Neoantigens evolutionary dynamics related tumors carry information on drug sensitivity and resistance to immune checkpoint blockade (ICB). However, the spectrum of somatic mutations are very heterogeneous between patients, making it difficult to track neoantigens by circulating tumor DNA (ctDNA) sequencing using a “one size fits all” commercial gene panel. Thus, individually adjustable panel (ICPs) that is needed to track the evolution of a comprehensive neoantigen during treatment ICB. dominant neoantigens estimated from all data that exome sequencing on tumor tissue that has not been treated.
The panel predicted neoantigens targeting is used to personalize ctDNA sequencing. Analyzing the ten patients with lung cancer non-small cell ICPs dominant neoantigens effective to track the most predictable (80-100%) in a series of peripheral blood samples, and to detect substantially more genes (18-30) of the capacity of the current commercial gene this panel. A decline of more than 50% in the concentration ctDNA after eight weeks of administration ICB associated with progression-free survival benefit. Furthermore, at the individual level, the magnitude of the initial ctDNA response correlated with subsequent changes in tumor burden. CtDNA ICP-based application of sequencing are expected to improve the understanding of the evolution of ICB-driven tumor and to provide personal management strategies that optimize the clinical benefit of immunotherapy.
Tracking Neoantigens by Personalized Circulating Tumor DNA Sequencing during Checkpoint Blockade Immunotherapy in Non-Small Cell Lung Cancer.
Identify locoregional gastric cancer patients at high risk for recurrence after resection can facilitate early intervention. By detecting the molecular residual disease (MRD), circulating tumor DNA (ctDNA) has been shown to predict postoperative recurrence in some cancers. Here, we aimed to evaluate the detection of MRD by ctDNA and its association with clinical outcomes in resected gastric cancer.
This prospective cohort study enrolled 46 patients with stage I-III gastric cancer who underwent resection with curative intent. Sixty resected tumor samples and 296 samples of plasma obtained for targeted sequencing within and extending ctDNA profiling. CtDNA detection correlated with clinicopathological features and postoperative disease-free (DFS) and overall survival (OS). ctDNA detected in 45% of plasma samples that have not been treated. As far as the primary tumor (T stage) were independently associated with preoperative positive ctDNA (p = 0.006)
