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

Statement of translational relevanceSensitive methods for recurrence risk stratification, monitoring therapeutic efficacy, and early recurrence detection may have a major impact on treatment decisions and outcomes for stage III colorectal cancer patients. Circulating tumor DNA assessments performed postoperative, postadjuvant, and serially during surveillance all allowed stratification of patients into high and low risk groups. CtDNA detected recurrence with a significant leadtime compared to CT-imaging and ctDNA growth rates were prognostic of survival.Treatment of ctDNA positive patients with standard adjuvant therapy prevented recurrence in only 20% of patients. Accordingly, further studies exploring the optimal treatment for ctDNA positive patients are needed, as well as interventional studies assessing the clinical utility of ctDNA-based risk-stratification. A promising opportunity is risk-stratified allocation of surveillance resources, which may improve both the cost-effectiveness and the overall clinical outcome of surveillance. Finally, ctDNA growth rates may identify patients who could benefit from immediate therapeutic intervention compared to awaiting recurrence.Research.

Salvage surgery of recurrent or persistent anal cancer following radiotherapy is often followed by perineal wound complications. We examined survival and perineal wound complications in anal cancer salvage surgery during a 10-year period with primary perineal reconstruction predominantly performed using vertical rectus abdominis myocutaneous (VRAM) flap. Between 1997 and 2006, 49 patients underwent anal cancer salvage surgery. Of these, 48 had primary reconstruction with VRAM. Overall survival was computed by the Kaplan-Meier method and mortality rate ratios (MRRs) by Cox regression. One patient (2%) died within 30 days postoperatively. Postoperative complications necessitated reoperation in eight (16%) patients. We found no major perineal wound infections. Major perineal wound breakdown occurred in the only patient in whom VRAM was not used. Five-year survival was 61% [95% confidence interval (CI) 43-75%]. Free resection margins (R0) were obtained in 78% of patients, with 5-year survival of 75% (95% CI 53-87%). Involved margins, microscopically only (R1) or macroscopically (R2), strongly predicted an adverse outcome [age-adjusted 2-year MRRs (95% CI) R1 vs. R0 = 4.1 (0.7-23.6), R2 vs. R0 = 10.9 (2.2-54.2)]. We conclude that anal cancer salvage surgery can yield long-time survival but obtaining free margins is critical. A low rate of perineal complications is achievable by primary perineal reconstruction using VRAM flap.

Compromised immune function may increase the risk of anal squamous cell carcinoma (SCC). We examined the risk of anal SCC in patients with HIV infection and other chronic disorders associated with immunosuppression. A population‐based cohort study was conducted using the Danish National Patient Registry and the Danish Cancer Registry (DCR). We identified all patients with a first‐time hospital contact or procedure for HIV infection, solid organ transplantation or autoimmune disease or a first‐time record of haematologic malignancy in the DCR, 1978–2005, and followed these for a subsequent anal SCC, starting follow‐up 1 year after diagnosis of the index disease. Standardised incidence ratios (SIRs) were computed as the ratio of observed to expected numbers of anal SCCs, based on national age‐, sex‐ and period‐specific rates. Among 4,488 patients with HIV, we observed 21 anal SCCs with 0.3 expected (SIR: 81.1 (95% confidence interval (CI): 51.6–121.9)). Risk of anal SCC was markedly increased among 5,113 solid organ recipients (SIR: 14.4 (CI: 7.0–26.4)) and 30,165 patients with haematologic malignancies (SIR: 2.3 (CI: 1.1–4.2)) but only moderately increased among 242,114 patients with autoimmune diseases (SIR: 1.3 (CI: 1.0–1.6)). SIRs varied according to type of autoimmune disease and were high in patients with Crohn's disease (SIR: 3.1 (CI: 1.2–6.4)), psoriasis (SIR: 3.1 (CI: 1.8–5.1)), polyarteritis nodosa (SIR: 8.8 (CI: 1.5–29.0)) and Wegener's granulomatosis (SIR: 12.4 (CI: 2.1–40.8)). In conclusion, we found HIV infection, solid organ transplantation, haematologic malignancies and a range of specific autoimmune diseases strongly associated with increased risk of anal SCC.