Abstract Book

S346

ESTRO 37

SP-0651 Clinical potential of human induced- pluripotent stem cells in the management of normal tissue radiation damage M. Benderitter 1 1 Institut de Radioprotection et de Sûreté Nucléaire, Laboratory of Radiobiology & Experimental Radiooncology, Fontenay-aux-Roses- Paris, France Cell therapy was demonstrated of main importance in the management of normal tissue radiation damage. Preclinical and clinical trial data suggest that mesenchymal stem cells (MSCs) are a practical and safe source of cells for stem cell-based therapies of severe tissue damage consecutive to radiation overexposure. MSCs were shown to migrate to damaged tissues supporting wound healing through a “cell drug” mode of action restoring skin and gut functions after irradiation. However, technical limits associated with large-scale ex vivo expansion indicate that alternative source is required to obtain sufficient cell numbers of the appropriate lineage to treat patients with severe disease. Based on their pluripotency and unlimited expansion potential, induced pluripotent stem cells (iPSCs) are considered a promising resource for regenerative medicine. Like naturally occurring stem cells, these artificially induced cells can self-renew and develop into almost any cell in the body (pluripotency). Clinical iPSC banks of selected universal donors should allow their use for large scale allogeneic grafts. The hiPSC-derived MSCs possess important advantages, including the capacity to generate a virtually unlimited supply of therapeutic cells and control differentiation to ensure optimum safety and potency before transplantation, which could in turn overcome the drawbacks of current MSC therapy. We demonstrate that 1) hiPSC-derived MSCs could be expanded using GMP- grade culture conditions, 2) by using a mouse model of radio-induced skin injury, hiPSC-derived MSCs have a therapeutic benefit for skin wound healing similar to adipose-derived MSCs. Moreover, our group describes a GMP-grade system to produce hiPSCs, a cell population capable of reconstituting human hematopoiesis. We demonstrate that i) hiPSC-derived hematopoietic stem cells (HSCs) from healthy donor are capable of reconstituting a functional human hematopoiesis in a radio-induced aplasia preclinical model, ii) hiPSC-derived HSCs from aplastic anemia patients or acute leukemia affected patients retain this ability. Our study prepares a new approach of autologous graft (from the cells of the patient) of cells for healthy tissue damage after radiation exposure. It could potentially pave the way to the constitution of universal banks of stem cells, which would radically increase the capacity of support and treatment of tissue exposed to high doses of ionizing radiation and in the management of chronic late radiotherapy side effects. SP-0652 Extreme hypofractionation for prostate cancer: is single fraction a future? P. Blanchard 1 1 Institut Gustave Roussy, Radiation Oncology, Villejuif, France Abstract text The most widely used regimen for external beam radiotherapy for prostate cancer is a conventional fractionation schedule that spans over around eight weeks. But it has been suggested that prostate cancer is sensitive to high doses per fraction. In the recent years, large scale randomized trials have demonstrated the non- Symposium: What is the limit of hypofractionation?

inferiority of moderately hypofractionated regimen, using typically 20 fractions of 3 Gy and hence cutting treatment duration by half. In the meantime, non- randomized studies have suggested the safety and efficacy of more severe hypofractionation regimens for low and intermediate risk patients using stereotactic body radiotherapy, with schedules typically using 5 fractions. The brachytherapy data, especially using high dose rate, have long demonstrated the efficacy of very hypofractionated schedules, which can typically use between two and five fractions for HDR brachytherapy. Many investigators are now embarking on the single fraction path, both using external beam and brachytherapy. However the adequate dose is yet to be defined and the efficacy/toxicity ratio of these single fraction regimens are to be tested in prospective trials. The goal of this talk is to discuss the rationale supporting extreme hypofractionation for prostate cancer, and to present recent results and ongoing trials that will soon support or invalidate this treatment option. SP-0653 Hypofractionation for breast cancer: 30, 15 or 5 fractions? M.C. Leonardi 1 , A. Morra 2 , S. Dicuonzo 2 , M. Gerardi 2 , V. Dell'Acqua 2 , D. Rojas 3 , A. Surgo 2 , S. Arculeo 3 , A. Casbarra 3 , C. Arrobbio 3 , R. Spoto 2 , F. Cattani 4 , R. Orecchia 5 , B. Jereczek Fossa 3 1 Leonardi Maria Cristina, Division of Radiotherapy, Milan, Italy 2 European Institute of Oncology, Division of Radiotherapy, Milan, Italy 3 European Institute of Oncology, Division of Radiotherapy and University of Milan, Milan, Italy 4 European Institute of Oncology, Division of Physics, Milan, Italy 5 European Institute of Oncology, Scientific Directorate, Milan, Italy Abstract text Since the early eighties interest in altered schedules for postoperative whole breast radiotherapy (WBI) has become considerable, in order to ease the burden of 5-7 weeks of treatment, even though the fractionation sensitivity of breast tumors was deemed to be high at that time (alfa/beta of 10 Gy), and, therefore, relatively insensitive to high dose per fraction. Four randomized trials (the Royal Marsden Hospital/ Gloucestershire Oncology Centre, the UK Standardisation of Breast Radiotherapy START A and B and the Canadian trials), all completed between 1986 and 2002, have pioneered and supported hypofractionation (HF-WBI) in breast cancer. The 10-year results of the above mentioned randomized studies have shown the equivalence in local control and tolerance between hypofractionated and conventional schedules. Amazingly, these studies have drawn the conclusion that breast cancer has an unexpected low alfa/beta of 3.5 Gy, which is similar to that of the adjacent normal tissues. The strict eligibility criteria of these trials raised important controversial issues concerning the appropriateness of HF-WBI for all breast cancer subtypes. Some uncertainties about the effectiveness of HF-WBI in aggressive tumor features or in young patients have slowed down the adoption of HF- WBI. ASTRO, ESTRO and NICE guidelines claimed the applicability of a moderate hypofractionation ( 2-3 Gy per fraction) for most patients with early breast cancer, recognizing the positive impact on social, economic and psycological aspects. In fact, considering the analysis of the cost-effectiveness of these treatments, HF-WBI should be preferred over CF-WBI, for a higher quality of life and lower costs. However, hypofractionation still meets with resistance and is adopted in varying degrees in clinical practice. Apart from controversies regarding tumor and patient sensitivity, concerns about tolerability of normal tissues might also be contributing