ESTRO 36 Abstract Book

S97 ESTRO 36 2017 _______________________________________________________________________________________________

evolution to current treatment intensity did not consider HPV-related disease. The profiles of patients with HPV- related OPC at risk of DM are now being better understood. There is opportunity to modify approaches so that intensive local treatment can be minimized while patients at risk of DM are still selected for systemic treatments. These strategies are being carefully explored in clinical trials using risk-stratified approaches directed by relevant end-points intended to safely return to less intensive treatments analogous to those used in a previous era. SP-0192 Potential of radiation therapy to convert the tumor into an in situ vaccine S. Formenti 1 1 Weill Cornell Medical Center of Cornell University, New York- NY, USA Radiation therapy contributes both immunogenic and immunosuppressive signals to the tumor microenvironment. Preclinical strategies to enhance the formers and/or mitigate the latter have demonstrated the concrete possibility to shift this balancing act toward a therapeutic success (J Natl Cancer Inst. 2013;105(4):256- 265). Preclinical experiments in several syngeneic mouse models that mimic the setting of advanced cancer have demonstrated promise of combining radiation and immunotherapy. The preclinical data has consistently found clinical confirmation. Particularly when combined with immune checkpoint blockade, radiotherapy has demonstrated to be a powerful adjuvant to immunotherapy (Clin Cancer Res. 2005;11:728-734). Clinical examples of synergy between radiation and immune checkpoint inhibitors have been reported (N Engl J Med. 2012;366(10):925-931; Transl Oncol. 2012;5(6):404-407; Int J Radiat Oncol Biol Phys. 2013;85(2):293-295; Cancer Immunol Res 2013;1(6):365- 372) and and interim results in our prospective clinical trial confirm this finding (presented in room 1, May 17 session 051). Currently, multiple clinical trials are exploring optimal combinations and scheduling of radiotherapy and immunotherapy. Early evidence from these trials confirms the hypothesis that radiation can enhances responses to immune checkpoint inhibitors but in the majority of patients tumors remain unresponsive, warranting research to identify markers that predict response. A recent study testing radiation with ipilimumab in melanoma suggested that tumor expression of PDL-1 may predict lack of response to radiation and ipilimumab. However, in lung cancer patients treated with radiation and ipilimumab we found high PDL-1 expression among patients achieving durable complete and partial responses, without addition of PD-1 pathway inhibitors (ASTRO Proceedings 2015, abstract #149). In fact, higher expression of immune checkpoints has been hypothesized as a marker of more immunogenic tumors (Science, 2015,October 9: 207-211). In addition, pre-treatment mutational load has been found to be associated with responses to immune checkpoint inhibitors (Science, 2015 Apr 3: 124-8). It will be important to determine if radiation can compensate tumors with a low mutational load, by inducing induce de novo T cell priming to multiple tumor antigens (12) and could, therefore, achieve responses in the absence of pre-existing neoantigens (Science 2015;348(6230):69-74). The overall degree of immune impairment of the patients may also be a critical predictor of response to radiation + immunotherapy. For instance, we found the pretreatment neutrophil / lymphocyte ratio might enable a priori selection of individuals with a propensity to develop abscopal responses to the combination of radiation and GM-CSF (Lancet Oncol. 2015 Jul;16(7):795-803). Strategies at reducing radiation-induced lymphopenia are warranted to assure adequate availability of naïve T cells when radiotherapy is harnessed to convert the tumor into an

individualized cancer vaccine. Overall, while radiation has emerged as a promising partner for immunotherapy and current research is focusing at identifying tumor and patient characteristics that can predict which patients should receive upfront the combination of immunotherapy with radiotherapy instead of immunotherapy alone.

SP-0193 Quality improvement in radiotherapy: history, significance and impact of dosimetry audits J. Izewska 1 1 IAEA - International Atomic Energy Agency, Dosimetry and Medical Radiation Physics Section, Vienna, Austria The concept of verification of radiation doses in medical applications was introduced in early 20th century, not long after radiation started to be used for treating cancer. Initially, to estimate the adequate daily fraction of radiation to be given to patients physicians exposed the skin of their own arms to radiation to produce the ‘erythema dose’. Since then, the methodologies, dose measurement tools and radiation therapy equipment have made a great progress. In 1925 R. Sievert established a circulating physical department for standardizing the Roentgen radiation used in cancer therapy in Sweden. The department found some unreliable dose meters and identified the need for better protective equipment. At the same time, the measurements of percentage depth doses collected during the visits were used as a reference dataset for the Roentgen facilities in Sweden. Another example of early dosimetry audits was documented in Poland; following the idea by Marie Curie, the Measurement Laboratory was established in 1936 for radiation dose measurements at Polish hospitals using radium and X-ray beams. The Dosimetry Laboratory of the International Atomic Energy Agency (IAEA) was set up in early 1960s with the aim of the provision of dosimetry audits for radiotherapy centres worldwide and for ensuring international consistency in radiation dosimetry. First trial inter- hospital comparisons were implemented by the IAEA in 1965–1966. In parallel, dosimetry comparisons of Co-60 and high energy beams from early medical accelerators were conducted among hospitals of France, Sweden, and in other countries. In USA, the Radiological Physics Center was established in 1968 to operate as an independent quality assurance office for multi-institutional cooperative group clinical trials. Since 1969, the calibration of radiotherapy beams in 2200 hospitals in 132 countries has been verified by the IAEA jointly with the World Health Organization (WHO) through postal dosimetry audits. One important part of the auditing process is related to resolving dosimetry discrepancies occurring in the audit; errors are traced, analysed and corrected. In early years, only approximately 50% audited centres had the acceptable beam calibration. Over the time, several radiotherapy centres improved their practices, and the current percentage of acceptable results exceeds 97%.