Tailored anticoagulant treatment after a first venous thromboembolism: protocol of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study - cohort-based randomised controlled trial.

INTRODUCTION: Patients with a first venous thromboembolism (VTE) are at risk of recurrence. Recurrent VTE (rVTE) can be prevented by extended anticoagulant therapy, but this comes at the cost of an increased risk of bleeding. It is still uncertain whether patients with an intermediate recurrence risk or with a high recurrence and high bleeding risk will benefit from extended anticoagulant treatment, and whether a strategy where anticoagulant duration is tailored on the predicted risks of rVTE and bleeding can improve outcomes. The aim of the Leiden Thrombosis Recurrence Risk Prevention (L-TRRiP) study is to evaluate the outcomes of tailored duration of long-term anticoagulant treatment based on individualised assessment of rVTE and major bleeding risks. METHODS AND ANALYSIS: The L-TRRiP study is a multicentre, open-label, cohort-based, randomised controlled trial, including patients with a first VTE. We classify the risk of rVTE and major bleeding using the L-TRRiP and VTE-BLEED scores, respectively. After 3 months of anticoagulant therapy, patients with a low rVTE risk will discontinue anticoagulant treatment, patients with a high rVTE and low bleeding risk will continue anticoagulant treatment, whereas all other patients will be randomised to continue or discontinue anticoagulant treatment. All patients will be followed up for at least 2 years. Inclusion will continue until the randomised group consists of 608 patients; we estimate to include 1600 patients in total. The primary outcome is the combined incidence of rVTE and major bleeding in the randomised group after 2 years of follow-up. Secondary outcomes include the incidence of rVTE and major bleeding, functional outcomes, quality of life and cost-effectiveness in all patients. ETHICS AND DISSEMINATION: The protocol was approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft. Results are expected in 2028 and will be disseminated through peer-reviewed journals and during (inter)national conferences. TRIAL REGISTRATION NUMBER: NCT06087952.

Time trends in treatment patterns and survival of older patients with synchronous metastatic colorectal cancer in the Netherlands: A population-based study.

New treatment strategies have improved survival of metastatic colorectal cancer in trials. However, it is not clear whether older patients benefit from these novel therapies, as they are often not included in pivotal trials. Therefore, we investigated treatment patterns and overall survival over time in older patients with metastatic colorectal cancer in a population-based study. We identified 22.192 Dutch patients aged ≥70 years diagnosed with synchronous metastatic colorectal cancer between 2005 and 2020 from the Netherlands Cancer Registry. Changes in treatment over time were assessed with logistic regression models. Survival was assessed by Cox proportional hazard ratios (HR). Results showed that chemotherapy use increased between 2005 and 2015, but declined from 2015 onwards, while more patients received best supportive care. Over time, fewer patients underwent primary tumor resection alone. Although survival of both metastatic colon and rectal cancer improved until 2014, survival of colon cancer decreased from 2014 onwards (HR 1.04, 95% confidence interval [CI] 1.01-1.05), which was seen in all age groups. Survival of metastatic rectal cancer patients remained unchanged from 2014 onwards (HR 1.00, 95% CI 0.98-1.03) in all age groups. In conclusion, treatment patterns of Dutch older patients with synchronous metastatic colorectal cancer rapidly changed from 2005 to 2020, with increasing percentages of patients receiving best supportive care. Survival of metastatic colon cancer decreased from 2014 onwards. The implementation of a colorectal cancer screening program and patient selection might explain why only a subset of older patients seem to benefit from the availability of novel treatment options.

MRI sequences for the detection of individual lymph nodes in regional breast radiotherapy planning.

OBJECTIVE: In regional radiotherapy (RT) for patients with breast cancer, lymph node (LN) targets are delineated on CT, defined by anatomical boundaries. By identifying individual LNs, MRI-based delineations may reduce target volumes and thereby toxicity. We optimized MRI sequences for this purpose. Our aim was to evaluate the techniques for LN delineation in RT planning. METHODS: Supine MRI was explored at 1.5 T in RT position (arms in abduction). 5 MRI techniques were optimized in 10 and evaluated in 12 healthy female volunteers. The scans included one T1 weighted (T1w), three T2 weighted (T2w) and a diffusion-weighted imaging (DWI) technique. Quantitative evaluation was performed by scoring LN numbers per volunteer and per scan. Qualitatively, scans were assessed on seven aspects, including LN contrast, anatomical information and insensitivity to motion during acquisition. RESULTS: Two T2w fast spin-echo (FSE) methods showed the highest LN numbers (median 24 axillary), high contrast, excellent fat suppression and relative insensitivity to motion during acquisition. A third T2w sequence and DWI showed significantly fewer LNs (14 and 10) and proved unsuitable due to motion sensitivity and geometrical uncertainties. T1w MRI showed an intermediate number of LNs (17), provided valuable anatomical information, but lacked LN contrast. CONCLUSION: Explicit LN imaging was achieved, in supine RT position, using MRI. Two T2w FSE techniques had the highest detection rates and were motion insensitive. T1w MRI showed anatomical information. MRI enables direct delineation of individual LNs. ADVANCES IN KNOWLEDGE: Our optimized MRI scans enable accurate target definition in MRI-guided regional breast RT and development of personalized treatments.