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…

Alain Hendlisz, Vassilis Golfinopoulos, Amelie Deleporte, Marianne Paesmans, Hazem El Mansy, Camilo Garcia, Marc Peeters, Lieven Annemans, Caroline Vandeputte, Marion Maetens, Ivan Borbath, Damien Dresse, Ghislain Houbiers, Michael Fried, Ahmad Awada, Martine Piccart, Jean-Luc Van Laethem, Patrick Flamen

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/designPePiTA 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 number2009-011445-13ClinicalTrials.gov numberNCT00994864.