Preoperative image-guided identification of response to neoadjuvant chemoradiotherapy in esophageal cancer (PRIDE): A multicenter observational study

A. S. Borggreve*, S. Mook, M. Verheij, V. E.M. Mul, J. J. Bergman, A. Bartels-Rutten, L. C. Ter Beek, R. G.H. Beets-Tan, R. J. Bennink, M. I. Van Berge Henegouwen, L. A.A. Brosens, I. L. Defize, J. M. Van Dieren, H. Dijkstra, R. Van Hillegersberg, M. C. Hulshof, H. W.M. Van Laarhoven, M. G.E.H. Lam, A. L.H.M.W. Van Lier, C. T. MuijsW. B. Nagengast, A. J. Nederveen, W. Noordzij, J. T.M. Plukker, P. S.N. Van Rossum, J. P. Ruurda, J. W. Van Sandick, B. L.A.M. Weusten, F. E.M. Voncken, D. Yakar, G. J. Meijer, B. M.P. Aleman, R. J.H. Borra, B. Van Etten, S. S. Gisbertz, L. Goense, N. Haj Mohammad, K. J. Hartemink, P. Kappert, G. Kats-Ugurlu, L. L. Kodach, T. Korteweg, K. K. Krishnadath, J. A. Langendijk, W. W.J. De Leng, S. L. Meijer, J. H. Potze, J. Stoker, E. Vegt, H. M. Verkooijen, S. E. Vollenbrock, F. Wessels

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

27 Citations (Scopus)


Background: Nearly one third of patients undergoing neoadjuvant chemoradiotherapy (nCRT) for locally advanced esophageal cancer have a pathologic complete response (pCR) of the primary tumor upon histopathological evaluation of the resection specimen. The primary aim of this study is to develop a model that predicts the probability of pCR to nCRT in esophageal cancer, based on diffusion-weighted magnetic resonance imaging (DW-MRI), dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT). Accurate response prediction could lead to a patient-tailored approach with omission of surgery in the future in case of predicted pCR or additional neoadjuvant treatment in case of non-pCR. Methods: The PRIDE study is a prospective, single arm, observational multicenter study designed to develop a multimodal prediction model for histopathological response to nCRT for esophageal cancer. A total of 200 patients with locally advanced esophageal cancer - of which at least 130 patients with adenocarcinoma and at least 61 patients with squamous cell carcinoma - scheduled to receive nCRT followed by esophagectomy will be included. The primary modalities to be incorporated in the prediction model are quantitative parameters derived from MRI and 18F-FDG PET-CT scans, which will be acquired at fixed intervals before, during and after nCRT. Secondary modalities include blood samples for analysis of the presence of circulating tumor DNA (ctDNA) at 3 time-points (before, during and after nCRT), and an endoscopy with (random) bite-on-bite biopsies of the primary tumor site and other suspected lesions in the esophagus as well as an endoscopic ultrasonography (EUS) with fine needle aspiration of suspected lymph nodes after finishing nCRT. The main study endpoint is the performance of the model for pCR prediction. Secondary endpoints include progression-free and overall survival. Discussion: If the multimodal PRIDE concept provides high predictive performance for pCR, the results of this study will play an important role in accurate identification of esophageal cancer patients with a pCR to nCRT. These patients might benefit from a patient-tailored approach with omission of surgery in the future. Vice versa, patients with non-pCR might benefit from additional neoadjuvant treatment, or ineffective therapy could be stopped. Trial registration: The article reports on a health care intervention on human participants and was prospectively registered on March 22, 2018 under Identifier: NCT03474341.

Original languageEnglish
Article number1006
JournalBMC Cancer
Issue number1
Publication statusPublished - 20 Oct 2018


  • ctDNA
  • DW-MRI
  • Esophageal cancer
  • Image-guided
  • MRI
  • Neoadjuvant chemoradiotherapy
  • Pathologic complete response
  • PET-CT


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