ESTRO 36 Abstract Book

S49 ESTRO 36 _______________________________________________________________________________________________

to the target –although inhomogeneous on the inside- with a rapid dose fall-off in the direction of the surrounding normal tissue, which is mainly due to the inverse square law. This, we have to recognise, is not a belief, but simple and straightforward physics. Consequently, the resulting ‘dosimetry’ compares very favourably with other radiation therapy techniques. When applied to the selected patient groups the clinical results in terms of survival and toxicity are the best you (i.e., the patient) can get, as has been shown in many clinical and comparative studies. Notwithstanding these apparent benefits, the numbers of patients treated with BT show a persistent tendency to decline, while the use of other techniques such as IMRT, volumetric arc therapies, and –in near future- particle therapies increases. This happens especially for those cancer types for which BT has outstanding prospects, such as in cervical, prostate, and breast cancer. Evidence for the benefits linked to a given BT standard of care seems to be bluntly ignored, but it is unclear for what reasons: are these economical reasons (time consumption, reimbursement issues for the institution and the radiation oncologist), complexity of treatment (invasive procedures, high skills and QA demands), or lacking technical solutions compared to other techniques (tissue inhomogeneity correction in TPS, advanced imaging facilities for advanced IGBT, BT treatment verification)? It is very clear that in these areas BT still has to work hard to make the necessary huge steps forward. Many studies exploring this are on-going. And all of this is really feasible! Precisely in the fields mentioned here the GEC- ESTRO Braphyqs group (started under the ESTRO-ESQUIRE project in 2001) made significant contributions over the years of its existence. A strong cooperation was developed in the entire radiation oncology community, including clinical and GEC committees, the physics committee of the ABS and the AAPM-BTSC, together with IAEA and the Euramet group of standard laboratories in Europe. The question is now whether or not time is allowed for these developments to reach the point of being fully introduced into clinical practice, while other and maybe at the first sight more ‘sexy’ radiation technology and possibly also other competing cancer treatment approaches are knocking on our doors. In all cases, it will be the patient who deserves her/his optimal treatment strategy. Title: free to John J. Osborne SP-0096 Cognitive perspective in the radiation oncology physics domain V. Valentini 1 1 Università Cattolica del Sacro Cuore - Policlinico A. Gemelli, Gemelli ART, Rome, Italy Cognitive technology can learn a new problem domain, reason through the hypotheses, resolve ambiguity, evolve towards more accuracy, and interact in natural means. Some prototype showed this approach to be enable to adapt and make sense of many data: “read” text, “see” images and “hear” natural speech with context; to interpret information, to organize it and to offer explanations of what it means, with rationale for the conclusions; to accumulate data and to derive insight at every interaction, indefinitely. The interest of this evolving technology in radiation oncology is very high. Radiotherapy is domain in medicine in which modeling the contents of the clinical choices permeates daily life. The opportunity to have a physic subdomain in radiation oncology and the interaction among all the professionals involved in this oncology field could represent a great opportunity to benefit of this approach. Possible implications of the cognitive approach in radiation Award Lecture: Honorary Physicist Award Lecture

oncology, starting from the physic subdomain, will be explored. Symposium: The optimal approach to treat oligometastastic disease: different ways to handle an indication quickly gaining acceptance SP-0097 Clinical approach to abscopal effects P.C. Lara Jimenez 1 1 Hospital Universitario de Gran Canaria Dr. Negrín, Radiation Oncology, Las Palmas de Gran Canaria- Ca, Spain SBRT is becoming a common approach to cancer treatment. By using this few, high dose per fraction schedules tumour responses are higher than predicted. Indirect cell death would account for this “extra cell kill” induced by high doses of radiotherapy. These indirect “non targeted” effects of radiotherapy could be related to vessel damage through radiation- induced endotelial apoptosis, but also, to an inmune response to reject the tumour cells. In fact, SBRT is probably the most convenient, less toxic and more powerful way to “autovaccinate” patients eliciting antigen release from dying tumour cells. Endothelial damage, increased vessel´s permeability, increased tumor infiltrating lymphocytes and “immune cell death” (ICD) types as necrosis or mitotic catastrophe that led to the release of calreticulin, ATP or HMBG-1, are mechanisms triggering the immune response. Later on, maduration of dendritic cells, APC-dependent antigen presentation to T cells in the nodes, microenviroment´s modification and immune response against the tumour, through interferón γ release, are already demonstrated. Besides this local effect, a distant immune-mediated non- targeted effect in tumor locations away from the radiotherapy treated disease, is called “abscopal effect”. Radiation-induced T cell maduration against tumour antigens “make visible” other distant tumour focii to this especifically adapted citotoxic lymphocytes (CTL). Abscopal effect after radiotherapy alone, is uncommonly observed in the clinical setting, probably due to the exhaustion of the immune response. The suppressor microenviroment surrounding the tumur focii, the CD8+ lymphocyte supression and/or PD1/PDL-1 overexpression could be major mediators of tumour resistance to the immune attack. Abscopal effect could be raised to clinical relevance by reverting this scenario, through reinvigorating the patient´s immune system. Immune chek point inhibitors (ICIs) are drugs that block the constitutive regulatory supressor mechanisms designed to prevent “autoinmune attacks” from the immune sytem, to normal tissue. These mechanisms are constitutive either in lymhocytes (CTL4/ PD-1/PD-L1) but also in tumour cells (PD-1/PDL-1). Then by “supressing the supressors” (using anti CTL4 , Anti PD-1 or anti PD-L1 antibodies) the immune system is free of the regulatory supressive signals and results reinvigorated to respond to antigen stimulii. Therefore, SBRT autovaccination-mediated antigen presentation results in increased abscopal effect as the immune system is reinvigorated by the ICI-mediated activation. Preclinical and clinical evidence support this approach. Abscopal effect rate of presentation is increased when ICIs are combined with SBRT without increase in toxicity. ICIs toxicity is mainly related to autoinmune reactions as hypophysitis, colitis etc and should be carefully monitored. Dose reduction, halt drug administration, systemic corticosteroids or in severe cases, anti-TNF a therapy should be taken in to account. But still some questions remain to be solved, namely, the best SBRT schedule, the temporal integration of SBRT and ICIs and the combinaton of SBRT and more tan one ICIs.