Mirthe J Klein Haneveld1, Mark J C van Treijen1, Carolina R C Pieterman1,2, Olaf M Dekkers3, Annenienke van de Ven4, Wouter W de Herder5, Wouter T Zandee6, Madeleine L Drent7, Peter H Bisschop8, Bas Havekes9, Menno R Vriens10, Annemarie A Verrijn Stuart11, Gerlof D Valk1, Rachel S van Leeuwaarde1. 1. Department of Endocrine Oncology, University Medical Centre Utrecht, 3584 CX, Utrecht, the Netherlands. 2. Department of Surgical Oncology, Section of Surgical Endocrinology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 3. Departments of Endocrinology and Metabolism and Clinical Epidemiology, Leiden University Medical Centre, 2333 ZA, Leiden, the Netherlands. 4. Department of Endocrinology, Radboud University Medical Center, 6525 GA, Nijmegen, the Netherlands. 5. Department of Internal Medicine, Erasmus Medical Center, 3015 GD, Rotterdam, the Netherlands. 6. Department of Endocrinology, University of Groningen, University Medical Centre Groningen, 9713 GZ, Groningen, the Netherlands. 7. Department of Internal Medicine, Section of Endocrinology, Amsterdam UMC, location VU University Medical Centre, 1081 HV, Amsterdam, the Netherlands. 8. Department of Endocrinology and Metabolism, Amsterdam UMC, location Academic Medical Centre, 1105 AZ, Amsterdam, the Netherlands. 9. Department of Internal Medicine, Division of Endocrinology, Maastricht University Medical Centre, 6229 HX, Maastricht, the Netherlands. 10. Department of Endocrine Surgery, University Medical Centre Utrecht, 3584 CX, Utrecht, the Netherlands. 11. Department of Paediatric Endocrinology, Wilhelmina Children's Hospital, University Medical Centre Utrecht, 3584 EA, Utrecht, the Netherlands.
Abstract
CONTEXT: Nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate. OBJECTIVE: The aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients. METHODS: Pancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥ 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease. RESULTS: Five of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET-free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively. CONCLUSION: Analyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered.
CONTEXT: Nonfunctioning pancreatic neuroendocrine tumors (NF-pNETs) are highly prevalent and constitute an important cause of mortality in patients with multiple endocrine neoplasia type 1 (MEN1). Still, the optimal age to initiate screening for pNETs is under debate. OBJECTIVE: The aim of this work is to assess the age of occurrence of clinically relevant NF-pNETs in young MEN1 patients. METHODS: Pancreatic imaging data of MEN1 patients were retrieved from the DutchMEN Study Group database. Interval-censored survival methods were used to describe age-related penetrance, compare survival curves, and develop a parametric model for estimating the risk of having clinically relevant NF-pNET at various ages. The primary objective was to assess age at occurrence of clinically relevant NF-pNET (size ≥ 20 mm or rapid growth); secondary objectives were the age at occurrence of NF-pNET of any size and pNET-associated metastasized disease. RESULTS: Five of 350 patients developed clinically relevant NF-pNETs before age 18 years, 2 of whom subsequently developed lymph node metastases. No differences in clinically relevant NF-pNET-free survival were found for sex, time frame, and type of MEN1 diagnosis or genotype. The estimated ages (median, 95% CI) at a 1%, 2.5%, and 5% risk of having developed a clinically relevant tumor are 9.5 (6.5-12.7), 13.5 (10.2-16.9), and 17.8 years (14.3-21.4), respectively. CONCLUSION: Analyses from this population-based cohort indicate that start of surveillance for NF-pNETs with pancreatic imaging at age 13 to 14 years is justified. The psychological and medical burden of screening at a young age should be considered.