Background: CDKN2A-p16-Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), with very poor survival. Surveillance may improve prognosis.... Show moreBackground: CDKN2A-p16-Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), with very poor survival. Surveillance may improve prognosis. Objective: To assess the cost-effectiveness of surveillance, as compared to no surveillance. Methods: In 2000, a surveillance program was initiated at Leiden University Medical Center with annual MRI and optional endoscopic ultrasound. Data were collected on the resection rate of screen-detected tumors and on survival. The Kaplan-Meier method and a parametric cure model were used to analyze and compare survival. Based on the surveillance and survival data from the screening program, a state-transition model was constructed to estimate lifelong outcomes. Results: A total of 347 mutation carriers participated in the surveillance program. PDAC was detected in 31 patients (8.9%) and the tumor could be resected in 22 patients (71.0%). Long-term cure among patients with resected PDAC was estimated at 47.1% (p < 0.001). The surveillance program was estimated to reduce mortality from PDAC by 12.1% and increase average life expectancy by 2.10 years. Lifelong costs increased by euro13,900 per patient, with a cost-utility ratio of euro14,000 per quality-adjusted life year gained. For annual surveillance to have an acceptable cost-effectiveness in other settings, lifetime PDAC risk needs to be 10% or higher. Conclusion: The tumor could be resected in most patients with a screen-detected PDAC. These patients had considerably better survival and as a result annual surveillance was found to be cost-effective. Show less
Ibrahim, I.S.; Vasen, H.F.A.; Wasser, M.N.J.M.; Feshtali, S.; Bonsing, B.A.; Morreau, H.; ... ; Hout, W.B. van den 2023
BackgroundCDKN2A-p16-Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), with very poor survival. Surveillance may improve prognosis... Show moreBackgroundCDKN2A-p16-Leiden mutation carriers have a high lifetime risk of developing pancreatic ductal adenocarcinoma (PDAC), with very poor survival. Surveillance may improve prognosis.ObjectiveTo assess the cost-effectiveness of surveillance, as compared to no surveillance.MethodsIn 2000, a surveillance program was initiated at Leiden University Medical Center with annual MRI and optional endoscopic ultrasound. Data were collected on the resection rate of screen-detected tumors and on survival. The Kaplan–Meier method and a parametric cure model were used to analyze and compare survival. Based on the surveillance and survival data from the screening program, a state-transition model was constructed to estimate lifelong outcomes.ResultsA total of 347 mutation carriers participated in the surveillance program. PDAC was detected in 31 patients (8.9%) and the tumor could be resected in 22 patients (71.0%). Long-term cure among patients with resected PDAC was estimated at 47.1% (p < 0.001). The surveillance program was estimated to reduce mortality from PDAC by 12.1% and increase average life expectancy by 2.10 years. Lifelong costs increased by €13,900 per patient, with a cost-utility ratio of €14,000 per quality-adjusted life year gained. For annual surveillance to have an acceptable cost-effectiveness in other settings, lifetime PDAC risk needs to be 10% or higher.ConclusionThe tumor could be resected in most patients with a screen-detected PDAC. These patients had considerably better survival and as a result annual surveillance was found to be cost-effective. Show less
Background In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is... Show moreBackground In the recent years two innovative approaches have become available for minimally invasiveen blocresections of large non-pedunculated rectal lesions (polyps and early cancers). One is Transanal Minimally Invasive Surgery (TAMIS), the other is Endoscopic Submucosal Dissection (ESD). Both techniques are standard of care, but a direct randomised comparison is lacking. The choice between either of these procedures is dependent on local expertise or availability rather than evidence-based. The European Society for Endoscopy has recommended that a comparison between ESD and local surgical resection is needed to guide decision making for the optimal approach for the removal of large rectal lesions in Western countries. The aim of this study is to directly compare both procedures in a randomised setting with regard to effectiveness, safety and perceived patient burden. Methods Multicenter randomised trial in 15 hospitals in the Netherlands. Patients with non-pedunculated lesions > 2 cm, where the bulk of the lesion is below 15 cm from the anal verge, will be randomised between either a TAMIS or an ESD procedure. Lesions judged to be deeply invasive by an expert panel will be excluded. The primary endpoint is the cumulative local recurrence rate at follow-up rectoscopy at 12 months. Secondary endpoints are: 1) Radical (R0-) resection rate; 2) Perceived burden and quality of life; 3) Cost effectiveness at 12 months; 4) Surgical referral rate at 12 months; 5) Complication rate; 6) Local recurrence rate at 6 months. For this non-inferiority trial, the total sample size of 198 is based on an expected local recurrence rate of 3% in the ESD group, 6% in the TAMIS group and considering a difference of less than 6% to be non-inferior. Discussion This is the first European randomised controlled trial comparing the effectiveness and safety of TAMIS and ESD for theen blocresection of large non-pedunculated rectal lesions. This is important as the detection rate of these adenomas is expected to further increase with the introduction of colorectal screening programs throughout Europe. This study will therefore support an optimal use of healthcare resources in the future. Show less