Observational Study

. 2018 Oct 20;18(1):1006.

doi: 10.1186/s12885-018-4892-6.

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

A S Borggreve^{1

2}, S Mook³, M Verheij⁴, V E M Mul⁵, J J Bergman⁶, A Bartels-Rutten⁷, L C Ter Beek⁷, R G H Beets-Tan⁷, R J Bennink⁸, M I van Berge Henegouwen⁹, L A A Brosens¹⁰, I L Defize^{11

3}, J M van Dieren¹², H Dijkstra¹³, R van Hillegersberg³, M C Hulshof¹⁴, H W M van Laarhoven¹⁵, M G E H Lam¹⁶, A L H M W van Lier¹¹, C T Muijs⁵, W B Nagengast¹⁷, A J Nederveen⁸, W Noordzij¹⁸, J T M Plukker¹⁹, P S N van Rossum¹¹, J P Ruurda³, J W van Sandick²⁰, B L A M Weusten²¹, F E M Voncken⁴, D Yakar¹³, G J Meijer¹¹; PRIDE study group

Collaborators, Affiliations

Collaborators

PRIDE study group:
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

Affiliations

¹ Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. A.S.Borggreve@umcutrecht.nl.
² Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. A.S.Borggreve@umcutrecht.nl.
³ Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
⁴ Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
⁵ Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
⁶ Department of Gastroenterology, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
⁷ Department of Radiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
⁸ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
⁹ Department of Surgical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
¹⁰ Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
¹¹ Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
¹² Department of Gastroenterology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
¹³ Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
¹⁴ Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
¹⁵ Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
¹⁶ Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
¹⁷ Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
¹⁸ Department of Nuclear Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
¹⁹ Department of Surgical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
²⁰ Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
²¹ Department of Gastroenterology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

PMID: 30342494
PMCID: PMC6195948
DOI: 10.1186/s12885-018-4892-6

Observational Study

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

A S Borggreve et al. BMC Cancer. 2018.

. 2018 Oct 20;18(1):1006.

doi: 10.1186/s12885-018-4892-6.

Authors

Collaborators

PRIDE study group:
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

Affiliations

¹ Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. A.S.Borggreve@umcutrecht.nl.
² Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands. A.S.Borggreve@umcutrecht.nl.
³ Department of Surgical Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
⁴ Department of Radiation Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
⁵ Department of Radiation Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
⁶ Department of Gastroenterology, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
⁷ Department of Radiology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
⁸ Department of Radiology and Nuclear Medicine, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
⁹ Department of Surgical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
¹⁰ Department of Pathology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
¹¹ Department of Radiation Oncology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
¹² Department of Gastroenterology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
¹³ Department of Radiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
¹⁴ Department of Radiation Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
¹⁵ Department of Medical Oncology, Cancer Center Amsterdam, Amsterdam University Medical Centers, Academic Medical Center, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
¹⁶ Department of Nuclear Medicine, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
¹⁷ Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
¹⁸ Department of Nuclear Medicine, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
¹⁹ Department of Surgical Oncology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GW, Groningen, The Netherlands.
²⁰ Department of Surgical Oncology, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX, Amsterdam, The Netherlands.
²¹ Department of Gastroenterology, University Medical Center Utrecht, Utrecht University, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.

PMID: 30342494
PMCID: PMC6195948
DOI: 10.1186/s12885-018-4892-6

Abstract

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 ClinicalTrials.gov Identifier: NCT03474341 .

Keywords: DCE-MRI; DW-MRI; Esophageal cancer; Image-guided; MRI; Neoadjuvant chemoradiotherapy; PET-CT; Pathologic complete response; ctDNA.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The study has been approved by the Medical Ethics Review Committee of the University Medical Center Utrecht (version 3.0, 04-04-2018, 17–941, NL62881.041.17) and covers all clinical sites involved in the study. The following 4 high-volume centers in the Netherlands participate in the study: University Medical Center Utrecht, The Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, University Medical Center Groningen and Amsterdam University Medical Centers. Recruitment of patients started in April 2018. Written, voluntary, informed consent to participate in the study will be obtained from all patients.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

See this image and copyright information in PMC

References

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

Collaborators

Affiliations

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

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Medical