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Article History

First Online: 15 June 2019

Compliance with Ethical Standards

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: The study was funded by the Hellenic Oncology Research Group (HORG) and the study drug (aflibercept) was provided free of charge by Sanofi (Paris, France), which had no involvement in the conduct of the trial, data collection, analysis, or the preparation of the manuscript. IM and DH were recipients of a fellowship from the Cretan Association for Biomedical Research (CABR).

: Vasilis Georgoulias has received research grants and honoraria for participation in advisory boards from AMGEN, Pfizer, Astra Zeneca, Roche, Sanofi-Aventis, and Novartis. John Souglakos has received research grants from Amgen, Merck and Roche, and has served as speaker and participated in advisory boards for Amgen, Merck, Roche, Sanofi, Servier, and Celgene. Athanasios Kotsakis has received research grants and honoraria for participation in advisory boards from MSD, Roche, Bristol, Astra Zeneca. Nikolaos Kentepozidis has received research grants and honoraria for participation in advisory boards from Roche, Pfizer, Amgen, Bristol. Adamantia Nikolaidi has served as speaker and participated in advisory boards for Merck, Roche, Pfizer, Leo and Astra Zeneca, and has received travel grants from Galenica. Alexios Matikas, Panagiotis Katsaounis, Panagiotis Kouroupakis, Nikolaos Pantazopoulos, Ippokratis Messaritakis, Ioanna Tzovara, Dora Hatzidaki and Efthimios Prinarakis have no conflicts of interest to disclose.

: All patients provided written informed consent prior to study enrollment. The study was conducted in accordance with the Declaration of Helsinki. The protocol was approved by the institutional review boards of the participating centers, the independent National Ethics Committee (decision number 96/15) and the Greek Medicinal Agency (EOF; registration number 56813/28-8-2015).

: AM drafted the manuscript; IS, AK, and VG had the initial conception and designed the trial; VG, DH, and EP performed the data and statistical analysis as well as data interpretation; PK, PK, NP, NK, and AN collected clinical data; IT performed the independent central review of imaging studies; IM conducted the CTC experiments. All authors provided critical revisions to the manuscript and approved the final version before submission. VG acts as the corresponding author.

: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.