Study protocol

NEOadjuvant therapy monitoring with PET and CT in Esophageal Cancer (NEOPEC-trial)

Mark van Heijl¹ , Jikke MT Omloo¹ , Mark I van Berge Henegouwen¹ , Olivier RC Busch¹ , Hugo W Tilanus² , Patrick MM Bossuyt³ , Otto S Hoekstra⁴ , Jaap Stoker⁵ , Maarten CCM Hulshof⁶ , Ate van der Gaast⁷ , Grard AP Nieuwenhuijzen⁸ , Han J Bonenkamp⁹ , John ThM Plukker¹⁰ , Ernst J Spillenaar Bilgen¹¹ , Fibo JW ten Kate¹² , Ronald Boellaard¹³ , Jan Pruim¹⁴ , Gerrit W Sloof¹⁵ and J Jan B van Lanschot^1,2

¹Department of Surgery, Academic Medical Center, Amsterdam, The Netherlands

²Department of Surgery, Erasmus Medical Center, Rotterdam, The Netherlands

³Department of Clinical Epidiomiology, Biostatistics and Bioinformatics, Academic Medical Center, Amsterdam, The Netherlands

⁴Department of Nuclear Medicine, VU Medical Center, Amsterdam, The Netherlands

⁵Department of Radiology, Academic Medical Center, Amsterdam, The Netherlands

⁶Department of Radiotherapy, Academic Medical Center, Amsterdam, The Netherlands

⁷Department of Medical Oncology, Erasmus Medical Center, Rotterdam, The Netherlands

⁸Department of Surgery, Catharina Hospital Eindhoven, Eindhoven, The Netherlands

⁹Department of Surgery, Radboud University Medical Center, Nijmegen, The Netherlands

¹⁰Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands

¹¹Department of Surgery, Rijnstate Hospital, Arnhem, The Netherlands

¹²Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands

¹³Department of Nuclear Medicine and PET research, VU Medical Center, Amsterdam, The Netherlands

¹⁴Department of Nuclear Medicine and Molecular Imaging, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

¹⁵Department of Nuclear Medicine, Academic Medical Center, Amsterdam, The Netherlands

author email corresponding author email

BMC Medical Physics 2008, 8:3doi:10.1186/1756-6649-8-3

Published:	31 July 2008

Abstract

Background

Surgical resection is the preferred treatment of potentially curable esophageal cancer. To improve long term patient outcome, many institutes apply neoadjuvant chemoradiotherapy. In a large proportion of patients no response to chemoradiotherapy is achieved. These patients suffer from toxic and ineffective neoadjuvant treatment, while appropriate surgical therapy is delayed. For this reason a diagnostic test that allows for accurate prediction of tumor response early during chemoradiotherapy is of crucial importance. CT-scan and endoscopic ultrasound have limited accuracy in predicting histopathologic tumor response. Data suggest that metabolic changes in tumor tissue as measured by FDG-PET predict response better. This study aims to compare FDG-PET and CT-scan for the early prediction of non-response to preoperative chemoradiotherapy in patients with potentially curable esophageal cancer.

Methods/design

Prognostic accuracy study, embedded in a randomized multicenter Dutch trial comparing neoadjuvant chemoradiotherapy for 5 weeks followed by surgery versus surgery alone for esophageal cancer. This prognostic accuracy study is performed only in the neoadjuvant arm of the randomized trial. In 6 centers, 150 consecutive patients will be included over a 3 year period. FDG-PET and CT-scan will be performed before and 2 weeks after the start of the chemoradiotherapy. All patients complete the 5 weeks regimen of neoadjuvant chemoradiotherapy, regardless the test results. Pathological examination of the surgical resection specimen will be used as reference standard. Responders are defined as patients with < 10% viable residual tumor cells (Mandard-score).

Difference in accuracy (area under ROC curve) and negative predictive value between FDG-PET and CT-scan are primary endpoints. Furthermore, an economic evaluation will be performed, comparing survival and costs associated with the use of FDG-PET (or CT-scan) to predict tumor response with survival and costs of neoadjuvant chemoradiotherapy without prediction of response (reference strategy).

Discussion

The NEOPEC-trial could be the first sufficiently powered study that helps justify implementation of FDG-PET for response-monitoring in patients with esophageal cancer in clinical practice.

Trial registration

ISRCTN45750457