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Background Circulating tumor DNA (ctDNA) detection following curative-intent surgery could directly reflect the presence of minimal residual disease, the ultimate cause of clinical recurrence. However, ctDNA is not postoperatively detected in ≥ 50% of patients with stage I-III colorectal cancer (CRC) who ultimately recur. Herein we sought to improve recurrence risk prediction by combining ctDNA with clinicopathological risk factors in stage I-III CRC. Methods Two independent cohorts, both consisting of early-stage CRC patients who underwent curative surgery, were included: (i) the discovery cohort (N = 124) with tumor tissues and postoperative plasmas for ctDNA determination; and (ii) the external validation cohort (N = 125) with available ctDNA results. In the discovery cohort, somatic variations in tumor tissues and plasmas were determined via a 733-gene and 127-gene next-generation sequencing panel, respectively. Results In the discovery cohort, 17 of 108 (15.7%) patients had detectable ctDNA. ctDNA-positive patients had a significantly high recurrence rate (76.5% vs. 16.5%, P Conclusion Combining postoperative ctDNA and clinical risk may better predict recurrence than ctDNA alone for developing a personalized postoperative management strategy for CRC.

Background: Immune checkpoint inhibitors (ICIs) of programmed cell death 1 (PD-1) and its ligand (PD-L1) have led to a paradigm shift in cancer treatment. Here we conducted a systematic review and meta-analysis to compare the efficacy and safety profile of anti-PD-1 and anti-PD-L1 in pan-cancer patients. Methods: We systematically searched PubMed, CENTRAL, and Embase from January, 2000 to March, 2019 for randomized controlled trials that compared anti-PD-1 and anti-PD-L1 with standard treatment in patients with solid tumors. We also reviewed abstracts and presentations from all major conference proceedings. Studies with anti-PD-1 and anti-PD-L1 were screened and paired upon the matching of clinical characteristics as mirror groups. For the main results, effect size for each mirror group was derived from the frequentist approach with R package netmeta, and pooled using a random-effects model. The primary outcome was the difference in overall survival (OS) between anti-PD-1 and anti-PD-L1. Findings: 19 randomized controlled trials involving 11,500 patients were included for the meta-analysis. Overall, anti-PD-1 exhibited superior OS (HR 0.75, 95% CI 0.65-0.86i¼ŒP