K-ACCELERATE: A multi-center prospective trial to evaluate the utility of a ctDNA-based assay for accelerating multi-cancer diagnosis among high-risk symptomatic participants.

Abstract

10555 Background: In low- and middle-income countries, most cancers are diagnosed after symptom onset, where non-specific symptoms complicate referral and delay diagnosis. We previously developed SPOT-MAS, a multi-cancer early detection test integrating epigenetic, genetic, and fragmentomic features of circulating tumor DNA (ctDNA). Here, we report results from K-ACCELERATE (NCT06391749), a prospective multi-center study evaluating SPOT-MAS as a diagnostic aid in symptomatic individuals. Methods: Adults (≥18 years) with symptoms suggestive of colorectal, gastric, breast, liver, or lung cancer were recruited across 13 hospitals in Vietnam from July 2024. All participants underwent SPOT-MAS testing alongside standard-of-care diagnostics and were followed for up to 12 months. Primary endpoints included sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and tissue-of-origin (TOO) accuracy, using imaging and/or biopsy as the reference standard, analyzed overall and by symptomatic pathway. Results: Of 972 eligible participants, 862 achieved diagnostic resolution and completed follow-up, including 130 cancer cases and 732 non-cancer cases. Overall sensitivity and specificity of SPOT-MAS were 65.4% (95% CI: 56.9–73.0) and 92.1% (95% CI: 89.9–93.8), respectively. Pathway-specific sensitivity was 58.7% for breast cancer, 62.1% for lung cancer, 64.3% for gastrointestinal cancers, 80.0% for liver cancer, and 100% for multiple-pathway presentations. Among confirmed cancer cases, ctDNA-based tissue-of-origin prediction achieved 82.4% accuracy. Incorporation of ctDNA testing into clinical triage increased PPV from 15.1% to 59.4%, representing a nearly four-fold improvement over symptom-based assessment, while maintaining a high NPV of 93.7%. Conclusions: This study provides clinical evidence supporting the feasibility of SPOT-MAS as a non-invasive adjunct diagnostic tool for individuals presenting with cancer-related symptoms in low-resource settings. These findings lay the foundation for future prospective interventional studies to evaluate the clinical impact of ctDNA-guided diagnostic pathways in high-risk symptomatic populations. Clinical trial information: NCT06391749 .