ESTRO 36 Abstract Book

S254 ESTRO 36 _______________________________________________________________________________________________

Maastricht, The Netherlands 3 Maastricht University Medical Centre, Nuclear Medicine, Maastricht, The Netherlands 4 Netherlands Cancer Institute-Antoni Van Leeuwenhoek Hospital, Nuclear Medicine, Amsterdam, The Netherlands Purpose or Objective Nitroglycerin is a nitric oxide donor being investigated because of its potential to increase tumour oxygenation. In phase II trial NCT01210378 nitroglycerin is added to radical radiotherapy in patients with NSCLC stage IB-IV. Using hypoxia PET tracer [ 18 F]HX4 and dynamic contrast enhanced CT-scans (DCE-CT) we investigate in a subtrial the effect of nitroglycerin on tumour hypoxia and perfusion. Here, we report the final results of all patients that entered the subtrial. Material and Methods Prior to the start of radiotherapy baseline [ 18 F]HX4 PET (4h p.i.) and DCE-CT scans were performed to measure hypoxia and perfusion in the primary gross tumour volume (GTVp) and nodes (GTVn). At least 48 hours later, DCE-CT and [ 18 F]HX4 PET scans were repeated after application of a Transiderm nitro 5 mg patch. Between scans, patients did not receive any treatment. GTVp and GTVn were defined on the planning FDG-PET-CT scan and copied onto the HX4 and DCE-CT scans after registration of the images to the planning CT. For HX4, tumour-to-blood ratio (HX4- TBR), hypoxic fraction (HX4-HF; fraction of volume with TBR >1.4) and hypoxic volume (HX4-HV; volume with TBR >1.4) were calculated for all lesions. Perfusion parameters blood volume (BV) and blood flow (BF) were calculated. Differences between paired measurements were assessed using the Wilcoxon Signed rank test. Correlation coefficients were calculated using Spearman’s correlation coefficient (SPSS, IBM, Germany). Results Performed scans are summarized in table 1.

Symposium with Proffered Papers: Novel approaches in thoracic tumour treatment

SP-0479 Primary human Lung (stem) cell models to study adverse effects of cancer treatments M. Vooijs 1 1 MAASTRO GROW Research Institute, Radiation Oncology, Maastricht, The Netherlands Lung cancer represents the leading cause of cancer death worldwide. The current standard of care includes combinations of surgery, , chemotherapy and radiotherapy. New treatments based on molecular insight of driver mutations in cancers are urgently needed to obtain more durable responses and longer survival. We and others have previously reported that deregulation of the NOTCH signaling pathway is associated with poor outcome and treatment resistance in non-small cell lung cancer in patients and in preclinical models. Cancer treatments are always limited by dose-limiting side-effects which negatively affects tumour control and quality of life. Reducing side effects may improve tumor control by increasing dose and treatment duration. What is currently lacking are robust primary human tissue models that enable evaluation of deleterious normal tissue effects. Here I will discuss the use of 2D and 3D primary human lung tissue models to study the effects of lung cancer treatments on normal tissue response. Such models may useful in parallel to in vitro tumor cell models to select the most optimal personalized precision treatment. SP-0480 Secretome as novel target for lung cancer M. Pruschy 1 1 University Hospital Zürich, Department of Radiation Oncology, Zurich, Switzerland For lung carcinoma, the initial biopsy material, fine needle aspirates, and in case of surgery the resected tumor, are often the only biological materials available for direct molecular analysis. The gold standard for molecular analysis therefore includes histological and cytogenetic analysis and DNA-extraction followed by mutational analysis. However, it is also of high importance to have access to tumor material during and in response to radiotherapy to gain insights into the treatment response on the molecular and cellular level and to develop putative (surrogate) markers. As such biomarker analysis of tumor-derived blood serum factors in tumor patients represents an additional minimally invasive approach to eventually identify predictive and prognostic factors. The serum proteome (secretome) can be analyzed prior to therapy start (basal level), following single high dose irradiation but also consecutively during the time course of a fractionated treatment regimen in order to identify (dynamic) responses to treatment. Such serum factors also affect the radiation resistance in an auto- and/or paracrine way via the tumor microenvironment and might act as potential targets for combined treatment modalities with ionizing radiation. Here we will discuss recent preclinical and clinical approaches and achievements to analyze the treatment-induced secretome from lung carcinoma and to exploit specific secretome factors as part of a combined treatment modality with radiotherapy. OC-0481 Effects of nitroglycerin on perfusion and hypoxia in non-small cell lung cancer lesions. B. Reymen 1 , A.J.G. Even 1 , C.M.L. Zegers 1 , W. Van Elmpt 1 , M. Das 2 , J. Wldberger 2 , F. Mottaghy 3 , E. Vegt 4 , D. De Ruysscher 1 , P. Lambin 1 1 MAASTRO Clinic, Radiation Oncology, Maastricht, The Netherlands 2 Maastricht University Medical Centre, Radiology,

In total 22/32 patients (69%) showed hypoxia at baseline in primary tumor and/or lymph nodes. In the 11 hypoxic tumors a significant negative correlation was found between baseline HX4-TBR and tumor blood flow (r=- 0.618, p=0.043) and blood volume (r=-0.736, p=0.010). (Fig 1).