Perioperative changes in cell-free DNA for patients undergoing surgery for colon cancer.

BACKGROUND: Various conditions with cellular decay are associated with elevated cell-free DNA (cfDNA). This study aimed to investigate if perioperatively measured cfDNA levels were associated with the surgical approach, complications, or recurrence. METHODS: Plasma was obtained from patients who underwent surgery for colon cancer at admission and at the time of discharge. Quantitative measurement of cfDNA was performed by amplifying two amplicons of 102 base pairs (bp) and 132 bp of Beta-2-Microglobulin (B2M) and Peptidyl-Prolyl cis-trans Isomerase A (PPIA), respectively. RESULTS: cfDNA was measured in 48 patients who underwent surgery for colonic cancer. Sixteen patients had recurrence during the follow-up period, fifteen developed a postoperative complication, and seventeen patients developed neither, acting as the control group. Postoperative cfDNA levels were significantly elevated from baseline samples, across all groups, with a median preoperatively B2M level of 48.3 alleles per mL and postoperatively of 220 alleles per mL and a median preoperatively level PPIA of 26.9 alleles per mL and postoperatively of 111.6 alleles per mL (p < 0.001 for B2M and p < 0.001 for PPIA). Postoperative levels of PPIA, but not B2M, were significantly higher in patients experiencing complications than in the control group (p = 0.036). However, a tendency towards an association between the surgical approach and the changes in cfDNA levels was found for PPIA (p = 0.058), and B2M (p = 0.087). CONCLUSIONS: Plasma cfDNA was increased after surgery in all patients with colon cancer. Postoperative PPIA levels were significantly higher in patients experiencing surgical complications but not in B2M levels.

Developing prediction models for short-term mortality after surgery for colorectal cancer using a Danish national quality assurance database.

PURPOSE: The majority of colorectal cancer surgeries are performed electively, and treatment is often decided at the multidisciplinary team conference. Although the average 30-day mortality rate is low, there is substantial population heterogeneity from young, healthy patients to frail, elderly patients. The individual risk of surgery can vary widely, and tailoring treatment for colorectal cancer may lead to better outcomes. This requires prediction of risk that is accurate and available prior to surgery. METHODS: Data from the Danish Colorectal Cancer Group database was transformed into the Observational Medical Outcomes Partnership Common Data Model. Models were developed to predict the risk of mortality within 30, 90, and 180 days after colorectal cancer surgery using only covariates decided at the multidisciplinary team conference. Several machine-learning models were trained, but due to superior performance, a Least Absolute Shrinkage and Selection Operator logistic regression was used for the final model. Performance was assessed with discrimination (area under the receiver operating characteristic and precision recall curve) and calibration measures (calibration in large, intercept, slope, and Brier score). RESULTS: The cohort contained 65,612 patients operated for colorectal cancer in the period from 2001 to 2019 in Denmark. The Least Absolute Shrinkage and Selection Operator model showed an area under the receiver operating characteristic for 30-, 90-, and 180-day mortality after colorectal cancer surgery of 0.871 (95% CI: 0.86-0.882), 0.874 (95% CI: 0.864-0.882), and 0.876 (95% CI: 0.867-0.883) and calibration in large of 1.01, 0.98, and 1.01, respectively. CONCLUSION: The postoperative short-term mortality prediction model showed excellent discrimination and calibration using only preoperatively known predictors.