Individualized ctDNA Fingerprints to Monitor Treatment Response and Recurrence in Multiple Cancer Types

Circulating tumor DNA (ctDNA) panels hold high promise of accurately predicting the therapeutic response of tumors while being minimally invasive and cost-efficient. However, their use has been limited to a small number of tumor types and patients. Here, we developed individualized ctDNA fingerprints suitable for most patients with multiple cancer types. The panels were designed based on individual whole-exome sequencing data in 521 Chinese patients and targeting high clonal population clusters of somatic mutations. Together, these patients represent 12 types of cancers and seven different treatments. The customized ctDNA panels have a median somatic mutation number of 19, most of which are patient-specific rather than cancer hotspot mutations; 66.8% of the patients were ctDNA-positive. We further evaluated the ctDNA content fraction (CCF) of the mutations, and analyzed the association between the change of ctDNA concentration and therapeutic response. We followed up 106 patients for clinical evaluation, demonstrating a significant correlation of changes in ctDNA with clinical outcomes, with a consistency rate of 93.4%. In particular, the median CCF increased by 204.6% in patients with progressive disease, decreased by 82.5% in patients with remission, and was relatively stable in patients with stable disease. Overall, 85% of the patients with a ctDNA-positive status experienced metastasis or relapse long before imaging detection, except for two patients who developed recurrence and metastasis almost simultaneously. The average lead time between the first ctDNA-positive finding and radiological diagnosis was 76 days in three patients that changed from a ctDNA-negative to -positive status. Our individualized ctDNA analysis can effectively monitor the treatment response, metastasis, and recurrence in multiple cancer types in patients with multiple treatment options, therefore offering great clinical applicability for improving personalized treatment in cancer. One Sentence Summary ctDNA fingerprint panels were customized to predict the treatment response for multiple cancer types from individual whole-exome sequencing data.