Abstract Book

S347

ESTRO 37

SP-0655 How much do we know on the biology of extreme hypofractionation? B. De Bari 1 1 Hôpital Univ. Jean Minjoz CHU Minjoz Jeans & Belfort- Montbéliard Hospital, Radiation Oncology, Besançon, France Abstract text Radiobiological models usually applied for standard radiotherapy treatments (i.e. 1.8 – 2 Gy/fraction repeated in several fractions) are being challenged in the modern era of radiotherapy. On the one hand, the very good clinical results of stereotactic body radiotherapy, and on the other the impression that the α/β ratio for some cancers is not high (i.e. 10 Gy), but it may be of the same order (or even lower) than that adopted to calculate late complications, are some of the factors that are clearly influencing our knowledge about the tumor response to radiation. Some other factors that should be considered in evaluating the biological impact of extreme hypofractionation are the impairment of re-oxygenation between fractions, the very high α/β for hypoxic cells and the radiation induced vascular damage. All these aspects are probably more noteworthy when higher doses are delivered, and could complicate the analysis of clinical outcomes. Aim of this lecture will be to summarize available radiobiological evidences and the work in progress in the field of extreme hypofractionation. SP-0657 What is the best choice of therapy in elderly with GBM: concomitant chemoradiation, radiotherapy or chemotherapy? A. Malmström 1 1 Linköping University Division of Radiological Sciences, Institutionen för klinisk och experimentell medicin IKE / Avdelningen för Cellbiologi CELLB, Linköping, Sweden Abstract text During the last decade a number of important randomized clinical trials have been published, asking the question of best treatment for elderly, diagnosed with GBM. The French study of Keime-Guibert found that for patients 70 years or older, 50 Gy was superior to best supportive care, prolonging survival from 4 to 7 months. A Canadian trial by Roa et al compared 60 Gy over 6 weeks versus 40 Gy in 3 weeks in 100 patients being 60 years or older, without finding a significant difference in survival. They later compared the same hypofractionated RT scheme of 40 Gy in 15 fractions to 25 Gy in 5 fractions, in 100 patients with poor performance status and age >50 years, also here without any clinically important difference in outcome. The Nordic trial randomized GBM patients 60 years or older between 60 Gy in 6 weeks or 34 Gy in 10 fractions over 2 weeks or temozolomide (TMZ) 200 mg/m2 days 1-5 q4 weeks, for 6 cycles. Best survival was noted for the TMZ arm, especially for patients with methylated tumor MGMT promotor and age >70 years. For those >70 years also hypofractionated radiotherapy over 2 weeks was superior to 60 Gy. In the German NOA-08 trial dose dense Symposium: Brain tumors in 2018: are there still unsolved problems? SP-0656 Two years since the release of new WHO classification of CNS tumors: what has come up new and how to implement this? A. von Deimling University of Heidelberg, Heidelberg, Germany Abstract received

to limit its utilization. Most ROs consider evidence still unsufficient to routinely adopt hypofractionation for regional node irradiation, even though in the only one neurologic injury in the arm receiving 41.6 Gy was reported. Admittedly, the randomized studies do not have a follow-up sufficiently long to allow a reliable assessment regarding cardiac toxicity. In addition, left- sided breast cancers very often require a certain level of technical complexity to minimise heart irradiation, especially in women with concomitant risk factors, and in this context the use of hypofractionation is considered an additional problem.In addition, HF-WBI is preferably delivered to small-moderate breast size, since large breast size may be more penalised by the so called “triple trouble” phenomenon, increasing the risk of fibrosis. Investigators from Spain highlighted how ROs were more likely to give HF-WBI to very old women, since elderly were deemed to be at lower risk of developing toxicity, being near the end of their lifespan.As a matter of fact, in most hypofractionated schedules, the total dose calculated in EQD2 (that is equivalent total dose delivered in 2 Gy fractions) is slightly reduced that that of CF-WBI. As Yarnod and coll. stated, a small decrease in total dose allows greater decrease in normal tissue toxicity under the acceptable compromise of local control. Therefore, hypofractionation should be gentler to normal tissue than conventional fractionation. Nevertheless, especially in case of very shortened hypofractionated schemes, the target population consists mostly of the elderly. Five fractions with high dose per fraction given once per week have been tested in several series, mainly including patients of advanced age or with co-morbidities. Only the UK FAST trial enrolled patients starting from the age of 50.There is a great variability in adopting hypofractionated schedules across countries and within the same country. These differences are due to different interpretation of the existing results and to a sort of reluctance and caution in the use of new schemes. While it is understandable to wait for more mature results in case of extreme forms of hypofractionation, there are few reasons not to apply moderate hypofractionation in almost all breast cancers. Three of the four randomized studies included early- and intermediate-stage breast cancer with a long follow-up. Of course, there might be several other reasons which contribute to slow adoption of hypofractionation. As part of the "Choosing Wisely" campaign by the American Board of Internal Medicine, aimed at avoiding unnecessary costs, ASTRO invited ROs to always consider HF-WBI in women aged over 50 with early breast cancer conservatively treated. Updated clinical guidelines could help to spread and homogenise hypofractionation. SP-0654 What is the limit of hypofractionation? M. Guckenberger 1 1 University Hospital Zürich, Department of Radiation Oncology, Zurich, Switzerland Abstract text The limit of hypo-fractionated radiotherapy for primary and secondary lung tumours is single-fraction radiosurgery. Prospective randomized studies comparing radiosurgery with fractionated SBRT for stage I NSCLC are promising for the single-fraction approach; however, long-term follow-up is missing and retrospective data suggest decreased efficacy compared to fractionated SBRT. Extreme hypo-hypo-fractionation for tumours with central or ultra-central does require risk-adapted fractionation, making the number of treatment fractions an additional degree of freedom in treatment planning. A major limitation is the current lack of validated dose constraints for many thoracic organs-at-risk, in particular in the setting of SBRT.