Peripheral arterial disease and systematic detection of circulating tumor cells: rationale and design of the DETECTOR prospective cohort study

Alexandra Yannoutsos, Manon Fontaine, Alexandre Galloula, Diane Damotte, Gilles Chatellier, Patrizia Paterlini-Bréchot, Guy Meyer, Jean Pastre, Véronique Duchatelle, Valéria Marini, Karl-Léo Schwering, Isabelle Lazareth, Parinaz Ghaffari, Audrey Stansal, Hélène Sanson, Cécile Labrousse, Hélène Beaussier, Nesrine Ben Nasr, Marc Zins, Sergio Salmeron, Emmanuel Messas, Jean-Patrick Lajonchère, Joseph Emmerich, Pascal Priollet, Jean Trédaniel, Alexandra Yannoutsos, Manon Fontaine, Alexandre Galloula, Diane Damotte, Gilles Chatellier, Patrizia Paterlini-Bréchot, Guy Meyer, Jean Pastre, Véronique Duchatelle, Valéria Marini, Karl-Léo Schwering, Isabelle Lazareth, Parinaz Ghaffari, Audrey Stansal, Hélène Sanson, Cécile Labrousse, Hélène Beaussier, Nesrine Ben Nasr, Marc Zins, Sergio Salmeron, Emmanuel Messas, Jean-Patrick Lajonchère, Joseph Emmerich, Pascal Priollet, Jean Trédaniel

Abstract

Background: Smoking is a strong risk factor for cancer and atherosclerosis. Cancer mortality, especially from lung cancer, overtakes cardiovascular (CV) death rate in patients with peripheral arterial disease (PAD). Only a few patients with lung cancer after PAD management may benefit from surgical excision. Circulating tumor cells (CTC) associated with low-dose chest CT (LDCT) may improve early cancer detection. This study focuses on a screening strategy that can address not only lung cancer but all tobacco-related cancers in this high-risk population.

Methods: DETECTOR Project is a prospective cohort study in two French University hospitals. Participants are smokers or former smokers (≥30 pack-years, quitted ≤15 years), aged ≥55 to 80 years, with atherosclerotic PAD or abdominal aortic aneurysm. After the first screening round combining LDCT and CTC search on a blood sample, two other screening rounds will be performed at one-year interval. Incidental lung nodule volume, volume doubling time and presence of CTC will be taken into consideration for adapted diagnostic management. In case of negative LDCT and presence of CTC, a contrast enhanced whole-body PET/CT will be performed for extra-pulmonary malignancy screening. Psychological impact of this screening strategy will be evaluated in population study using a qualitative methodology. Assuming 10% prevalence of smoking-associated cancer in the studied population, a total of at least 300 participants will be enrolled.

Discussion: Epidemiological data underline an increase incidence in cancer and related death in the follow-up of patients with PAD, compared with the general population, particularly for tobacco-related cancers. The clinical benefit of a special workup for neoplasms in patients with PAD and a history of cigarette smoking has never been investigated. By considering CTCs detection in this very high-risk selected PAD population for tobacco-induced cancer, we expect to detect earlier pulmonary and extra-pulmonary malignancies, at a potentially curable stage.

Trial registration: The study was registered in the French National Agency for Medicines and Health Products Safety (No N° EUDRACT_ID RCB: 2016-A00657-44) and was approved by the ethics Committee for Persons Protection (IRB number 1072 and n° initial agreement 2016-08-02; ClinicalTrials.gov identifier NCT02849041).

Keywords: Cancer; Circulating tumor cells; Screening; Tobacco.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Adapted screening strategy in case of negative low-dose chest CT or incidental lung nodule(s) with a volume 3 and presence of circulating tumor cells (CTCs)

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