Adenocarcinoma of the small intestine cohort: prospectively collecting real-world data to improve care and quality of life for patients with a rare cancer
DOI:
https://doi.org/10.2340/ao.v65.45471Keywords:
Small intestinal adenocarcinoma, prospective, real-world data, quality of life, rare cancerAbstract
Background and purpose: Small intestinal adenocarcinoma (SIA) is a rare cancer with a poor prognosis. Optimal treatment strategies are unclear as biological understanding of the disease is limited and randomized controlled trials are lacking. Current management is based on protocols for other gastrointestinal cancers. Therefore, the AdenoCarcinoma of the Small Intestine (ACSI) cohort was initiated, a subcohort of the nationwide Prospective Dutch ColoRectal Cancer cohort (PLCRC) study. The ACSI cohort aims to provide a large-scale, prospective SIA cohort, where clinical and molecular data will be combined to improve knowledge on tumor biology, treatment responsiveness, disease outcome and patient reported outcomes (PROs).
Patient/material and methods: All adult SIA patients in the Netherlands are eligible for inclusion. Nationwide inclusion is facilitated by 68 hospitals. Clinical data are collected, as well as optional PROs, pathology- and blood samples.
Results: Until June 2025, 143 patients have been enrolled. Data of the first 105 patients show a median age of 65 years (interquartile range 58–73) at diagnosis with a slight male predominance (60%). Most tumors are located in the duodenum (57%) and 27% of patients present with stage IV disease, with a majority having single-site metastases (64%). Primary tumor resection is performed in 80%, while systemic treatment is administered in 42%. Four patients did not receive any anti-tumor treatment (14%). Mismatch repair deficiency is detected in 28% of patients.
Interpretation: The ACSI cohort enables structured national collection of clinical data, tumor samples and PROs of SIA patients. These data provide a valuable source for further research and improvement of care for this patient group.
Downloads
References
Legue LM, Bernards N, Gerritse SL, van Oudheusden TR, de Hingh IH, Creemers GM, et al. Trends in incidence, treatment and survival of small bowel adenocarcinomas between 1999 and 2013: a population-based study in the Netherlands. Acta Oncol. 2016;55(9–10):1183–9. DOI: https://doi.org/10.1080/0284186X.2016.1182211
Bilimoria KY, Bentrem DJ, Wayne JD, Ko CY, Bennett CL, Talamonti MS. Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg. 2009;249(1):63–71. DOI: https://doi.org/10.1097/SLA.0b013e31818e4641
Netherlands Cancer Registry [Internet]. [cited 2026 Jan 23]. Available from: https://iknl.nl/nkr-cijfers
Hatzaras I, Palesty JA, Abir F, Sullivan P, Kozol RA, Dudrick SJ, et al. Small-bowel tumors: epidemiologic and clinical characteristics of 1260 cases from the Connecticut tumor registry. Arch Surg. 2007;142(3):229–35. DOI: https://doi.org/10.1001/archsurg.142.3.229
De Heus E, Duijts SFA, van der Zwan JM, Kapiteijn E, Nieveen van Dijkum EJM, van Herpen CML, et al. The gap between rare and common cancers still exists: results from a population-based study in the Netherlands. Eur J Cancer. 2022;167:103–11. DOI: https://doi.org/10.1016/j.ejca.2022.03.001
Botta L, Gatta G, Trama A, Bernasconi A, Sharon E, Capocaccia R, et al. Incidence and survival of rare cancers in the US and Europe. Cancer Med. 2020;9(15):5632–42. DOI: https://doi.org/10.1002/cam4.3137
Trama A, Bernasconi A, Canete A, Carulla M, Daubisse-Marliac L, Rossi S, et al. Incidence and survival of rare adult solid cancers in Europe (EUROCARE-6): a population-based study. Eur J Cancer. 2025;214:115147. DOI: https://doi.org/10.1016/j.ejca.2024.115147
Pillai RK, Jayasree K. Rare cancers: challenges & issues. Indian J Med Res. 2017;145(1):17–27. DOI: https://doi.org/10.4103/ijmr.IJMR_915_14
Overman MJ, Hu CY, Kopetz S, Abbruzzese JL, Wolff RA, Chang GJ. A population-based comparison of adenocarcinoma of the large and small intestine: insights into a rare disease. Ann Surg Oncol. 2012;19(5):1439–45. DOI: https://doi.org/10.1245/s10434-011-2173-6
Haan JC, Buffart TE, Eijk PP, van de Wiel MA, van Wieringen WN, Howdle PD, et al. Small bowel adenocarcinoma copy number profiles are more closely related to colorectal than to gastric cancers. Ann Oncol. 2012;23(2):367–74. DOI: https://doi.org/10.1093/annonc/mdr122
Gelsomino F, Balsano R, De Lorenzo S, Garajová I. Small bowel adenocarcinoma: from molecular insights to clinical management. Curr Oncol. 2022;29(2):1223–36. DOI: https://doi.org/10.3390/curroncol29020104
Schrock AB, Devoe CE, McWilliams R, Sun J, Aparicio T, Stephens PJ, et al. Genomic profiling of small-bowel adenocarcinoma. JAMA Oncol. 2017;3(11):1546–53. DOI: https://doi.org/10.1001/jamaoncol.2017.1051
Aparicio T, Svrcek M, Henriques J, Afchain P, Lievre A, Tougeron D, et al. Panel gene profiling of small bowel adenocarcinoma: results from the NADEGE prospective cohort. Int J Cancer. 2021;148(7):1731–42. DOI: https://doi.org/10.1002/ijc.33392
De Back T, Nijskens I, Schafrat P, Chalabi M, Kazemier G, Vermeulen L, et al. Evaluation of systemic treatments of small intestinal adenocarcinomas: a systematic review and meta-analysis. JAMA Netw Open. 2023;6(2):e230631. DOI: https://doi.org/10.1001/jamanetworkopen.2023.0631
Christopoulos P, Schlenk R, Kazdal D, Blasi M, Lennerz J, Shah R, et al. Real-world data for precision cancer medicine – a European perspective. Genes Chromosomes Cancer. 2023;62(9):557–63. DOI: https://doi.org/10.1002/gcc.23135
Rivera DR, Henk HJ, Garrett-Mayer E, Christian JB, Belli AJ, Bruinooge SS, et al. The friends of cancer research real-world data collaboration pilot 2.0: methodological recommendations from oncology case studies. Clin Pharmacol Ther. 2022;111(1):283–92. DOI: https://doi.org/10.1002/cpt.2453
Coebergh van den Braak RRJ, van Rijssen LB, van Kleef JJ, Vink GR, Berbee M, van Berge Henegouwen MI, et al. Nationwide comprehensive gastro-intestinal cancer cohorts: the 3P initiative. Acta Oncol. 2018;57(2):195–202. DOI: https://doi.org/10.1080/0284186X.2017.1346381
Burbach JP, Kurk SA, Coebergh van den Braak RR, Dik VK, May AM, Meijer GA, et al. Prospective Dutch colorectal cancer cohort: an infrastructure for long-term observational, prognostic, predictive and (randomized) intervention research. Acta Oncol. 2016;55(11):1273–80. DOI: https://doi.org/10.1080/0284186X.2016.1189094
ASCO CancerLinQ Database [Internet]. [cited 2026 Jan 23]. Available from: www.cancerlinq.org/solutions/researchers
SEER Database. [Internet]. [cited 2026 Jan 23]. Available from: https://seer.cancer.gov/data-software/documentation/
Skovlund E, Leufkens HGM, Smyth JF. The use of real-world data in cancer drug development. Eur J Cancer. 2018;101:69–76. DOI: https://doi.org/10.1016/j.ejca.2018.06.036
Arlett P, Kjaer J, Broich K, Cooke E. Real-world evidence in EU medicines regulation: enabling use and establishing value. Clin Pharmacol Ther. 2022;111(1):21–3. DOI: https://doi.org/10.1002/cpt.2479
Derksen JWG, Vink GR, Elferink MAG, Roodhart JML, Verkooijen HM, van Grevenstein WMU, et al. The Prospective Dutch Colorectal Cancer (PLCRC) cohort: real-world data facilitating research and clinical care. Sci Rep. 2021;11(1):3923. DOI: https://doi.org/10.1038/s41598-020-79890-y
Von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP, et al. The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies. Lancet. 2007;370(9596):1453–7. DOI: https://doi.org/10.1016/S0140-6736(07)61602-X
Mackay TM, Smits FJ, Latenstein AEJ, Bogte A, Bonsing BA, Bos H, et al. Impact of nationwide enhanced implementation of best practices in pancreatic cancer care (PACAP-1): a multicenter stepped-wedge cluster randomized controlled trial. Trials. 2020;21(1):334. DOI: https://doi.org/10.1186/s13063-020-4180-z
Aparicio T, Henriques J, Manfredi S, Tougeron D, Bouche O, Pezet D, et al. Small bowel adenocarcinoma: results from a nationwide prospective ARCAD-NADEGE cohort study of 347 patients. Int J Cancer. 2020;147(4):967–77. DOI: https://doi.org/10.1002/ijc.32860
De Back TR, Linssen JDG, van Erning FN, Verbakel CSE, Schafrat PJM, Vermeulen L, et al. Incidence, clinical management and prognosis of patients with small intestinal adenocarcinomas from 1999 through 2019: a nationwide Dutch cohort study. Eur J Cancer. 2024;199:113529. DOI: https://doi.org/10.1016/j.ejca.2024.113529
Linssen JDG, Schafrat PJM, de Back TR, van Erning FN, van Leerdam ME, Dekker E, et al. Predisposing conditions in patients with small intestinal adenocarcinomas in the Netherlands: a 20-year nationwide cohort study. Int J Cancer. 2025;157(2):218–31. DOI: https://doi.org/10.1002/ijc.35354
Maio M, Ascierto PA, Manzyuk L, Motola-Kuba D, Penel N, Cassier PA, et al. Pembrolizumab in microsatellite instability high or mismatch repair deficient cancers: updated analysis from the phase II KEYNOTE-158 study. Ann Oncol. 2022;33(9):929–38. DOI: https://doi.org/10.1016/j.annonc.2022.05.519
Pedersen KS, Foster NR, Overman MJ, Boland PM, Kim SS, Arrambide KA, et al. ZEBRA: a Multicenter Phase II Study of Pembrolizumab in patients with advanced small-bowel adenocarcinoma. Clin Cancer Res. 2021;27(13):3641–8. DOI: https://doi.org/10.1158/1078-0432.CCR-21-0159
Overman MJ, Pozadzides J, Kopetz S, Wen S, Abbruzzese JL, Wolff RA, et al. Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine. Br J Cancer. 2010;102(1):144–50. DOI: https://doi.org/10.1038/sj.bjc.6605449
Evans TRJ, Aparicio T, Malicot KL, et al. GLOBAL BALLAD: An International Rare Cancers Initiative trial to evaluate the potential benefit of adjuvant chemotherapy for small bowel adenocarcinoma (IRCI 002). J Clin Oncol. 2016;34(15)(suppl):TPS4154. DOI: https://doi.org/10.1200/JCO.2016.34.15_suppl.TPS4154
Aparicio T, Turpin A, Zaanan A, de la Fouchardiere C, Le Malicot K, Lonardi S, et al. FOLFIRINOX or FOLFOX for locally advanced or metastatic small bowel adenocarcinoma: PRODIGE 86 – FFCD-GONO – ENGIC 02 – FOLFIRINOX SBA phase II randomized trial. Dig Liver Dis. 2025;57(10):2001–5. DOI: https://doi.org/10.1016/j.dld.2025.07.018
Downloads
Additional Files
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2026 Pascale J.M. Schafrat, Tim R. de Back, Felice N. van Erning, Frederieke H. van der Baan, Geraldine R. Vink, Miriam Koopman, Ruben S.A. Goedegebuure, Louis Vermeulen, Ignace H.J.T. de Hingh, Dirkje W. Sommeijer
This work is licensed under a Creative Commons Attribution 4.0 International License.
