2 nd ESTRO Forum 2013 S117 DEBATE: THIS HOUSE BELIEVES THAT NORMAL STRUCTURES DELINEATIONS SHOULD BE DELEGATED TO RTTS? SP-0302 For the motion M.E. Mast 1 1 Radiotherapy Centre West, Radiotherapy, The Hague, The Netherlands With the increasing age of the European population, the number of cancer patients will increase further in the coming decades. Besides surgery and systemic therapy, radiation therapy is an important part of the primary (and palliative) treatment in many tumour sites. The radiation oncologist is spending more and more time on the multi- disciplinary approach of the cancer patient. Furthermore, preparing modern radiotherapy is becoming more time consuming for the radiation oncologist. And, among others, organs at risk have to be delineated. Because, in doing so, the dose to the OAR can be kept low resulting in a lower probability of radiation induced side effects. Also, highly conformal techniques and hypofractionation schemes become the current practice and, a precise delineation of the OARS becomes even more important. Automatic delineation programs exist and can be helpful to perform a standardized OAR delineation to guide the RTT to an optimal delineation of OAR. Proper training is necessary to distinguish between normal tissue and tumour extension. The RTT is more and more involved in the treatment planning process and delineating the OARs overlap for several tumoursites. In the training of the RTTs the delineation on MRI on PET-CT should be included as well, it appeared that for some tumoursites the OARs can be visualised better on those imaging modalities. Finally, when the guidelines for delineation of the OARs are defined precisely, we can move over to another level in the delineation of structures. Radiation therapists might perform the delineation of the CTV of some tumour sites, to increase the departmental efficiency and to decrease the interobserver variability of delineating the CTVs. Batumulai et al. stated that the interobserver variability between radiation oncologists and radiation therapists was low, and their study provided support in CTVBreast delineation by the radiation therapists based on a standardized protocol [Batumulai et al, 2011]. Conclusion: To avoid a delay in the treatment and to increase the level of uniformity, delineation of the OARs by properly trained radiation therapists is the next step in the process of preparing an optimal radiation treatment. Reference: Batumulai V, Koh ES, Delaney GP, et al. Interobserver variability in Clinical Target Volume delineation in tangential breast irradiation: a comparison between radiation oncologists and radiation therapists. Clinical Oncology 2011; 23: 108-113. SP-0303 Against the motion F. Moura 1 1 Hospital Cuf Descobertas, Department of Radiotherapy, Lisboa, Portugal The perspective of changing the paradigm, from 2D unclear volumes and surrounding tissues to 3D/4D morphological and functional imaging information, clear and unambigous OARs delineation, take a pivotal importance when highly conformal techniques and hypofractionation schemes become the current practice. Against the motion, arguments will focus on: medical issues, legal aspects and policies; educational curricula, basic/advanced education and training; continuous professional development with the gain of specific knowledge, skills and competences; role development and professional recognition. The scientific debate will highlight relevant aspects, related to the delineation of OARs in QUANTEC era; dose response relationships; dose volumes constraints and endpoints; radiobiologic NTCP models; imaging for volumes delineation and interobserver variability. SYMPOSIUM: REGENERATIVE THERAPY SP-0304 When and how is regenerative therapy an option after radiotherapy R.P. Coppes 1 1 University of Groningen University Medical Center Groningen, Departments of Radiation Oncology and Cell Biology, Groningen, The Netherlands Normal tissue damage after radiotherapy may cause severe, life threatening complications that may even interfere with the dose that can be applied to the tumour. Normally tissues respond to damage by activating stem and/or progenitor cells, which multiply by asymmetric division to form stemcells and newly differentiated cells. After irradiation this response may be affected due to the lethal amount of DNA damage and/or to a changed environment, which inhibits the remaining stem/progenitor cells to exert there regenerative potential. Regenerative therapy can be used to rejuvenate the tissues stem/progenitor cells or stimulate remaining stem cells to re-establish homeostasis. Preclinical studies will be discussed that have shown that remaining stem cells can be stimulated to enhance regeneration inirradiated tissue by the application of growth factors and bone marrow derived cells. These therapies however only have therapeutic potential when sufficientstem/progenitor cells have survived the radiation insult. If not, stem cell therapy could be an option. The use of embryonic stem cells or induced pluripotent stem cells (iPS), however is still in its infancies. Therefore, adult stem cell therapy is preferable in the near future. For patients receiving radiotherapy, collection of tissue stem cells before cancer treatmentseems feasible. As such bone marrow transplantation has been used for many years re-establish the haematopoiesis. For several organs adult stem cells have now been isolated and characterized. Recent developments in the use of adult stem cells therapies will be discussed in relation to their potential use after radiotherapy. SP-0305 Haematopoietic stem cells and radiation P. Romeo 1 , S. Moreira 1 , F. Hoffshir 1 , S. Moreno 1 , M.C. Vozenin 2 , D. Lewandowski 1 , N. Gault 1 1 CEA - Université Paris Diderot - Paris 7, Département des Sciences du Vivant, Fontenay aux roses, France 2 IGR, Inserm U1030, Villejuif, France The paradigm of DNA damage and mutagenesis has been a driving force for understanding the biological and health consequences of ionizing radiation (IR) and, among the cellular target cells of IR, somatic stem cells are of particular interest. Somatic stem cells can self-renew and can produce numerous types of mature effector cells throughout life and thus, accumulating genetic alterations after irradiation can compromise their genomic integrity and may potentially give rise to cancer. Adult hematopoiesis, one of the best- studied models to understand the biology of adult stem cells in vivo and in vitro, is a hierarchic process in which immature hematopoietic progenitors undergo progressive changes, including proliferation and differentiation steps that finally lead to the production of mature cells. The hematopoietic hierarchy can be declined into four main compartments: stem cells (HSCs), immature progenitors, precursors and mature cells. Long-term-HSCs (LT-HSCs) are the most immature population in the hematopoietic system. They are rare and mostly quiescent and, in response to extrinsic/intrinsic signals, they self- renew and/or give rise to short-term-HSC (ST-HSCs). ST-HSCs are less quiescent and have limited self-renewal compared to LT-HSCs. They can give rise to multipotent progenitors (MPP), which undergo multiple rounds of division to produce the various immature progenitors that can differentiate into mature hematopoietic cells. Compared to hematopoietic progenitors, hematopoietic stemcells (HSCs) are more resistant to IR when exposed to doses ranging from 1Gy to 4Gy, however this resistance is associated with genomic instability in HSCs, asHSCs repair DNA damages by the non-homologous end joining (NHEJ), an error-prone mechanism. In contrast to the effects of high doses of IR, the effects of low doses on hematopoietic stem cells have not been extensively studied. We have determined if low doses of irradiation could have an impact on hematopoietic stem cells (HSCs) function. An enriched HSCs population was irradiated at 0.02Gy 0.1Gy, 0.25Gy or at 2.5Gy and the irradiated cells were transplanted into a lethally irradiated recipient mice.Six months after primary transplantation the only compartment affected was the HSCs compartment with a reduction of LT-HSCs pool for doses as low as 0.1Gy.The bone marrow of those mice were transplanted into secondary recipient mice and we found that LT-HSCs reconstitution capacity was decreased from 0.02Gy, showing defectual self-renewal. Finally, treatment of the mice with 5-FU showed that mice that have received irradiated HSCs at doses as low as 0.02Gy died prematurely compared to mice transplantated with non- irradiated HSCs. Thus, doses as low as 0.02Gy can drive multiple defects in HSCs, affecting their function in the long-term. We will discuss these results and show data on the molecular basis of this HSCs sensitivity to low doses of irradiation.