Utility of ctDNA in Personalized Therapy for Non-small-cell Lung Cancer

Lung cancer is the most common fatal cancer among men and women worldwide and the 5-year survival rate is about 16%, which has only improved minimally in the last decade. In recent years, better understanding of oncogenic drivers has led to the targeted therapies which have the potential to improve survival substantially. One of the major challenges of targeted therapies is an inevitable occurance of resistance and as a result only a relatively small proportion of patients benefit from these therapies. Often, reistance can be detected by a tissue biopsy at teh time of recurrence, but, repeated procedures to mnitor for the development of treatment are invasive and undesirable for patients. Circulating tumor DNA (ctDNA) in the blood plasma has been widely used as an alternative to detect the small number of known actionable mutations. Studies using a next-generation sequencing (NGS) panel consisting of all known actionable mutations have small cohorts and are few in njumber. Therefore, in the proposed study, we will evaluate the utility of ct DNA using our custom NGS-based gene panel for personalized therapy prediction and for monitoring treatment response. We will use ultra-deep sequencing approach to sequence target regions in the circulating free DNA (cfDNA) to identify the somatic mustations in the ctDNA in 100 new patients. We will then compare these results with the somatic mutations detected in the DNA from tissue ciopsies, performed as part of routine clinical care, to evaluate the efficiency of this approach. To evaluate the utility of this approach in monitoring treatment response, we will sequence cfDNA from 20 out of these 100 patients who undergo targeted therapy and compare the ctDNA level from pre and post treatment smaples with the radiographically measured tumor volumes.