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Circulating tumour DNA (ctDNA) is a potential biomarker that could contribute to more judicious patient selection for personalised treatment. This review and meta-analysis gives an overview of the current knowledge in the literature investigating the value of ctDNA in patients with colorectal liver metastases (CRLM). A systematic search was conducted in electronic databases for studies published prior to the 26th of May 2023. Studies investigating the association between ctDNA and oncological outcomes in patients undergoing curative-intent local therapy for CRLM were included. Meta-analyses were performed to pool hazard ratios (HR) for the recurrence-free survival (RFS) and overall survival (OS). A total of eleven studies were included and nine were eligible for meta-analyses. Patients with detectable ctDNA after surgery experienced a significantly higher chance of recurrence (HR 3.12, 95% CI 2.27–4.28, p < 0.000010) and shorter OS (HR 5.04, 95% CI 2.53–10.04, p < 0.00001) compared to patients without detectable ctDNA. A similar association for recurrence was found in patients with detectable ctDNA after the completion of adjuvant therapy (HR 6.39, 95% CI 2.13–19.17, p < 0.0009). The meta-analyses revealed no association between detectable ctDNA before surgery and the RFS and OS. These meta-analyses demonstrate the strong association between detectable ctDNA after treatment and oncological outcomes in CRLM patients.

Background: Involved lateral lymph nodes (LLNs) have been associated with increased local recurrence (LR) and ipsi-lateral LR (LLR) rates. However, consensus regarding the indication and type of surgical treatment for suspicious LLNs is lacking. This study evaluated the surgical treatment of LLNs in an untrained setting at a national level. Methods: Patients who underwent additional LLN surgery were selected from a national cross-sectional cohort study regarding patients undergoing rectal cancer surgery in 69 Dutch hospitals in 2016. LLN surgery consisted of either ‘node-picking’ (the removal of an individual LLN) or ‘partial regional node dissection’ (PRND; an incomplete resection of the LLN area). For all patients with primarily enlarged (≥7 mm) LLNs, those undergoing rectal surgery with an additional LLN procedure were compared to those undergoing only rectal resection. Results: Out of 3057 patients, 64 underwent additional LLN surgery, with 4-year LR and LLR rates of 26% and 15%, respectively. Forty-eight patients (75%) had enlarged LLNs, with corresponding recurrence rates of 26% and 19%, respectively. Node-picking (n = 40) resulted in a 20% 4-year LLR, and a 14% LLR after PRND (n = 8; p = 0.677). Multivariable analysis of 158 patients with enlarged LLNs undergoing additional LLN surgery (n = 48) or rectal resection alone (n = 110) showed no significant association of LLN surgery with 4-year LR or LLR, but suggested higher recurrence risks after LLN surgery (LR: hazard ratio [HR] 1.5, 95% confidence interval [CI] 0.7–3.2, p = 0.264; LLR: HR 1.9, 95% CI 0.2–2.5, p = 0.874). Conclusion: Evaluation of Dutch practice in 2016 revealed that approximately one-third of patients with primarily enlarged LLNs underwent surgical treatment, mostly consisting of node-picking. Recurrence rates were not significantly affected by LLN surgery, but did suggest worse outcomes. Outcomes of LLN surgery after adequate training requires further research.

Background: Circulating 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. Methods: A 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). Results: A 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. Conclusions: This 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.

Background: In current practice, rates of locally recurrent rectal cancer (LRRC) are low due to the use of the total mesorectal excision (TME) in combination with various neoadjuvant treatment strategies. However, the literature on LRRC mainly consists of single- and multicenter retrospective cohort studies, which are prone to selection bias. The aim of this study is to provide a nationwide, population-based overview of LRRC after TME in the Netherlands. Patients and Methods: In total, 1431 patients with nonmetastasized primary rectal cancer diagnosed in the first six months of 2015 and treated with TME were included from the nationwide, population-based Netherlands Cancer Registry. Data on disease recurrence were collected for patients diagnosed in these 6 months only. Competing risk cumulative incidence, competing risk regression, and Kaplan–Meier analyses were performed to assess incidence, risk factors, treatment, and overall survival (OS) of LRRC. Results: Three-year cumulative incidence of LRRC was 6.4%; synchronous distant metastases (LRRC-M1) were present in 44.9% of patients with LRRC. Distal localization, R1–2 margin, (y)pT3-4, and (y)pN1-2 were associated with an increased LRRC rate. No differences in LRRC treatment and OS were found between patients who had been treated with or without prior n(C)RT. Curative-intent treatment was given to 42.9% of patients with LRRC, and 3-year OS thereafter was 70%. Conclusions: Nationwide LRRC incidence was low. A high proportion of patients with LRRC underwent curative-intent treatment, and OS of this group was high in comparison with previous studies. Additionally, n(C)RT for primary rectal cancer was not associated with differences in treatment and OS of LRRC.

Purpose: Intraoperative radiation therapy (IORT), delivered by intraoperative electron beam radiation therapy (IOERT) or high-dose-rate intraoperative brachytherapy (HDR-IORT), may reduce the local recurrence rate in patients with locally advanced and locally recurrent rectal cancer (LARC and LRRC, respectively). The aim of this study was to compare the oncological outcomes between both IORT modalities in patients with LARC or LRRC who underwent a microscopic irradical (R1) resection.Methods: All consecutive patients who received IORT because of an R1 resection of LARC or LRRC between 2000 and 2016 in two tertiary referral centers were included. In LARC, a resection margin ofResults: In total, 215 patients with LARC were included, of whom 151 (70%) received IOERT and 64 (30%) received HDR-IORT; in addition, 158 patients with LRRC were included, of whom 112 (71%) received IOERT and 46 (29%) received HDR-IORT. After multivariable analyses, the overall survival was not significantly different between the two IORT modalities. The local recurrence-free survival was significantly longer in patients treated with HDR-IORT, both in LARC (hazard ratio [HR], 0.496; 95% CI, 0.253-0.973; P = .041) and LRRC (HR, 0.567; 95% CI, 0.349-0.920; P = .021). In patients with LARC, major postoperative complications were similar for both IORT modalities (IOERT, 30%; HDR-IORT, 27%), whereas in patients with LRRC, the incidence of major postoperative complications was higher after HDR-IORT (IOERT, 26%; HDR-IORT, 46%).Conclusions: This study showed a significantly better local recurrence-free survival in favor of HDR-IORT in patients with an R1 resection for LARC or LRRC. Optimization of the IOERT technique seems warranted. (C) 2021 Elsevier Inc. All rights reserved.

Aim: To describe the incidence, treatment and survival of patients with rare types of rectal malignancies in the Netherlands. Methods: Data of patients with rectal malignancies diagnosed in the Netherlands between 1989 and 2018 were retrieved from the Netherlands Cancer Registry and grouped according to the RARECARE cancer list. Age-standardised incidence rates were calculated using the European Standard Rate. The Joinpoint Regression Program was used for analysing trends and joinpoints and for the estimation of annual percentage changes (APCs). Patient characteristics, treatment details and relative survival (RS) were reported for different histological types of rectal malignancies and compared between different time periods. RS was assessed using Kaplan-Meier analysis and log-rank test. Results: A total of 88,299 cases of rectal malignancies were included of which 2125 (2.5%) were categorised as rare histological subtypes. The incidence of rectal neuro-endocrine tumours (NET) (APC: 6.2%, 95% confidence interval [CI]: 5.4%; 7.1%), rectal sarcoma (APC: 5.8%, 95% CI: 2.9%; 8.7%) and rectal adenocarcinoma (APC 1.0%, 95% CI: 0.26%; 1.8%) increased. Prognosis was best in patients with rectal NET (5-year RS: 72.4%, 95% CI: 70.1%; 74.7%) and worst in patients with rectal melanoma (5-year RS: 8.9%, 95% CI: 5.1%; 15.7%). RS has improved in patients with rectal adenocarcinoma, rectal sarcoma and rectal lymphoma in 2008–2018 (p-values p < 0.001, p = 0.023 and p = 0.029). Conclusion: Significant increases in incidence were observed for different types of rectal malignancies. Differences in incidence, treatment and survival found in this study could be useful to make clinicians aware of specific diseases.

BACKGROUND: Pelvic exenteration for locally advanced rectal cancer (LARC) and locally recurrent (LRRC) rectal cancer provides radical resection and local control, but is associated with considerable morbidity. The aim of this study was to determine risk factors, including nutritional status and body composition, for postoperative morbidity and survival after pelvic exenteration in patients with LARC or LRRC.METHODS: Patients with LARC or LRRC who underwent total or posterior pelvic exenteration in a tertiary referral centre from 2003 to 2018 were analysed retrospectively. Nutritional status was assessed using the Malnutrition Universal Screening Tool (MUST). Body composition was estimated using standard-of-care preoperative CT of the abdomen. Logistic regression analyses were performed to identify risk factors for complications with a Clavien-Dindo grade of III or higher. Risk factors for impaired overall survival were calculated using Cox proportional hazards analysis.RESULTS: In total, 227 patients who underwent total (111) or posterior (116) pelvic exenteration were analysed. Major complications (Clavien-Dindo grade at least III) occurred in 82 patients (36.1 per cent). High risk of malnutrition (MUST score 2 or higher) was the only risk factor for major complications (odds ratio 3.99, 95 per cent c.i. 1.76 to 9.02) in multivariable analysis. Mean follow-up was 44.6 months. LRRC (hazard ratio (HR) 1.61, 95 per cent c.i. 1.04 to 2.48) and lymphovascular invasion (HR 2.20, 1.38 to 3.51) were independent risk factors for impaired overall survival.CONCLUSION: A high risk of malnutrition according to the MUST is a strong risk factor for major complications in patients with LARC or LRRC undergoing exenteration surgery.