ESTRO 36 Abstract Book

S750 ESTRO 36 2017 _______________________________________________________________________________________________

8 University of Maryland, School of Medicine, Baltimore, USA 9 University of Manchester, Manchester Academic Health Science Centre- The Christie NHS Foundation Trust, Manchester, United Kingdom 10 University of Rochester, Medical Center, Rochester, USA 11 University of Manchester, Translational Radiobiology Group I Institute of Cancer Sciences- The Christie NHS Foundation Trust, Manchester, United Kingdom Purpose or Objective To define the optimal design and patient selection for interventional trials in radiogenomics, as radiogenomics do not give binary information like in e.g. targetable mutation biomarkers. Here, the risk to develop severe side effects is continuous, with increasing incidences of side effects with higher doses and/or volumes. Material and Methods The most appropriate interventions, endpoints, trial designs, model performance, identification of patient groups that could benefit most from a radio-genomic biomarker, and patient considerations were identified. Patients’ advocacy representatives were part of this work. Results Interventions that can be considered are: alternative treatment, dose modification, altered radiotherapy, mitigation / amelioration and the omission of postoperative radiotherapy in patients with a low risk for tumour recurrence. The optimal intervention is dependent on pre-defined risk factors, which were identified. There is clearly no simple endpoint or time point that can be selected when designing a clinical trial. Composite endpoints should be considered. Randomised clinical trials and retrospective observational studies have pros and cons in radiogenomics, which will be discussed. As model precision improves, thresholds can be relaxed, e.g., a very precise model could select patients for receiving a higher radiation dose with no risk of undue toxicity. Although more precise models will typically result in more benefit, less precise models might be informative to some degree. The consequences of the incidence of toxicity/toxicities on the number of patients needed for prospective validation as a function of the prevalence of a genetic profile must be considered. A polygenic risk score will likely be needed as individual genetic variants each contribute only modestly to risk of developing toxicity. Decreasing the standard radiation dose in the most susceptible patients is highly dependent on the dose- effect relationship.. These relations are highly dependent on the endpoint, e.g. radiation pneumonitis vs. fibrosis. An in-depth knowledge of the dose-volume relation for a specific endpoint taking into account the clinical usefulness of the dose reduction is needed in order to select the correct patient for this strategy. For the results of a study to be of value for patients, there should be a therapeutic alternative for the standard of care radiotherapy and the quantitative gain should be measurable and relevant. The incidence of peak reactions after radiotherapy is not the only parameter that should be taken into account. It is their severity, reversibility, the possible salvage treatments and the overall influence on quality of life that is also crucial to take into account. Conclusion The REQUITE and radiogenomics consortium has defined recommendations for the optimal design and patient selection for interventional trials using radiogenomic biomarkers, which will be presented in detail. Funding: EU 601826 SK: K07CA187546 NCI USA

supporting treatment. Therefore, the ROSETTA ( R and O mized S tudy E xploring the combination of radio T herapy with T wo types of A cupuncture treatment) trial was initiated as a prospective randomized phase II trial. It examines if traditional (verum-) acupuncture can reduce RT-related side effects significantly in comparison to sham (false-) acupuncture. Material and Methods A total of 74 patients are to be recruited. In the experimental arm (n=37) an experienced acupuncture- trained person will treat dedicated acupuncture points. In the control arm (n=37) sham-acupuncture will be performed to provide a blinded comparison of results. The Ethics Committee of the Technical University of Munich (TUM) approved the nature and content of the study with the project number 512/15. To evaluate quality of life, patients receive a standardized questionnaire (EORTC QLQ C-30) before their first, after their fourth and after their last acupuncture treatment. Further, a study investigator questions patients about their feelings and symptoms as well as documents detailed information regarding their course of disease. The main endpoint of the trial is the improvement of QoL and reduction of fatigue. Secondary endpoints are the reduction of RT-related side effects such as headache, nausea, and pain. Results The ROSETTA trial is currently recruiting. Initial results from 30 patients (verum acupuncture n=15; sham acupuncture n=15) are presented. All the following items are scaled from 0 to 100. A high score in a symptom scale represents an aggravation of symptoms, whereas a high score in QoL shows an improvement. Concerning nausea/vomiting and QoL no significant difference can be observed between the sham- acupuncture and the verum group. Thus, patients suffer from a constant level of these side effects during RT. From the first examination to the last visit, fatigue increases in the group receiving sham acupuncture (from 21 to 44). Meanwhile, fatigue remains constant in the verum group (from 40 to 40). Verum-acupuncture shows positive effects in reduction of pain (first visit: 21, last visit: 25) in comparison to the sham-acupuncture group (first visit: 23, last visit: 30). Conclusion We present first results of the ROSETTA trial, which show preliminary tendencies in 30 randomized patients. Comparing the verum and the sham-acupuncture group, some differences regarding fatigue and pain are apparent. In spite of undergoing RT, patients in both groups do not feel worse concerning the examined features. Our results and ongoing research will generate an excellent data basis on how to include certain complementary medicine methods into high-end oncology treatment. EP-1419 Optimal design and patient selection for interventional trials using radiogenomic biomarkers D. De Ruysscher 1 , G. Defraene 2 , B. Ramaekers 3 , P. Lambin 4 , E. Briers 5 , H. Stobart 6 , T. Ward 7 , S. Bentzen 8 , T. Van Staa 9 , S. Kerns 10 , C. West 11 1 MAASTRO Clinic, Radiation Oncology, Maastricht, The Netherlands 2 KU Leuven, Radiation Oncology, Leuven, Belgium 3 Maastricht University Medical Center, Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht, The Netherlands 4 Maastricht University Medical Center, GROW School for Oncology and developmental Biology- Department of Radiation Oncology MAASTRO Clinic, Maastricht, The Netherlands 5 Patient Advocate, Patient Advocate, Hasselt, Belgium 6 Patient Advocate, Patient Advocate, Cambridge, United Kingdom 7 Patient Advocate, Patient Advocate, Manchester, United Kingdom

EP-1420 Effects of Japanese traditional Kampo medicines “Goreisan” for acute radiation enteritis