Search

BackgroundCirculating tumour DNA (ctDNA) has been established as a promising (prognostic) biomarker with the potential to personalise treatment in cancer patients. The objective of this systematic review is to provide an overview of the current literature and the future perspectives of ctDNA in non-metastatic rectal cancer.MethodsA comprehensive search for studies published prior to the 4th of October 2022 was conducted in Embase, Medline, Cochrane, Google scholar, and Web of Science. Only peer-reviewed original articles and ongoing clinical trials investigating the association between ctDNA and oncological outcomes in non-metastatic rectal cancer patients were included. Meta-analyses were performed to pool hazard ratios (HR) for recurrence-free survival (RFS).ResultsA total of 291 unique records were screened, of which 261 were original publications and 30 ongoing trials. Nineteen original publications were reviewed and discussed, of which seven provided sufficient data for meta-analyses on the association between the presence of post-treatment ctDNA and RFS. Results of the meta-analyses demonstrated that ctDNA analysis can be used to stratify patients into very high and low risk groups for recurrence, especially when detected after neoadjuvant treatment (HR for RFS: 9.3 [4.6 – 18.8]) and after surgery (HR for RFS: 15.5 [8.2 – 29.3]). Studies investigated different types of assays and used various techniques for the detection and quantification of ctDNA.ConclusionsThis literature overview and meta-analyses provide evidence for the strong association between ctDNA and recurrent disease. Future research should focus on the feasibility of ctDNA-guided treatment and follow-up strategies in rectal cancer. A blueprint for agreed-upon timing, preprocessing, and assay techniques is needed to empower adaptation of ctDNA into daily practice.

Abstract Background Colorectal cancer is the third most common type of cancer in the world. We characterize a cohort of patients who survived up to 5 years without recurrence and identify factors predicting the probability of cure. Methods We analyzed data of patients who underwent curative intent surgery for stage I–III CRC between 2007 and 2012 and who had had been included in a large multicenter study in the Netherlands. Cure was defined as 5-year survival without recurrence. Survival data were retrieved from a national registry. Results Analysis of data of 754 patients revealed a cure rate of 65% (n = 490). Patients with stage I disease and T1- and N0-tumor had the highest probability of cure (94%, 95% and 90%, respectively). Those with a T4-tumor or N2-tumor had the lowest probability of cure (62% and 50%, respectively). A peak in the mortality rate for older patients early in follow-up suggests early excess mortality as an explanation. A similar trend was observed for stage III disease, poor tumor grade, postoperative complications, sarcopenia, and R1 resections. Patients with stage III disease, poor tumor grade, postoperative complications, sarcopenia, and R1 resections show a similar trend for decrease in CSS deaths over time. Conclusion In the studied cohort, the probability of cure for patients with stage I–III CRC ranged from 50 to 95%. Even though most patients will be cured from CRC with standard therapy, standard therapy is insufficient for those with poor prognostic factors, such as high T- and N-stage and poor differentiation grade.

Background and AimsFailing immune surveillance in pancreatic ductal adenocarcinoma (PDAC) is related to poor prognosis. PDAC is also characterized by its substantial alterations to patients’ body composition. Therefore, we investigated associations between the host systemic immune inflammation response and body composition in patients with resected PDAC.MethodsPatients who underwent a pancreatectomy for PDAC between 2004 and 2016 in two tertiary referral centers were included. Skeletal muscle mass quantity and muscle attenuation, as well as subcutaneous and visceral adipose tissue at the time of diagnosis, were determined by CT imaging measured transversely at the third lumbar vertebra level. Baseline clinicopathological characteristics, laboratory values including the systemic immune inflammation index (SIII), postoperative, and survival outcomes were collected.ResultsA total of 415 patients were included, and low skeletal muscle mass quantity was found in 273 (65.7%) patients. Of the body composition indices, only low skeletal muscle mass quantity was independently associated with a high (≥900) SIII (OR 7.37, 95% CI 2.31-23.5, p=0.001). The SIII was independently associated with disease-free survival (HR 1.86, 95% CI 1.12-3.04), and cancer-specific survival (HR 2.21, 95% CI 1.33-3.67). None of the body composition indices were associated with survival outcomes.ConclusionThis study showed a strong association between preoperative low skeletal muscle mass quantity and elevated host systemic immune inflammation in patients with resected PDAC. Understanding how systemic inflammation may contribute to changes in body composition or whether reversing these changes may affect the host systemic immune inflammation response could expose new therapeutic possibilities for improving patients’ survival outcomes.

Changes in body composition are associated with chemotherapy-related toxicities and effectiveness of treatment. It is hypothesized that the pharmacokinetics (PK) of chemotherapeutics may depend on body composition. The effects of body composition on the variability of paclitaxel PK were studied in patients with esophageal cancer. Skeletal muscle index (SMI), visceral adipose tissue (VAT), and skeletal muscle density (SMD) were measured at the third lumbar vertebra on computed tomography (CT) scans performed before treatment. Paclitaxel PK data were collected from a prospective study performed between May 2004 and January 2014. Non-linear mixed-effects modeling was used to fit paclitaxel PK profiles and evaluate the covariates body surface area (BSA), SMI, VAT, and SMD using a significance threshold of p < 0.001. Paclitaxel was administered to 184 patients in a dose range of 50 to 175 mg/m2. Median BSA was 1.98 m2 (range of 1.4 to 2.8 m2). SMI, VAT, and SMD were not superior to BSA in predicting paclitaxel PK. The additive value of SMI, VAT, and SMD to BSA was also negligible. We did not find evidence that paclitaxel dosing could be further optimized by correcting for SMI, VAT, or SMD.

Low skeletal muscle mass is associated with poor postoperative outcomes in cancer patients. Furthermore, it is associated with increased healthcare costs in the United States. We investigated its effect on hospital expenditure in a Western-European healthcare system, with universal access.Skeletal muscle mass (assessed on CT) and costs were obtained for patients who underwent curative-intent abdominal cancer surgery. Low skeletal muscle mass was defined based on pre-established cut-offs. The relationship between low skeletal muscle mass and hospital costs was assessed using linear regression analysis and Mann-Whitney U-tests.452 patients were included (median age 65, 61.5% males). Patients underwent surgery for colorectal cancer (38.9%), colorectal liver metastases (27.4%), primary liver tumours (23.2%), and pancreatic/periampullary cancer (10.4%). In total, 45.6% had sarcopenia. Median costs were €2,183 higher in patients with low compared with patients with high skeletal muscle mass (€17,144 versus €14,961; P