1918MO - Circulating tumor DNA in relation to tumor volume in gastro-intestinal stromal tumors

Background

Locally advanced/metastatic gastro-intestinal stromal tumors (GIST) are followed with 3-6 monthly CT-scans to evaluate treatment response with tyrosine kinase inhibitors (TKIs). As a result, patients are exposed to accumulative levels of radiation. Therefore, a growing interest on the use of circulating tumor DNA (ctDNA) to monitor treatment response has arisen. Previous research reported the correlation of ctDNA with tumor volume as new tool for monitoring treatment response. The aim of this exploratory study was to evaluate the use of ctDNA testing in GIST patients treated with TKIs, and to compare changes in the levels of ctDNA with tumor volume (3D) with CT-scan results assessed according to RECIST 1.1.

Methods

147 plasma samples from 7 GIST patients with a KIT exon 11 mutation were prospectively collected before or during treatment and follow-up between 2014-2021. Plasma ctDNA levels were determined using a validated KIT exon 11 digital droplet PCR (ddPCR) drop-off assay. RECIST outcome was extracted from routine imaging reports of follow-up CT scans. Clinical relevant samples were selected based on RECIST outcome (response to treatment or progressive disease) or start of a new treatment line. Total tumor volume measurements with a semi-automated manner, allowing for manual correction, were performed by an independent radiologist.

Results

101 clinically relevant plasma samples were analyzed. In all baseline samples the primary tumor KIT exon 11 mutation could be detected in ctDNA, ranging from 1.54 to 2287.81 copies per mL plasma. Upon response to treatment, ctDNA completely disappeared in all patients. At progressive disease, ctDNA could be, at least once, detected in 6 of 7 patients. Higher tumor volumes (from 450 mL) correlated with higher levels of ctDNA. In each individual patient with progressive disease on imaging, undetectable ctDNA was consistent with lower tumor volumes than detectable ctDNA.

Conclusions

Total tumor volume measurement is the most accurate indicator of GIST disease activity. No absolute cut-off value of tumor volume in which ctDNA could be detected could (yet) be determined to indicate active (progressive) disease. CtDNA can be a promising and cost-effective additional follow-up tool to monitor treatment response.

Clinical trial identification

NCT02331914.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

This project is funded by the Dutch Cancer Foundation (KWF), Alpe d’HuZes research grant RUG 2013-6355.

Disclosure

All authors have declared no conflicts of interest.