Abstract Book

S341

ESTRO 37

SOC plus SRT is low in many countries, except for some countries like the UK, where the use of SRT is more strictly regulated. 2) The situation of oligo-metastases is complex and diverse in terms of primary cancer type, time of oligo- metastases development, previous treatment of the loco- regional primary cancer, imaging used for staging of oligo-metastases, number, location and size of oligometastases, integration of local treatment into a systemic treatment strategy, choice of radical local treatment approach and clinical endpoint. Systematically addressing all these questions through traditional prospective clinical trials is not possible. Consequently, there is a strong clinical and scientific need to pursue alternative strategies to advance the field of oligometastases. Traditional prospective interventional trials are required for answering answer proof-of- principle questions. On the other side, the broad clinical implementation and practice of stereotactic radiotherapy for oligometastases within the European community offers the opportunity to establish a large European prospective registry trial. The diversity inherent to oligometastases treatment techniques requires a European approach to ensure the collection of data from a sufficiently large patient cohort in order to answer the questions listed below. This type of pragmatic trial, also referred to as “practical” or “effectiveness” trials, has been widely advocated as means of addressing limitations of traditional efficacy trials. These designs rely on simplified data-collection processes, strategies such as broad eligibility criteria for both patients and providers, and an acceptance of protocol “violations” such as crossover, nonadherence, and loss to follow-up that make the trial conditions similar to the way in which care is delivered in routine practice. OLIGO-CARE is a prospective registry trial of oligometastatic disease. It aims to evaluate patterns-of- care and patterns-of-outcome after radical treatment for oligometastatic disease and to evaluate patient, tumor, diagnostic and treatment factors influencing outcome. The study is characterized by a collaborative, global, pragmatic and adaptive design. These aspects will be addressed during the talk. SP-0643 RT-drug combinations: Targeted radiosensitisation M. Verheij 1 1 Netherlands Cancer Institute, Radiation Oncology, Amsterdam, The Netherlands Abstract text Increased understanding of the molecular mechanisms underlying tumor and normal cell radiosensitivity has led to the identification of a variety of potential targets for rational intervention. However, despite many studies on radiation-targeted drug combinations, the clinical implementation of such new strategies has been limited so far. Therefore, several issues need to be considered to optimize the combination of radiation-targeted agents, including tumor-specific target modulation and normal tissue toxicity, scheduling and biologically effective dosing, and the availability of robust biomarkers. These considerations will be discussed on the basis of the combined use of radiation and DNA repair inhibitors. DNA damage repair and response inhibition are promising strategies to potentiate radio- or chemotherapy. Among such approaches, PARP inhibitors are particularly attractive as radio-enhancers due to the cellular replication-dependent radiosensitizing and vasodilatory properties. Potent radiosensitization capacity combined with a favorable low systemic toxicity profile provides a strong rational for radiotherapy PARP inhibitors combinations. Several ongoing phase I-II studies evaluate the safety and tolerability of the PARP inhibitor olaparib, in combination with radiotherapy.

Biomarkers that assess the activity of drugs or the combination are important to guide such trials. We developed and evaluated a PARP inhibitor pharmacodynamics assay that allows sensitive assessment of PARP inhibitor activity. In a healthy volunteer study we determined that the sensitivity and accuracy to quantify PARP inhibition exceeded those of the established PAR pharmacodynamic assay by several fold. Implemented in clinical combination trials, the assay showed superior detection of PARP inhibition in patients treated with the PARP inhibitor olaparib and establishes strong PARP inhibitory activities at low daily doses. In summary, radiation-targeted agent combinations are attractive but in many ways challenging strategies that require a rational study design. SP-0644 Structuring clinical research for particle therapy D.C. Weber 1 1 Paul Scherrer Institute PSI, Radiation Oncology, Villigen PSI, Switzerland Abstract text Particle therapy, including proton and carbon ion therapy, is currently been developed in Europe with the opening of a number of new centers by 2018-2021. Although proton therapy has been delivered to cancer patients since the 1970’s, this treatment modality remained a niche therapeutic strategy until approximately 2010 when a number of new facilities opened worldwide, with an exponential increase in the US, first with a passive scattering paradigm and then with pencil beam scanning delivery. Although approximately 150’000+ and 25’000+ patients have been treated with protons and carbon ions, respectively, there is no level I evidence supporting this costly treatment modality. The reasons for the lack of clinical prospective trials included but are not limited to the lack of particle network, critical mass of particle centers and the divide between the particle and photon communities. This lack of evidence has been identified as a major issue for particle therapy and a number of prospective trials, including phase III studies, have been launched and are currently actively accruing patients. One of the main issues is that these studies tend usually to be stemming from one or two institutions highlighting the need for a cooperative scientific network. Moreover the number of accrued patients is modest, as revealed in the recent phase III trial for advanced lung cancer performed by the MDACC in the US including only 255 patients in this important trial (Clinical trial information: NCT00915005). In the US, there has been an incentive to produce rapidly some prospective data, more for insurance/reimbursement issues than for real scientific purposes. Clinical research in particle therapy may also be hampered by the rarity of the disease treated by this modality and different beam delivery technics and RBE to name a few additional issues. In Europe, the EORTC has established a clinical network of researchers since the 1970s, aiming to improve treatment and patient care by approaching clinical and translational research from a multidisciplinary perspective. The inclusion of Biology/imaging-driven trials, innovative screening bio- platforms and integrating translational research could well increase the scientific output for research in particle therapy and serve the scientific interests of this community. Moreover data sharing from EORTC databases could stimulate investigators within and outside the EORTC to access particle therapy datasets. One solution to tackle the divide observed among health professionals from the particle and photon therapy communities is to bring these individuals in one umbrella society. As such the European Particle Therapy Network (EPTN) has been created in 2015 and is now a task force of ESTRO (https://www.estro.org/about-us/governance-