patients present with advanced disease and are simultaneously diagnosed, staged and their tumors molecularly tested for targeted therapy using fine needle aspiration (FNA)-derived cytology specimen obtained during endobronchial ultrasound (EBUS). Liquid-based cytology slides, especially ThinPrep slides, have proven superior to formalin-fixed paraffin-embedded (FFPE) cell blocks for assessing ALK gene status by DNA fluorescent in situ hybridization (FISH). However, the number of ThinPrep slides that can be prepared from a typical EBUS-FNA specimen is limited (usually 2-3). In order to perform multiple testing, an in situ method with multiplexing capability beyond conventional FISH and immunohistochemistry (IHC) is needed. In this Phase I study, we propose to leverage the high sensitivity and multiplexing capability of a recently developed RNA in situ hybridization technology (RNAscope(R)) to develop a novel companion diagnostic algorithm that can efficiently and accurately detect multiple rare but actionable oncogenic gene fusions (ALK, ROS1, RET, NTRK1 and others) in NSCLC patients using FNA-derived ThinPrep slides.
The current increasing use of minimally invasive diagnostic procedures in oncology poses a number of challenges to companion diagnostic testing. First, while the number of molecular targets to be tested is increasing on a regular basis, the amount of diagnostic specimen is decreasing. Second, most of the molecular changes of interest are present only in small subsets (~1%) of patients. Therefore, there is an urgent need to develop molecular diagnostic methods that have multiplexing capability beyond conventional fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) yet maintain the benefits of in situ biomarker detection. In this Phase I study, we propose to leverage the high sensitivity and multiplexing capability of the RNAscope RNA ISH technology to develop a novel companion diagnostic algorithm that can efficiently and accurately detect multiple rare but 'actionable' oncogenic fusions in non-small cell lung cancer (NSCLC) using limited fine needle aspiration (FNA)-derived cytology samples.