ESTRO 2020 Abstract book

S299 ESTRO 2020

Boost doses are linked to image intensities via prescription functions. Newer ways in which prescription functions are being derived from imaging and recurrence data will be described, emphasizing the need for the functions to reflect mechanistic considerations. A current ambiguity in image interpretation is whether a region of high tracer uptake contains more cells that are radio-resistant or cells that are more radio-resistant – semantics with very large implications for the success of dose-painting. The relative utilities of dynamic and static PET imaging for radiotherapy dose-painting will be characterized using results from a study that determined strengths of correlations between RNA sequencing data and kinetic versus static metrics of FDG uptake by breast tumours. Lastly, the importance of developing motion/mitigation strategies tailored to dose-painted treatments will be considered. [1] Trani D et al 2015 Preclinical assessment of efficacy of radiation dose painting based on intratumoral FDG-PET uptake. Clin. Cancer Res. 215511-5518 SP-0498 Theragnostic approaches for hypoxic tumours J. Adam Academic Medical Center, Amsterdam, The Netherlands Abstract text There is compelling evidence for hypoxia in tumor tissue and its therapeutic importance makes hypoxia a high priority target for cancer therapy. Hypoxia is therefore arguably one of the best validated targets in oncology, however yet to be exploited therapeutically. The mainstream strategies for hypoxia modification have been focusing on 1) improving oxygen modification using e.g. hyperbaric oxygen, carbogen, nicotinamide or nitroglycerin, 2) hypoxic cell radiation sensitization with e.g. nimorazole or 3) selectively targeting hypoxic cells using cytotoxic agents such as e.g. tirapazamine or evofosfamide. Other approaches exploit dose painting strategies to escalate radiation dose to these hypoxic areas or metabolic targeting of angiogenesis, oxygen consumption, DNA repair or autophagy. Several of these approaches however failed in advanced clinical trials due to lack of proper patient selection. Fortunately, both invasive immunohistochemical and non-invasive imaging PET and MRI methods as well as blood biomarkers and gene signatures are available to detect baseline tumoral hypoxia for patient stratification, but can also be used in a window-of-opportunity concept to assess efficacy of hypoxia targeting strategies. Abstract not received SP-0499 Biological approaches to hypoxia modification L. Dubois 1 , A. Yaromina 1 , J. Theys 1 , P. Lambin 1 1 maastricht University, Precision Medicine, Maastricht, The Netherlands

Joint Symposium: ESTRO-EANM: Targeting the microenvironment in radiotherapy: where are we now?

SP-0496 Novel approaches to characterise the tumour microenvironment U. Haberkorn 1 1 DKFZ, Nuclear Medicine, Heidelberg, Germany Abstract text Cancer associated fibroblasts (CAFs) constitute a vital subpopulation of the tumor stroma and are present in more than 90% of epithelial carcinomas. These cancer- associated fibroblasts have been shown to play an important role for different aspects of malignant tumors such as migration, metastasis, resistance to chemotherapy and immunosuppression. Therefore, a targeting of these cells may be useful for both imaging and therapy. Since many of these CAFs express the fibroblast activation protein (FAP) which is expressed in activated fibroblasts, but not in quiescent fibroblasts, this membrane-anchored enzyme can be used as a target for radionuclide-based approaches for diagnosis, therapy planning and treatment of tumors, but also for the diagnosis of non-malignant diseases associated with a remodelling of the extracellular matrix. A selective targeting of a variety of tumors can be achieved by inhibitor-based radiopharmaceuticals (FAPIs). Several compounds have been recently introduced as theranostic radiotracer and demonstrated high uptake into different FAP-positive tumors in patients. SP-0497 The BTV turns 21: Current status of clinical trials and future directions J. Fenwick 1,2 1 institute Of Translational Medicine- University Of Liverpool, Molecular And Clinical Cancer Medicine, Liverpool, United Kingdom ; 2 clatterbridge Cancer Centre, Physics, Wirral, United Kingdom Abstract text Dose-painting of biological target volumes identified from functional images was proposed by Ling at the 1998 ESTRO conference. The concept was published in 2000, initiating large-scale endeavors to make radiotherapy dose-painting a reality. Subsequent studies validated tumour functional images against histopathological markers, determined correlations between images and outcomes, characterized image stability during radiotherapy, and showed that boosting of selected tumour subvolumes was dosimetrically feasible. Phase I/II dose-painting trials have been run to determine safety and indicative efficacy, and results from phase III trials are awaited. In this lecture phase I/II trial results will be reviewed for head-and-neck, lung and prostate treatments. And the headroom for safe focal dose-boosting provided by dose- painting will be compared to estimates of the degree of dose-escalation required to achieve meaningful survival improvements when uniform doses are delivered across tumour volumes. Results will also be reviewed for a preclinical study of rhabdomyosarcoma dose-painting [1]. Unexpectedly, this study found that growth-delays were shorter for tumours treated by boosting regions of high FDG uptake than for tumours treated homogeneously with the same mean radiation doses; and that growth-delays were similar for tumours receiving boost treatments, irrespective of whether the boosts were delivered to regions of high or low FDG uptake.

Symposium: How to combine different treatment modalities in rectal cancer

SP-0500 How to select patients for a multimodal approach G. Beets (The Netherlands)

Abstract not received