Characteristics of cancer patients undergoing molecular residual disease testing with a tumor-informed assay.

568 Background: Detection of circulating tumor DNA (ctDNA) is strongly associated with recurrence across a variety of cancers. The use of ctDNA testing to measure molecular residual disease (MRD) is still in its infancy, and understanding sample characteristics may help set expectations for oncologists and their patients. Methods: For the first thousand patients with MRD testing in Exact Sciences’ commercial laboratory, the tumor and first plasma sample were used to record tumor type, tumor sample type (biopsy/surgical), tumor stage, MRD assay panel size (up to 200 variants), cfDNA levels, and ctDNA status (qualitative and quantitative), and, when data were available, presence of targetable alterations (TAs) were recorded. Results: A total of 1088 samples with valid results were included. Patients were mostly female (N=703, 64.6%) with a median age of 64 (range 17–97) years, and most had either breast (N=380, 34.9%) or colorectal (N=335, 30.8%) cancer. Most (N=632, 58.1%) tumor samples were surgical, and average number of variants for MRD assays from 86 in ovarian cancer to 189 in melanoma. Plasma cfDNA yield ranged from 15 ng (the minimum required) to 10,709 ng and was significantly higher in 412 ctDNA+ (median 86.1 ng, mean 239.7 ng) compared to ctDNA– (median 73.5 ng, mean 114.6 ng) samples (p<0.001). In 13 cancers with at least 10 patient samples, only breast cancer showed a difference in the average number of identified variants between sample types (biopsy: 129.1 versus surgical: 101.5), stage IV cancers had more cfDNA than stage I, range of ctDNA+ samples was from 27% in melanoma to 65% in gastroesophageal cancers, and ctDNA+ proportion tended to increase with stage: 26 (14.2%) of 183 stage I, 84 (32.1%) of 262 stage II, 140 (38.9%) of 360 stage III, and 140 (65.1%) of 215 stage IV. ctDNA+ samples had levels between 2.6 and ≥352,000 parts per million (PPM), with 27 (6.6%) samples below 15 PPM, 40 (9.7%) between 15 and 50 PPM, and 345 (83.7%) above 50 PPM. Genomic profiling was performed on 158 samples, most from breast (N=50, 31.6%) and colorectal (N=17, 10.8%) cancer patients. The mean number of TAs per sample was 4.6, with little difference between the 114 ctDNA+ patients (mean = 4.4, range 0–24) and 44 ctDNA– patients (mean = 5.1, range 1–29). TAs were present in 83 (72.8%) and 36 (81.8%) tumors in ctDNA+ and ctDNA– patients, respectively. Of note, both high microsatellite instability and high tumor mutational burden tumors had numerically higher proportion in ctDNA– (15.9% and 9.1%, respectively) compared to ctDNA+ (5.3% in both) patients. Conclusions: ctDNA+ frequency varied by cancer type and cfDNA yields and ctDNA+ proportion increased numerically with stage, though where patients were in their treatment cycles was unknown. Of patients with profiling results, a large proportion of patients had TAs regardless of ctDNA status, indicating a potential for immediate consideration of matched therapies in ctDNA+ patients.