ESTRO 36 Abstract Book

S483 ESTRO 36 2017 _______________________________________________________________________________________________

adjusted and thresholded to create a binary 3D vessel map (VM). Hoechst-negative vessels were excluded from the VM. These VMs were used to simulate 3D oxygen distributions based on a Michaelis-Menten relation. An average input function (AIF) was determined by fitting activities in the left ventricles over 4 mice to derive mean parameters. Based on oxygen distribution and AIF, FMISO retention was simulated on the same VMs. FMISO-positive regions of 3x3mm2 in the tumor center in 5 random sections were compared against manually contoured pimo-positive regions to validate the simulation by determining hypoxic fraction (HF) and overlap ratio. Necrosis was excluded based on H/E staining on the same sections. To compare 3D and 2D simulations, the simulations and analysis were repeated in 2D. Parameters for all simulations were set to commonly used values (Mönnich et al., 2011).

realistic VMs can help to optimize clinical imaging protocols and image analysis tools. PO-0888 Response monitoring by 18FDG-PET in locally advanced NSCLC treated with concurrent chemoradiotherapy J.N.A. Van Diessen 1 , M. La Fontaine 2 , M. Van den Heuvel 3 , W. Vogel 4 , J.S.A. Belderbos 1 , J.J. Sonke 2 1 Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Radiation Oncology, Amsterdam, The Netherlands 2 Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Academic Physics, Amsterdam, The Netherlands 3 Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Pulmonology, Amsterdam, The Netherlands 4 Netherlands Cancer Institute Antoni van Leeuwenhoek Hospital, Nuclear Medicine, Amsterdam, The Netherlands Purpose or Objective The randomized phase 2 Raditux-trial (NTR2230) in locally advanced non-small cell lung cancer (NSCLC), investigating the additional benefit of Cetuximab to concurrent chemoradiotherapy (CCRT) did not show improved survival but revealed a remarkable 5-year overall survival (OS) of 37.3% [1]. Patients were staged with 18 FDG-PET-scans before and 4 weeks after CCRT. The purpose of this study was to investigate whether PET metrics have prognostic value in relation to local, regional, and distant failure. Material and Methods In the Raditux-trial, 102 stage IIIA-B NSCLC patients were included. CCRT consisted of 66 Gy in 24 fractions (using IMRT) combined with daily low dose Cisplatin. A subgroup of the patients had a repeat 18 FDG-PET-scan for response evaluation of the primary tumor and lymph nodes after a median of 4.2 weeks (range, 1.6-10.1). Twenty patients underwent additional surgery and were excluded. Ten patients were excluded due to technical reasons. The pre- and post-treatment 18 FDG-PET-scans from the remaining 42 patients were anatomically registered with the planning CT-scan. The following pre-and post-treatment PET metrics were calculated of the primary tumor (PT) as well as the combined lymph nodes (LNs): SUV max , total lesion glycolysis (TLG) and metabolic tumor volume (MTV). The response ratio between the pre- and post-treatment values was also calculated. These parameters were tested as prognostic factors using the Kaplan-Meier method and Cox regression analysis for univariate and multivariate analyses. Results Forty-two patients were evaluated for the prognostic value of the PET metrics. The median follow-up and OS was 32 and 33 months, respectively. Median GTV of the PT and the LNs was 80 cc (range, 2-439) and 27 cc (range, 2- 195). The SUV max of both PT and LNs decreased significantly as well as TLG of the PT and MTV of the LNs (p≤0.001). The post-treatment and the response ratio of the SUV max of the LNs was correlated significantly with regional failure (p=0.009; p=0.009) (Table 1). The response ratio of the SUV max of the LNs was also significantly correlated with OS (p=0.014). No parameters corresponded with local and distant failure. Table 1 The P-values and HR of the PET metrics of the primary tumor (PT) related to local failure and combined lymph nodes (LNs) related to regional failure of the pre- and post-treatment 18 FDG-PET-scan as well as the response ratio.

Results Differences in experimental and 3D-simulated hypoxic fractions (HF) were not significant, while differences between experimental and 2D-simulated HF was significantly different for Tumor 2 (p=0.02, cf. Table). 3D simulations matched much better with pimo distribution than 2D simulations only. The true-positive rate was increased about 0.2 for both tumors, the true- negative rate by about 0.08 for 3D simulations when compared to 2D. 56% of 3D-simulated FMISO-positive voxels were located within pimo-positive areas, while another 14% were located within 50µm distance, as to 37% and 8% for 2D, respectively (cf Table, Figure). Conclusion When performing hypoxia tracer simulations on actual VMs, 3D models accounting for out-of-plane diffusion must be used to obtain realistic results. In a 3D vascular model, spatial tracer distributions similar to those observed in vivo can be simulated. Hence, 3D FMISO simulation on