52P - The concentration of mutated copies of driver genes in plasma closely mirrors the disease course in colorectal cancer, lung cancer, and melanoma patients

Background

The majority of colorectal cancers (CRCs), lung carcinomas (LCs) and melanomas contain hot-spot mutations in driver genes. This study evaluated the feasibility of disease monitoring using individual single-mutation tests for the analysis of circulating tumor DNA (ctDNA) in plasma.

Methods

The study included 49 patients with KRAS/BRAF-mutated CRC, EGFR-mutated LC, or BRAF-mutated melanoma, who received systemic treatment for metastatic disease. Blood samples were collected every 25-30 days; the number of time points varied from 2 to 12 for each patient with the individual follow-up ranging from 29 to 523 days (mean 208.7 ± 18.16). A total of 242 plasma samples were analyzed by droplet digital PCR to quantify ctDNA fragments carrying the corresponding driver mutation.

Results

In 25 patients (49%) no circulating mutant copies were detected in any of the serial samples; 24/25 (96%) of these ctDNA-negative subjects experienced either the reduction of tumor lumps or stable disease during the entire observation period. Twenty-four patients showed variations in the ctDNA status during the disease course. In 21/24 (88%) of these patients, the changes in the concentration of mutated ctDNA closely followed the dynamics of tumor volume as observed by computed tomography (CT). There were instances in which tumor progression was detected by liquid biopsy earlier than by imaging tools. One LC patient demonstrated an emergence of EGFR T790M mutation in the blood 126 days prior to tumor progression as registered by CT; in two other cases, the tumor growth was radiologically documented 23 and 34 days after the appearance of mutated ctDNA in plasma.

Conclusions

Serial ddPCR-based assessment of single driver mutations in ctDNA allows efficient monitoring of the efficacy of therapy in diverse categories of cancer patients. This work has been supported by the Russian Science Foundation grant #17-75-30027.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

The authors.

Funding

Russian Science Foundation grant #17-75-30027.

Disclosure

All authors have declared no conflicts of interest.