Open Access Highly Accessed Study protocol

Neoadjuvant chemoradiation followed by surgery versus surgery alone for patients with adenocarcinoma or squamous cell carcinoma of the esophagus (CROSS)

M van Heijl1*, JJB van Lanschot12, LB Koppert2, MI van Berge Henegouwen1, K Muller3, EW Steyerberg4, H van Dekken5, BPL Wijnhoven2, HW Tilanus2, DJ Richel6, ORC Busch1, JF Bartelsman7, CCE Koning8, GJ Offerhaus9 and A van der Gaast10

Author Affiliations

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

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

3 Department of Radiotherapy-Oncology, Erasmus Medical Center, Rotterdam, The Netherlands

4 Department of Clinical Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands

5 Department of Pathology, Erasmus Medical Center, Rotterdam, The Netherlands

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

7 Department of Gastroenterology, Academic Medical Center, Amsterdam, The Netherlands

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

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

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

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BMC Surgery 2008, 8:21  doi:10.1186/1471-2482-8-21

Published: 26 November 2008

Abstract

Background

A surgical resection is currently the preferred treatment for esophageal cancer if the tumor is considered to be resectable without evidence of distant metastases (cT1-3 N0-1 M0). A high percentage of irradical resections is reported in studies using neoadjuvant chemotherapy followed by surgery versus surgery alone and in trials in which patients are treated with surgery alone. Improvement of locoregional control by using neoadjuvant chemoradiotherapy might therefore improve the prognosis in these patients. We previously reported that after neoadjuvant chemoradiotherapy with weekly administrations of Carboplatin and Paclitaxel combined with concurrent radiotherapy nearly always a complete R0-resection could be performed. The concept that this neoadjuvant chemoradiotherapy regimen improves overall survival has, however, to be proven in a randomized phase III trial.

Methods/design

The CROSS trial is a multicenter, randomized phase III, clinical trial. The study compares neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with potentially curable esophageal cancer, with inclusion of 175 patients per arm.

The objectives of the CROSS trial are to compare median survival rates and quality of life (before, during and after treatment), pathological responses, progression free survival, the number of R0 resections, treatment toxicity and costs between patients treated with neoadjuvant chemoradiotherapy followed by surgery with surgery alone for surgically resectable esophageal adenocarcinoma or squamous cell carcinoma. Over a 5 week period concurrent chemoradiotherapy will be applied on an outpatient basis. Paclitaxel (50 mg/m2) and Carboplatin (Area-Under-Curve = 2) are administered by i.v. infusion on days 1, 8, 15, 22, and 29. External beam radiation with a total dose of 41.4 Gy is given in 23 fractions of 1.8 Gy, 5 fractions a week. After completion of the protocol, patients will be followed up every 3 months for the first year, every 6 months for the second year, and then at the end of each year until 5 years after treatment. Quality of life questionnaires will be filled out during the first year of follow-up.

Discussion

This study will contribute to the evidence on any benefits of neoadjuvant treatment in esophageal cancer patients using a promising chemoradiotherapy regimen.

Trial registration

ISRCTN80832026