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In solid tumor oncology, circulating tumor DNA (ctDNA) is poised to transform care through accurate assessment of minimal residual disease (MRD) and therapeutic response monitoring. To overcome the sparsity of ctDNA fragments in low tumor fraction (TF) settings and increase MRD sensitivity, we previously leveraged genome-wide mutational integration through plasma whole genome sequencing (WGS). We now introduce MRD-EDGE, a composite machine learning-guided WGS ctDNA single nucleotide variant (SNV) and copy number variant (CNV) detection platform designed to increase signal enrichment. MRD-EDGE uses deep learning and a ctDNA-specific feature space to increase SNV signal to noise enrichment in WGS by 300X compared to our previous noise suppression platform MRDetect. MRD-EDGE also reduces the degree of aneuploidy needed for ultrasensitive CNV detection through WGS from 1Gb to 200Mb, thereby expanding its applicability to a wider range of solid tumors. We harness the improved performance to track changes in tumor burden in response to neoadjuvant immunotherapy in non-small cell lung cancer and demonstrate ctDNA shedding in precancerous colorectal adenomas. Finally, the radical signal to noise enrichment in MRD-EDGE enables de novo mutation calling in melanoma without matched tumor, yielding clinically informative TF monitoring for patients on immune checkpoint inhibition.

Purpose: Colorectal cancer (CRC) recurrence is not routinely recorded in Danish health data registries. Here, we aimed to revalidate a registry-based algorithm to identify recurrences in a contemporary cohort and to investigate the accuracy of estimating the time to recurrence (TTR). Patients and Methods: We ascertained data on 1129 patients operated for UICC TNM stage I-III CRC during 2012-2017 registered in the CRC biobank at the

IIA was found to be a feasible and safe technique in laparoscopic resections of the right colon with an AL rate of 4.2%.

Circulating tumor DNA detection using next-generation sequencing (NGS) data of plasma DNA is promising for cancer identification and characterization. However, the tumor signal in the blood is often low and difficult to distinguish from errors. We present DREAMS (Deep Read-level Modelling of Sequencing-errors) for estimating error rates of individual read positions. Using DREAMS, we develop statistical methods for variant calling (DREAMS-vc) and cancer detection (DREAMS-cc). For evaluation, we generate deep targeted NGS data of matching tumor and plasma DNA from 85 colorectal cancer patients. The DREAMS approach performs better than state-of-the-art methods for variant calling and cancer detection.

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BackgroundPatients with peritoneal malignancy treated by cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) are prone to develop postoperative paralytic ileus (POI). POI is associated with significant increase in both morbidity and mortality. CRS and HIPEC commonly result in prolonged POI (PPOI). The objective was to clarify the extent of PPOI in patients treated by CRS and HIPEC for peritoneal malignancy.MethodsThis was a prospective multicenter study including patients operated with CRS and HIPEC at the Department of Surgery, Aarhus University Hospital, Denmark and the Peritoneal Malignancy Institute, Basingstoke, United Kingdom. A total of 85 patients were included over 5 months. Patients prospectively reported parameters of postoperative gastrointestinal function in a diary from post-operative day 1 (POD1) until discharge. PPOI was defined as first defecation on POD6 or later.ResultsMedian time to first flatus passage was 4 days (range 1–12). Median time to first defecation was 6 days (1–14). Median time to removal of nasojejunal tube was 4 days (3–13) and 7 days (1–43) for nasogastric tube. Forty-six patients (54%) developed PPOI. Patients with PPOI had longer time to first flatus (p<0.0001) and longer time to removal of nasojejunal tube (p=0.001). Duration of surgery correlated to time to first flatus (p=0.015) and time to removal of nasogastric or nasojejunal tube (p<0.0001) but not to time to first defecation (p=0.321).ConclusionsPostoperative gastrointestinal paralysis remains a common and serious problem in patients treated with CRS and HIPEC.