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Open Access Study protocol

Preoperative chemosensitivity testing as Predictor of Treatment benefit in Adjuvant stage III colon cancer (PePiTA): Protocol of a prospective BGDO (Belgian Group for Digestive Oncology) multicentric study

Alain Hendlisz1*, Vassilis Golfinopoulos1, Amelie Deleporte1, Marianne Paesmans2, Hazem El Mansy1, Camilo Garcia3, Marc Peeters4, Lieven Annemans5, Caroline Vandeputte1, Marion Maetens1, Ivan Borbath6, Damien Dresse7, Ghislain Houbiers8, Michael Fried9, Ahmad Awada1, Martine Piccart1, Jean-Luc Van Laethem10 and Patrick Flamen3

Author Affiliations

1 Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium

2 Data Center, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium

3 Nuclear Medicine Department, Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium

4 Department of Oncology, Antwerp University Hospital, Antwerp, Belgium

5 Health Economics, Department of Public Health, Ghent University, Ghent, Belgium

6 Gastroenterology Department, Cliniques Universitaires Saint-Luc, Université Catholique de Louvain, Brussels, Belgium

7 Service de Chirurgie Abdominale et Générale, Centre Hospitalier Régional La Citadelle, Liège, Belgium

8 Service d’Oncologie et d’Hématologie, CH Saint Joseph, Liège, Belgium

9 Oncology department, Ziekenhuis Netwerk Antwerpen, Antwerpen, Belgium

10 Gastroenterology Department, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium

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BMC Cancer 2013, 13:190  doi:10.1186/1471-2407-13-190

Published: 12 April 2013

Abstract

Background

Surgery is a curative treatment for patients with locally advanced colon cancer, but recurrences are frequent for those with stage III disease. FOLFOX adjuvant chemotherapy has been shown to improve recurrence-free survival and overall survival by more than 20% and is nowadays considered a standard of care. However, the vast majority of patients will not benefit from receiving cytotoxic drugs because they have either already been cured by surgery or because their tumor cells are resistant to the chemotherapy, for which predictive factors are still not available.

Identifying which patients are unlikely to respond to adjuvant chemotherapy from among those who are eligible for such treatment would be a major step towards treatment personalization. It would spare such patients from unnecessary toxicities and would improve the allocation of societal healthcare resources.

Methods/design

PePiTA is a prospective, multicenter, non-randomised trial built on the hypothesis that preoperative chemosensitivity testing using FDG-PET/CT before and after one course of FOLFOX can identify the patients who are unlikely to benefit from 6 months of adjuvant FOLFOX treatment for stage III colon cancer.

The study’s primary objective is to examine the ability of PET/CT-assessed tumor FDG uptake after one course of preoperative chemotherapy to predict the outcome of adjuvant therapy, as measured by 3-year disease-free survival.

Secondary objectives are to examine the predictive value of changes in PET/CT-assessed tumor FDG uptake on overall survival, to define the best cut-off value of FDG uptake for predicting treatment outcome, and to analyse the cost-effectiveness of such preoperative chemo-sensitivity testing.

At study planning, exploratory translational research objectives were 1) to assess the predictive value of circulating tumor cells for disease-free survival, 2) to examine the predictive value of single nucleotide polymorphisms for disease-free survival with respect to genes related either to toxicity or to drug targets, 3) to assess genomic rearrangements associated with response or resistance to FOLFOX treatment, 4) to identify an immunologic signature associated with metabolic tumor response to FOLFOX therapy and, finally, 5) to create a bank of frozen tumor samples for future studies.

Discussion

PePiTA is the first study to use the primitive tumor chemosensitivity assessed by metabolic imaging as a guidance for adjuvant therapy in colon cancer. It could pave the way for tailoring the treatment and avoiding useless toxicities for the patients and inadequate expenses for the society. It could also give an interesting insight into tumoral heterogeneity, resistance to chemotherapy, genetic predisposants to oxaliplatin toxicity and immune response to cancer.

EudraCT number

2009-011445-13

Trial registration

ClinicalTrials.gov number, NCT00994864

Keywords:
Colon cancer; Adjuvant; Early assessment; Chemosensitivity; FDG-PET; PET/CT