Circulating Tumour DNA as Biomarker for Colorectal Liver Metastases: A Systematic Review and Meta-Analysis.

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.

Circulating tumour DNA as biomarker for rectal cancer: A systematic review and meta-analyses.

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.

Locally Recurrent Rectal Cancer: Toward a Second Chance at Cure? A Population-Based, Retrospective Cohort Study.

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.

Omentoplasty in Patients Undergoing Abdominoperineal Resection After Long-Course Chemoradiation for Locally Advanced and Locally Recurrent Rectal Cancer: A Comparative Single-Institution Cohort Study.

BACKGROUND: Omentoplasty is a commonly performed procedure after abdominoperineal resection for rectal cancer, but its effectiveness to reduce pelviperineal complications is not firmly established. OBJECTIVE: This study aimed to assess the impact of omentoplasty on postoperative outcomes after long-course (chemo) radiotherapy and abdominoperineal resection in patients with locally advanced and locally recurrent rectal cancer. DESIGN: Retrospective cohort study. SETTINGS: Single center. PATIENTS: All patients with locally advanced and locally recurrent rectal cancer undergoing abdominoperineal resection after neoadjuvant (chemo)radiation in a tertiary referral center between 2008 and 2020 were retrospectively reviewed. MAIN OUTCOME MEASURES: Multivariable logistic and linear regression analyses were performed to analyze the association between omentoplasty and pelviperineal complications, duration of nasogastric tube drainage, and length of hospital stay. RESULTS: A total of 305 patients were analyzed, of whom 245 underwent omentoplasty (80%). Pelviperineal complications occurred in 151 patients (50%) overall, in 125 patients (51%) with omentoplasty, and in 26 patients (43%) without omentoplasty. Independent predictors of pelviperineal complications in multivariable analyses were smoking (OR 2.68; 95% CI, 1.46-4.94) and high BMI (OR 1.68; 95% CI, 1.00-2.83), but not omentoplasty (OR 1.36; 95% CI, 0.77-2.40). The mean duration of nasogastric tube drainage was longer after omentoplasty (6 vs 4 d) with a significant association in multivariable analysis (ß coefficient 1.97; 95% CI, 0.35-3.59). Patients undergoing omentoplasty had a significantly longer hospital stay (14 vs 10 d), and omentoplasty remained associated with a prolonged hospital stay after adjusting for confounding (ß coefficient 3.05; 95% CI, 0.05-5.74). LIMITATIONS: Retrospective design. CONCLUSION: Omentoplasty was not associated with a reduced risk of the occurrence of short-term pelviperineal complications after abdominoperineal resection in patients undergoing long-course (chemo)radiotherapy. Furthermore, in patients undergoing omentoplasty, prolonged duration of nasogastric tube drainage and hospital stay was observed. See Video Abstract at http://links.lww.com/DCR/C124 . OMENTOPLASTIA EN PACIENTES SOMETIDOS A RESECCIN ABDOMINOPERINEAL DESPUS DE QUIMIORRADIOTERAPIA DE CURSO LARGO PARA EL CNCER DE RECTO LOCALMENTE AVANZADO Y LOCALMENTE RECURRENTE ESTUDIO DE COHORTE COMPARATIVO DE UNA SOLA INSTITUCIN: ANTECEDENTES:La omentoplastía es un procedimiento que se realiza comúnmente después de la resección abdominoperineal por cáncer de recto, pero su efectividad para reducir las complicaciones pelvicoperineales no está firmemente establecida.OBJETIVO:Evaluar el impacto de la omentoplastía en las complicaciones pelvicoperineales a corto plazo y los resultados postoperatorios después quimioradioterapia de curso largo y resección abdominoperineal en pacientes con cáncer de recto localmente avanzado y localmente recurrente.DISEÑO:Estudio de cohorte retrospectivo.ESCENARIO:Centro único.PACIENTES:Se revisaron retrospectivamente todos los pacientes con cáncer de recto localmente avanzado y localmente recurrente sometidos a resección abdominoperineal después de quimioradiación neoadyuvante en un centro de referencia de tercer nivel entre 2008 y 2020.PRINCIPALES MEDIDAS DE RESULTADO:Se realizaron análisis de regresión lineal y logística multivariable para examinar la asociación entre la omentoplastía y las complicaciones pelvicoperineales (p. ej., problemas de heridas perineales y abscesos pélvicos), la duración del drenaje por sonda nasogástrica y la duración de la estancia hospitalaria.RESULTADOS:Se analizaron un total de 305 pacientes de los cuales 245 fueron sometidos a omentoplastía (80%). Las complicaciones pelvicoperineales ocurrieron en 151 pacientes (50%) en general, y en 125 (51%) y 26 (43%) de los pacientes con o sin omentoplastía, respectivamente. Los predictores independientes de complicaciones pelvicoperineales en análisis multivariable fueron el tabaquismo (OR 2.68, IC del 95% 1.46 a 4.94) y un IMC alto (OR 1.68, IC del 95% 1.00 a 2.83), pero no la omentoplastía (OR 1.36, IC del 95% 0.77 a 2.40) . La duración media del drenaje por sonda nasogástrica fue mayor después de la omentoplastía (6 frente a 4 días) con una asociación significativa en el análisis multivariable (coeficiente ß 1.97, IC del 95%: 0.35-3.59). Los pacientes que se sometieron a una omentoplastía tuvieron una estancia hospitalaria significativamente más larga (14 frente a 10 días), y la omentoplastía permaneció asociada con una estancia hospitalaria prolongada después de ajustar por factores de confusión (coeficiente ß 3.05, IC del 95%: 0.05-5.74).LIMITACIONES:Diseño retrospectivo.CONCLUSIÓN:La omentoplastía no se asoció con un riesgo reducido de aparición de complicaciones pelvicoperineales a corto plazo después de la resección abdominoperineal en pacientes sometidos a quimioradioterapia de larga duración. Adicionalmente, en los pacientes sometidos a omentoplastía se observó una duración prolongada del drenaje por sonda nasogástrica y la estancia hospitalaria. Consulte Video Resumen en http://links.lww.com/DCR/C124 . (Traducción-Dr. Jorge Silva Velazco ).

Impact of nutritional status and body composition on postoperative outcomes after pelvic exenteration for locally advanced and locally recurrent rectal cancer.

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.

The incidence, treatment and survival of patients with rare types of rectal malignancies in the Netherlands: A population-based study between 1989 and 2018.

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.

Intraoperative Electron Beam Radiation Therapy (IOERT) Versus High-Dose-Rate Intraoperative Brachytherapy (HDR-IORT) in Patients With an R1 Resection for Locally Advanced or Locally Recurrent Rectal Cancer.

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 of ≤2 mm was considered R1. A resection margin of 0 mm was considered R1 in LRRC. RESULTS: 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.

Endovascular Treatment for Acute Ischemic Stroke in Patients on Oral Anticoagulants: Results From the MR CLEAN Registry.

Background and Purpose- The use of oral anticoagulants (OAC) is considered a contra-indication for intravenous thrombolytics as acute treatment of ischemic stroke. However, little is known about the risks and benefits of endovascular treatment in patients on prior OAC. We aim to compare outcomes after endovascular treatment between patients with and without prior use of OAC. Methods- Data of patients with acute ischemic stroke caused by an intracranial anterior circulation occlusion, included in the nationwide, prospective, MR CLEAN Registry between March 2014 and November 2017, were analyzed. Outcomes of interest included symptomatic intracranial hemorrhage and functional outcome at 90 days (modified Rankin Scale score). Outcomes between groups were compared with (ordinal) logistic regression analyses, adjusted for prognostic factors. Results- Three thousand one hundred sixty-two patients were included in this study, of whom 502 (16%) used OAC. There was no significant difference in the occurrence of symptomatic intracranial hemorrhage between patients with and without prior OACs (5% versus 6%; adjusted odds ratio, 0.63 [95% CI, 0.38-1.06]). Patients on OACs had worse functional outcomes than patients without OACs (common odds ratio, 0.57 [95% CI, 0.47-0.66]). However, this observed difference in functional outcome disappeared after adjustment for prognostic factors (adjusted common odds ratio, 0.91 [95% CI, 0.74-1.13]). Conclusions- Prior OAC use in patients treated with endovascular treatment for ischemic stroke is not associated with an increased risk of symptomatic intracranial hemorrhage or worse functional outcome compared with no prior OAC use. Therefore, prior OAC use should not be a contra-indication for endovascular treatment.