ESTRO 36 Abstract Book

S6 ESTRO 36 _______________________________________________________________________________________________

OC-0018 Chemoradiation-induced altered profile of PD-L1 and CD8+ TILs indicated prognosis in rectal cancer Y.J. Lim 1 , J. Koh 2 , S. Kim 2 , S.R. Jeon 3 , E.K. Chie 1 , K. Kim 4 , G.H. Kang 2 , S.W. Han 5 , T.Y. Kim 5 , S.Y. Jeong 6 , K.J. Park 6 , H.G. Wu 1 1 Seoul National University Hospital, Radiation Oncology, Seoul, Korea Republic of 2 Seoul National University Hospital, Pathology, Seoul, Korea Republic of 3 Seoul National University, Cancer Research Institute, Seoul, Korea Republic of 4 Ewha Womans University School of Medicine, Radiation Oncology, Seoul, Korea Republic of 5 Seoul National University Hospital, Internal Medicine, Seoul, Korea Republic of 6 Seoul National University Hospital, Surgery, Seoul, Korea Republic of Purpose or Objective Cytotoxic chemoradiotherapy (CRT)-induced impact on the programmed death-1 (PD-1)/ programmed death-ligand 1 (PD-L1) checkpoint activity in human cancers has not been much explored. This study evaluated CRT-induced changes in the expression levels of PD-L1 and CD8 + tumor-infiltrating lymphocytes (TILs) and prognostic associations in rectal cancer. Material and Methods We analyzed pre-CRT biopsies and the corresponding post-CRT resected tissues of 123 rectal cancer patients undergoing preoperative CRT followed by surgery between 2005 and 2012. Immunohistochemical staining of PD-L1 and CD8 was performed for the paired specimens. Results The median values of PD-L1 H-score and density of CD8 + TILs for pre and post-CRT tissues were 0 and 100, and 319.66 and 787.05 cells/mm 2 , respectively. CRT induced increases in the expression levels of PD-L1 and CD8 + TILs (P < 0.001 for both), and patients with sustained high level of PD-L1 both at pre and post-CRT showed less increase in the density of CD8 + TILs than the others (P = 0.020). Defining the low or high level of the PD-L1 and CD8 + TILs before and after CRT, patients with high-to-high level of PD-L1 had poorer overall survival (OS) and disease- free interval (DFI) (P = 0.018 and 0.029, respectively), whereas the low-to-low density of CD8 + TILs was associated with inferior DFI (P = 0.010). Considering the existence or non-existence of the high-to-high PD-L1 level or low-to-low density of CD8 + TILs, patients with one or more of the factors showed significantly worse OS and DFI (P = 0.020 and 0.002, respectively). Conclusion This study verified that preoperative CRT resulted in the immunologic shift toward increases in the PD-L1 expression and density of CD8 + TILs in rectal cancer. The poor prognostic subset was identified based on the CRT-induced change profiles, suggesting the potential candidates who can benefit from combining checkpoint inhibitors and CRT. Joint symposium ESTRO-AAPM: New technological and computational developments in particle therapy SP-0019 Scaling down proton therapy facilities to fit into photon vaults T. Bortfeld 1 , S. Yan 1 , B. Clasie 1 1 Mass. General Hospital, Radiation Oncology, Boston- MA, USA Proton therapy technology is rapidly evolving. Newer designs exhibit substantial reduction in size, weight and cost compared to the first generation. In the first part of this talk, we will review state of the art compact proton therapy systems. We will focus particularly on single room solutions and highlight the physics and technology behind solutions that enable the size reduction of accelerator and gantry designs.

In spite of the already achieved and remarkable progress towards more compact and affordable proton therapy systems, all current systems require construction of dedicated buildings to house them which are significantly larger (and more costly) than conventional treatment rooms for photon therapy. In the second part of this talk, we will explore the potential to build even more compact proton systems. We will first review a project that is underway at the Massachusetts General Hospital where we retrofit a proton therapy system into two neighboring photon vaults within an existing building. The system is almost installed and awaiting testing and commissioning. The progress and challenges with this approach will be discussed. Finally, we will give an outlook with possible designs that enable a proton therapy system to be installed in a single conventional photon therapy vault. We will discuss the technical hurdles that need to be overcome to realize this vision. These ultra-compact solutions will likely not include a gantry but rather a fixed beamline with advanced robotics and imaging solutions for patient positioning. SP-0020 Integrating CBCT in ion beam therapy: challenges and opportunities beyond anatomical guidance K. Teo 1 1 Hospital of the University of Pennsylvania, Department of Radiation Oncology TRC 2 West, Philadelphia- PA, USA Cone beam CT (CBCT) is an important imaging modality for image guided radiation therapy (IGRT). In ion beam therapy, volumetric imaging offered by CBCT has important potential applications beyond anatomical guidance. Ion beam therapy dose distribution is sensitive to daily setup variation, motion and anatomical change such as tumor response, atelectasis, pleural effusion, bowel gas and organ filling. While CBCT may be used to assess these variations in a qualitative manner, a more quantitative analysis requires accurate Hounsfield units (HUs) for conversion to ion stopping power. In this presentation, the methods to improve the accuracy of CBCT HUs are reviewed. These techniques will enable water equivalent thickness (WET) measurements and dose estimation to be performed using CBCT. We demonstrate both qualitative and quantitative analyses of CBCT for different treatment sites and discuss the development of tools that will streamline adaptive proton therapy. These include extraction of image and dosimetric features that are predictive of the need for replanning as well as online replanning tools. SP-0021 New horizons in probabilistic and robust treatment planning in particle therapy M. Alber 1 1 Alber Markus, Department of Radiation Oncology, Heidelberg, Germany Treatment related uncertainties give rise to the risk of loss in all quality scores of a treatment plan. Risk mitigation strategies can be largely blind to the magnitude and frequency of losses, and still be effective, like the PTV concept in photon therapy. However, all risk mitigation in one quality score comes at a price in most others. In particular, risk mitigation of systematic errors (by treatment planning) can be costly, ineffective and even in the best case: unfair. For example, whenever a protocol requires that a larger volume than the CTV is irradiated because some patients need this, all other patients pay the price. Ultimately, the precise quantification of loss- risk-distributions becomes a necessity. The term “robust optimization” is commonly used to express that the source of the uncertainty is directly considered during dose optimization instead of solving a substitute problem that is construed to yield a robust result (such as the PTV