Panels of various sizes exist for NGS analysis of tumor samples. However, not much is known regarding the panel size that represents the best choice for specific cancer types. Therapeutic goal of NGS sequencing is to facilitate therapy and clinical trial identification based on a patient’s specific mutation profile. GenomOncology’s proprietary Match software enables us to generate therapy and trial recommendations from molecular marker data. We set out to discover whether the use of large gene panel leads to the generation of a greater number of recommendations for certain tumor types.
We analyzed therapy and trials recommendations for the patients in the GENIE consortium (www.aacr.org/Research/Research/Pages/aacr-project-genie.aspx). Patients were grouped by size of NGS panels used in the study: large gene panels (275 genes or greater), and small gene panels (74 genes or fewer). Therapy and trial recommendations were analyzed separately. We calculated and compared the number of unique recommendations, percent of patients receiving recommendations per tumor type, and median number of unique recommendations per patient per tumor type. GenomOncology's therapy database is based on FDA, NCCN, ASCO, and My Cancer Genome, and includes database of all cancer-related clinical trials from clinicaltrials.gov.
We did not find an observable difference between proportion of patients receiving trial recommendations between institutions using large and small gene panels. A significant increase in the median number of trial recommendations was found for 22 tumor types in institutions using large gene panels. Predictably, we found an appreciable (>25%) increase in percent of patients receiving therapy recommendations in institutions using large panels for ovarian cancer, esophagogastric cancer, pancreatic cancer, glioma, bladder cancer, breast cancer and prostate cancer. A significant increase in the median number of therapy recommendations for institutions using large gene panels was found for breast cancer. Increase in recommendations for larger panels was driven by the presence of BRCA1 and BRCA2, as well as gene fusions, on the large gene panels. ARID1A, BRCA2, FLT4, ROS1 and TSC2 alterations generated the greatest number of breast cancer trial recommendations in large panel institutions.
The use of large gene panels may be advantageous when gathering therapy and trial recommendations for breast cancer patients. This occurred due to detection of gene fusions and amplifications, as well as BRCA1, ARID1A, BRCA2, FLT4, ROS1 and TSC2 mutations in large gene panels. Increasing panel size significantly increases the number of trial recommendations for a number of tumor types, whereas it was only found to significantly increase the number of therapy recommendations in breast cancer.