Abstract C220: Combining novel targeted therapies and radiotherapy: A challenge to overcome.
Authors: Rivera Sofia , Vens Conchita , Maingon Philippe , Govaerts Anne Sophie , Shash Emad , Lacombe Denis , Grant Warren , Grégoire Vincent 
Published: August 2014

Abstract
Radiotherapy is a major cancer treatment modality involved in 50% of cancer treatments and 40% of cancer cure. Modern radiotherapy techniques such as Intensity Modulated Radiation Therapy (IMRT) and high precision image guided radiotherapy (IGRT), as well as dose escalation strategies to limited volumes, have demonstrated not only improved effectiveness but also reduced toxicity. Despite these advances, loco-regional relapse remains an issue. Opportunities to further improve loco-regional disease control and cure rates lay in molecularly targeted therapies that combine radiotherapy with targeted agents. Such novel combination strategies should preferably result in the specific radio-sensitization of tumors and/or provide normal tissue protection. Increasing knowledge in understanding the molecular and cellular response to ionizing radiation and genetic alteration in tumors enabled the development of novel drug-radiotherapy combinations strategies of which some have already started to affect the outcome after radiotherapy. Promising agents and drug classes for such radiotherapy combination strategies have been identified and include DNA damage response pathways inhibitors, PI3K-AKT pathway inhibitors, hypoxia modifiers or epigenetic modulators. However, despite these opportunities and strong rationales, less than 40 phase III trials combining novel agents with radiotherapy have been published to date and drugs are often tested for radiotherapy combinations late in their development. The variation in possible radiotherapy sites, settings and schedules, the complexity of such approaches, lack of expertise and the shortage of successful examples may cause the procrastination. In conclusion, novel radiotherapy combination strategies are highly promising and the challenges of combining targeted therapies and radiotherapy need to be overcome. By the implementation of a robust methodology while rigorously assessing the potential benefits and toxicities of the possible combinations in relevant preclinical models we propose to establish a comprehensive development strategy that aims at clinical translation in the most promising settings. A stringent evaluation early in the development that will help to prioritize radiotherapy settings, agents and tumor sites could be realized in a collaboration of academic institutions, collaborative groups and industry. With the objective to foster the development of these combined treatments the EORTC ROG has created a working group that established and coordinates a unique European multicentric platform. Providing state-of-the-art clinical and preclinical radiotherapy modalities, molecular diagnostic tools and imaging platforms it integrates the expertise of different radiobiology and radio-oncology centers, to define research strategies from proof of concept to clinical trials.
Citation Information: Mol Cancer Ther 2013;12(11 Suppl):C220.
Citation Format: Sofia Rivera, Conchita Vens, Philippe Maingon, Anne Sophie Govaerts, Emad Shash, Denis Lacombe, Warren Grant, Vincent Grégoire. Combining novel targeted therapies and radiotherapy: A challenge to overcome. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr C220.