6. of diagnostic accuracy Barnet, M.B., et al., Advanced NSCLC and Response to EGFR Tyrosine Kinase Inhibitors. J Thorac Oncol, online Sep 2016 ahead of publication, Australian study into the impact of (double or multiple mutation), compared with a single mutation, of the EGFR gene on response to tyrosine kinase inhibitors (TKIs) in patients with metastatic non small cell lung cancer (NSCLC). The study included 62 patients; eight (12.9%) with a co-mutation. Progression-free survival (PFS) in patients with EGFR co-mutation was shorter, and response rate significantly lower, than in patients with a single mutation. The study demonstrated that data from multipanel testing identifies subgroups of patients who are likely to respond poorly to standard treatment and clarification of these subgroups may improve patient care. Sep 2016 7. Clinical trial Hollebecque A, Massard C, De Baere T, Auger N, Lacroix L, Koubi-Pick V, et al. Molecular screening for cancer treatment optimization (MOSCATO 01): A prospective molecular triage results. J Clin Oncol 2013; 31, (suppl; abstr 2512). Clinical of patients with advanced solid tumours who had failed a standard therapy. Biopsies of the patients’ metastatic cancers were sequenced for 30 target genes. PFS using therapy based on the genomic alterations (GA) was compared to PFS on most recent therapy [129 patients, 111 (86%) had tumor biopsy, 52 had an actionable target (40%); 25 pts (23% of biopsied pts) treated with a targeted therapy]. The trial interim results demonstrate improved anti-tumour activity results for specific GA. 2013 8. Cost-benefit analysis Kircher SM, Mohindra N, Nimeiri H: Cost estimates and economic implications of expanded RAS testing US cost-benefit study of expanding RAS testing for metastatic colorectal cancer. The study concluded that the increased societal cost of expanded RAS testing 2015
in metastatic colorectal cancer. Oncologist 2015; 20:14-8. versus standard approved KRAS exon 2 testing was inconsequential when compared with the amount of money saved by not treating the additional 18% of patients who harbor additional RAS mutations (beyond exon 2) with therapy. 9 Study of diagnostic accuracy Sakai K, Tsurutani J, Yamanaka T, et al: Extended RAS and BRAF Mutation Analysis Using Next-Generation Sequencing. PLoS ONE 10:e0121891, 2015 A study into the clinical utility of multiplex deep sequencing to detect somatic mutations in KRAS, NRAS and BRAF in colorectal cancer [100 clinical formalin-fixed paraffin embedded (FFPE) tumour specimens, 15 plasma samples]. The genetic screening assay using a sequencer was validated for the detection of clinically relevant RAS and BRAF mutations using FFPE and liquid samples. 2015 10. Clinical review Kruglyak KM, Lin E, Ong FS. Next-Generation Sequencing and Applications to the Diagnosis and Treatment of Lung Cancer. Adv Exp Med Biol. Review of NGS technology in the diagnosis and treatment of lung cancer, providing a high-level overview of the role of NGS in precision oncology and the technical challenges involved. 2016 11. Clinical guidelines Sepulveda AR, Hamilton SR, Allegra CJ, et al: Molecular Biomarkers for the Evaluation of Colorectal Cancer: Guideline From the American Society for Clinical Pathology, College of American Pathologists, Association for Molecular Clinical practice guidelines recommending molecular biomarkers for best practice in the diagnosis and treatment of colorectal cancer. These guidelines highlight the importance of concurrent knowledge of the RAS and BRAF status of mCRC. 2017