SummaryThe early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies

This cohort study investigates the use of longitudinal data from ultradeep sequencing of cell-free DNA in Danish patients with colorectal cancer.

Objective To estimate performance of a single-nucleotide-polymorphism–based noninvasive prenatal screen for fetal aneuploidy in high-risk and low-risk populations upon single venopuncture. Methods One thousand sixty-four maternal blood samples from 7 weeks of gestation and beyond were included; one thousand fifty-one were within specifications, 518 (49.3%) low-risk. Cell-free DNA was amplified, sequenced, and analyzed using the Next-generation Aneuploidy Test Using SNPs algorithm. Samples were called as trisomies 21, 18, 13, or monosomy X, or euploid, and male or female. Results Nine hundred sixty-six samples (91.9%) successfully generated a cell-free DNA result. Among these, sensitivity was 100% for trisomy 21 (58/58, CI: 93.8–100%), trisomy 13 (12/12, CI: 73.5–100%), and fetal sex (358/358 female, CI:99.0–100%; 418/418 male, CI: 99.1–100%), 96.0% for trisomy 18 (24/25, CI: 79.7–99.9%), and 90% for monosomy X (9/10, CI: 55.5–99.8%). Specificity for trisomies 21 and 13 was 100% (905/905 [CI: 99.6–100%] and 953/953 [CI: 99.6–100%], respectively) and for trisomy 18 and monosomy X was 99.9% (938/939 [CI: 99.4–100%] and 953/954 [CI: 99.4–100%], respectively). However, 16% (20/125) of aneuploid samples did not return a result; 50% (10/20) had a fetal fraction below the 1.5th percentile of euploid pregnancies. Aneuploidy rate was significantly higher in these samples (p<0.001, odds ratio: 9.2, CI: 4.4–19.0). Sensitivity and specificity did not differ in low-risk and high-risk populations. Conclusions This noninvasive prenatal screen performed with high sensitivity and specificity in high-risk and low-risk cohorts. Aneuploid samples were significantly more likely to not return a result; the number of aneuploidy samples was especially increased among samples with low fetal fraction. This underscores the importance of redraws or, in rare cases, invasive procedures based on low fetal fraction.